21 CFR 336.10 - Antiemetic active ingredients.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Antiemetic active ingredients. 336.10 Section 336...) DRUGS FOR HUMAN USE ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 336.10 Antiemetic active ingredients. The active ingredient of the product consists of any of the following when...
21 CFR 336.10 - Antiemetic active ingredients.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Antiemetic active ingredients. 336.10 Section 336...) DRUGS FOR HUMAN USE ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 336.10 Antiemetic active ingredients. The active ingredient of the product consists of any of the following when...
21 CFR 336.10 - Antiemetic active ingredients.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antiemetic active ingredients. 336.10 Section 336...) DRUGS FOR HUMAN USE ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 336.10 Antiemetic active ingredients. The active ingredient of the product consists of any of the following when...
21 CFR 336.10 - Antiemetic active ingredients.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Antiemetic active ingredients. 336.10 Section 336...) DRUGS FOR HUMAN USE ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 336.10 Antiemetic active ingredients. The active ingredient of the product consists of any of the following when...
21 CFR 336.10 - Antiemetic active ingredients.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Antiemetic active ingredients. 336.10 Section 336...) DRUGS FOR HUMAN USE ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 336.10 Antiemetic active ingredients. The active ingredient of the product consists of any of the following when...
Anti-emetic principles of Poria cocos.
Tai, T; Akita, Y; Kinoshita, K; Koyama, K; Takahashi, K; Watanabe, K
1995-12-01
The triterpenes isolated from P. cocos and their derivatives were examined for anti-emetic activity. Some of these triterpenes inhibited emetic action induced by oral administration of copper sulfate pentahydrate to leopard frog. The triterpenes having an exomethylene group at C-24 showed anti-emetic activity to frogs.
[Research on antiemetics: an Italian model of success].
Roila, F
1998-01-01
At the beginning of the 80's the Italian Group for Clinical Research (G.O.I.R.C.) identified chemotherapy-induced nausea and vomiting as one of the most distressing adverse events, and decided to plan and execute clinical trials on antiemetics in order to reduce this negative impact on patients. Therefore, some consecutive double-blind randomized trials were conducted on cisplatin-treated patients. The first was a dose-finding study on four different high-doses of domperidone, followed by a study comparing two different high-doses of metoclopramide, and a study comparing the addition of a corticosteroid to high-dose metoclopramide with respect to metoclopramide alone. Finally, a study demonstrating that a combination of a higher dose of metoclopramide (3 mg/kg x 2) plus dexamethasone and diphenhydramine was significantly superior with respect to a lower dose of metoclopramide (1 mg/kg x 4) combined with methylprednisolone was carried out. With the introduction of the 5-HT3 receptor antagonists the interest for antiemetic therapy increased and other Italian gynecological and medical oncology centres became involved in the antiemetic research. The Italian Group for Antiemetic Research was formed in 90's and its first study demonstrated the superiority of a combination of a 5-HT3 receptor antagonist plus dexamethasone with respect to the standard three drug combination of high doses of metoclopramide in the prevention of cisplatin-induced acute emesis. In the following years, the Group contributed to the identification of the best antiemetic prophylaxis for acute emesis induced by moderately emetogenic chemotherapy, and for delayed emesis induced by cisplatin. Also a drug utilization review on antiemetics in clinical practice has recently been carried out. Today, the interest of the Group is concentrated in studying the optimal antiemetic prophylaxis for delayed emesis induced by moderately emetogenic chemotherapy. The rules always followed by the Italian Group for
The effect of antiemetics in childhood gastroenteritis
2013-01-01
Introduction Diarrheal diseases are the second leading cause of childhood morbidity and mortality in developing countries and an important cause of malnutrition. An estimated 0.75 million children below 5 years of age die from diarrhea. Vomiting associated with acute gastroenteritis (AGE) is a distressing symptom and limits the success of oral rehydration in AGE leading to an increased use of intravenous rehydration, prolonged emergency department stay and hospitalization. In this review we estimate the effect of antiemetics in gastroenteritis in children. Methods We conducted a systematic review of all the efficacy and effectiveness studies. We used a standardized abstraction and grading format and performed meta-analyses for all outcomes with more than two studies. The estimated effect of antiemetics was determined by applying the standard Child Health Epidemiology Reference Group (CHERG) rules. Results We included seven studies in the review. Antiemetics significantly reduced the incidence of vomiting and hospitalization by 54%. Antiemetics also significantly reduced the intravenous fluid requirements by 60%, while it had a non-significant effect on the ORT tolerance and revisit rates. Conclusion Antiemetics are effective for the management of gastroenteritis in children and have the potential to decrease morbidity and mortality burden due to diarrhea, when introduced and scaled up. PMID:24564795
Enhanced Patient Expectant and Antiemetic Drug Efficacy
1999-07-01
Breast Cancer Nausea and Vomiting Expectancy Patient Information Antiemetic Side Effect 15. NUMBER OF PAGES 15 16. PRICE CODE 17. SECURITY ...CLASSIFICATION OF REPORT Unclassified 18. SECURITY CLASSIFICATION OF THIS PAGE Unclassified 19. SECURITY CLASSIFICATION OF ABSTRACT...5-HT3 receptor antagonist class of antiemetics (ondansetron, granisetron , tropisitron) have greatly reduced chemotherapy-related vomiting, this has
Enhanced Patient Expectation and Antiemetic Drug Efficacy
1999-07-01
NUMBER OF PAGES 15 Breast Cancer Expectancy Antiemetic Nausea and Vomiting Patient Information Side Effect 16. PRICE CODE 17. SECURITY CLASSIFICATION 18... SECURITY CLASSIFICATION OF THIS 19. SECURITY CLASSIFICATION 20. LIMITATION OF ABSTRACT OF REPORT PAGE OF ABSTRACT Unclassified Unclassified...by the introduction of the 5-HT 3 receptor antagonist class of antiemetics (ondansetron, granisetron , tropisitron) have greatly reduced chemotherapy
Antiemetic therapy for non-anthracycline and cyclophosphamide moderately emetogenic chemotherapy.
Inui, Naoki
2017-05-01
Although antiemetic management in cancer therapy has improved, chemotherapy-induced nausea and vomiting remain common and troubling adverse events. Chemotherapeutic agents are classified based on their emetogenic effects, and appropriate antiemetics are recommended according to this categorization. Chemotherapy categorized as moderately emetogenic is associated with a wide spectrum of emetic risks. Combined anthracycline and cyclophosphamide regimens have been recently reclassified as highly emetogenic chemotherapy regimen. This review focuses on antiemetic pharmacotherapy in patients receiving non-anthracycline and cyclophosphamide-based moderately emetogenic chemotherapy regimens. Combination therapy with a 5-hydroxytryptamine-3 receptor agonist, preferably palonosetron, and dexamethasone is the standard therapy in moderately emetogenic chemotherapy, although triple therapy with add-on neurokinin-1 receptor antagonist is used as an alternative treatment strategy. Among moderately emetogenic chemotherapy regimens, carboplatin-containing chemotherapy has considerable emetic potential, particularly during the delayed phase. However, the additional of a neurokinin-1 receptor antagonist to the standard antiemetic therapy prevents carboplatin-induced nausea and vomiting. For regimens including oxaliplatin, the benefit of adding neurokinin-1 receptor antagonist requires further clarification.
Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--an update.
Grunberg, Steven M; Osoba, David; Hesketh, Paul J; Gralla, Richard J; Borjeson, Sussanne; Rapoport, Bernardo L; du Bois, Andreas; Tonato, Maurizio
2005-02-01
Development of effective antiemetic therapy depends upon an understanding of both the antiemetic agents and the emetogenic challenges these agents are designed to address. New potential antiemetic agents should be studied in an orderly manner, proceeding from phase I to phase II open-label trials and then to randomized double-blind phase III trials comparing new agents and regimens to best standard therapy. Use of placebos in place of antiemetic therapy against highly or moderately emetogenic chemotherapy is unacceptable. Nausea and vomiting should be evaluated separately and for both the acute and delayed periods. Defining the emetogenicity of new antineoplastic agents is a challenge, since such data are often not reliably recorded during early drug development. A four-level classification system is proposed for emetogenicity of intravenous antineoplastic agents. A separate four-level classification system for emetogenicity of oral antineoplastic agents, which are often given over an extended period of time, is also proposed.
Yu, Shiying; Burke, Thomas A; Chan, Alexandre; Kim, Hoon-Kyo; Hsieh, Ruey Kuen; Hu, Xichun; Liang, Jin-Tung; Baños, Ana; Spiteri, Carmel; Keefe, Dorothy M K
2015-01-01
This paper reports prescribing patterns for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in six Asia Pacific countries. In a prospective noninterventional study, 31 sites in Australia, China, India, Singapore, South Korea, and Taiwan recorded details of CINV prophylaxis for the acute phase (first 24 h) and delayed phase (days 2-5) after single-day HEC or MEC for adult patients. Additional information on CINV prophylactic medications was collected from 6-day patient diaries. Primary antiemetic therapies were defined as corticosteroids, the 5-hydroxytryptamine-3 receptor antagonists (5HT3-RAs), and neurokinin-1 receptor antagonists (NK1-RAs). Evaluable patients in cycle 1 numbered 648 (318 [49%] HEC and 330 [51%] MEC) of mean (SD) age of 56 (12) years, including 58% women. For the acute phase after HEC, overall (and country range), 96% (91-100%) of patients received a 5HT3-RA, 87% (70-100%) a corticosteroid, and 43% (0-91%) an NK1-RA. CINV prophylaxis for the HEC delayed phase was more variable: including 22% (7-65%) 5HT3-RA, 52% (12-93%) corticosteroid, and 46% (0-88%) NK1-RA. For the MEC acute phase, 97% (87-100%) of patients received 5HT3-RA and 86% (73-97%) a corticosteroid. For the MEC delayed phase, 201 patients (61%) received a primary antiemetic, including 5HT3-RA (41%), corticosteroid (37%), and/or NK1-RA (4%). The 5HT3-RAs were prescribed consistently in all countries, while prescribing of other antiemetic therapies was variable, and corticosteroids were under-prescribed for CINV prophylaxis, particularly in the delayed phase.
Anti-emetic principles of Magnolia obovata bark and Zingiber officinale rhizome.
Kawai, T; Kinoshita, K; Koyama, K; Takahashi, K
1994-02-01
Magnolol and honokiol, biphenyl compounds, were isolated as anti-emetic principles from the methanolic extract of Magnolia obovata bark. [6]-, [8]-, and [10]-shogaols and [6]-, [8]-, and [10]-gingerols were isolated from the methanolic extract of Zingiber officinale rhizome as anti-emetic principles. Some phenyl-propanoids with allyl side-chains were found to show the same activity. They inhibited the emetic action induced by the oral administration of copper sulfate pentahydrate to leopard and ranid frogs.
Anti-emetic principles of Inula linariaefolia flowers and Forsythia suspensa fruits.
Kinoshita, K; Kawai, T; Imaizumi, T; Akita, Y; Koyama, K; Takahashi, K
1996-05-01
The anti-emetic effects of 40 extracts made from 12 traditional Chinese herbal drugs were examined. Ten extracts inhibited emesis induced by copper sulfate pentahydrate; all were administered orally, and one extract inhibited emesis induced by apomorphine hydrochloride given to leopard and ranid frogs. Taraxasteryl palmitate and acetate, bigelovin and dihydrobigelovin were isolated from the CHCl(3) extract of Inula linariaefolia flowers, and identified as the active antiemetic agents when emesis was induced by copper sulfate. In addition, chlorogenic acid was isolated from the MeOH extract as an anti-emetic principle for the emesis induced by apomorphine hydrochloride. Rengyol, phillyrin and rutin were isolated from the MeOH extract of Forsythia suspensa fruits and identified as the inhibitors of emesis induced by copper sulfate pentahydrate. Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.
Antiemetic Medicines: OTC Relief for Nausea and Vomiting
... used as antiemetics. These include: Bismuth subsalicylate (2 brand names: Kaopectate, Pepto-Bismol). It may help treat ... vomiting caused by motion sickness. These include dimenhydrinate (brand name: Dramamine) and meclizine hydrochloride (brand name: Dramamine ...
Antiemetics With Concomitant Sedative Use in Civil Aviation Pilot Fatalities: From 2000 to 2006
2007-10-01
Unclassified Unclassified 13 Form DOT F 1700.7 (8-72) Reproduction of completed page authorized iii CONTENTS INTRODUCTION...sedative hypnotics , and ethanol. Antiemetics and drugs with antiemetic properties such as metoclopramide, diphenhydramine (a sedating...antihistamines, ethanol, barbiturates, serotonin modulators, and/or sedative- hypnotics . Antihistamines such as diphenhydramine are commonly used. The
Off-label prescribing patterns of antiemetics in children: a multicenter study in Italy.
Zanon, Davide; Gallelli, Luca; Rovere, Francesca; Paparazzo, Rossella; Maximova, Natalia; Lazzerini, Marzia; Reale, Antonio; Corsetti, Tiziana; Renna, Salvatore; Emanueli, Tullia; Mannelli, Francesco; Manteghetti, Francesco; Da Dalt, Liviana; Palleria, Caterina; Banchieri, Nicola; Urbino, Antonio; Miglietta, Mario; Cardoni, Giovanni; Pompilio, Adriana; Arrighini, Alberto; Lazzari, Clara; Messi, Gianni
2013-03-01
Acute gastroenteritis (AG) represents both the main cause of acute vomiting in children under 3 years old and a major cause of access to the emergency department. Even if several drugs may be able to reduce the emesis, the pharmacological treatment of vomiting in children remains a controversial issue, and several drugs are prescribed outside their authorized drug label with respect dosage, age, indication, or route of administration and are named as off-label. The aim of present study was to assess the off-label use of antiemetic drugs in patients less than 18 years with vomiting related to AG. This study was carried out in eight pediatric emergency departments in Italy. The following data were obtained crossing the pharmacy distribution records with emergency departments' patient data: sex and age of the patients and detailed information for each drug used (indication, dose, frequency, and route of administration). We recorded that antiemetic drugs were prescribed in every year, particularly in children up to 2 years old, and compared with both literature data and data sheet; 30 % of the administered antiemetics were used off-label. In particular, domperidone was the only antiemetic used labeled for AG treatment in pediatric patients, while metoclopramide and ondansetron have been off-label for both age and indications (i.e., AG treatment). In conclusion, we documented an off-label use of antiemetics in children, and this could represents a problem of safety for the patient and a legal risk for the prescribing physician if patients have an unwanted or bad outcome from treatment.
Mantione, Nina L; Otto, Cynthia M
2005-12-01
To characterize the use of antiemetic agents in dogs with canine parvovirus (CPV)-associated enteritis in a veterinary teaching hospital. Retrospective case series. 77 dogs with CPV-associated enteritis. Medical records of 560 dogs with confirmed CPV-associated enteritis that were admitted to a veterinary teaching hospital were reviewed. Exclusion criteria included vaccination against CPV infection within the preceding 2 weeks, hospitalization for < 24 hours or removal from the hospital against advice, or an incomplete record. Signalment, duration of hospitalization, and daily antiemetic administrations were assessed; WBC counts and clinical findings were used to classify dogs as having systemic inflammatory response syndrome (SIRS). 77 dogs were included in the study; 55 (71%) received antiemetics (53 received metoclopramide at least once). Seventy-one dogs survived, and 6 dogs died (all 6 received antiemetics). Compared with dogs that did not receive antiemetics, duration of hospitalization was significantly longer for antiemetic-treated dogs. Daily values of rectal temperature and heart and respiratory rates did not predict administration of antiemetics or duration of hospitalization; however, compared with survivors, SIRS developed more frequently among nonsurvivors. Assessment of emetic events recorded hourly for 17 dogs indicated that antiemetic treatment did not control emesis. Many dogs with CPV-associated enteritis had persistent vomiting despite antiemetic administration. The apparent difference in duration of hospitalization between antiemetic-treated dogs and other dogs may reflect a difference in disease severity between groups, although antiemetic-associated adverse events (e.g., signs of depression, hypotension, and immune modulation) may prolong hospitalization.
Matok, Ilan; Clark, Shannon; Caritis, Steve; Miodovnik, Menachem; Umans, Jason G; Hankins, Gary; Mattison, Donald R; Koren, Gideon
2014-12-01
Vitamin B6 has been known to possess antiemetic effects since 1942. This water soluble compound has several forms in the circulation including pyridoxine, pyridoxal, and pyridoxal phosphate. The active antiemetic form of vitamin B6 is unknown. This was a pre-specified substudy of a randomized, placebo-controlled trial comparing the antiemetic effect of the doxylamine-vitamin B6 combination (Diclectin®) (n = 131) to placebo (n = 126) in women with nausea and vomiting of pregnancy. Serum concentrations of pyridoxine, pyridoxal, and pyridoxal 5' phosphate (PLP) and doxylamine were measured on Days 4, 8, and 15. With Diclectin® exhibiting a significant antiemetic effect in pregnancy, serum concentrations of pyridoxine were unmeasurable in almost all patients and those of pyridoxal were undetectable in half of patients. In contrast, PLP was measurable at sustained, stable steady-state levels in all patients. Our data suggest that there is a correlation between PLP levels and PUQE score of morning sickness symptoms when pyridoxine and pyridoxal levels are undetectable, and hence they might be prodrugs of PLP, which may be the active antiemetic form of vitamin B6. © 2014, The American College of Clinical Pharmacology.
Anti-emetic effect of oculo-acupuncture on dogs with xylazine induced vomiting.
Liu, Jianzhu; Lee, Yoo-Teak; Lee, Sang-Eun; Lee, Jung-Yeon; Kim, Duck-Hwan
2007-01-01
The present study was conducted in order to clarify the anti-emetic effect of oculo-acupuncture (OA) on dogs with xylazine-induced vomiting, and also to compare the anti-emetic effect of OA and body acupuncture (AP). Twelve dogs induced to vomit by xylazine were selected from total 29 mongrel dogs in preliminary experiment and were used as subjects in this study. This study was comprised of two experiments. In experiment 1, the anti-emetic effects of OA on dogs were examined in the stomach/spleen region (experimental group I), the zhongjiao region (experimental group II), and the stomach/spleen region plus the zhongjiao region (experimental group III) using 12 dogs induced to vomit for one week interval repeatedly. On the other hand, needle acupuncture (AP) (BL20 + BL21, experimental group A) and OA (stomach/spleen and zhong jiao regions) combined with needle AP (BL20 + BL21) (experimental group B) were examined using 6 vomiting dogs, for one week interval repeatedly in experiment 2. As a result, the vomiting rates of experimental group I (50%, p < 0.05), experimental group II (58.3%) and experimental group III (41.6%, p < 0.01) were lower than that of control (100%), respectively in experiment 1. The vomiting rates of both experimental group A (50%, p < 0.05) and experimental group B (50%, p < 0.05) were lower than that of control (100%) in experiment 2. The starting vomiting time in experimental groups was similar to that of the control groups in experiment 1 and 2. This study demonstrated that OA had anti-emetic effects on dogs with xylazine-induced vomiting and OA in the stomach/spleen region plus the zhongjiao region was the most effective in anti-emesis among the experimental groups. In addition, body AP and OA combined with body AP had a similar anti-emetic effect on dogs with xylazine-induced vomiting.
Rabin, B M; Hunt, W A
1983-04-01
A series of experiments were run to evaluate the effect of antiemetics on the acquisition and recall of a conditioned taste aversion induced by exposure to ionizing radiation or by injection of lithium chloride. Groups of male rats were exposed to 100 rad gamma radiation or 3 mEq/kg lithium chloride following consumption of a 10% sucrose solution. They were then injected with saline or with one of three antiemetics (prochlorperazine, trimethobenzamide, or cyclizine) at dose levels that have been reported to be effective in attenuating a previously acquired lithium chloride-induced taste aversion. The pretreatments with antiemetics had no effect on the acquisition or recall of either the lithium chloride- or radiation-induced taste aversion. The data suggest that antiemetics do not disrupt lithium chloride-induced taste aversions as previously reported, nor do they effect radiation-induced taste aversion learning.
Patil, Vijay; Noronha, Vanita; Joshi, Amit; Parikh, Purvish; Bhattacharjee, Atanu; Chakraborty, Santam; Jandyal, Sunny; Muddu, Vamshi; Ramaswamy, Anant; Babu, K. Govinda; Lokeshwar, Nilesh; Hingmire, Sachin; Ghadyalpatil, Nikhil; Banavali, Shripad
2017-01-01
Purpose Adherence to international antiemetic prophylaxis guidelines like those of ASCO can result in better control of chemotherapy-induced nausea and vomiting; however, the extent of implementation of such guidelines in India is unknown. Therefore, this survey was planned. Methods This study was an anonymized cross-sectional survey approved by the ethics committee. Survey items were generated from the clinical questions given in the ASCO guidelines. The survey was disseminated through personal contacts at an oncology conference and via e-mail to various community oncology centers across India. The B1, B2, and B3 domains included questions regarding the optimal antiemetic prophylaxis for high, moderate, and low-minimal emetogenic regimens. Results Sixty-six (62.9%) of 105 responded and 65 centers (98.5%) were aware of the published guidelines. The partial, full, and no implementation scores were 92.5%, 4.5%, and 3.0%, respectively. Full implementation was better for the low-minimal emetogenic regimens (34.8%) than the highly emetogenic regimens (6.1%). The three most frequent reasons for hampered implementation of ASCO guidelines in routine chemotherapy practice cited by centers were a lack of sensitization (26 centers; 39.4%), lack of national guidelines (12 centers; 18.2%), and lack of administrative support (10 centers; 15.2%). Conclusion Awareness regarding ASCO antiemetic guidelines is satisfactory in Indian oncology practices; however, there is a need for sensitization of oncologists toward complete implementation of these guidelines in their clinical practice. PMID:28831443
Hardy, Janet; Skerman, Helen; Glare, Paul; Philip, Jennifer; Hudson, Peter; Mitchell, Geoffrey; Martin, Peter; Spruyt, Odette; Currow, David; Yates, Patsy
2018-05-02
Nausea/vomiting (N/V) not related to anti-cancer treatment is common in patients with advanced cancer. The standard approach to management is to define a dominant cause, and treat with an antiemetic selected through pathophysiologic knowledge of emetic pathways. High rates of N/V control have been reported using both etiology-based guideline-driven antiemetic regimens and an empiric approach using single agents in uncontrolled studies. These different approaches had never been formally compared. This randomized, prospective, open label, dose-escalating study used readily available antiemetics in accordance with etiology-based guidelines or single agent therapy with haloperidol. Participants had a baseline average nausea score of ≥3/10. Response was defined as a ≥ 2/10 point reduction on a numerical rating scale of average nausea score with a final score < 3/10 at 72 h. Nausea scores and distress from nausea improved over time in the majority of the 185 patients randomized. For those who completed each treatment day, a greater response rate was seen in the guideline arm than the single agent arm at 24 h (49% vs 32%; p = 0.02), but not at 48 or 72 h. Response rates at 72 h in the intention to treat analysis were 49 and 53% respectively, with no significant difference between arms (0·04; 95% CI: -0·11, 0·19; p = 0·59). Over 80% of all participants reported an improved global impression of change. There were few adverse events worse than baseline in either arm. An etiology-based, guideline-directed approach to antiemetic therapy may offer more rapid benefit, but is no better than single agent treatment with haloperidol at 72 h. Australian New Zealand Clinical Trials Registry: ANZCTRN12610000481077 .
[Anti-emetic effect of granisetron in patients undergoing cranial and craniospinal radiotherapy].
Yamasaki, Fumiyuki; Watanabe, Yosuke; Nosaka, Ryo; Kenjo, Masahiro; Nakamura, Kazuhiro; Takayasu, Takeshi; Saito, Taiichi; Tominaga, Atsushi; Sugiyama, Kazuhiko; Kurisu, Kaoru
2014-01-01
Approximately 30-59% of patients undergoing cranial or craniospinal radiotherapy experience nausea and/or vomiting. Here, we evaluated the effectiveness of granisetron for controlling emesis in patients treated with cranial or craniospinal radiotherapy. Between December 2011 and January 2013, 34 patients(19 males, 15 females;age range, 3-80 years)received cranial or craniospinal radiotherapy at our department. All but one male patient, who developed meningitis during the irradiation period were enrolled in this retrospective study. Patients who experienced irradiation-induced vomiting(grade 1)or nausea(grade 2)were treated with granisetron as a rescue anti-emetic. Episodes were graded as(1)no vomiting, no nausea, no anti-emetic;(2)no vomiting, nausea, no anti-emetic;(3)no vomiting, nausea with anti-emetic;and(4)vomiting. Of the 9 patients who underwent whole-brain or whole neural-axis irradiation, 5(55.6%)experienced grade 2 nausea or vomiting. Two of 6 patients(33.3%)treated with whole ventricle irradiation experienced grade 2 nausea or vomiting. Three of 18 patients(16.7%)who underwent local-field irradiation experienced grade 2 nausea or vomiting. Patients who underwent wide-field irradiation experienced nausea, vomiting, and anorexia(p<0.05). Complete response(no vomiting, no additional rescue anti-emetic, and no nausea)was observed in 5 of 9 patients treated with granisetron. Four of 9 patients(44.4%)treated with granisetron experienced constipation(grade 1 or 2);its administration had no major adverse effects in our study population. Rescue therapy with granisetron is safe and effective to treat nausea and vomiting in patients subjected to cranial or craniospinal irradiation.
Jeong, Yusook; Han, Hye Sook; Lee, Hyo Duk; Yang, Jiyoul; Jeong, Jiwon; Choi, Moon Ki; Kwon, Jihyun; Jeon, Hyun-Jung; Oh, Tae-Keun; Lee, Ki Hyeong; Kim, Seung Taik
2016-10-01
Dexamethasone is a mainstay antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting. The aim of this pilot study was to assess the incidence of and factors associated with steroid-induced diabetes in cancer patients receiving chemotherapy with dexamethasone as an antiemetic. Non-diabetic patients with newly diagnosed gastrointestinal cancer who received at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Fasting plasma glucose levels, 2-hour postprandial glucose levels, and hemoglobin A 1C tests for the diagnosis of diabetes were performed before chemotherapy and at 3 and 6 months after the start of chemotherapy. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index for measurement of insulin resistance, defined as a HOMA-IR ≥ 2.5. Between January 2012 and November 2013, 101 patients with no history of diabetes underwent laboratory tests for assessment of eligibility; 77 of these patients were included in the analysis. Forty-five patients (58.4%) were insulin resistant and 17 (22.1%) developed steroid-induced diabetes at 3 or 6 months after the first chemotherapy, which included dexamethasone as an antiemetic. Multivariate analysis showed significant association of the incidence of steroid-induced diabetes with the cumulative dose of dexamethasone (p=0.049). We suggest that development of steroid-induced diabetes after antiemetic dexamethasone therapy occurs in approximately 20% of non-diabetic cancer patients; this is particularly significant for patients receiving high doses of dexamethasone.
Tsuji, Daiki; Kim, Yong-Il; Nakamichi, Hidenori; Daimon, Takashi; Suwa, Kaori; Iwabe, Yutaro; Hayashi, Hideki; Inoue, Kazuyuki; Yoshida, Masayuki; Itoh, Kunihiko
2013-01-01
Resistance to antiemetic treatment with 5-hydroxytryptamine 3 receptor antagonists is a problem, with 20-30% of patients showing unsatisfactory responses. Efflux transport by P-glycoprotein, encoded by the ATP-binding cassette ABCB1 gene in the blood-brain barrier, has been the suggested resistance mechanism. We evaluated the association between the antiemetic efficacy of granisetron plus dexamethasone and ABCB1 polymorphisms 3435C>T and 2677G>T/A. Sixty-four breast cancer patients treated with doxorubicin plus cyclophosphamide were evaluated for their responses to antiemetic therapy. Genotyping of patient DNA samples for ABCB1 single nucleotide polymorphisms was performed; the genotypes were then investigated for their association with the efficacy of prophylactic antiemetics. The acute phase complete response rate was 83% in GG subjects (n = 12), and 69% (n = 35) and 41% (n = 17) in heterozygous and homozygous carriers of the 2677T/A allele, respectively (p = 0.047). The ABCB1 2677 TT genotype group showed significantly lower rates of complete control of acute emesis than the group with GG genotypes (p = 0.045). No significant association with complete response was found for 3435C>T (p = 0.190). ABCB1 polymorphisms may influence the extent of acute emesis control in granisetron-treated patients, making the ABCB1 genotype a predictor of prophylactic antiemetic response.
de Wit, R.; van den Berg, H.; Burghouts, J.; Nortier, J.; Slee, P.; Rodenburg, C.; Keizer, J.; Fonteyn, M.; Verweij, J.; Wils, J.
1998-01-01
We have reported previously that the anti-emetic efficacy of single agent 5HT3 antagonists is not maintained when analysed with the measurement of cumulative probabilities. Presently, the most effective anti-emetic regimen is a combination of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment of efficacy of such a combination in 125 patients, scheduled to receive cisplatin > or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs. Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg of dexamethasone and 1 mg of granisetron twice daily by oral administration. Protection was assessed during all cycles and calculated based on cumulative probability analyses using the method of Kaplan-Meier and a model for transitional probabilities. Irrespective of the type of analysis used, the anti-emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial complete acute emesis protection rate of 66% decreased to 30% according to the method of Kaplan-Meier and to 39% using the model for transitional probabilities. For delayed emesis, the initial complete protection rate of 52% decreased to 21% (Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed that protection failure in the delayed emesis period adversely influenced the acute emesis protection in the next cycle. We conclude that the anti-emetic efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple cycles of highly emetogenic chemotherapy, and that the acute emesis protection is adversely influenced by protection failure in the delayed emesis phase. PMID:9652766
Sato, Junya; Kashiwaba, Masahiro; Komatsu, Hideaki; Ishida, Kazushige; Nihei, Satoru; Kudo, Kenzo
2016-05-01
Triplet antiemetic therapy with neurokinin 1 receptor blocker, 5-hydroxytryptamine receptor blocker and steroids is commonly used in patients who are highly emetic after chemotherapy. However, an alternative antiemetic therapy for patients who are resistant to triplet antiemetic therapy is not established. Olanzapine is recommended in the guidelines as an optional antiemetic drug. However, the effectiveness of adding olanzapine to triplet antiemetic therapy is unknown. In this study, the effectiveness and safety of adding olanzapine to triplet antiemetic therapy with aprepitant, palonosetron and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for primary breast cancer patients were prospectively investigated. Forty-five patients with breast cancer who experienced >Grade 1 nausea or any vomiting after the first cycle of chemotherapy using both epirubicin and cyclophosphamide were included. Low-dose olanzapine (2.5 mg/day) was administered orally from the first day of chemotherapy for 4 days, and the number of episodes of vomiting, scale of nausea, dietary intake and somnolence were compared with the symptoms after the first cycle. As the primary endpoint, the nausea grade was significantly improved by adding olanzapine (P < 0.05). As the secondary endpoints, mean nausea scale (3.2→1.9, Day 1; 3→1.3-1, Days 2-6) and dietary intake (33.6→53.8%, Day 1; 42.0→60.7-78.1%, Days 2-6) were improved by adding olanzapine. Only four patients withdrew due to somnolence and/or dizziness. This study demonstrated the effectiveness and tolerability of adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, steroid and aprepitant. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Uchida, M; Nakamura, T; Makihara, Y; Suetsugu, K; Ikesue, H; Mori, Y; Kato, K; Shiratsuchi, M; Hosohata, K; Miyamoto, T; Akashi, K
2018-05-01
The antiemetic effects and safety of granisetron and palonosetron against chemotherapy-induced nausea and vomiting (CINV) were retrospectively evaluated in patients with non-Hodgkin lymphoma receiving bendamustine-based chemotherapy. A total of 61 patients were eligible for this study. Before starting the bendamustine-based chemotherapy, granisetron or palonosetron were intravenously administered with or without aprepitant and/or dexamethasone. The proportions of patients with complete control (CC) during the overall (during the 6 days after the start of the chemotherapy), acute (up to 2 days), and delayed (3 to 6 days) phases were assessed. CC was defined as complete response with only grade 0-1 nausea, no vomiting, and no use of antiemetic rescue medication. Granisetron or palonosetron alone were administered to 9 and 19 patients, respectively. Aprepitant and/or dexamethasone were combined with granisetron and palonosetron in 28 and 5 patients, respectively. Acute CINV was completely controlled in all patients. Both granisetron monotherapy and palonosetron combination therapy could provide good control of delayed CINV, although the CC rates during the delayed and overall phases were not significantly different among mono- and combination therapy of the antiemetics. There was no significant difference in the frequencies of adverse drug events between the granisetron and palonosetron treatment groups. The present study showed that the antiemetic efficacy and safety of granisetron-based therapy were non-inferior to those of palonosetron-based therapy. Taken together with treatment costs, granisetron monotherapy would be adequate to prevent CINV in patients with non-Hodgkin lymphoma receiving bendamustine-based chemotherapy.
Fang, Bao-xia; Li, Peng; Shi, Xiao-ya; Chen, Fu-chao; Wang, Lin-hai
2016-01-01
Abstract The administration of drugs by patient-controlled analgesia (PCA) is routinely practiced for the management of postoperative pain. It is common for 2 or more drugs to be combined in PCA solutions. The combination of analgesics and antiemetic agents is frequently required. Unfortunately, the compatibility and stability of lornoxicam and antiemetic agents, such as droperidol, ondansetrone, granisetron, and tropisetron, has not been determined. The aim of this study was to evaluate the compatibility and stability of solutions containing lornoxicam with the 4 antiemetic agents in combination for PCA administration. In our study, test samples were prepared in triplicate by adding 40 mg lornoxicam and 5 mg droperidol, 8 mg ondansetron, 6 mg granisetron, or 5 mg tropisetron to 100-mL polyolefin bags of sodium chloride 0.9% and stored at 25 °C. The analgesic mixture samples were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. Drug concentrations were determined using high-performance liquid chromatographic (HPLC) analysis. No loss of lornoxicam occurred with any of the 4 antiemetic agents tested for up to 48 hours. However, the contents of droperidol, ondansetron, granisetron, and tropisetron were significant loss >48 hours. After storage of 4.0 to 48.0 hours, the presence of a slight precipitate was observed in all the injection combinations. The results indicate that combinations of lornoxicam with droperidol, ondansetrone, granisetron, or tropisetron in infusion solution during simulated intravenous PCA administration were incompatibility when stored protected from light at 25 °C. PMID:27336868
This randomized phase III trial studies antiemetic therapy with olanzapine to see how well they work compared to antiemetic therapy alone in preventing chemotherapy-induced nausea and vomiting in patients with cancer receiving highly emetogenic (causes vomiting) chemotherapy. Antiemetic drugs, such as palonosetron hydrochloride, ondansetron, and granisetron hydrochloride, may
Development and evaluation of a sublingual film of the antiemetic granisetron hydrochloride.
Kalia, Vani; Garg, Tarun; Rath, Gautam; Goyal, Amit Kumar
2016-05-01
The objective of this study was to develop an oral transmucosal formulation of an antiemetic drug that can not only serve in the active form but also provide a controlled release profile. In this study, sublingual films based on the biodegradable and water-soluble polymers, that is HPMCK-4M and PVPK-30, were developed by the solvent casting method, and were loaded with the antiemetic drug granisetron hydrochloride (granisetron HCl). The entrapment efficiency of the developed formulation was found to be 86%. The in vitro profile showed an instant release of the drug from the sublingual film, in a pattern following the first order kinetics array. The in vivo studies showed that granisetron HCl was delivered in its active state and showed effective results, as compared to its activity in the marketed formulation.
NASA Astrophysics Data System (ADS)
Kharbikar, Bhushan N.; Kumar S., Harish; Kr., Sindhu; Srivastava, Rohit
2015-12-01
Chemotherapy Induced Nausea and Vomiting (CINV) is a serious health concern in the treatment of cancer patients. Conventional routes for administering anti-emetics (i.e. oral and parenteral) have several drawbacks such as painful injections, poor patient compliance, dependence on skilled personnel, non-affordability to majority of population (parenteral), lack of programmability and suboptimal bioavailability (oral). Hence, we have developed a trans-epidermal antiemetic drug delivery patch using out-of-plane hollow silicon microneedle array. Microneedles are pointed micron-scale structures that pierce the epidermal layer of skin to reach dermal blood vessels and can directly release the drug in their vicinity. They are painless by virtue of avoiding significant contact with dermal sensory nerve endings. This alternate approach gives same pharmacodynamic effects as par- enteral route at a sparse drug-dose requirement, hence negligible side-effects and improved patient compliance. Microneedle design attributes were derived by systematic study of human skin anatomy, natural micron-size structures like wasp-sting and cactus-spine and multi-physics simulations. We used deep reactive ion etching with Bosch process and optimized recipe of gases to fabricate high-aspect-ratio hollow silicon microneedle array. Finally, microneedle array and polydimethylsiloxane drug reservoir were assembled to make finished anti-emetic patch. We assessed microneedles mechanical stability, physico-chemical properties and performed in-vitro, ex- vivo and in-vivo studies. These studies established functional efficacy of the device in trans-epidermal delivery of anti-emetics, its programmability, ease of use and biosafety. Thus, out-of-plane hollow silicon microneedle array trans-epidermal antiemetic patch is a promising strategy for painless and effective management of CINV at low cost in mainstream healthcare.
Lauretti, G R; Mattos, A L; Gomes, J M; Pereira, N L
1997-01-01
Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine were investigated in a randomized, double-blind, placebo-controlled trial of 100 patients undergoing abdominal hysterectomy. The patients were assigned to one of five groups (n = 20), and received intravenous prior to the spinal block the antiemetic test drug (except propofol) and 0.05 mg/kg midazolam. The control group (group C), the neostigmine group (group N), and the propofol group (group P) received saline as the test drug. The droperidol group (group D) received 0.5 mg intravenous droperidol, and the metoclopramide group (group M) 10 mg intravenous metoclopramide. Group P was single-blinded and had an intravenous continuous propofol infusion (2-4 mg/kg/h) turned on 10 minutes after the spinal injection. The intrathecal drugs administered were 20 mg hyperbaric bupivacaine (0.5%) associated with either 100 microg neostigmine or saline (for group C). Nausea, emetic episodes, and the need for rescue medication were recorded for the first 24 hours postoperative and scored by the Visual Analog Scale (VAS). Time-to-first-rescue medication and rescue medications in 24 hours were similar among the groups (P = .2917 and P = .8780, respectively). Intrathecal 100 microg neostigmine was associated with a high incidence of nausea and vomiting perioperative, leading to a high consumption of antiemetics (P < .002). None of the antiemetic test drugs were effective in preventing nausea and vomiting after 100 microg neostigmine. Intrathecal neostigmine (100 microg) was ineffective for postoperative analgesia after abdominal hysterectomy due to side effects of nausea and vomiting.
Anti-Emetic Drug Effects on Performance Phase 1: Laboratory Study.
1995-12-01
The objectives of this study were to evaluate the effects of two anti-emetic drugs, granisetron ( 2 mg p.o.) and ondansetron ( 8 mg p.o.) on basic...drugs of interest, granisetron and ondansetron, were extremely well tolerated and with no obvious side effects when compared to the placebo condition...evidence of any cognitive, psychomotor or subjective state changes caused by either granisetron or ondansetron.
Hayashi, Toshinobu; Ikesue, Hiroaki; Esaki, Taito; Fukazawa, Mami; Abe, Motoaki; Ohno, Shinji; Tomizawa, Tatsuru; Oishi, Ryozo
2012-08-01
The purposes of this study were to evaluate the effect of implementation of institutional guidelines for low emetic risk chemotherapy with docetaxel and estimate the cost saving for all low emetic risk chemotherapies. We examined the clinical effect of preparing and implementing institutional antiemetic guidelines for the breast cancer patients receiving adjuvant docetaxel therapy. Although the antiemetic medication for such patients used to be ondansetron 4 mg plus dexamethasone 8 mg (OND + DEX), it was changed to dexamethasone (DEX) 12 mg alone after implementation of the institutional guidelines. The effectiveness and adverse effects of DEX alone (56 patients, 205 courses) were compared with those of OND + DEX (41 patients, 151 courses). The cost saving was calculated from the antiemetic costs in both groups. The annual cost saving was estimated from the number of all low emetic risk chemotherapies in a year. The incidences of nausea (19.5% versus 16.1%), vomiting (2.4% versus 0%), constipation (34.1% versus 30.4%), and insomnia (17.1% versus 17.9%) were not significantly different between the OND + DEX group and DEX alone group. In all low emetic risk chemotherapies, US $78,883 of potential cost saving was estimated in the first year after changing the antiemetic treatment. The present results suggest that DEX alone is equally effective for preventing nausea and vomiting and less expensive compared with a 5-HT(3) receptor antagonist plus DEX in low emetic risk chemotherapy with docetaxel.
Chan, Alexandre; Low, Xiu Hui; Yap, Kevin Yi-Lwern
2012-06-01
There are little prevalence data in the literature on nonadherence to outpatient antiemetic regimens for prophylaxis of chemotherapy-induced nausea and vomiting (CINV). It is unclear whether adherence with outpatient antiemetic regimens is associated with better CINV control. Our previous survey research supports the work of clinical pharmacists in collaborative practice with medical oncologists in improving adherence with antiemetic therapy in women undergoing highly emetic chemotherapy for breast cancer. To (a) evaluate the impact of adherence to delayed antiemetics (days 2-4 following anthracycline-based chemotherapy) on CINV control in breast cancer patients after anthracycline-based chemotherapy and (b) identify patient-related factors associated with nonadherence to delayed antiemetics. A single-center, prospective, observational study was conducted from December 2006 to January 2011 in breast cancer patients receiving anthracycline-based chemotherapy (doxorubicin or epirubicin) and antiemetics at the National Cancer Centre Singapore (NCCS), the largest ambulatory cancer center in Singapore. Included patients were aged 21 years or older with confirmed diagnoses of breast cancer and receiving anthracycline-containing chemotherapy with antiemetics. Patients were excluded if they (a) were diagnosed with intestinal obstruction or received concurrent radiotherapy that predisposed them to nausea and vomiting, (b) had vomited in the 24 hours preceding chemotherapy, or (c) had brain metastases that would impair their judgment. Patients documented in a standardized diary their emesis events, severity of nausea, use of rescue therapy with metoclopramide, and compliance with dose instructions for antiemetic drug therapy for 5 days: day 1 was the day of chemotherapy and first day of antiemetic therapy, and day 5 was the day after completion of delayed antiemetic therapy (days 2-4). Three definitions were used to describe the CINV outcomes: (a) complete response (no
Anti-Emetic Drug Effects on Pilot Performance, Phase 2: Simulation Test.
1996-04-01
The objectives of this study were to evaluate the effects of two anti-emetic drugs, granisetron (2 mg oral dose) and ondansetron (8 mg oral dose), on...and preduce no cognitive, psychomotor or subjective state changes. In this study, there was no evidence of performance degradation caused by either granisetron or ondansetron when tested in a complex military task environment.
Lee, Jiyeon; Oh, Heeyoung
2013-03-01
To evaluate the effect of ginger as an antiemetic modality for the control of chemotherapy-induced nausea and vomiting (CINV). Databases searched included MEDLINE® (PubMed), Embase, CINAHL®, Cochrane Central Register of Controlled Trials, Korean Studies Information Service System, Research Information Sharing Service by the Korean Education and Research Information Service, and Dissertation Central. A systematic review was conducted of five randomized, controlled trials involving 872 patients with cancer. Ginger was compared with placebo or metoclopramide. The participant characteristics, chemotherapy regimen and antiemetic control, ginger preparation and protocol, measurements, results of the studies, adherence to the treatment protocol, and side effects were reviewed systematically. The incidence and severity of acute and delayed CINV were subject to meta-analysis. The incidence of acute nausea (p = 0.67), incidence of acute vomiting (p = 0.37), and severity of acute nausea (p = 0.12) did not differ significantly between the ginger and control groups. Current evidence does not support the use of ginger for the control of CINV. Ginger did not contribute to control of the incidence of acute nausea and vomiting or of the severity of acute nausea. Ginger has long been regarded as a traditional antiemetic modality, but its effectiveness remains to be established. The findings of this study could be incorporated into clinical guidelines, such as the Oncology Nursing Society's Putting Evidence Into Practice resources. Current evidence supports the need for more methodologically rigorous studies in this area. Although ginger is known as a traditional antiemetic, current evidence does not support the effect of ginger in CINV control. The findings of this study inform healthcare providers that its effectiveness remains to be established from methodologically rigorous future trials.
Woodall, Rachel; Arnold, John J; McKay, Doug; Asbill, C Scott
2013-01-01
The purpose of this study was to assess the impact of altering formulation pH on the transdermal penetration of several commonly used antiemetic, weakly basic drugs incorporated into poloxamer lecithin organogel vehicle. Poloxamer lecithin organogel formulations containing promethazine hydrochloride (25 mg/mL), metoclopramide hydrochloride (10 mg/mL), and ondansetron hydrochloride (8 mg/mL) were examined for both drug release and transdermal penetration across porcine skin in modified Franz diffusion cells for a period of 24 hours. For the transdermal studies, each antiemetic drug was formulated at a pH above and below their acid dissociation constant (pKa) in an attempt to assure that the drug would be primarily in their respective ionized or non-ionized states. In addition, drug content in skin was assessed at the end of the 24-hour experiment. Drug content analysis was determined via high-performance liquid chromatography. As a percent of total drug release from the poloxamer lecithin organogel vehicle, promethazine hydrochloride demonstrated the most transdermal drug penetration after 24 hours (30.2% +/- 20.2%), followed by ondansetron hydrochloride (2.7% +/- 1.1%) and metoclopramide hydrochloride (1.8% +/- 1.6%). Subsequently, the pH of the Pluronic F-127 gel was adjusted in order to ensure that each antiemetic drug would be primarily in its unionized state. The transdermal permeation of each antiemetic drug primarily in its unionized state increased over that observed with the drug primarily in its ionized state after 24 hours (promethazine: 1.6-fold increase; metoclopramide: 1.3-fold increase; ondansetron: 1.8-fold increase). A similar trend was noted in the amount of each drug found in the skin after 24 hours (promethazine: 1.2-fold increase; metoclopramide: 2.4-fold increase; ondansetron: 3.0-fold increase). These results suggest that proper optimization of drug ionization state may be a useful strategy for compounding pharmacists to increase the efficacy
Bioavailability of the antiemetic metopimazine given as a microenema
HERRSTEDT, JØRN; JØRGENSEN, MORTEN; ANGELO, HELLE RIIS; RASSING, MARGRETHE RØMER; MØLLER-SONNERGAARD, JØRN; DOMBERNOWSKY, PER
1996-01-01
The absorption of the antiemetic metopimazine (MPZ) given as a single dose of (a) 40 mg microenema, (b) 40 mg orally and (c) 10 mg as a 60 min i.v. continuous infusion was investigated in six healthy volunteers. Blood samples were drawn and the serum concentrations of MPZ and its acid metabolite were measured. The bioavailability of MPZ given orally and as enemas was 22.3 and 19.5% respectively. Partial avoidance of hepatic first pass metabolism was seen with the enemas, which in contrast to suppositories, seems to represent a reliable form of rectal administration. PMID:8799530
Bruera, E; Seifert, L; Watanabe, S; Babul, N; Darke, A; Harsanyi, Z; Suarez-Almazor, M
1996-03-01
The purpose of this retrospective study is to assess the frequency and intensity of chronic nausea in patients admitted to the Palliative Care Unit and the results of a metoclopramide-based treatment regimen. We reviewed the medical records of 100 consecutive patients admitted to the Palliative Care Unit at the Edmonton General Hospital until death during 1992-1993. All patients had terminal cancer and normal cognitive function. All patients completed the Functional Analogue Scale for appetite, nausea, pain, activity, shortness of breath, and sensation of well-being at 1000 and 1600 hours every day. Patients who complained of nausea initially received metoclopramide 10 mg every 4 hr orally or subcutaneously (Step 1). If nausea persisted, dexamethasone 10 mg twice daily was added (Step 2). Step 3 consisted of a continuous subcutaneous infusion of metoclopramide of 60-120 mg/day plus dexamethasone. If no response was observed, other antiemetics were administered (Step 4). Upon admission to the unit, 32 patients (32%) presented with nausea. During the average admission of 25 +/- 13 days, 98 patients (98%) developed nausea. Twenty-five patients (25%) required other antiemetics because of bowel obstruction (18), extrapyramidal side effects (3), or other reasons (4). Most patients without bowel obstruction achieved excellent control of nausea using the metoclopramide-based regimen. During the first 5 days and last 5 days of admission, nausea had significantly lower intensity than the rest of the symptoms that were monitored. Our results suggest that, although nausea is very frequent, it can be well controlled in the majority of patients using safe and simple antiemetic regimens.
Schwartzberg, Lee; Jackson, James; Jain, Gagan; Balu, Sanjeev; Buchner, Deborah
2011-08-01
It is recommended that patients initiate triple antiemetic therapy with one of the 5-hydroxytryptamine receptor antagonists (5-HT(3) RAs), aprepitant (or its intravenous prodrug fosaprepitant) and dexamethasone prior to the start of highly emetogenic chemotherapy (HEC). However, the impact of 5-HT(3) RA selection within triple antiemetic regimens on the risk of uncontrolled chemotherapy-induced nausea and vomiting (CINV) with HEC has not been well studied. To assess the likelihood of an uncontrolled CINV event following antiemetic prophylaxis with the 5-HT(3) RA palonosetron + aprepitant/fosaprepitant + dexamethasone (palonosetron cohort) versus any of the other 5-HT(3) RAs + aprepitant/fosaprepitant + dexamethasone (other 5-HT(3) RA cohort) among single-day HEC cycles. Single-day HEC cycles (a gap of at least 5 days between two administrations) among patients with a cancer diagnosis and receiving antiemetic prophylaxis with the aforementioned regimens between 1/1/2006 and 6/30/2010 were identified from the IMS LifeLink claims database. Uncontrolled CINV events were identified through ICD-9-CM codes (nausea and vomiting), Current Procedural Terminology codes (hydration), rescue medications and/or use of antiemetic therapy from days 2-5 following HEC administration. Risks for an uncontrolled CINV event among all patients, and within breast cancer and multiple cancer subpopulations, were analyzed at cycle level using logistic multivariate regression models. A total of 8018 cycles for the palonosetron cohort and 1926 cycles for the other 5-HT(3) RA cohort (3574 and 978 patients, respectively) were analyzed. Single-day HEC cycles received by the palonosetron cohort had a significantly lower unadjusted risk of an uncontrolled CINV event (17.5 vs 20.7% for the other 5-HT(3) RA cohort; p = 0.0010), with a 17% lower adjusted risk for palonosetron-administered cycles (odds ratio: 0.83; 95% CI: 0.73-0.94; p = 0.0042). Results in the breast cancer and multiple cancer
Han, Hye Sook; Park, Ji Chan; Park, Suk Young; Lee, Kyu Taek; Bae, Sang Byung; Kim, Han Jo; Kim, Samyoung; Yun, Hwan Jung; Bae, Woo Kyun; Shim, Hyun-Jeong; Hwang, Jun-Eul; Cho, Sang-Hee; Park, Moo-Rim; Shim, Hyeok; Kwon, Jihyun; Choi, Moon Ki; Kim, Seung Taik; Lee, Ki Hyeong
2015-12-01
In a previous pilot study, adrenal suppression was found to be common after antiemetic dexamethasone therapy in cancer patients. The objective of this large prospective multicenter study was to confirm the incidence and factors associated with secondary adrenal suppression related to antiemetic dexamethasone therapy in cancer patients receiving chemotherapy. Chemotherapy-naïve patients who were scheduled to receive at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Patients with a suppressed adrenal response before chemotherapy or those administered corticosteroids within 6 months of enrollment in the study were excluded. Between October 2010 and August 2014, 481 patients receiving chemotherapy underwent the rapid adrenocorticotropic hormone (ACTH) stimulation test to assess eligibility; 350 of these patients were included in the final analysis. Fifty-six patients (16.0%) showed a suppressed adrenal response in the rapid ACTH stimulation test at 3 or 6 months after the start of the first chemotherapy. The incidence of adrenal suppression was affected by age, performance status, stage, and use of megestrol acetate in univariate analysis. Multivariate analysis revealed that secondary adrenal suppression associated with antiemetic dexamethasone therapy was significantly associated with megestrol acetate treatment (odds ratio: 3.06; 95% confidence interval: 1.60 to 5.86; p < .001). This large prospective study indicates that approximately 15% of cancer patients receiving chemotherapy with a normal adrenal response show suppressed adrenal responses after antiemetic dexamethasone therapy. This result was particularly significant for patients cotreated with megestrol acetate. ©AlphaMed Press.
Furukawa, Takako Yoshino; Nakayama, Hiroe; Kikuchi, Aya; Imazumi, Katsunori; Yamakuni, Hisashi; Sogabe, Hajime; Yamasaki, Sachiko; Takeshita, Koji; Matsuo, Masahiko; Manda, Toshitaka; Uchida, Wataru
2013-01-01
The antiemetic properties of a novel neurokinin-1 (NK1) receptor antagonist, FK886 ([3,5-bis(trifluoromethyl)phenyl][(2R)-2-(3-hydroxy-4-methylbenzyl)-4-{2-[(2S)-2-(methoxymethyl)morpholin-4-yl]ethyl}piperazin-1-yl]methanone dihydrochloride), were studied in dog models of cisplatin- and apomorphine-induced emesis. Intravenously administered FK886 (0.32-1 mg/kg) significantly inhibited cisplatin-induced acute emesis during the 5-h observation period. Nearly complete inhibition was observed at 1 mg/kg. At an equivalent dose range, orally administered FK886 also significantly inhibited emesis, indicating good oral absorption. Similarly, FK886 inhibited apomorphine-induced emetic responses effectively following both intravenous and oral administration. The effects were long lasting, with 1.6 mg/kg of FK886 completely blocking apomorphine-induced retching and vomiting after a 12-h pretreatment period. Furthermore, FK886 showed rapid onset of antiemetic activity after oral administration. At doses of 0.32 mg/kg or more, a pretreatment time of 0.5 h was sufficient for complete inhibition of apomorphine-induced emetic responses. This fast onset after oral administration was supported by pharmacokinetic data, which demonstrated plasma levels of FK886 after oral administration reached levels similar to those 30 min after intravenous administration. These results suggest that FK886 has excellent antiemetic properties in dogs, and that its rapid-onset and long-lasting properties might make it a promising antiemetic agent.
Ullah, Ihsan; Subhan, Fazal; Ayaz, Muhammad; Shah, Rehmat; Ali, Gowhar; Haq, Ikram Ul; Ullah, Sami
2015-02-26
Zingiber officinale (ZO, family Zingiberaceae) has been reported for its antiemetic activity against cancer chemotherapy induced emesis in animal models and in clinics. Current study was designed to investigate ZO for potential usefulness against cisplatin induced vomiting in pigeon and its effects on central and peripheral neurotransmitters involved in the act of vomiting. Zingiber officinale acetone fraction (ZO-ActFr) was investigated for attenuation of emesis induced by cisplatin in healthy pigeons. Neurotransmitters DA, 5HT and their metabolites DOPAC, HVA and 5HIAA were analyzed using High Performance Liquid Chromatography system coupled with electrochemical detector in area postrema, brain stem and intestine. Antiemetic effect of ZO-ActFr was correlated with central and intestinal neurotransmitters levels in pigeon. Cisplatin (7 mg/kg i.v.) induced emesis without lethality upto the observation period. ZO-ActFr (25, 50 & 100 mg/kg) attenuated cisplatin induced emesis ~ 44.18%, 58.13% (P < 0.05) and 27.9%, respectively; the reference drug, metoclopramide (MCP; 30 mg/kg), produced ~ 48.83% reduction (P < 0.05). ZO-ActFr reduced (P < 0.05 - 0.001) 5-hydroxytryptamine (5HT) concentration in the area postrema, brain stem and intestine at 3(rd) hour of cisplatin administration, while at the 18(th) hour ZO treatments attenuated the dopamine upsurge (P < 0.001) caused by cisplatin in the area postrema and 5HT concentration (P < 0.01 - 0.001) in the brain stem and intestine. ZO treatments alone did not altered the basal neurotransmitters and their metabolites in the brain areas and intestine. The behavioral study verify the antiemetic profile of ZO against cisplatin induced emesis in the pigeon, where central and peripheral neural evidences advocate the involvement of serotonergic mechanism at initial time point (3(rd) hr), while the later time point (18(th) hr) is associated with serotonergic and dopaminergic component in the mediation
Safety and efficacy of antiemetics used to treat nausea and vomiting in pregnancy.
Leathem, A M
1986-08-01
The safety and efficacy of antiemetic drugs used in the treatment of nausea and vomiting during pregnancy are reviewed. Confirmation of the teratogenicity of drugs in humans is difficult; the risk can be estimated from results of cohort studies and case-control studies. The possible teratogenicity of Bendectin (doxylamine succinate and pyridoxine hydrochloride) was studied thoroughly; although the risk was minimal, the drug was withdrawn from the U.S. market. Whether phenothiazines are teratogenic has still not been conclusively determined. A large number of epidemiological studies have not shown meclizine to be teratogenic in humans. More information about metoclopramide is necessary before it can be safely recommended for use during pregnancy. The risks of using dimenhydrinate and diphenhydramine appear to be low. Pyridoxine is considered safe for use during pregnancy, but its efficacy in treating nausea and vomiting has not been determined. The relative efficacy of these agents has not been determined. The available data suggest that meclizine and dimenhydrinate are the antiemetics that present the lowest risk of teratogenicity; meclizine is the drug of first choice. Phenothiazines should be reserved for treating persistent vomiting that threatens the maternal nutritional status.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Siddiqi, Nasir H., E-mail: siddiqin@mir.wustl.ed; Khan, Atif J.; Devlin, Phillip M.
Nausea and vomiting may occur in a significant minority of patients following hepatic artery embolization with yttrium-90 spheres (K. T. Sato et al. Radiology 247:507-515, 2008). This encumbers human and economic resources and undercuts the assertion that it is as a well-tolerated outpatient treatment. A single intravenous dose of palonosetron HCl was administered before hepatic artery embolization with yttrium-90 spheres to ameliorate posttreatment nausea and vomiting, in 23 consecutive patients. The patients were discharged the day of procedure on oral antiemetics, steroids, and blockers of gastric acid release. All patients had clinical and laboratory evaluation at 2 weeks after themore » procedure. The data were gathered and reviewed retrospectively. At 2-week follow-up, none reported significant nausea, vomiting, additional antiemetic use, need for parenteral therapy, hospital readmission, or palonosetron-related side effects. All patients recovered from postembolization symptoms within a week after treatment. In conclusion, this retrospective study suggests that single-dose palonosetron is feasible, safe, and effective for acute and delayed nausea and vomiting in this group of patients. The added cost may be offset by benefits.« less
Söderpalm, A H; Schuster, A; de Wit, H
2001-01-01
Although the public debate about the legalization of marijuana has continued for as long as 25 years, few controlled studies have been conducted to assess its potential medical benefits. The present study examined the antiemetic effect of smoked marijuana cigarettes (8.4 and 16.9 mg Delta(9)-tetrahydrocannabinol [THC]) compared to a highly potent antiemetic drug, ondansetron (8 mg) in 13 healthy volunteers. Nausea and emesis were induced by syrup of ipecac. Marijuana significantly reduced ratings of "queasiness" and slightly reduced the incidence of vomiting compared to placebo. Ondansetron completely eliminated the emetic effects of ipecac. These findings support and extend previous results, indicating that smoked marijuana reduces feelings of nausea and also reduces emesis in this model. However, its effects are very modest relative to ondansetron, and the psychoactive effects of marijuana are likely to limit its clinical usefulness in the general population.
Honarmand, Azim; Safavi, Mohammadreza; Chegeni, Mansoureh; Hirmanpour, Anahita; Nazem, Masoud; Sarizdi, Seyyad Hamid
2016-01-01
The purpose of the present study was to evaluate the efficacy of midazolam-ondansetron combination in prevention of postoperative nausea and vomiting (PONV) after middle ear surgery and its comparison with using midazolam or ondansetron alone. One hundred and forty patients were enrolled in four groups to receive midazolam 0.75 mg/kg in group M, ondansetron 4 mg in group O, midazolam 0.75 mg/kg and ondansetron 4 mg in group MO, and saline 0.90% in group S intravenously just before anesthesia. Assessment of nausea, vomiting, rescue antiemetic, and side effects of study drugs such as headache and dizziness was carried out postoperatively for 24 h. The incidence of PONV was significantly smaller in group MO than group M and group O, while there was no significant difference between group M and group O during the first 24 h postoperatively. Requirement to the additional antiemetic was significantly more in group S (71.4%) compared to other groups, while in group MO (11.4%) was lower than group M (31.4%) and group O (34.3%). Our study showed that prophylactic administration of midazolam 0.75 mg/kg combined with ondansetron 4 mg was more effective than using midazolam or ondansetron alone in prevention of PONV after middle ear surgery.
Keat, Chan Huan; Ghani, Norazila Abdul
2013-01-01
In a prospective cohort study of antiemetic therapy conducted in Malaysia, a total of 94 patients received low emetogenic chemotherapy (LEC) with or without granisetron injections as the primary prophylaxis for chemotherapy-induced nausea and vomiting (CINV). This study is a retrospective cost analysis of two antiemetic regimens from the payer perspective. This cost evaluation refers to 2011, the year in which the observation was conducted. Direct costs incurred by hospitals including the drug acquisition, materials and time spent for clinical activities from prescribing to dispensing of home medications were evaluated (MYR 1=$0.32 USD). As reported to be significantly different between two regimens (96.1% vs 81.0%; p=0.017), the complete response rate of acute emesis which was defined as a patient successfully treated without any emesis episode within 24 hours after LEC was used as the main indicator for effectiveness. Antiemetic drug acquisition cost per patient was 40.7 times higher for the granisetron-based regimen than for the standard regimen (MYR 64.3 vs 1.58). When both the costs for materials and clinical activities were included, the total cost per patient was 8.68 times higher for the granisetron-based regimen (MYR 73.5 vs 8.47). Considering the complete response rates, the mean cost per successfully treated patient in granisetron group was 7.31 times higher (MYR 76.5 vs 10.5). The incremental cost-effectiveness ratio (ICER) with granisetron-based regimen, relative to the standard regimen, was MYR 430.7. It was found to be most sensitive to the change of antiemetic effects of granisetron-based regimen. While providing a better efficacy in acute emesis control, the low incidence of acute emesis and high ICER makes use of granisetron as primary prophylaxis in LEC controversial.
Honarmand, Azim; Safavi, Mohammadreza; Chegeni, Mansoureh; Hirmanpour, Anahita; Nazem, Masoud; Sarizdi, Seyyad Hamid
2016-01-01
Objective: The purpose of the present study was to evaluate the efficacy of midazolam-ondansetron combination in prevention of postoperative nausea and vomiting (PONV) after middle ear surgery and its comparison with using midazolam or ondansetron alone. Methods: One hundred and forty patients were enrolled in four groups to receive midazolam 0.75 mg/kg in group M, ondansetron 4 mg in group O, midazolam 0.75 mg/kg and ondansetron 4 mg in group MO, and saline 0.90% in group S intravenously just before anesthesia. Assessment of nausea, vomiting, rescue antiemetic, and side effects of study drugs such as headache and dizziness was carried out postoperatively for 24 h. Findings: The incidence of PONV was significantly smaller in group MO than group M and group O, while there was no significant difference between group M and group O during the first 24 h postoperatively. Requirement to the additional antiemetic was significantly more in group S (71.4%) compared to other groups, while in group MO (11.4%) was lower than group M (31.4%) and group O (34.3%). Conclusion: Our study showed that prophylactic administration of midazolam 0.75 mg/kg combined with ondansetron 4 mg was more effective than using midazolam or ondansetron alone in prevention of PONV after middle ear surgery. PMID:26985431
Endo, Junki; Iihara, Hirotoshi; Yamada, Maya; Yanase, Koumei; Kamiya, Fumihiko; Ito, Fumitaka; Funaguchi, Norihiko; Ohno, Yasushi; Minatoguchi, Shinya; Itoh, Yoshinori
2012-09-01
The acute antiemetic effect was compared between oral azasetron and intravenous granisetron based on the 5-hydroxytryptamine(3) (5-HT(3)) receptor occupancy theory. Receptor occupancy was estimated from reported data on plasma concentrations and affinity constants to 5-HT(3) receptor. A randomized non-inferiority study comparing acute antiemetic effects between oral azasetron and intravenous granisetron was performed in 105 patients receiving the first course of carboplatin-based chemotherapy for lung cancer. Azasetron exhibited the highest 5-HT(3) receptor occupancy among various first-generation 5-HT(3) antagonists. The complete response to oral azasetron was shown to be non-inferior to that of intravenous granisetron, in which the risk difference was 0.0004 (95% confidence interval: -0.0519-0.0527). The lower limit of the confidence intervals did not exceed the negative non-inferiority margin (-0.1). The complete response during the overall period was not different (68% versus 67%). Oral azasetron was found to be non-inferior to intravenous granisetron in the acute antiemetic effect against moderately emetogenic chemotherapy.
A review of granisetron, 5-hydroxytryptamine3 receptor antagonists, and other antiemetics.
Hsu, Eric S
2010-01-01
Nausea and vomiting are 2 of the most upsetting adverse reactions of chemotherapy. Current guidelines propose 5-hydroxytryptamine3 (5-HT3) receptor antagonists as a pharmacologic intervention for acute and delayed nausea and vomiting [chemotherapy-induced nausea and vomiting (CINV)] associated with moderately and highly emetogenic chemotherapy. Meanwhile, both postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting are challenging situations after surgeries and procedures. Prophylactic and therapeutic combinations of antiemetics are recommended in patients at high risk of suffering from PONV and postdischarge nausea and vomiting. Granisetron (Kytril) is a selective 5-HT3 receptor antagonist that does not induce or inhibit the hepatic cytochrome P-450 system in vitro. There are also 4 other antagonists of 5-HT3 receptor (dolasetron, ondansetron, palonosetron, and tropisetron) being metabolized via the CYP2D6 and are subject to potential genetic polymorphism. The launch of a new class of antiemetics, the substance P/neurokinin1 receptor antagonists, was attributed to the scientific update on the central generator responsible for emesis and role of substance P. There has been mounting interest in exploring integrative medicine, either acupuncture or acustimulation of P6 (Nei-Kuwan), to complement the western medicine for prevention and management of nausea and vomiting. The potential application of cannabinoids, either alone or in combination with other agents of different mechanism, could contribute further to improve outcome in CINV. Implementation of future treatment guidelines for more effective management of CINV and PONV could certainly improve the efficacy and outcome of cancer and postoperative care.
Evaluation of oral maropitant as an antiemetic in cats receiving morphine and dexmedetomidine.
Martin-Flores, Manuel; Sakai, Daniel M; Mastrocco, Alicia; Learn, McKenzie M; Campoy, Luis; Kirch, Pati J; Boesch, Jordyn M; Gleed, Robin D
2016-11-01
Objectives The aim of the study was to evaluate the antiemetic effects of maropitant, after oral administration, in cats receiving morphine and dexmedetomidine. Methods This prospective, blinded, randomized controlled trial involved 98 healthy female domestic shorthair cats. Cats were randomly assigned to receive maropitant PO 8 mg total (group M) administered 18 h prior to sedation with intramuscular dexmedetomidine 20 µg/kg and morphine 0.1 mg/kg, or no antiemetic treatment (group C). The occurrence of signs of nausea (sialorrhea and lip-licking), retching and emesis during the 30 mins following administration of dexmedetomidine and morphine was measured for each group. Results Two cats were excluded from the investigation. Cats in group M (n = 46) received an average of 2.5 mg/kg of maropitant PO. Compared with group C (n = 50), cats in group M had lower incidences of emesis (M: 4% vs C: 40%), retching (M: 8% vs C: 40%) and lip-licking (M: 30% vs C: 52%) (all P <0.05). The incidence of sialorrhea was not different between groups (M: 21% vs C: 22%). Conclusions and relevance Maropitant 8 mg total PO was effective in reducing morphine and dexmedetomidine-induced emesis by 10-fold, when administered as early as 18 h in advance to healthy cats. Maropitant PO could be useful for administration the evening prior to a scheduled procedure requiring sedation/anesthesia to decrease the incidence of emesis.
[Morphine-antiemetics mixtures for continuous subcutaneous infusion in terminal cancer].
Ottesen, S; Monrad, L
1992-05-30
Simultaneous pain, nausea and vomiting are not uncommon in terminal suffering requiring treatment with various compounds of analgesics and antiemetics. At Baerum Hospital the pump reservoirs for continuous, subcutaneous drug delivery are routinely filled by the hospital pharmacist. We examined the physico-chemical stability of various concentrations of mixtures of morphine-metoclopramide and morphine-metoclopramide-haloperidol at 25 degrees C. We found good stability for at least seven days. Addition of haloperidol seems to reduce stability. Plain morphine-haloperidol solutions are unstable. Split products were not found in any of the mixtures. We also examined the osmolality of current clinical compounds, focusing on local irritant effect at the infusion site. All solutions except for one with a high concentration of haloperidol were found to be close to isoosmolarl.
Reviewing current and emerging antiemetics for chemotherapy-induced nausea and vomiting prophylaxis.
Natale, James J
2015-01-01
This review provides background information on chemotherapy-induced nausea and vomiting (CINV) classification and pathophysiology and reviews various antiemetic agents for CINV prophylaxis, including corticosteroids, serotonin receptor antagonists (5-HT3 RAs), tachykinin NK1 receptor antagonists (NK1 RAs), and olanzapine. Other less commonly used agents are briefly discussed. Practical considerations are reviewed as well, including emetogenicity of chemotherapeutic regimens, patient-specific risk factors for CINV, principles of CINV management, health economics outcome research, and quality of life. Available data on the newly FDA-approved antiemetic combination netupitant/palonosetron (NEPA) is also reviewed. Prevention of CINV is an important goal in managing patients with cancer and is especially difficult with respect to nausea and delayed CINV. Corticosteroids are a mainstay of CINV prophylaxis and are usually given in combination with other therapies. The 5-HT3 RA palonosetron has shown increased efficacy over other agents in the same class for prevention of delayed emesis with moderately emetogenic chemotherapy and NK1 RAs improve emesis prevention in combination with 5-HT3 RAs and dexamethasone. Olanzapine has shown efficacy for CINV prophylaxis and the treatment of breakthrough CINV. The new combination therapy, NEPA, has been shown to be efficacious for the prevention of acute, delayed, and overall CINV. Risk factors that have been identified for CINV include gender, age, and alcohol intake. It is important to assess the emetogenicity of chemotherapy regimens as well as the potential impact of patient risk factors in order to provide adequate prophylaxis. Acute and delayed CINV are severe, burdensome side effects of chemotherapy; however, new data on prevention and the discovery of new agents can further improve CINV control.
Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.
Derry, Sheena; Moore, R Andrew; McQuay, Henry J
2010-11-10
Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting commonly associated with migraine. To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010. We included randomised, double-blind, placebo- or active-controlled studies using self-administered paracetamol to treat a migraine headache episode, with at least 10 participants per treatment arm. Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Ten studies (2769 participants, 4062 attacks) compared paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs of 12, 5.2 and 5.0 for 2-hour pain-free and 1- and 2-hour headache relief, respectively, when medication was taken for moderate to severe pain. Nausea, photophobia and phonophobia were reduced more with paracetamol than with placebo at 2 hours (NNTs of 7 to 11); more individuals were free of any functional disability at 2 hours with paracetamol (NNT 10); and fewer participants needed rescue medication over 6 hours (NNT 6).Paracetamol 1000 mg plus metoclopramide 10 mg was not significantly different from oral sumatriptan 100 mg for 2-hour headache relief; there were no 2-hour pain-free data. There was no significant
Poon, R. T.; Chow, L. W.
1998-01-01
A double-blind randomized crossover trial was performed to compare the antiemetic efficacy of two 5-HT3 receptor antagonists, granisetron and ondansetron, in Chinese patients receiving adjuvant chemotherapy (cyclophosphamide, methotrexate and 5-fluorouracil) for breast cancer. Twenty patients were randomized to receive chemotherapy with either granisetron on day 1 and ondansetron on day 8 of the first cycle followed by the reverse order in the second cycle, or vice versa. The number of vomiting episodes and the severity of nausea in the first 24 h (acute vomiting/nausea) and the following 7 days (delayed vomiting/nausea) were studied. Acute vomiting was completely prevented in 29 (72.5%) cycles with granisetron and 27 (67.5%) cycles with ondansetron, and treatment failure (>5 vomiting episodes) occurred in two (5%) cycles with each agent (P = NS). Acute nausea was completely controlled in 15 (37.5%) cycles with granisetron and 14 (35%) cycles with ondansetron, whereas severe acute nausea occurred in four (10%) cycles with each agent (P = NS). However, complete response for delayed vomiting was observed in only 21 (52.5%) cycles with granisetron and 22 (55%) cycles with ondansetron (P = NS), and delayed nausea was completely controlled in only 11 (27.5%) and ten (25%) cycles respectively (P = NS). In conclusion, both granisetron and ondansetron are effective in controlling acute nausea and vomiting in Chinese patients, with equivalent antiemetic efficacy. Control of delayed nausea and vomiting is less satisfactory. PMID:9635849
Palonosetron as an anti-emetic and anti-nausea agent in oncology.
Aapro, Matti S
2007-12-01
Palonosetron (Aloxi(®), Onicit(®), Paloxi(®)) is a second-generation 5-HT(3) receptor antagonist (RA) with an extended half-life of ~40 hours and high binding affinity for the 5-HT₃ receptor that is markedly different from other 5-HT(3) RAs. Phase III trials demonstrate that a single dose of palonosetron compared with traditional 5-HT₃ RAs is more effective in preventing chemotherapy-induced nausea and vomiting (CINV) during the first 24 hours following chemotherapy (acute CINV), and also exhibits prolonged efficacy to provide significantly better protection from CINV in the delayed and overall phases. This superior and extended protection from CINV conferred by palonosetron following a single intravenous dose before chemotherapy simplifies dosing schedules. Recent research has focused on optimization of palonosetron-based antiemetic regimens, particularly in combination with steroids and neurokinin-1 RAs. The available clinical data indicate high control rates for palonosetron, suggesting a synergistic potential for protection in patients scheduled to receive emetogenic drug regimens.
Tayarani-Najaran, Z; Talasaz-Firoozi, E; Nasiri, R; Jalali, N; Hassanzadeh, MK
2013-01-01
Background: This study is aimed at determining the efficacy of Mentha spicata (M. spicata) and Mentha × piperita (M. × piperita) in preventing chemotherapy-induced nausea and vomiting (CINV). Methods: This was a randomised, double-blind clinical trial study. Prior to the study, patients were randomly assigned into four groups to receive M. spicata or M. × piperita. Statistical analysis included the χ2 test, relative risk, and Student’s t-test. Fifty courses were analysed for each group that met our eligibility criteria. The treatment and placebo groups applied essential oils of M. spicata, M. × piperita, or a placebo, while the control group continued with their previous antiemetic regimen. Patients or guardians recorded the number of emetic events, the intensity of nausea over 20 h of chemotherapy, as well as any possible adverse effects that occurred during this time. Results: There was a significant reduction in the intensity and number of emetic events in the first 24 h with M. spicata and M. × piperita in both treatment groups (p < 0.05) when compared with the control and no adverse effects were reported. The cost of treatment was also reduced when essential oils were used. Conclusion: M. spicata or M. × piperita essential oils are safe and effective for antiemetic treatment in patients, as well as being cost effective. PMID:23390455
Garra, Gregory; Singer, Adam J; Bamber, Danny; Chohan, Jasmine; Troxell, Regina; Thode, Henry C
2009-04-01
Ingestion of diatrizoate meglumine before abdominal computed tomography (CT) is time consuming. We hypothesized that pretreatment with metoclopramide or ondansetron would result in faster ingestion of diatrizoate meglumine than placebo. The study was a double-blind, randomized controlled trial on adults requiring oral contrast abdominal CT. Patients were randomized to placebo, metoclopramide 10 mg, or ondansetron 4 mg intravenously 15 minutes before ingesting 2 L of diatrizoate meglumine. The primary outcome was time to complete diatrizoate meglumine ingestion. Secondary outcome measures included volume of diatrizoate meglumine ingested, 100-mm visual analog scale for nausea at 15-minute intervals, time to CT, vomiting, and use of rescue antiemetics. The study was powered to detect a 60-minute difference in diatrizoate meglumine ingestion time between saline and medication groups. One hundred six patients were randomized; placebo (36), metoclopramide (35), and ondansetron (35). Groups were similar in baseline characteristics. Median (interquartile range) times for diatrizoate meglumine ingestion were placebo 109 minutes (82 to 135 minutes); metoclopramide 105 minutes (75 to 135 minutes); and ondansetron 110 minutes (79 to 140 minutes) (P=.67). Vomiting was less frequent with metoclopramide (3%) than placebo (18%) or ondansetron (9%) (P=.11). The visual analog scale for nausea at each point was not significantly different between groups (P=.11). The need for rescue antiemetics was lowest for metoclopramide (3%) compared with placebo (27%) and ondansetron (12%) (P=.02). Pretreatment with ondansetron or metoclopramide does not reduce oral contrast solution ingestion time.
Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.
Derry, Sheena; Moore, R Andrew
2013-04-30
This is an updated version of the original Cochrane review published in Issue 11, 2010 (Derry 2010). Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting, which are commonly associated with migraine. To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared with placebo and other active interventions in the treatment of acute migraine in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010 for the original review, and to 13 February 2013 for the update. Two clinical trials registers (ClinicalTrials.gov and gsk-clinicalstudyregister.com) were also searched on both occasions. We included randomised, double-blind, placebo- or active-controlled studies using self-administered paracetamol to treat a migraine headache episode, with at least 10 participants per treatment arm. Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared with placebo or other active treatment. Searches for the update identified one additional study for inclusion. Eleven studies (2942 participants, 5109 attacks) compared paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs of 12 (19% response with paracetamol, 10% with placebo), 5.0 (56% response with paracetamol, 36% with placebo) and 5.2 (39% response with paracetamol, 20% with placebo) for 2-hour pain-free and 2- and 1
Dranitsaris, George; Leung, Pauline
2004-01-01
Decision analysis is commonly used to perform economic evaluations of new pharmaceuticals. The outcomes of such studies are often reported as an incremental cost per quality-adjusted life year (QALY) gained with the new agent. Decision analysis can also be used in the context of estimating drug cost before market entry. The current study used neurokinin-1 (NK-1) receptor antagonists, a new class of antiemetics for cancer patients, as an example to illustrate the process using an incremental cost of dollars Can20,000 per QALY gained as the target threshold. A decision model was developed to simulate the control of acute and delayed emesis after cisplatin-based chemotherapy. The model compared standard therapy with granisetron and dexamethasone to the same protocol with the addition of an NK-1 before chemotherapy and continued twice daily for five days. The rates of complete emesis control were abstracted from a double-blind randomized trial. Costs of standard antiemetics and therapy for breakthrough vomiting were obtained from hospital sources. Utility estimates characterized as quality-adjusted emesis-free days were determined by interviewing twenty-five oncology nurses and pharmacists by using the Time Trade-Off technique. These data were then used to estimate the unit cost of the new antiemetic using a target threshold of dollars Can20,000 per QALY gained. A cost of dollars Can6.60 per NK-1 dose would generate an incremental cost of dollars Can20,000 per QALY. The sensitivity analysis on the unit cost identified a range from dollars Can4.80 to dollars Can10.00 per dose. For the recommended five days of therapy, the total cost should be dollars Can66.00 (dollars Can48.00-dollars Can100.00) for optimal economic efficiency relative to Canada's publicly funded health-care system. The use of decision modeling for estimating drug cost before product launch is a powerful technique to ensure value for money. Such information can be of value to both drug manufacturers and
Pirri, Carlo; Bayliss, Evan; Trotter, James; Olver, Ian N; Katris, Paul; Drummond, Peter; Bennett, Robert
2013-03-01
Despite significant antiemetic advances, almost 50% of treated cancer patients still experience nausea and vomiting (N&V). The goal of antiemetic therapy--complete prevention of treatment-induced nausea and/or vomiting (TIN+/-V)--remains elusive for several reasons. Potentially, N&V may be part of a symptom cluster where co-occurring symptoms negatively affect antiemetic management. Consequently, we examined TIN+/-V incidence and the impact of nausea, vomiting and symptom cluster(s) containing them, respectively, on patients' quality of life (QoL) and psychological adjustment across treatment. A longitudinal secondary analysis was performed on data from a prospective, observational QoL study involving 200 newly diagnosed cancer patients who underwent combined modality treatment. QoL, psychological adjustment and patient/clinical characteristics were examined at pretreatment, on-treatment (8 weeks) and post-treatment. Overall, 62% of patients experienced TIN+/-V, with TIN (60%) doubling TIV incidence (27 %). Exploratory factor analyses of QoL scores at each treatment time point identified a recurrent gastrointestinal symptom cluster comprising nausea, vomiting and appetite loss. Approximately two thirds of patients reported co-occurrence of all three symptoms, which exerted synergistic effects of multiplicative proportions on overall QoL. Patients who reported co-occurrence of these symptoms during treatment experienced significantly greater QoL impairment (physical, role and social functioning, fatigue, N&V, appetite loss, overall physical health, overall QOL) and psychological distress (cancer distress, premorbid neuroticism) than those unaffected (0.001 > p ≤ 0.05). Moreover, nausea was more pervasive than vomiting or appetite loss across treatment and had a greater impact on overall QoL. While antiemetic therapy was effective for vomiting and helped prevent/relieve associated appetite loss, the benefits for appetite loss were seemingly constrained by its
Kim, Sioh; Seo, Jeongwon; Jeon, Younghoon
2010-01-01
Background: Nausea and vomiting are frequent adverse effects of patient-controlled epidural analgesia (PCEA) with opioids. Objective: This study was designed to assess the antiemetic effect of midazolam added to fentanyl—ropivacaine PCEA. Methods: In a prospective, randomized, double-blind, controlled trial, smoking patients with gastric cancer undergoing elective subtotal gastrectomy were evenly allocated to 1 of 2 treatment groups to manage postoperative pain: 0.2% ropivacaine mixed with fentanyl 4 μg/mL and midazolam 0.2 mg/mL (test group) or 0.2% ropivacaine mixed with fentanyl 4 μg/mL (control group). The PCEA infusion was set to deliver 4 μL/h of the study solution, with a bolus of 2 mL per demand and a 15-minute lockout time. The incidence of postoperative nausea and vomiting (PONV), pain intensity, sedation score, usage of rescue analgesia and rescue antiemetic, respiratory depression, urinary retention, and pruritus were recorded at 2, 6, 12, 24, 48, and 72 hours after surgery. Total infused volume of PCEA at 72 hours after surgery was measured. Results: A total of 60 patients were approached and randomized to treatment. No patients were excluded by exclusion criteria and all enrolled patients completed this study. Incidence of nausea (7% vs 33%; P = 0.02) in the test group was significantly lower than in the control group. The overall frequency of PONV in the test group was significantly less than that of the control group (7% vs 40%; P = 0.006). In addition, the mean (SD) infused volume of PCEA in the test group was significantly lower than that in the control group (392.3 [68.9] vs 351.2 [49.8] mL; P = 0.01). However, there were no significant differences in pain intensity, usage of rescue antiemetics and rescue analgesics, and mild pruritus between groups. No patient reported moderate or severe sedation, respiratory depression, or hypoxemia. In addition, there were no severe adverse events. Conclusions: Midazolam added to fentanyl-ropivacaine PCEA
April, Michael D; Oliver, Joshua J; Davis, William T; Ong, David; Simon, Erica M; Ng, Patrick C; Hunter, Curtis J
2018-02-17
We compare aromatherapy with inhaled isopropyl alcohol versus oral ondansetron for treating nausea among emergency department (ED) patients not requiring immediate intravenous access. In a randomized, blinded, placebo-controlled trial, we enrolled a convenience sample of adults presenting to an urban tertiary care ED with chief complaints including nausea or vomiting. We randomized subjects to 1 of 3 arms: inhaled isopropyl alcohol and 4 mg oral ondansetron, inhaled isopropyl alcohol and oral placebo, and inhaled saline solution placebo and 4 mg oral ondansetron. The primary outcome was mean nausea reduction measured by a 0- to 100-mm visual analog scale from enrollment to 30 minutes postintervention. Secondary outcomes included receipt of rescue antiemetic medications and adverse events. We enrolled 122 subjects, of whom 120 (98.3%) completed the study. Of randomized subjects, 40 received inhaled isopropyl alcohol and oral ondansetron, 41 received inhaled isopropyl alcohol and oral placebo, and 41 received inhaled saline solution placebo and oral ondansetron. The mean decrease in nausea visual analog scale score in each arm was 30 mm (95% confidence interval [CI] 22 to 37 mm), 32 mm (95% CI 25 to 39 mm), and 9 mm (95% CI 5 to 14 mm), respectively. The proportions of subjects who received rescue antiemetic therapy in each arm were 27.5% (95% CI 14.6% to 43.9%), 25.0% (95% CI 12.7% to 41.2%), and 45.0% (95% CI 29.3% to 61.5%), respectively. There were no adverse events. Among ED patients with acute nausea and not requiring immediate intravenous access, aromatherapy with or without oral ondansetron provides greater nausea relief than oral ondansetron alone. Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
Uchida, Mayako; Mori, Yasuo; Nakamura, Tsutomu; Kato, Koji; Kamezaki, Kenjiro; Takenaka, Katsuto; Shiratsuchi, Motoaki; Kadoyama, Kaori; Miyamoto, Toshihiro; Akashi, Koichi
2017-01-01
In the present study, the antiemetic effect of palonosetron, not combined with dexamethasone and aprepitant, on chemotherapy-induced nausea and vomiting was evaluated in patients with malignant lymphoma receiving first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy, and was compared to that of granisetron. A total of 74 patients with non-Hodgkin lymphoma were included in this study (April 2007 to December 2015). Palonosetron (0.75 mg) or granisetron (3 mg) was intravenously administered before R-CHOP therapy. The proportions of patients with complete response (CR) during the overall (0-120 h after the start of R-CHOP therapy), acute (0-24 h) and delayed (24-120 h) phases were evaluated. CR was defined as no vomiting and no use of antiemetic rescue medication. A total of 32 and 42 patients were treated with palonosetron and granisetron, respectively. The CR rate in the palonosetron group was significantly higher than that in the granisetron group during the delayed phase (90.6 and 61.9%, respectively; p=0.007). Logistic regression analysis showed that use of palonosetron improved the CR rate during the delayed phase, compared to use of granisetron. Female sex, age less than 60 years, no habitual alcohol intake, and Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 1 were significant risk factors associated with non-CR. The findings of this study suggested the superiority of palonosetron to granisetron, without accompanying dexamethasone and aprepitant, for chemotherapy-induced nausea and vomiting in patients with malignant lymphoma.
Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update
Basch, Ethan; Prestrud, Ann Alexis; Hesketh, Paul J.; Kris, Mark G.; Feyer, Petra C.; Somerfield, Mark R.; Chesney, Maurice; Clark-Snow, Rebecca Anne; Flaherty, Anne Marie; Freundlich, Barbara; Morrow, Gary; Rao, Kamakshi V.; Schwartz,, Rowena N.; Lyman, Gary H.
2011-01-01
Purpose To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology. Methods A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library, and meeting materials from ASCO and the Multinational Association for Supportive Care in Cancer were all searched. Primary outcomes of interest were complete response and rates of any vomiting or nausea. Results Thirty-seven trials met prespecified inclusion and exclusion criteria for this systematic review. Two systematic reviews from the Cochrane Collaboration were identified; one surveyed the pediatric literature. The other compared the relative efficacy of the 5-hydroxytryptamine-3 (5-HT3) receptor antagonists. Recommendations Combined anthracycline and cyclophosphamide regimens were reclassified as highly emetic. Patients who receive this combination or any highly emetic agents should receive a 5-HT3 receptor antagonist, dexamethasone, and a neurokinin 1 (NK1) receptor antagonist. A large trial validated the equivalency of fosaprepitant, a single-day intravenous formulation, with aprepitant; either therapy is appropriate. Preferential use of palonosetron is recommended for moderate emetic risk regimens, combined with dexamethasone. For low-risk agents, patients can be offered dexamethasone before the first dose of chemotherapy. Patients undergoing high emetic risk radiation therapy should receive a 5-HT3 receptor antagonist before each fraction and for 24 hours after treatment and may receive a 5-day course of dexamethasone during fractions 1 to 5. The Update Committee noted the importance of continued symptom monitoring throughout therapy. Clinicians underestimate the incidence of nausea, which is not as well controlled as emesis. PMID:21947834
Basu, Anjana; Saha, Debdas; Hembrom, Bani P; Roy, Amit; Naaz, Anjum
2011-05-01
The objective of the study was to compare the efficacy of palanosetron (0.25 mg), granisetron (3.0 mg) and ondansetron (8.0 mg) used as anti-emetics for the prevention of postoperative nausea/vomiting in patients undergoing middle ear surgery. The study was done among 75 adult patients (age group 30-45 years) of which 50 were males and rest (25) females, all of ASA I and ASA II. The patients were randomly allocated into 3 equal groups: Group I (n = 25) received injection palanosetron (0.25 mg) IV, group II (n = 25) received injection granisetron (3 mg) IV and group III (n = 25) received injection ondansetron (8.0 mg) IV at the end of the surgical procedure. A standard general anaesthesia technique was employed. Emetic episodes and safety assessments were performed during two periods of 0-6 hours in the postanaesthesia care unit and 6-24 hours in the ward after anaesthesia. The incidence of emesis-free patients during the 0-6 hours period was 100% for group I; 72% for group II and 56% for group III. During the 6-24 hours period incidence of emesis-free patients were 96% for group I; 56% for group II and 32% for group III. So to conclude, a single dose of palanosetron (0.25 mg) is a superior anti-emetic to granisetron (3.0 mg) or ondansetron (8.0 mg) in complete prevention of postoperative nausea and vomiting after middle ear surgery during the first 24 hours period.
Hanai, Akiko; Ishiguro, Hiroshi; Sozu, Takashi; Tsuda, Moe; Arai, Hidenori; Mitani, Akira; Tsuboyama, Tadao
2016-01-01
Research on patient-reported outcomes indicates that constipation is a common adverse effect of chemotherapy, and the use of 5-hydroxytryptamine (serotonin; 5HT3) receptor antagonists aggravates this condition. As cancer patients take multiple drugs as a part of their clinical management, a non-pharmacological self-management (SM) of constipation would be recommended. We aimed to evaluate the effectiveness of a SM program on antiemetic-induced constipation in cancer patients. Thirty patients with breast cancer, receiving 5HT3 receptor antagonists to prevent emesis during chemotherapy were randomly assigned to the intervention or control group. The SM program consisted of abdominal massage, abdominal muscle stretching, and education on proper defecation position. The intervention group started the program before the first chemotherapy cycle, whereas patients in the wait-list control group received the program on the day before their second chemotherapy cycle. The primary outcome was constipation severity, assessed by the constipation assessment scale (CAS, sum of eight components). The secondary outcome included each CAS component (0-2 points) and mood states. A self-reported assessment of satisfaction with the program was performed. The program produced a statistically and clinically significant alleviation of constipation severity (mean difference in CAS, -3.00; P = 0.02), decrease in the likelihood of a small volume of stool (P = 0.03), and decrease in depression and dejection (P = 0.02). With regards to program satisfaction, 43.6 and 26.4 % patients rated the program as excellent and good, respectively. Our SM program is effective for mitigating the symptoms of antiemetic-induced constipation during chemotherapy.
A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients.
Bleiberg, H; Piccart, M; Lips, S; Panzer, J M; N'Koua Mbon, J B
1992-02-01
Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.
Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki
2015-01-01
The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. PMID:25533447
Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki
2015-03-01
The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Li, Hongjia; Le, Qiqi; Liu, Shanshan; Zong, Shaoqi; Zheng, Leizhen; Hou, Fenggang
2016-01-01
A variety of triple antiemetic regimens are being used to prevent cisplatin-based chemotherapy induced delayed emesis and nausea in cancer patients. We performed a network meta-analysis to compare the efficacies of the different regimens. Electronic searches of the PubMed, Cochrane Library and MEDLINE databases were performed to identify randomized controlled trials, and data were analyzed using JAGS, Stata 14.0 and R project. The primary outcome was a complete response (CR). The secondary outcomes were no vomiting (NV) and no nausea (NN). Among the 398 studies identified, 10 were eligible and included, providing data on nine regimens. In the CR analysis, the absolute rank of netupitant + palonosetron + dexamethasone (NEPA) was 0.8579. In the NV and NN analyses, NEPA's absolute ranks were 0.8631 and 0.7902, respectively. The compliance of patients treated with rolapitant + granisetron + dexamethasone (RGD) was the best due to a low incidence of adverse events, and good compliance was also observed with NEPA. It was difficult to achieve good compliance with aprepitant + granisetron + dexamethasone (AGD). Overall, NEPA was the best regimen, and aprepitant + ondansetron + dexamethasone (AOD) is also worthy of recommendation because of its low cost and good effect. For patients with severe constipation, hiccups, asthenia and/or delayed nausea, RGD is worthy of consideration. PMID:27015550
Sanchez-Ledesma, M J; López-Olaondo, L; Pueyo, F J; Carrascosa, F; Ortega, A
2002-12-01
In this study we compared the efficacy and safety of three antiemetic combinations in the prevention of postoperative nausea and vomiting (PONV). Ninety ASA status I-II women, aged 18-65 yr, undergoing general anesthesia for major gynecological surgery, were included in a prospective, randomized, double-blinded study. A standardized anesthetic technique and postoperative analgesia (intrathecal morphine plus IV patient-controlled analgesia (PCA) with morphine) were used in all patients. Patients were randomly assigned to receive ondansetron 4 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 1, n = 30), dexamethasone 8 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 2, n = 30), or ondansetron 4 mg plus dexamethasone 8 mg after the induction of anesthesia and placebo 12 h later (Group 3, n = 30). A complete response, defined as no PONV in 48 h, occurred in 80% of patients in Group 1, 70% in Group 3, and 40% in Group 2 (P = 0.004 versus Groups 1 and 3). The incidences of side effects and other variables that could modify the incidence of PONV were similar among groups. In conclusion, ondansetron, in combination with droperidol or dexamethasone, is more effective than dexamethasone in combination with droperidol in women undergoing general anesthesia for major gynecological surgery with intrathecal morphine plus IV PCA with morphine for postoperative analgesia. The combination of ondansetron plus dexamethasone or droperidol was significantly better than the combination of dexamethasone plus droperidol in the prophylaxis of postoperative nausea and vomiting in women undergoing general anesthesia for major gynecological surgery, with intrathecal and IV morphine (patient-controlled analgesia) for management of postoperative pain.
Santos, Luiz Cesar P; Ludders, John W; Erb, Hollis N; Martin-Flores, Manuel; Basher, Karen L; Kirch, Pati
2011-07-01
To determine the effect of ondansetron on the incidence of vomiting in cats pre-medicated with dexmedetomidine and buprenorphine. Randomized, blinded, controlled trial. Eighty-nine female domestic shorthair cats, aged 3-60 months (median, 12 months) and weighing 1.2-5.1 kg. Each cat received dexmedetomidine (40 μg kg(-1)) plus buprenorphine (20 μg kg(-1)), intramuscularly as pre-anesthetic medication. Cats were assigned to three treatment groups: ondansetron (0.22 mg kg(-1), intramuscular [IM]), either 30 minutes before the pre-anesthetic medication (ONDA group, n = 31) or with the pre-anesthetic medication (OPM group, n = 30) mixed with the pre-anesthetic medications in the same syringe, or not to receive the antiemetic (control group, n = 28). Emesis was recorded as an all-or-none response. The number of episodes of emesis and the time until onset of the first emetic episode were recorded for each cat. Clinical signs of nausea were recorded whenever they occurred, and a numerical rating scale was used to quantify these signs. Data were analyzed using Kruskal-Wallis and Chi-square test; a Bonferroni correction was made for six comparisons; thus, the two-sided p for significance was 0.05/6 = 0.008. There was a significant reduction in the number of cats vomiting, in the episodes of vomiting/cat, the time elapsed between the premedication and the first vomiting and the severity of nausea in the OPM group compared to the ONDA and control groups. In cats, the administration of ondansetron (0.22 mg kg(-1)) ameliorates and reduced the severity of dexmedetomidine-induced nausea and vomiting only when it was administered in association with this drug. © 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.
Belosic Halle, Zeljka; Vlainic, Josipa; Drmic, Domagoj; Strinic, Dean; Luetic, Kresimir; Sucic, Mario; Medvidovic-Grubisic, Maria; Pavelic Turudic, Tatjana; Petrovic, Igor; Seiwerth, Sven; Sikiric, Predrag
2017-05-17
The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H 2 O)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased
NASA Astrophysics Data System (ADS)
Wang, Yaqiong; Liu, Shaopu; Liu, Zhongfang; Yang, Jidong; Hu, Xiaoli
2013-03-01
In 0.1 mol L-1 HCl medium, antiemetic drugs (ATM), such as granisetron hydrochloride (GS) and tropisetron hydrochloride (TS), reacted with H3PW12O40·nH2O and formed 3:1 ion-association complex of [(ATM)3PW12O40], then self-aggregated into nanoparticles-[(ATM)3PW12O40]n with an average size of 100 nm. The reaction resulted in the enhancement of resonance Rayleigh scattering (RRS) and the absorption spectra. The increments of scattering intensity (ΔIRRS) and the change of absorbance (ΔA) were both directly proportional to the concentrations of ATM in certain ranges. Accordingly, two new RRS and spectrophotometric methods were proposed for ATM detection. The detection limits (3σ) of GS and TS were 3.2 ng mL-1 and 4.0 ng mL-1(RRS method), 112.5 ng mL-1 and 100.0 ng mL-1(spectrophotometric method). These two methods were applied to determine GS in orally disintegrating tablets and the results were in good agreement with the official method. The ground-state geometries and electronic structures of GS and TS were optimized by the hybrid density functional theory (DFT) method and the shape of [(ATM)3PW12O40]n was characterized by atomic force microscopy (AFM). Take the RRS method with higher sensitivity as an example, the reaction mechanism and the reasons for enhancement of scattering were discussed.
Kitazaki, Takeshi; Fukuda, Yuichi; Fukahori, Susumu; Oyanagi, Kazuhiko; Soda, Hiroshi; Nakamura, Yoichi; Kohno, Shigeru
2015-01-01
The purpose of the study is to investigate the usefulness of the triplet regimen comprising aprepitant, palonosetron, and dexamethasone in patients treated with highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). Patients with lung cancer (aged 65.8 ± 8.4 years) who received carboplatin-based MEC and those treated with cisplatin-based HEC were enrolled. The antiemetic regimen for both types of chemotherapy consisted of aprepitant, palonosetron, and dexamethasone based on the May 2010 guidelines prepared by the Japan Society of Clinical Oncology. The incidence of chemotherapy-induced nausea and vomiting (CINV) and the use of salvage treatment were assessed. The primary endpoints were the percentage of patients with a complete response (CR: no nausea and no salvage treatment) during the entire study period (5 days) after chemotherapy, during the acute phase (day 1), and during the delayed phase (days 2-5). CR rates for the entire period were 86 and 71% in patients receiving carboplatin-based and cisplatin-based chemotherapy, respectively. CR rates were respectively 98 and 100% in the acute phase versus 87 and 71% in the delayed phase. Most of the patients could ingest food throughout the entire period after chemotherapy. Assessment of various risk factors for acute and delayed CINV (gender, age, prior vomiting due to antineoplastic therapy, prior experience of motion sickness, and history of drinking) revealed no significant influence of these factors on the CR rate for the entire period in patients receiving either carboplatin-based or cisplatin-based chemotherapy. The present triple therapy can be recommended for supporting both carboplatin-based and cisplatin-based chemotherapy regimens.
Qazi, Faaiza; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Nasiri, Muhammad Iqbal; Ahmed, Kamran; Ahmad, Mansoor
2017-04-12
Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated. Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol ® ), Glyceryl palmitostearate (Precirol ® ), Glyceryl behenate (Compritol ® ) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found. Sphericity indicated by shape factor (e R ) varied with type and concentration of lipids: Geleol ® (e R = 0.891-0.997), Precirol ® (e R = 0.611-0.743), Compritol ® (e R = 0.665-0.729) and Carnauba wax (e R = 0.499-0.551). Highly spherical pellets were obtained with Geleol ® (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol ® and Compritol ® , (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax. Scanning electron microscopy of Compritol ® pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol ® and Compritol ® pellets, explained by Korsmeyer-Peppas (R 2 = 0.978-0.993) indicated
Nakamura, Fumiaki; Higashi, Takahiro
2013-12-01
Chemotherapy-induced nausea and vomiting (CINV) substantially affects patient quality of life. Although several guidelines have recommended the use of 5-hydroxytryptamine 3 (5HT3) receptor antagonists with glucocorticoids to alleviate acute CINV, studies in other countries have reported that these recommendations were often not followed. We aimed to assess antiemetic use in community practices just before the Japanese Guidelines for the Appropriate Use of Antiemetics were published. Using the insurance claims submitted to a public insurance program that covers residents up to 75 years old operated by a city with a population of 250,000, we examined the concurrent use of 5HT3 receptor antagonists and glucocorticoids with high or moderate emetic risk chemotherapy. Overall, 448 patients received high or moderate emetic risk chemotherapy 1,342 times during the study period. The recommended antiemetic therapy was provided in 61.9 % (95 % confidence interval 55.5-68.3 %) of the treated patients, but the moderate emetic risk chemotherapy group received the recommended antiemetic therapy less frequently than the high emetic risk chemotherapy group (55.5 vs. 82.1 %, P < 0.01). A multivariate analysis showed that the use of non-recommended antiemetics and high emetic risk chemotherapy were associated with the recommended antiemetic therapy. Breast and lung cancer patients receiving high emetic risk chemotherapy received the recommended antiemetics in 100 % of cases, while only 67 % of patients with other cancer types received the recommended antiemetics. Despite several limitations associated with analysis of insurance claims, our study indicates that substantial room for improvement exists in the practice of preventing CINV.
Rock, Erin M; Goodwin, Jennifer M; Limebeer, Cheryl L; Breuer, Aviva; Pertwee, Roger G; Mechoulam, Raphael; Parker, Linda A
2011-06-01
The interaction between two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), which have been reported to act as a 5-hydroxytryptamine 1A (5-HT(1A)) agonist and antagonist, respectively, was evaluated. To evaluate the potential of CBG to reverse the anti-nausea, anti-emetic effects of CBD. In experiment 1, rats were pre-treated with CBG (0.0, 1, 5, and 10 mg/kg, ip), 15 min prior to being treated with CBD (experiment 1a: VEH or 5 mg/kg, ip) or 8-OH-DPAT (experiment 1b: VEH or 0.01 mg/kg, ip). Thirty minutes later, all rats received a pairing of 0.1% saccharin solution and LiCl (20 ml/kg of 0.15 M, ip). Seventy-two hours later, the rats received a drug-free taste reactivity test with saccharin to evaluate the effects of the treatments on the establishment of conditioned gaping reactions (a model of nausea). As well, conditioned saccharin avoidance was measured. In experiment 2, Suncus murinus were injected with CBG (5 mg/kg, ip) or VEH 15 min prior to CBD (5 mg/kg) or VEH and 30 min later were injected with LiCl (60 ml/kg of 0.15 M, i.p.), and the number of vomiting episodes were measured. CBD (5 mg/kg) suppressed conditioned gaping in rats and vomiting in shrews, which were reversed by pre-treatment with all doses of CBG. CBG also prevented the anti-nausea effects of 8-OH-DPAT. Interactions between moderate doses of CBG and CBD may oppose one another at the 5-HT(1A) receptor in the regulation of nausea and vomiting.
Konmun, J; Danwilai, K; Ngamphaiboon, N; Sripanidkulchai, B; Sookprasert, A; Subongkot, S
2017-04-01
6-Gingerol is a natural compound extracted from ginger. Preclinical studies demonstrated that 6-gingerol has an anti-emetic activity by inhibiting neurokinin-1, serotonin, and dopamine receptors. Several clinical trials examined crude ginger powder for preventing chemotherapy-induced nausea and vomiting (CINV), but none of them was conducted with a standardized bioactive compound. Patients who received moderately to highly emetogenic adjuvant chemotherapy were randomized to receive 6-gingerol 10 mg or placebo orally twice daily for 12 weeks. Ondansetron, metoclopramide, and dexamethasone were given to all patients. The primary endpoint was complete response (CR) rate defined as no emesis or rescue treatment at any time. Eighty-eight patients were randomized to receive 6-gingerol (N = 42) or placebo (N = 46). Most patients received highly emetogenic chemotherapy (93%). Overall CR rate was significantly higher in 6-gingerol group as compared with that of the placebo (77 vs. 32%; P < 0.001). The difference in means of appetite score was significant (P = 0.001) and more noticeable over time. Mean FACT-G score indicating quality of life was significantly higher (86.21) in 6-gingerol group at 64 days as compared with that of placebo group (72.36) (P < 0.001). No toxicity related to 6-gingerol was observed. Patients treated with 6-gingerol reported significantly less grade 3 fatigue (2 vs. 20%; P = 0.020). 6-Gingerol significantly improved overall CR rate in CINV, appetite and quality of life in cancer patients receiving adjuvant chemotherapy. A phase III randomized study of 6-gingerol is warranted to confirm these results.
Vidall, Cheryl; Fernández-Ortega, Paz; Cortinovis, Diego; Jahn, Patrick; Amlani, Bharat; Scotté, Florian
2015-11-01
Chemotherapy/radiotherapy-induced nausea and vomiting (CINV/RINV) can affect half of oncology patients, significantly impacting daily life. Nausea without vomiting has only recently been thought of as a condition in its own right. As such, the incidence of nausea is often underestimated. This survey investigated the incidence and impact of CINV/RINV in patients compared with estimations of physicians/oncology nurses to determine if there is a perceptual gap between healthcare professionals and patients. An online research survey of physicians, oncology nurses and patients was conducted across five European countries. Participants had to have experience prescribing/recommending or have received anti-emetic medication for CINV/RINV treatment. Questionnaires assessed the incidence and impact of CINV/RINV, anti-emetic usage and compliance, and attribute importance of anti-emetic medication. A total of 947 (375 physicians, 186 oncology nurses and 386 patients) participated in this survey. The incidence of nausea was greater than vomiting: 60 % of patients reported nausea alone, whereas 18 % reported vomiting. Physicians and oncology nurses overestimated the incidence of CINV/RINV but underestimated its impact on patients' daily lives. Only 38 % of patients reported full compliance with physicians'/oncology nurses' guidelines when self-administering anti-emetic medication. Leading factors for poor compliance included reluctance to add to a pill burden and fear that swallowing itself would induce nausea/vomiting. There is a perceptual gap between healthcare professionals and patients in terms of the incidence and impact of CINV/RINV. This may lead to sub-optimal prescription of anti-emetics and therefore management of CINV/RINV. Minimising the pill burden and eliminating the requirement to swallow medication could improve poor patient compliance with anti-emetic regimens.
Bourdon, F; Lecoeur, M; Leconte, L; Ultré, V; Kouach, M; Odou, P; Vaccher, C; Foulon, C
2016-12-30
The objective of this study was to evaluate five commercial ready-to-use transdermal vehicles (Phytobase ® , Lipovan ® , Pentravan ® , Pentravan ® Plus and Pluronic Lecithin Organogel (PLO)), for the compounding of three antiemetic drugs (ondansetron, dexamethasone and aprepitant) and their administration in combination to treat chemotherapy-induced nausea and vomiting (CINV) at the hospital. Drugs were individually formulated in these vehicles and in mixture in Pentravan ® Plus using different penetration enhancers. Quality control of the forms has demonstrated that formulation process was mastered and convenient for the hospital (time required: 20min). Diffusion experiments through synthetic membranes and pig ear epidermis performed using Franz-type diffusion cells, have shown that the release and permeation process were greater for ondansetron than for dexamethasone and aprepitant, with a release step not limiting. As permeation of aprepitant was too low, it was discarded of the study. When ondansetron and dexamethasone were compounded in combination in Pentravan ® Plus, the most efficient vehicle, a permeation decrease was observed. Finally, the use of tween 20 instead of EtOH as chemical enhancer has led to 2-fold factor increase in the flux of dexamethasone, resulting in fluxes convenient for transdermal administration of ondansetron to a child, but insufficient for an adult and for dexamethasone. Copyright © 2016 Elsevier B.V. All rights reserved.
Nawa-Nishigaki, Minako; Kobayashi, Ryo; Suzuki, Akio; Hirose, Chiemi; Matsuoka, Rie; Mori, Ryutaro; Futamura, Manabu; Sugiyama, Tadashi; Yoshida, Kazuhiro; Itoh, Yoshinori
2018-02-01
Chemotherapy-induced nausea and vomiting (CINV) is one of most distressing adverse events during cancer chemotherapy. In breast cancer patients receiving anthracycline and cyclophosphamide (AC) chemotherapy, CINV is poorly controlled. The prevalence of guideline-consistent antiemetic medication and control of CINV were investigated retrospectively in breast cancer patients receiving the first cycle of AC chemotherapy. Risks for CINV were analyzed by the multivariate logistic regression analysis. The effect of olanzapine added to the standard antiemetic medication on the incidence of CINV was subsequently evaluated in separate patients who received the first cycle of AC chemotherapy. Although the guideline-consistent antiemetic medication was performed in all subjects, the control rate of nausea (32%), but not vomiting (78%) was low. Risk analysis indicated that age younger than 55-year-old was a significant factor that reduces the control of both nausea and vomiting. Olanzapine (5 mg/day for 5 days), when added to the standard three-drug antiemetic medication, significantly improved the control of nausea and complete response. CINV was poorly controlled in breast cancer patients receiving AC chemotherapy, in which age younger than 55-year-old was a significant risk for both nausea and vomiting. Olanzapine was effective for improvement of the control of CINV associated with AC chemotherapy. Therefore, care should be taken to prevent CINV in young patients receiving AC chemotherapy by adding olanzapine to the standard three-drug antiemetic medication. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Effects of acupuncture on vasopressin-induced emesis in conscious dogs.
Tatewaki, Makoto; Strickland, Carmen; Fukuda, Hiroyuki; Tsuchida, Daisuke; Hoshino, Etsuo; Pappas, Theodore N; Takahashi, Toku
2005-02-01
Although acupuncture has a significant clinical benefit, the mechanism of acupuncture remains unclear. Vasopressin, a posterior pituitary hormone, is involved in nausea and vomiting in humans and dogs. To investigate the antiemetic effects of acupuncture on vasopressin-induced emesis, gastroduodenal motor activity and the frequency of retching and vomiting were simultaneously recorded in conscious dogs. In seven dogs, four force transducers were implanted on the serosal surfaces of the gastric body, antrum, pylorus, and duodenum. Gastroduodenal motility was continuously monitored throughout the experiment. Vasopressin was intravenously infused at a dose of 0.1 U x kg(-1) x min(-1) for 20 min. Electroacupuncture (EA, 1-30 Hz) at pericardium-6 (PC6), bladder-21 (BL21), or stomach-36 (ST36) was performed before, during, and after the vasopressin infusion. To investigate whether the opioid pathway is involved in EA-induced antiemetic effects, naloxone (a central and peripheral opioid receptor antagonist) or naloxone methiodide (a peripheral opioid receptor antagonist) was administered before, during, and after EA and vasopressin infusion. Intravenous infusion of vasopressin induced retching and vomiting in all dogs tested. Retrograde peristaltic contractions occurred before the onset of retching and vomiting. EA (10 Hz) at PC6 significantly reduced the number of episodes of retching and vomiting. EA at PC6 also suppressed retrograde peristaltic contractions. In contrast, EA at BL21 or ST36 had no antiemetic effects. The antiemetic effect of EA was abolished by pretreatment with naloxone but not naloxone methiodide. It is suggested that the antiemetic effect of acupuncture is mediated via the central opioid pathway.
Mirabile, Aurora; Celio, Luigi; Magni, Michele; Bonizzoni, Erminio; Gianni, Alessandro Massimo; Di Nicola, Massimo
2014-12-01
Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.
White, Paul F; Tang, Jun; Song, Dajun; Coleman, Jayne E; Wender, Ronald H; Ogunnaike, Babatunde; Sloninsky, Alexander; Kapu, Rajani; Shah, Mary; Webb, Tom
2007-01-01
Given the controversy regarding the use of droperidol and the high cost of the 5-HT3 antagonists, a cost-effective alternative for routine use as a prophylactic antiemetic would be desirable. We designed two parallel, randomized, double-blind sham and placebo-controlled studies to compare the early and late antiemetic efficacy and adverse event profile of transdermal scopolamine (TDS) 1.5 mg, to ondansetron 4 mg IV, and droperidol 1.25 mg IV for antiemetic prophylaxis as part of a multimodal regimen in "at risk" surgical populations. A total of 150 patients undergoing major laparoscopic (n = 80) or plastic (n = 70) surgery procedures received either an active TDS patch (containing scopolamine 1.5 mg) or a similar appearing sham patch 60 min before entering the operating room. All patients received a standardized general anesthetic technique. A second study medication was administered in a 2-mL numbered syringe containing either saline (for the two active TDS groups), droperidol, 1.25 mg, or ondansetron, 4 mg (for the sham patch groups), and was administered IV near the end of the procedure. The occurrence of postoperative nausea and vomiting/retching, need for rescue antiemetics, and the complete response rates (i.e., absence of protracted nausea or repeated episodes of emesis requiring antiemetic rescue medication) was reported. In addition, complaints of visual disturbances, dry mouth, drowsiness, and restlessness were noted up to 72 h after surgery. There were no significant differences in any of the emetic outcomes or need for rescue antiemetics among the TDS, droperidol, and ondansetron groups in the first 72 h after surgery. The complete response rates varied from 41% to 51%, and did not significantly differ among the treatment groups. The overall incidence of dry mouth was significantly more frequent in the TDS groups than in the droperidol and ondansetron groups (21% vs 3%). Premedication with TDS was as effective as droperidol (1.25 mg) or ondansetron (4
DOE Office of Scientific and Technical Information (OSTI.GOV)
King, G.L.; Landauer, M.R.
1990-06-01
The antiemetic and locomotor effects of two substituted benzamides, zacopride and batanopride (BMY25801), were compared in ferrets after bilateral 60Co irradiation at 2, 4 or 6 Gy. Both zacopride and BMY25801 were effective against emesis and related signs. Zacopride, tested at several doses (0.003, 0.03 and 0.3 mg/kg), appeared to be more potent because it abolished emesis at 100-fold lower doses than did BMY25801 (3 mg/kg). The ED50 value for the antiemetic effect of zacopride was 0.026 mg/kg (confidence levels = 0.0095, 0.072 mg/kg). However, analysis of emetic parameters recorded from vomiting animals (e.g., latency to first emesis) demonstrated thatmore » BMY25801 provided greater antiemetic protection in this population than zacopride without any apparent side effects. Locomotor activity was significantly depressed by both radiation (all doses) and zacopride alone (0.03 mg/kg and 0.3 mg/kg). BMY25801 alone did not affect locomotor activity, and protected against the radiation-induced locomotor decrement. Although zacopride potentiated the locomotor decrement to radiation, no clear dose-response relationship was evident. Bilateral abdominal vagotomy significantly increased the latency to the first emetic episode and significantly reduced the number of retches, but did not alter the duration of the prodromal response to 4-Gy irradiation. Unilateral vagotomies had no effect. Zacopride (at 0.03 mg/kg and 0.3 mg/kg) remained an effective antiemetic in animals that received a bilateral vagotomy, abolishing emesis in four of eight and two of eight ferrets, respectively. These data suggest that the antiemetic action of zacopride does not fully depend on intact vagal innervation and also acts via other pathways.« less
Effects of serotonin antagonists on motion sickness and its suppression by 8-OH-DPAT in cats
NASA Technical Reports Server (NTRS)
Lucot, James B.
1990-01-01
The antagonist properties of (-)propranolol, (+)propranolol, metergoline and BMY 7378 on the known effect of 8-OH-DPAT (DPAT) to decrease motion sickness in cats has been evaluated. (-)Propranolol produced a greater decrease in the antiemetic effect of DPAT than did (+)propranolol. Although metergoline produced a decrease in the antiemetic effect of DPAT, the decrease could not be clearly attributed to interactions with 5-HT(1A) receptors because metergoline alone slightly enhanced motion sickness. Depletion of 5-HT with PCPA produced a weaker, nonsignificant enhancement of motion sickness, while mesulergine had no effect. As neither nonspecific 5-HT receptor blockade with metergoline nor depletion of 5-HT mimicked the antiemetic effect of DPAT, it was concluded that DPAT acts on postsynaptic 5-HT(1A) receptors to prevent emesis. BMY 7378 alone decreased the incidence of motion sickness. A dose just below this agonist range did not decrease the effects of DPAT.
Pharmacokinetics of Scopolamine Intranasal Gel Formulation (INSCOP) During Antiorthostatic Bedrest
NASA Technical Reports Server (NTRS)
Putcha, Lakshmi; Boyd, J. L.; Du, B.; Daniels, V.; Crady, C.
2011-01-01
Space Motion sickness (SMS) is an age old problem for space travelers on short and long duration space flight Oral antiemetics are not very effective in space due to poor bioavailability. Scopolamine (SCOP) is the most frequently used drug by recreational travelers V patch, tablets available on the market. Common side effects of antiemetics, in general, include drowsiness, sedation, dry mouth and reduced psychomotor performance. Severity and persistence of side effects are often dose related Side effects can be detrimental in high performance demanding settings, e.g. space flight, military.
[Cannabis and cannabinoids. Possibilities of their therapeutic use].
Heim, M E
1982-03-04
Newer aspects of therapeutic potentials of cannabis and cannabinoids are reviewed. The major active constituent of cannabis sativa, delta-9-tetrahydrocannabinol and synthetic cannabinoids are evaluated in several clinical trials on their antiemetic efficacy in cancer chemotherapy induced vomiting. 80% of patients refractory to standard antiemetic treatment could be improved with the synthetic cannabinoid levonantradol. Other therapeutic effects, which are presently investigated in clinical trials are analgesia, antispasticity, anticonvulsion and the reduction of intraocular pressure in glaucoma. The future goal of cannabinoid research is the separation between specific pharmacologic activities and undesirable psychotropic effects.
Acute radiation sickness amelioration analysis. Technical report, 20 July 1990-19 July 1993
DOE Office of Scientific and Technical Information (OSTI.GOV)
Robinson, S.I.; Feister, A.J.; Bareis, D.L.
1994-05-01
Three tasks were conducted under the Acute Radiation Sickness Amelioration Analysis in support of the Defense Nuclear Agency (DNA) and NATO Army Armaments Group (NAAG) Project Group 29 (PG-29) on drugs for the prevention of radiation-induced nausea and vomiting: (1) documents were collected and entered into a data base, (2) data reviews and analyses were performed, and (3) PG-29 and Triservice meetings involving anti-emetic drug development were supported and documented. Approximately 2000 documents were collected, with 1424 complete bibliographic citations entered into a WordPerfect 5.1 data base. Eight reviews and analyses addressing different aspects of the safety and efficacy ofmore » the candidate anti-emetic drugs ondansetron and granistron were prepared. Support was provided for seven international PG-29 meetings and two U.S. Triservice meetings in which the efforts of PG-29 were discussed. These tasks have enabled the DNA and PG-29 to make good progress toward the goal of recommending a serotonin type-3 (5-HT3) receptor antagonist anti-emetic drug for use in military personnel.« less
Hickok, Jane T; Roscoe, Joseph A; Morrow, Gary R; Ryan, Julie L
2007-09-01
Despite the widespread use of 5-HT3 receptor antagonist antiemetics such as ondansetron and granistron, up to 70% of patients with cancer receiving highly emetogenic chemotherapy agents experience postchemotherapy nausea and vomiting. Delayed postchemotherapy nausea (nausea that occurs >/= 24 hours after chemotherapy administration) and anticipatory nausea (nausea that develops before chemotherapy administration, in anticipation of it) are poorly controlled by currently available antiemetic agents. Scientific studies suggest that ginger (Zingiber officinale) might have beneficial effects on nausea and vomiting associated with motion sickness, surgery, and pregnancy. In 2 small studies of patients with cancer receiving chemotherapy, addition of ginger to standard antiemetic medication further reduced the severity of postchemotherapy nausea. This article describes a phase II/III randomized, dose-finding, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for nausea associated with chemotherapy for cancer. The study is currently being conducted by private practice oncology groups that are funded by the National Cancer Institute's Community Clinical Oncology Program and affiliated with the University of Rochester Cancer Center Community Clinical Oncology Program Research Base.
DOE Office of Scientific and Technical Information (OSTI.GOV)
King, G.L.; Landauer, M.R.
1990-01-01
The antiemetic and locomotor effects of two substituted benzamides, zacopride and batanopride (BMY25801), were compared in ferrets after bilateral Co irradiation at 2, 4, or 6 Gy. Both zacopride and BMY25801 were effective against emesis and related signs. Zacopride, tested at several doses (0.003, 0.03 and 0.3 mg/kg), appeared to be more potent because it abolished emesis at 100-fold lower doses than did BMY25801 (3mg/kg). The ED value for the antiemetic effect of zacopride was 0.026 mg/kg (confidence levels = 0.0095, 0.072 mg/kg). However, analysis of emetic parameters recorded from vomiting animals (e.g., latency to first emesis) demonstrated that BMY25801more » provided greater antiemetic protection in this population than zacopride without and apparent side effects. Locomotor activity was significantly depressed by both radiation (all doses) and zacopride alone (0.03 mg/kg and 0.3 mg/kg). BMY25801 alone did not affect locomotor activity, and protected against the radiation-induced locomotor decrement.« less
Toyonaga, Shinya; Shinozuka, Norihiro; Dobashi, Tamae; Iiyori, Nao; Sudo, Tomoko
2016-05-01
Intravenous droperidol has strong evidence for antiemetic efficacy in high risk patients for prevention of postoperative nausea and vomiting (PONV). However it is not clear whether continuous epidural administration of doroperidol prevent PONV. It has been reported that epidural adrenaline decreases PONV; therefore we prospectively compared the effectiveness of epidural droperidol and adrenaline for prophylaxis of PONV. Eighty-six patients were scheduled for abdominal gynecological surgery under general-epidural anesthesia in the study. Patients were randomly assigned to droperidol group or adrenaline group. We investigated the incidences of PONV, the frequency of using the antiemetics. There was no statistical difference between the groups. The incidences of PONV were 27.9% (doropeidol group) and 58.1% (adrenaline group), respectively (P = 0.0046). The frequency of the anti-emetics use were 18.6% and 41.9%, respectively (P = 0.0189). There was one patient who needed cancellation of continuous epidural administration for vomiting in adrenaline group, but no patient in doropeidol group. The results suggest that epidural droperidol effectively decreases PONV in high risk patients. However epidural adrenaline might be ineffective.
Daniel, Divya; Waddell, Aubrey
2016-02-01
Nausea and vomiting are common adverse events exhibited by patients receiving chemotherapy. Prophylactic use of anti-emetic agents has been shown to reduce chemotherapy-induced nausea and vomiting. Compliance with the National Comprehensive Cancer Network anti-emesis guidelines (Version 1.2013) by practitioners in a community out-patient hospital (Blount Memorial Hospital) has been reviewed and the results are presented herein. Retrospective study of patients receiving their first cycle of chemotherapy. A total of 487 patients were reviewed from January 2005 to July 2012. In total, 70 patients were categorized in the high-risk category, 292 patients were categorized in the moderate-risk category, 60 patients were categorized in the low-risk category, and 65 patients were categorized in the minimal-risk category as per the National Comprehensive Cancer Network guidelines. Included patients were being administered the first cycle of their first treatment at Blount Memorial Hospital. Data were collected retrospectively from patient chemotherapy dispensing folders. In all, 63% of the patients received appropriate anti-emetic prophylaxis medications as per the National Comprehensive Cancer Network guidelines. Post-comparison between outcomes based on the risk category showed that patients in the moderate-risk category were most likely (91%) and patients in the low-risk category were least likely (6.67%) to receive appropriate anti-emetic prophylaxis as per the National Comprehensive Cancer Network guidelines. Overall compliance with guidelines is acceptable. Patients in the moderate risk category are most likely to receive appropriate anti-emetic prophylaxis. © The Author(s) 2014.
Felix-Ukwu, Femi; Reichert, Kate; Bernhardt, M Brooke; Schafer, Eric S; Berger, Amanda
2018-02-01
Chemotherapy-induced nausea and vomiting (CINV) negatively impacts patients' quality of life. The emetogenicity of high-dose methotrexate in children and adolescents with cancer is incompletely characterized. At our institution, a number of patients with acute lymphoblastic leukemia (ALL) have received aprepitant with courses of high-dose methotrexate after poor CINV control with prior courses. We conducted a retrospective cohort analysis on patients with ALL who received methotrexate 5 g/m 2 /dose with and without concomitant aprepitant at Texas. Children's Hospital between October 1, 2010 and January 31, 2016. We identified 16 patients who received a total of 69 courses of methotrexate. An enhanced antiemetic regimen containing aprepitant was administered with 42 methotrexate courses and resulted in a 54% reduction in the use of as-needed antiemetics (P = 0.002, 95% CI: 21-89%). There were no statistically significant differences in methotrexate area under the curve values (2,209 μM⋅hr/l ± 151 vs. 2,051 μM⋅hr/l ± 94, P = 0.355) or end-infusion methotrexate concentrations (80.5 μM ± 5.6 vs. 74.7 μM ± 3.2, P = 0.335) in patients receiving a standard versus an enhanced antiemetic regimen. The addition of aprepitant reduces both CINV and the use of rescue antiemetics. Aprepitant does not appear to affect the pharmacokinetics of methotrexate. Granisetron was prescribed more frequently than ondansetron, but selection of secondary and tertiary agents, if any, was highly variable. © 2017 Wiley Periodicals, Inc.
Zou, Zhenhong; Jiang, Yuming; Xiao, Mingjia; Zhou, Ruiyao
2014-01-01
Background We carried out a systematic review and meta-analysis to evaluate the impact of prophylactic dexamethasone on post-operative nausea and vomiting (PONV), post-operative pain, and complications in patients undergoing thyroidectomy. Methods We searched Pubmed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) that evaluated the prophylactic effect of dexamethasone versus placebo with or without other antiemetics for PONV in patients undergoing thyroidectomy. Meta-analyses were performed using RevMan 5.0 software. Results Thirteen RCTs that considered high quality evidence including 2,180 patients were analyzed. The meta-analysis demonstrated a significant decrease in the incidence of PONV (RR 0.52, 95% CI 0.43 to 0.63, P<0.00001), the need for rescue anti-emetics (RR 0.42, 95% CI 0.30 to 0.57, P<0.00001), post-operative pain scores (WMD –1.17, 95% CI –1.91 to –0.44, P = 0.002), and the need for rescue analgesics (RR 0.65, 95% CI 0.50–0.83, P = 0.0008) in patients receiving dexamethasone compared to placebo, with or without concomitant antiemetics. Dexamethasone 8–10mg had a significantly greater effect for reducing the incidence of PONV than dexamethasone 1.25–5mg. Dexamethasone was as effective as other anti-emetics for reducing PONV (RR 1.25, 95% CI 0.86–1.81, P = 0.24). A significantly higher level of blood glucose during the immediate post-operative period in patients receiving dexamethasone compared to controls was the only adverse event. Conclusions Prophylactic dexamethasone 8–10mg administered intravenously before induction of anesthesia should be recommended as a safe and effective strategy for reducing the incidence of PONV, the need for rescue anti-emetics, post-operative pain, and the need for rescue analgesia in thyroidectomy patients, except those that are pregnant, have diabetes mellitus, hyperglycemia, or contraindications for dexamethasone. More high quality trials are warranted to
Weingarten, Toby N; McGlinch, Brian P; Liedl, Lavonne; Kendrick, Michael L; Kellogg, Todd A; Schroeder, Darrell R; Sprung, Juraj
2015-03-01
Nicotine is a known analgesic. Our primary aim was to test the hypothesis that intranasal nicotine administered intraoperatively reduces the need for postoperative opioids. The secondary outcomes included evaluation of both postoperative pain and nausea and vomiting (PONV). Nonsmoking female patients undergoing laparoscopic bariatric operations were randomized to receive either 3 mg intranasal nicotine (N = 42) or placebo spray (N = 47) at the conclusion of surgery. Postoperative opioid use converted to intravenous morphine equivalents (iv MEQ) and PONV rates were recorded during both the recovery room postanesthesia care unit (PACU) stay and the first 24 postoperative hours. All patients received multimodal antiemetic prophylaxis. Total iv MEQ were not significantly reduced during the PACU stay in patients receiving nicotine (median [interquartile range (IQR)], 5.3 [0, 10.0] mg for nicotine vs. 5.2 [0, 12.7] mg for placebo, one-tailed P = 0.414) or for the first 24 h following PACU discharge (39.6 [20.0, 52.5] mg for nicotine vs. 32.7 [20.3, 51.3] mg for placebo, one-tailed P = 0.752). For the combined period (PACU + 24-h post-PACU discharge), iv MEQ were 45.8 [27.0, 58.6] mg for nicotine and 39.4 [23.5, 60.0] mg for placebo, one-tailed P = 0.801. Compared to placebo, a higher percentage of patients administered nicotine received antiemetics in the PACU (57.1 vs. 25.5 %, P = 0.002). Intraoperative intranasal nicotine did not exhibit opioid-sparing effect in nonsmoking bariatric female patients. Despite antiemetic prophylaxis, the use of nicotine was associated with the higher frequency of the use of rescue antiemetics in PACU.
Kranke, Peter; Eberhart, Leopold H J
2011-11-01
The incidence of postoperative nausea and vomiting (PONV) after a standard anaesthetic technique consisting of inhalational anaesthetics and opioids and no PONV prophylaxis is up to 30%. Being one of the most common complaints following surgery under general anaesthesia, it is not surprising that PONV is a considerable cause of dissatisfaction with recovery from anaesthesia and remains one of the most commonly used items in surveys assessing patient satisfaction with the perioperative period and in scoring systems for the quality of recovery following anaesthesia. The weakest link in the chain from research to patient benefit is the implementation of well proven strategies. Rather than simply following existing consensus guidelines, anaesthesiologists should critically assess whether the algorithms introduced produce the desired effect. Risk-adapted strategies may work, but recent implementation studies suggest that compliance with these algorithms may be poor and that high-risk patients often do not receive appropriate antiemetic prophylaxis. Multimodal prevention may represent a more simple approach and, thus, a more reliable strategy to reduce the incidence of PONV. Such an approach would circumvent the inherent weaknesses of the need to undertake a risk assessment for each individual patient. Anaesthesiologists need to know about the new agents available to manage PONV, such as the NK1-antagonists or the newer 5-HT3 antagonists, but should not forget the traditional and well established antiemetics that are valuable components in the current portfolio. The low cost of most of the currently available antiemetics and the low incidence of side-effects suggests that a liberal antiemetic prophylaxis regimen is a meaningful option in order to eliminate or substantially reduce the 'big little problem'.
Oyama, Katsunobu; Fushida, Sachio; Kaji, Masahide; Takeda, Toshiya; Kinami, Shinichi; Hirono, Yasuo; Yoshimoto, Katsuhiro; Yabushita, Kazuhisa; Hirosawa, Hisashi; Takai, Yuki; Nakano, Tatsuo; Kimura, Hironobu; Yasui, Toshiaki; Tsuneda, Atsushi; Tsukada, Tomoya; Kinoshita, Jun; Fujimura, Takashi; Ohta, Tetsuo
2013-11-01
We aimed to evaluate the efficacy of a new combination antiemetic therapy comprising aprepitant, granisetron, and dexamethasone in gastric cancer patients undergoing chemotherapy with cisplatin and S-1. Gastric cancer patients scheduled to receive their first course of chemotherapy with cisplatin (60 mg/m(2)) and S-1 (80 mg/m(2)) were treated with a new combination antiemetic therapy aprepitant, granisetron, and dexamethasone on day 1; aprepitant and dexamethasone on days 2 and 3; and dexamethasone on day 4. The patients reported vomiting, nausea, use of rescue therapy, and change in the amount of diet intake, and completed the Functional Living Index-Emesis (FLIE) questionnaire. The primary endpoint was complete response (CR; no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after cisplatin administration). The secondary endpoints included complete protection (CP; CR plus no significant nausea); change in the amount of diet intake; and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily life during the overall, acute (0-24 h), and delayed (24-120 h) phases. Fifty-three patients were included. CR was achieved in 88.7, 98.1, and 88.7% of patients in the overall, acute, and delayed phases, respectively. The corresponding rates of CP were 67.9, 96.2, and 67.9%. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 79.5% of patients reported "minimal or no impact of CINV on daily life". Addition of aprepitant to standard antiemetic therapy was effective in gastric cancer patients undergoing treatment with cisplatin and S-1.
Nakashima, Kazuhisa; Murakami, Haruyasu; Yokoyama, Kouichi; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Nishiyama, Fumie; Kikugawa, Mami; Kaneko, Masayo; Iwamoto, Yumiko; Koizumi, Satomi; Mori, Keita; Isobe, Takeshi; Takahashi, Toshiaki
2017-09-01
The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients. We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy. Patients received 5 mg oral olanzapine on Days 1-5 in combination with standard antiemetic therapy. The primary endpoint was complete response (no vomiting and no use of rescue therapy) during the overall Phase (0-120 h post-chemotherapy). Twenty-three men and seven women were enrolled between May and October 2015. The median age was 64 years (range: 36-75 years). The most common chemotherapy regimen was 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed, which was administered to 14 patients. Complete response rates in acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy) and overall phases were 100%, 83% and 83% (90% confidence interval: 70-92%; 95% confidence interval: 66-93%), respectively. There were no Grade 3 or Grade 4 adverse events. Although four patients (13%) experienced Grade 1 somnolence, no patients discontinued olanzapine. The addition of 5 mg oral olanzapine to standard antiemetic therapy demonstrates promising efficacy in preventing cisplatin-based chemotherapy-induced nausea and vomiting and an acceptable safety profile in patients with thoracic malignancy. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
8-OH-DPAT suppresses vomiting in the cat elicited by motion, cisplatin or xylazine
NASA Technical Reports Server (NTRS)
Lucot, James B.; Crampton, George H.
1989-01-01
Vomiting was suppressed in cats pretreated with 8-OH-DPAT and then challenged with an emetic stimulus; motion, xylazine or cisplatin. The antiemetic effect is likely due to stimulation of postsynaptic serotonin-1A receptors. The most parsimonious explanation is that it acts at a convergent structure, presumably at or near the vomiting center. If so, 8-OH-DPAT may block emesis elicited by virtually any other stimulus. A supplementary experiment revealed that lorazepam suppressed motion sickness at a dose that produced ataxia, but did not suppress xylazine-induced emesis. These results do not support the possibility that the antiemetic effects of 8-OH-DPAT were the result of anxiolytic activity.
Aapro, M. S.; Kirchner, V.; Terrey, J. P.
1994-01-01
Anticipatory nausea and vomiting (ANV) after repeated cycles of cytotoxic chemotherapy is thought to be a conditioned response to a conditioning stimulus. Good control of acute and delayed emesis may result in a lower incidence of ANV. We have analysed data from 574 chemotherapy patients who received granisetron as their antiemetic treatment during repeat cycle chemotherapy. Per treatment cycle, less than 10% of patients displayed symptoms of anticipatory nausea and 2% or less had symptoms of anticipatory vomiting. It is concluded that the use of granisetron as an antiemetic during the acute phase of chemotherapy may result in a lower incidence of ANV in patients undergoing repeat cycle chemotherapy. PMID:8180031
The effect of transdermal scopolamine for the prevention of postoperative nausea and vomiting.
Antor, María A; Uribe, Alberto A; Erminy-Falcon, Natali; Werner, Joseph G; Candiotti, Keith A; Pergolizzi, Joseph V; Bergese, Sergio D
2014-01-01
Postoperative nausea and vomiting (PONV) is one of the most common and undesirable complaints recorded in as many as 70-80% of high-risk surgical patients. The current prophylactic therapy recommendations for PONV management stated in the Society of Ambulatory Anesthesia (SAMBA) guidelines should start with monotherapy and patients at moderate to high risk, a combination of antiemetic medication should be considered. Consequently, if rescue medication is required, the antiemetic drug chosen should be from a different therapeutic class and administration mode than the drug used for prophylaxis. The guidelines restrict the use of dexamethasone, transdermal scopolamine, aprepitant, and palonosetron as rescue medication 6 h after surgery. In an effort to find a safer and reliable therapy for PONV, new drugs with antiemetic properties and minimal side effects are needed, and scopolamine may be considered an effective alternative. Scopolamine is a belladonna alkaloid, α-(hydroxymethyl) benzene acetic acid 9-methyl-3-oxa-9-azatricyclo non-7-yl ester, acting as a non-selective muscarinic antagonist and producing both peripheral antimuscarinic and central sedative, antiemetic, and amnestic effects. The empirical formula is C17H21NO4 and its structural formula is a tertiary amine L-(2)-scopolamine (tropic acid ester with scopine; MW = 303.4). Scopolamine became the first drug commercially available as a transdermal therapeutic system used for extended continuous drug delivery during 72 h. Clinical trials with transdermal scopolamine have consistently demonstrated its safety and efficacy in PONV. Thus, scopolamine is a promising candidate for the management of PONV in adults as a first line monotherapy or in combination with other drugs. In addition, transdermal scopolamine might be helpful in preventing postoperative discharge nausea and vomiting owing to its long-lasting clinical effects.
Duran, Marta; Pérez, Eulàlia; Abanades, Sergio; Vidal, Xavier; Saura, Cristina; Majem, Margarita; Arriola, Edurne; Rabanal, Manel; Pastor, Antoni; Farré, Magí; Rams, Neus; Laporte, Joan-Ramon; Capellà, Dolors
2010-11-01
Despite progress in anti-emetic treatment, many patients still suffer from chemotherapy-induced nausea and vomiting (CINV). This is a pilot, randomized, double-blind, placebo-controlled phase II clinical trial designed to evaluate the tolerability, preliminary efficacy, and pharmacokinetics of an acute dose titration of a whole-plant cannabis-based medicine (CBM) containing delta-9-tetrahydrocannabinol and cannabidiol, taken in conjunction with standard therapies in the control of CINV. Patients suffering from CINV despite prophylaxis with standard anti-emetic treatment were randomized to CBM or placebo, during the 120 h post-chemotherapy period, added to standard anti-emetic treatment. Tolerability was measured as the number of withdrawals from the study during the titration period because of adverse events (AEs). The endpoint for the preliminary efficacy analysis was the proportion of patients showing complete or partial response. Seven patients were randomized to CBM and nine to placebo. Only one patient in the CBM arm was withdrawn due to AEs. A higher proportion of patients in the CBM group experienced a complete response during the overall observation period [5/7 (71.4%) with CMB vs. 2/9 (22.2%) with placebo, the difference being 49.2% (95% CI 1%, 75%)], due to the delayed period. The incidence of AEs was higher in the CBM group (86% vs. 67%). No serious AEs were reported. The mean daily dose was 4.8 sprays in both groups. Compared with placebo, CBM added to standard antiemetic therapy was well tolerated and provided better protection against delayed CINV. These results should be confirmed in a phase III clinical trial. © 2010 Department of Health, Generalitat of Catalonia. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.
Morrow, Gary R; Navari, Rudolph M; Rugo, Hope S
2014-03-01
Chemotherapy-induced nausea and vomiting (CINV) has long been one of the most troublesome adverse effects of chemotherapy, leading to significant detriments in quality of life and functioning, increased economic costs, and, in some cases, the discontinuation of effective cancer therapy. The past 2 decades have witnessed a dramatic increase in the number of effective antiemetic agents, with the introduction of the serotonin (5-hydroxytryptamine [5-HT₃]) receptor antagonists (ondansetron, granisetron, and palonosetron), the neurokinin-1 (NK₁) receptor antagonists (aprepitant and fosaprepitant), and the identification of other agents that have demonstrated efficacy against CINV, including corticosteroids. These agents often provide excellent control of emesis. Nausea, however, has proven more intractable, particularly in the days after administration of chemotherapy. Newer antiemetic agents under study may provide additional CINV control, particularly against delayed nausea. New agents undergoing review by the US Food and Drug Administration for the prevention of CINV include the novel NK₁ receptor antagonist rolapitant and a fixed-dose combination consisting of the novel NK₁ receptor antagonist netupitant and palonosetron (NEPA). Adherence to clinical practice guidelines has been shown to significantly improve CINV control. As antiemetic therapy continues to evolve, it will be important for clinicians to stay informed of new developments and changes in guidelines.
Cannabinoids for nausea and vomiting related to chemotherapy: Overview of systematic reviews.
Schussel, Victor; Kenzo, Lucas; Santos, Andreia; Bueno, Júlia; Yoshimura, Ellen; de Oliveira Cruz Latorraca, Carolina; Pachito, Daniela Vianna; Riera, Rachel
2018-04-01
Nausea and vomiting are common and distressing adverse events of chemotherapy. This review focuses on the findings and quality of systematic reviews (SRs) of cannabinoids for chemotherapy-induced nausea and vomiting (CINV). Review of SRs, a systematic literature search, was conducted in several electronic databases and included SRs evaluating cannabinoids for CINV in cancer patients. Methodological quality and quality of reporting were evaluated by AMSTAR and PRISMA, respectively. Initial search retrieved 2,206 records, and 5 SRs were included. On the basis of findings of the sole SR judged as high methodological quality, cannabinoids seem to be more effective than placebo, equal to prochlorperazine for reducing CINV, and to be preferred by patients. The response to different combinations of antiemetic agents seems to be equal to 1 antiemetic alone. The average of AMSTAR score was 5, and the average of PRISMA score was 13.2. Cannabinoids represent a valuable option for treating CINV, despite the adverse events related to treatment, such as drowsiness and cognitive impairment. There is no good quality evidence to recommend or not the use of cannabinoids for CINV. More studies are still needed to evaluate the effectiveness of cannabinoids when compared with modern antiemetics. Copyright © 2017 John Wiley & Sons, Ltd.
Martín, M; Díaz-Rubio, E
1989-06-10
Forty-one patients treated with cisplatin (100-120 mg/m2), alone or associated with vindesine (3 mg/m2), were included in a randomized crossover pilot study which compared 3 different doses of intravenous clebopride with intravenous metoclopramide. The patients were randomly assigned to receive clebopride in the first chemotherapy course in one of the three dose levels used (0.5 mg/kg, 21 patients; 0.75 mg/kg, 11 patients; 1 mg/kg, 10 patients) or metoclopramide (10 mg/kg). In the second course of the same chemotherapy the patients received the alternative antiemetic, and thus each patient was his own control. The total dose of both antiemetic drugs was infused in 5 intravenous fractions given every 2 hours. The antiemetic activity of clebopride was moderately lower to that of metoclopramide with the first two tested doses (overall doses of 0.5 and 0.75 mg/kg) and similar with the last dose (1 mg/kg). Clebopride was reasonably well tolerated at the used dosages, inducing sedation in 20% of cases (versus 24% with metoclopramide) and diarrhea in 37% (versus 20% with metoclopramide). Extrapyramidal reactions developed in 17% of the courses which included metoclopramide and in none including clebopride. This difference was statistically significant.
Methotrexate-induced nausea in the treatment of juvenile idiopathic arthritis.
Falvey, Sonja; Shipman, Lauren; Ilowite, Norman; Beukelman, Timothy
2017-06-19
Methotrexate is the most commonly used disease modifying antirheumatic drug in the treatment of juvenile idiopathic arthritis and can be effective in controlling disease in many patients. A significant proportion of patients experience nausea and vomiting induced by methotrexate therapy, which can lead to decreased quality of life and discontinuation of treatment with methotrexate. Many strategies have been employed in attempts to reduce methotrexate-induced nausea, including folate supplementation, switching from oral to subcutaneous methotrexate, anti-emetic therapy, behavioral therapy, and others. Anticipatory nausea can be difficult to treat, making primary prevention of nausea with anti-emetics an attractive approach. Understanding the prevalence and impact of methotrexate-induced nausea, as well as potentially effective interventions, may help maximize the therapeutic benefits of methotrexate.
21 CFR 522.1962 - Promazine hydrochloride.
Code of Federal Regulations, 2010 CFR
2010-04-01
..., preanesthetic, or for minor operative procedures in conjunction with local anesthesia; and as adjunctive therapy... conjunction with local anesthesia, as adjunctive therapy for tetanus, and as an antiemetic prior to worming...
21 CFR 522.1962 - Promazine hydrochloride.
Code of Federal Regulations, 2011 CFR
2011-04-01
..., preanesthetic, or for minor operative procedures in conjunction with local anesthesia; and as adjunctive therapy... conjunction with local anesthesia, as adjunctive therapy for tetanus, and as an antiemetic prior to worming...
Code of Federal Regulations, 2014 CFR
2014-04-01
... operative procedures in conjunction with local anesthesia; and as adjunctive therapy for tetanus. (B) For... with local anesthesia, as adjunctive therapy for tetanus, and as an antiemetic prior to worming; or to...
Darmani, Nissar A.; Wang, Yaozhi; Abad, Joseph; Ray, Andrew P.; Thrush, Gerald R.; Ramirez, Juan
2008-01-01
solitarius, and the dorsal motor nucleus of the vagus, but not the area postrema. Ablation of peripheral NK1 receptors attenuated the ability of GR73632 to induce a maximal frequency of emesis and shifted its percent animals vomiting dose-response curve to the right. The NK1-ablated shrews exhibited scratching behavior after systemic GR73632-injection. These results, for the first time, affirm a cardinal role for central NK1 receptors in SP-induced vomiting, and a facilitatory role for gastrointestinal NK1 receptors. In addition, these data support the validation of the least shrew as a specific and rapid behavioral animal model to screen concomitantly both the CNS penetration and the antiemetic potential of tachykinin NK1 receptor antagonists. PMID:18471804
Le, Tran N; Adler, Michael T; Ouillette, Holly; Berens, Pamela; Smith, Judith A
2017-07-01
Objective The objective of this study was to observe the efficacy of antiemetic therapy (no emesis/retching episodes and no rescue medication use) when granisetron is administered via a transdermal patch system (TDS) in women who are 6 to 14 weeks pregnant when compared with oral ondansetron by evaluating the frequency of the use of rescue medications for control of nausea/vomiting of pregnancy (NVP). Methods This was an observational case series study to observe the potential benefits of granisetron TDS compared with oral ondansetron for management of NVP in pregnant patients during the first trimester. Dates of data collection were September 1, 2014, through December 31, 2015. There was no direct contact with patient. The oral ondansetron and granisetron TDS patients were matched by age, 4:1. The proportion of patients who received rescue antiemetics was calculated from those patients who continued to experience NVP. Risk factors for NVP were identified and compared between groups. Descriptive statistics were used to describe study results. Results Patients were prescribed rescue antiemetics in 0/3 patients in the granisetron TDS group compared with 2/12 patients in the oral ondansetron group. Conclusion Prospective efficacy studies on the use of granisetron TDS for management of NVP are needed to confirm this clinical observation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Gonella, Silvia; Berchialla, Paola; Bruno, Benedetto; Di Giulio, Paola
2014-09-01
Nausea and vomiting (NV) related to DMSO affect patients undergoing auto-SCT despite antiemetic measures. Orange flavoring may reduce gastrointestinal symptoms. A multicenter, randomized, three-arm, open-label trial in four Italian large bone marrow transplant centers was conducted to assess the effectiveness of orange aroma in preventing NV related to DMSO. Patients were randomized to orange ice lollies, non-citrus ice lollies, and routine treatment (deep breaths) during reinfusion. Data on NV were collected up to 5 days after infusion; 69/98 patients were randomized: 23 to orange, 21 to non-citrus ice lollies, and 25 to routine treatment. Although 48 h after transplantation no differences were observed in controlled nausea (Numerical Rating Scale (NRS) 0-100, ≤25) or vomiting, significantly fewer patients had no episodes of vomiting, no antiemetic rescue therapy, and no nausea (NRS <5) in the deep breath vs lollies groups (P = 0.017). The intensity of nausea over time differed significantly between ice lollies vs routine care (P = 0.001) groups, but not between the orange and non-citrus groups (P = 0.428). The vasoconstrictive action of ice may prevent NV related to DMSO in the acute phase and reduce the need for rescue antiemetic therapy. Ice lollies offer a simple, noninvasive, and economic means for relieving nausea and vomiting related to this preservative.
21 CFR 522.1962 - Promazine hydrochloride.
Code of Federal Regulations, 2013 CFR
2013-04-01
... for tetanus. (B) For use as a tranquilizer and preanesthetic. (iii) Limitations. Not for use in horses... conjunction with local anesthesia, as adjunctive therapy for tetanus, and as an antiemetic prior to worming...
21 CFR 522.1962 - Promazine hydrochloride.
Code of Federal Regulations, 2012 CFR
2012-04-01
... for tetanus. (B) For use as a tranquilizer and preanesthetic. (iii) Limitations. Not for use in horses... conjunction with local anesthesia, as adjunctive therapy for tetanus, and as an antiemetic prior to worming...
Gan, Tong J; Candiotti, Keith A; Klein, Stephen M; Rodriguez, Yiliam; Nielsen, Karen C; White, William D; Habib, Ashraf S
2009-11-01
Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) are common problems after surgery. Prophylactic combination antiemetic therapy is recommended for patients at high risk for developing PONV and PDNV. Granisetron, a serotonin antagonist, is an effective antiemetic that is devoid of sedative side effect. Although promethazine is effective, commonly used doses are associated with sedation. This study investigates the combination of low doses of granisetron and promethazine for the prevention of PONV. Women undergoing ambulatory gynecological laparoscopy were enrolled. A standard general anesthetic regimen was prescribed. Fifteen minutes before the expected end of surgery, the patients were randomly assigned to receive granisetron 0.1 mg iv, promethazine 6.25 mg iv, or a combination of the two drugs. Prophylaxis with oral promethazine 12.5 mg, granisetron 1 mg, or both was started in the respective groups 12 hr after the end of surgery and continued every 12 hr until postoperative day 3 (a total of five oral doses). The following outcomes were recorded: total response rate (defined as no vomiting, no more than mild nausea, and no use of rescue antiemetic); incidence of nausea, vomiting, and use of rescue antiemetics; severity of nausea; patient activity level; and patient satisfaction with PONV management. Patients in the combination group had a higher total response rate at 6, 24, 48, and 72 hr after surgery compared with those who received promethazine alone (at 24 hr, Combination 69.6%, Promethazine 36.2%, Granisetron 53.3%; P = 0.0079). The maximum nausea scores were also lower in the combination group at 6, 24, 48, and 72 hr (Combination 1.7 +/- 2.2, Promethazine 4.0 +/- 3.6, Granisetron 3.1 +/- 3.2 at 24 hr; P < 0.05). There was no difference in the sedation scores, incidence of drowsiness, patient activity level, and satisfaction with PONV management. Low-dose granisetron and promethazine combination was more effective in
Kranke, Peter; Bergese, Sergio D; Minkowitz, Harold S; Melson, Timothy I; Leiman, David G; Candiotti, Keith A; Liu, Ngai; Eberhart, Leopold; Habib, Ashraf S; Wallenborn, Jan; Kovac, Anthony L; Diemunsch, Pierre; Fox, Gabriel; Gan, Tong J
2018-06-01
Postoperative nausea and vomiting causes distress for patients and can prolong care requirements. Consensus guidelines recommend use of multiple antiemetics from different mechanistic classes as prophylaxis in patients at high risk of postoperative nausea and vomiting. The prophylactic efficacy of the dopamine D2/D3 antagonist amisulpride in combination with other antiemetics was investigated. This double-blind, randomized, placebo-controlled, international, multicenter trial was conducted in 1,147 adult surgical patients having three or four postoperative nausea and vomiting risk factors. Patients were randomized to receive either intravenous amisulpride (5 mg) or matching placebo at induction of general anesthesia, in addition to one standard, nondopaminergic antiemetic, most commonly ondansetron or dexamethasone. Vomiting/retching, nausea, and use of rescue medication were recorded for 24 h after wound closure. The primary endpoint was complete response, defined as no emesis or rescue medication use in the 24-h postoperative period. Complete response occurred in 330 of 572 (57.7%) of the amisulpride group and 268 of 575 (46.6%) of the control group (difference 11.1 percentage points; 95% CI, 5.3 to 16.8; P < 0.001). The incidences of emesis (13.8% vs. 20.0%, P = 0.003), any nausea (50.0% vs. 58.3%, P = 0.002), significant nausea (37.1% vs. 47.7%, P < 0.001), and rescue medication use (40.9% vs. 49.4%, P = 0.002) were significantly lower in the amisulpride group. Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently with amisulpride than with placebo. Intravenous amisulpride was safe and effective as prophylaxis of postoperative nausea and vomiting when given in combination with an antiemetic from another class to adult patients at high risk for suffering postoperative nausea and vomiting undergoing elective surgery under inhalational general anesthesia. An online visual overview is available for this article at http
... class of medications called antiemetics. It works by blocking the action of neurokinin and substance P, natural ... swallowing; shortness of breath; swelling of the eyes, face, mouth, tongue, or throat; chest pain; stomach pain ...
Nausea, gastroparesis, and aerophagia.
Hasler, William L
2005-01-01
Nausea, gastroparesis, and aerophagia are gastrointestinal phenomena that have variable impact on affected patients. The causes of nausea are varied; treatment of these conditions relates to the underlying etiology. Antiemetic agents acting on several distinct receptor subtypes produce benefits in distinct patient subsets. Gastroparesis is characterized by delays in gastric emptying, usually defined scintigraphically. Standard care of gastroparesis relies on dietary modification, antiemetic drug therapy, and initiation of medications that stimulate gastric motor activity. Recent advances include pyloric injection of botulinum toxin and surgical implantation of an electrical neurostimulator. Other surgical therapies are reserved for refractory cases. Aerophagia presents in individuals of normal and impaired cognitive function, most commonly with symptoms of overdistension or eructation. There are no pharmaceutical remedies for this condition; thus, therapy relies on behavioral treatments.
Baba, Yoshifumi; Baba, Hideo; Yamamoto, Sachiko; Shimada, Hideaki; Shibata, Tomotaka; Miyazaki, Tatsuya; Yoshikawa, Takaki; Nakajima, Yasuaki; Tsuji, Yasushi; Shimokawa, Mototsugu; Kitagawa, Yuko; Aiba, Keisuke
2017-02-01
Chemotherapy is an indispensable therapeutic approach for esophageal cancer. Although chemotherapy-induced nausea and vomiting (CINV) is one of the most crucial adverse events, the current state of CINV in patients with esophageal cancer remains unclear. This multicenter prospective observational study analyzed data for 192 patents with esophageal cancer who underwent moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). The patients recorded their CINV incidence and severity daily for 7 days after receiving chemotherapy, using visual analog scales (VAS). Of the 192 patients, 181 received HEC including cisplatin, and 11 patients received MEC including nedaplatin. Approximately 81% of HEC and 82% of MEC patients received antiemetic therapy in compliance with guidelines. Although CINV was controlled relatively well in the early phase (days 1-4), it was not fully controlled in late phase (days 5-7) for both the HEC and MEC groups. Female sex was a major risk factor for delayed vomiting (P=0.034). Multivariate logistic regression analysis for VAS revealed that motion sickness, age, and use of other antiemetics were risk factors for delayed nausea. Adherence to antiemetic guidelines effectively controls vomiting but is less effective against delayed CINV in both HEC and MEC patients. Identification of individual risk factors, such as female sex, will help develop personalized treatments for CINV. In the clinical setting for esophageal cancer, regimens that include nedaplatin might need to be treated as HEC. © 2016 International Society for Diseases of the Esophagus.
McKinney, P. A.; Cartwright, R. A.; Stiller, C. A.; Hopton, P. A.; Mann, J. R.; Birch, J. M.; Hartley, A. L.; Waterhouse, J. A.; Johnston, H. E.
1985-01-01
Attention has recently focused on the possible teratogenic effects of the combination antiemetic doxylamine succinate, dicyclomine hydrochloride and pyridoxine hydrochloride (Debendox/Bendectin) prescribed to pregnant women. The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC), a case-control investigation has analysed data derived from interview reports and medical records of 555 mothers of children (under 15 years) with cancer and 1110 mothers of matched control children. Separate analyses of interview reports and medical records both suggested that antiemetic ingestion during the index pregnancy does not increase the risk of developing childhood malignant disease in the exposed foetus. No dose-response relationship was evident. The lack of any significant relative risks held good for diagnostic sub-groups and when the trimester of ingestion was considered. Our results suggest that antimetics of this type are unlikely to be transplacental carcinogens. PMID:4074645
McKinney, P A; Cartwright, R A; Stiller, C A; Hopton, P A; Mann, J R; Birch, J M; Hartley, A L; Waterhouse, J A; Johnston, H E
1985-12-01
Attention has recently focused on the possible teratogenic effects of the combination antiemetic doxylamine succinate, dicyclomine hydrochloride and pyridoxine hydrochloride (Debendox/Bendectin) prescribed to pregnant women. The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC), a case-control investigation has analysed data derived from interview reports and medical records of 555 mothers of children (under 15 years) with cancer and 1110 mothers of matched control children. Separate analyses of interview reports and medical records both suggested that antiemetic ingestion during the index pregnancy does not increase the risk of developing childhood malignant disease in the exposed foetus. No dose-response relationship was evident. The lack of any significant relative risks held good for diagnostic sub-groups and when the trimester of ingestion was considered. Our results suggest that antimetics of this type are unlikely to be transplacental carcinogens.
Advances in pediatric dehydration therapy.
Niescierenko, Michelle; Bachur, Richard
2013-06-01
To review the advances in the assessment, treatment, and evaluation of care for pediatric dehydration. Recent studies have added new information across the spectrum of care for dehydration. Advances in the assessment of dehydration allow more accurate clinical evaluation, but do not help predict the treatment outcomes. Antiemetics as an adjunct to oral rehydration therapy have been proven well tolerated, efficacious, and cost-effective. Rapid, large-volume intravenous rehydration for outpatients with dehydration did not show any benefit over more standard regimens. Clinical guidelines incorporate all these aspects of care; however, physicians show poor adherence to the guidelines despite the evidence that guidelines improve outcomes and reduce cost. Dehydration burdens the healthcare system worldwide. Through advances in its assessment, treatment with antiemetics and intravenous fluids, and standardization of practice with clinical guidelines, this burden could be reduced.
Aromatherapy for treatment of postoperative nausea and vomiting.
Hines, Sonia; Steels, Elizabeth; Chang, Anne; Gibbons, Kristen
2012-04-18
Postoperative nausea and vomiting is a common and unpleasant phenomenon and current therapies are not always effective for all patients. Aromatherapy has been suggested as a possible addition to the available treatment strategies. This review sought to establish what effect the use of aromatherapy has on the severity and duration of established postoperative nausea and vomiting and whether aromatherapy can be used with safety and clinical effectiveness comparable to standard pharmacological treatments. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3); MEDLINE; EMBASE; CINAHL; CAM on PubMed; Meditext; LILACS; and ISI Web of Science as well as grey literature sources and the reference lists of retrieved articles. We conducted database searches up to August 2011. We included all randomized controlled trials (RCTs) and controlled clinical trials (CCTs) where aromatherapy was used to treat postoperative nausea and vomiting. Interventions were all types of aromatherapy. Aromatherapy was defined as the inhalation of the vapours of any substance for the purposes of a therapeutic benefit. Primary outcomes were the severity and duration of postoperative nausea and vomiting. Secondary outcomes were adverse reactions, use of rescue anti-emetics and patient satisfaction with treatment. Two review authors assessed risk of bias in the included studies and extracted data. As all outcomes analysed were dichotomous, we used a fixed-effect model and calculated relative risk (RR) with associated 95% confidence interval (95% CI). The nine included studies comprised six RCTs and three CCTs with a total of 402 participants. The mean age and range data for all participants were not reported for all studies. The method of randomization in four of the six included RCTs was explicitly stated and was adequate. Incomplete reporting of data affected the completeness of the analysis. Compared with placebo, isopropyl alcohol vapour
DOE Office of Scientific and Technical Information (OSTI.GOV)
Salvo, Nadia; Doble, Brett; Khan, Luluel
Purpose: To systematically review the effectiveness and safety of 5-hydroxytryptamine-3 receptor antagonists (5-HT3 RAs) compared with other antiemetic medication or placebo for prophylaxis of radiation-induced nausea and vomiting. Methods and Materials: We searched the following electronic databases: MEDLINE, Embase, the Cochrane Central Register of Controlled Clinical Trials, and Web of Science. We also hand-searched reference lists of included studies. Randomized, controlled trials that compared a 5-HT3 RA with another antiemetic medication or placebo for preventing radiation-induced nausea and vomiting were included. We excluded studies recruiting patients receiving concomitant chemotherapy. When appropriate, meta-analysis was conducted using Review Manager (v5) software. Relativemore » risks were calculated using inverse variance as the statistical method under a random-effects model. We assessed the quality of evidence by outcome using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: Eligibility screening of 47 articles resulted in 9 included in the review. The overall methodologic quality was moderate. Meta-analysis of 5-HT3 RAs vs. placebo showed significant benefit for 5-HT3 RAs (relative risk [RR] 0.70; 95% confidence interval [CI] 0.57-0.86 for emesis; RR 0.84, 95% CI 0.73-0.96 for nausea). Meta-analysis comparing 5-HT3 RAs vs. metoclopramide showed a significant benefit of the 5-HT3 RAs for emetic control (RR 0.27, 95% CI 0.15-0.47). Conclusion: 5-Hydroxytryptamine-3 RAs are superior to placebo and other antiemetics for prevention of emesis, but little benefit was identified for nausea prevention. 5-Hydroxytryptamine-3 RAs are suggested for prevention of emesis. Limited evidence was found regarding delayed emesis, adverse events, quality of life, or need for rescue medication. Future randomized, controlled trials should evaluate different 5-HT3 antiemetics and new agents with novel mechanisms of action such at
Ca2+ signaling and emesis: Recent progress and new perspectives.
Zhong, Weixia; Picca, Andrew J; Lee, Albert S; Darmani, Nissar A
2017-01-01
Cisplatin-like chemotherapeutics cause vomiting via calcium (Ca 2+ )-dependent release of multiple neurotransmitters (dopamine, serotonin, substance P, etc.) from the gastrointestinal enterochromaffin cells and/or the brainstem. Intracellular Ca 2+ signaling is triggered by activation of diverse emetic receptors (including tachykininergic NK 1 , serotonergic 5-HT 3 , dopaminergic D 2 , cholinergic M 1 , or histaminergic H 1 ) , whose activation in vomit-competent species can evoke emesis. Other emetogens such as cisplatin, rotavirus NSP4 protein and bacterial toxins can also induce intracellular Ca 2+ elevation. Netupitant is a highly selective neurokinin NK 1 receptor (NK 1 R) antagonist and palonosetron is a selective second-generation serotonin 5-HT 3 receptor (5-HT 3 R) antagonist with a distinct pharmacological profile. An oral fixed combination of netupitant/palonosetron (NEPA; Akynzeo(®)) with >85% antiemetic efficacy is available for use in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Cannabinoid CB 1 receptor agonists possess broad-spectrum antiemetic activity since they prevent vomiting caused by a variety of emetic stimuli including the chemotherapeutic agent cisplatin, 5-HT 3 R agonists, and D 2 R agonists. Our findings demonstrate that application of the L-type Ca 2+ channel (LTCC) agonist FPL 64176 and the intracellular Ca 2+ mobilizing agent thapsigargin (a sarco/endoplasmic reticulum Ca 2+ -ATPase inhibitor) cause vomiting in the least shrew. On the other hand, blockade of LTCCs by corresponding antagonists (nifedipine or amlodipine) not only provide broad-spectrum antiemetic efficacy against diverse agents that specifically activate emetogenic receptors such as 5-HT 3 , NK 1 , D 2 , and M 1 receptors, but can also potentiate the antiemetic efficacy of palonosetron against the non-specific emetogen, cisplatin. In this review, we will provide an overview of Ca 2+ involvement in the emetic process; discuss the
Aromatherapy for treatment of postoperative nausea and vomiting.
Hines, Sonia; Steels, Elizabeth; Chang, Anne; Gibbons, Kristen
2018-03-10
Postoperative nausea and vomiting (PONV) is a common, unpleasant phenomenon and current therapies are not always effective for all patients. Aromatherapy has been suggested as an addition to the available treatment strategies. This review was originally published in 2012 and updated in 2017. The main objective was to establish the efficacy and safety of aromatherapy comparable to standard pharmacological treatments for PONV in adults and children. We searched CENTRAL; MEDLINE; Embase; CINAHL; CAM on PubMed; Informit; LILACS; and ISI Web of Science as well as grey literature sources and the reference lists of retrieved articles up to March 2017. The original search was performed in August 2011. We included all randomized controlled trials (RCTs) and controlled clinical trials (CCTs) where aromatherapy was used to treat PONV. Interventions were all types of aromatherapy compared to placebo or with standard antiemetics. Primary outcomes were severity and duration of PONV. Secondary outcomes were adverse reactions, use of rescue antiemetics and patient satisfaction. Two review authors independently assessed risk of bias in the included studies and extracted data. For dichotomous outcome variables, we used a random-effects model and calculated risk ratio (RR) with associated 95% confidence interval (95% CI). For continuous outcome variables, we used a random-effects model and calculated standardized mean difference (SMD) with associated 95% CI. We used the GRADE software to compile 'Summary of findings' tables. We included seven new studies with 663 participants in the 2017 update; five RCTs and two CCTs. These were added to the nine previously included studies (six RCTs and three CCTs with a total of 373 participants) for a total of 16 included studies and 1036 participants in this updated review. The mean age and range data for all participants were not reported for all studies. We identified two registered trials that met the inclusion criteria for this review
Moradian, Saeed; Walshe, Catherine; Shahidsales, Soodabeh; Ghavam Nasiri, Mohammad Reza; Pilling, Mark; Molassiotis, Alexander
2015-06-01
Pharmacological therapy is only partially effective in preventing or treating chemotherapy induced nausea and vomiting (CINV). Therefore, exploring the complementary role of non-pharmacological approaches used in addition to pharmacological agents is important. Nevasic uses specially constructed audio signals hypothesized to generate an antiemetic reaction. The aim of this study was to examine the feasibility of conducting a randomized controlled trial (RCT) to evaluate the effectiveness of Nevasic to control CINV. A mixed methods design incorporating an RCT and focus group interviews. For the RCT, female breast cancer patients were randomized to receive either Nevasic plus usual care, music plus usual care, or usual care only. Data were analysed using descriptive statistics and linear mixed-effects models. Five focus group interviews were conducted to obtain participants' views regarding the acceptability of the interventions in the trial. 99 participants were recruited to the RCT and 15 participated in focus group interviews. Recruitment targets were achieved. Issues of Nevasic acceptability were highlighted as weaknesses of the program. This study did not detect any evidence for the effectiveness of Nevasic; however, the results showed statistically significant less use of anti-emetics (p = 0.003) and borderline non-significant improvement in quality of life (p = 0.06). Conducting a non-pharmacological intervention using such an audio program is feasible, although difficulties and limitations exist with its use. Further studies are required to investigate the effectiveness of Nevasic from perspectives such as anti-emetic use, as well as its overall effect on the levels of nausea and vomiting. Copyright © 2014 Elsevier Ltd. All rights reserved.
Emergency department management of gastro-enteritis in Australia and New Zealand.
Schutz, Jacquie; Babl, Franz E; Sheriff, Nisa; Borland, Meredith
2008-10-01
Comparison of clinical practice guideline (CPG) recommendations and reported physician management of gastro-enteritis at Paediatric Research in Emergency Departments International Collaborative (PREDICT) network sites as a baseline for further randomised controlled trials. Two part survey comprising: (i) review of CPGs from PREDICT sites for gastro-enteritis; and (ii) survey of senior emergency department physicians regarding the management of gastro-enteritis. All 11 PREDICT sites participated. Nine CPGs were available with three sites using a common CPG. For moderate dehydration, eight CPGs advocated nasogastric (NG) rehydration in preference to intravenous (IV) rehydration. The IV route was reserved for severe dehydration or failed NG rehydration. In the second component of the survey, 78 of 83 (94%) physicians responded. In moderate dehydration, 82% of respondents used NG rehydration. In severe dehydration, 86% used IV fluids; 12% used NG and 3% an initial IV bolus followed by NG fluid. Serum electrolytes were measured universally with IV fluid use and by 22% using NG rehydration. The IV fluid bolus was with normal saline (86%). Fifty-four per cent used anti-emetics 'rarely' or 'sometimes'. The commonest agents were ondansetron (60%) and metoclopramide (29%). CPG recommendations and physician practice for the management of gastro-enteritis were similar across PREDICT sites with a focus on NG for moderate dehydration and IV for severe dehydration. A variety of fluids and administration rates were used. Anti-emetics were used infrequently. The efficacy and safety of newer anti-emetics should be explored in collaborative studies. Collaborative development of new CPGs should be considered to simplify fluid regimens.
Badowski, Melissa E
2017-09-01
Oral cannabinoids (i.e., dronabinol, nabilone) containing the active component of marijuana, delta(Δ)9-tetrahydrocannabinol (THC), are available for the treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer who have failed to adequately respond to conventional antiemetic therapy. The aim of this article is to provide an overview of the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety of oral cannabinoids for patients with CINV. A PubMed search of the English-language literature available through 4 January 2017 was conducted to identify relevant articles for inclusion in the review. Oral cannabinoids have been shown to have similar or improved efficacy compared with conventional antiemetics for the resolution of nausea and/or vomiting in patients with cancer. However, oral THC has high PK variability, with variability in oral dronabinol peak plasma concentrations (C max ) estimated between 150 and 200%. A new oral dronabinol solution has decreased intraindividual variability (area under the curve) vs oral dronabinol capsules. Further, oral THC has a slower time to C max compared with THC administered intravenously (IV) or by smoking, and a lower systemic availability than IV or smoked THC. The PD profile (e.g., "high") of oral THC differs from that of IV or smoked THC in healthy individuals. Oral cannabinoids are associated with greater incidence of adverse effects compared with conventional antiemetic therapy or placebo (e.g., dizziness, hypotension, and dysphoria or depression). A new formulation of oral cannabinoids (i.e., dronabinol oral solution) minimized the PK/PD variability currently observed with capsule formulations.
Pharmacovigilance in Hospice/Palliative Care: Net Effect of Haloperidol for Nausea or Vomiting.
Digges, Madeline; Hussein, Akram; Wilcock, Andrew; Crawford, Gregory B; Boland, Jason W; Agar, Meera R; Sinnarajah, Aynharan; Currow, David C; Johnson, Miriam J
2018-01-01
Haloperidol is widely prescribed as an antiemetic in patients receiving palliative care, but there is limited evidence to support and refine its use. To explore the immediate and short-term net clinical effects of haloperidol when treating nausea and/or vomiting in palliative care patients. A prospective, multicenter, consecutive case series. Twenty-two sites, five countries: consultative, ambulatory, and inpatient services. When haloperidol was started in routine care as an antiemetic, data were collected at three time points: baseline; 48 hours (benefits); day seven (harms). Clinical effects were assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE). Data were collected (May 2014-March 2016) from 150 patients: 61% male; 86% with cancer; mean age 72 (standard deviation 11) years and median Australian-modified Karnofsky Performance Scale 50 (range 10-90). At baseline, nausea was moderate (88; 62%) or severe (11; 8%); 145 patients reported vomiting, with a baseline NCI CTCAE vomiting score of 1.0. The median (range) dose of haloperidol was 1.5 mg/24 hours (0.5-5 mg/24 hours) given orally or parenterally. Five patients (3%) died before further data collection. At 48 hours, 114 patients (79%) had complete resolution of their nausea and vomiting, with greater benefit seen in the resolution of nausea than vomiting. At day seven, 37 (26%) patients had a total of 62 mild/moderate harms including constipation 25 (40%); dry mouth 13 (21%); and somnolence 12 (19%). Haloperidol as an antiemetic provided rapid net clinical benefit with low-grade, short-term harms.
Opportunities for the replacement of animals in the study of nausea and vomiting
Holmes, AM; Rudd, JA; Tattersall, FD; Aziz, Q; Andrews, PLR
2009-01-01
Nausea and vomiting are among the most common symptoms encountered in medicine as either symptoms of disease or side effects of treatments. Developing novel anti-emetics and identifying emetic liability in novel chemical entities rely on models that can recreate the complexity of these multi-system reflexes. Animal models (especially the ferret and dog) are the current gold standard; however, the selection of appropriate models is still a matter of debate, especially when studying the subjective human sensation of nausea. Furthermore, these studies are associated with animal suffering. Here, following a recent workshop held to review the utility of animal models in nausea and vomiting research, we discuss the limitations of some of the current models in the context of basic research, anti-emetic development and emetic liability detection. We provide suggestions for how these limitations may be overcome using non-animal alternatives, including greater use of human volunteers, in silico and in vitro techniques and lower organisms. PMID:19371333
Carmichael, J.; Bessell, E. M.; Harris, A. L.; Hutcheon, A. W.; Dawes, P. J.; Daniels, S.; Bessel, E. M.
1994-01-01
Two hundred and seventy-eight adult chemonaive patients, receiving moderately emetogenic chemotherapy were randomly allocated to receive either intravenous (i.v.) granisetron 3 mg plus i.v. dexamethasone 8 mg or i.v. granisetron 3 mg plus i.v. placebo dexamethasone prior to chemotherapy. Eight-two per cent of all patients recruited were female, and 91% of all patients consumed less than 10 units of alcohol per week, suggesting a study population with an increased risk of nausea and vomiting. In the first 24 h 85% of patients who received granisetron plus dexamethasone were complete responders compared with 75.9% of the patients receiving granisetron alone (P = 0.053). There were statistically significant improvements in complete response over 7 days (P = 0.029) and in the numbers of patients receiving rescue antiemetic (P = 0.0004). Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone. PMID:7981069
The effect of aromatherapy on postoperative nausea in women undergoing surgical procedures.
Ferruggiari, Luisa; Ragione, Barbara; Rich, Ellen R; Lock, Kathleen
2012-08-01
Postoperative nausea and vomiting (PONV) is a common source of patient discomfort and decreased satisfaction. Aromatherapy has been identified as a complementary modality for the prevention and management of PONV. The purpose of this study was to assess the effect of aromatherapy on the severity of postoperative nausea (PON) in women undergoing surgical procedures in the postanesthesia care unit. Women complaining of PON received traditional antiemetics, inhalation of peppermint oil, or saline vapor. A visual analog scale was used to rate nausea at the first complaint; at 5 minutes after intervention; and, if nausea persisted, at 10 minutes after intervention. At both 5 and 10 minutes, statistical analysis showed no significant differences between intervention and nausea rating. Obtaining eligible subjects was challenging. Although many women consented, most received intraoperative antiemetics and did not report nausea postoperatively. Copyright © 2012 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.
Momani, Tha'er G; Berry, Donna L
Chemotherapy-induced nausea and vomiting (CINV) continues to be a common symptom experienced by children undergoing cancer treatment despite the use of contemporary antiemetics. Integrative therapeutic approaches in addition to standard pharmacologic antiemetic regimes offer potential to control CINV. The purpose of this review was to identify current evidence on integrative therapeutic approaches for the control of CINV in children with cancer. Online search engines (PubMed, CINAHL, PsychINFO) were queried using MESH terms. Titles, abstracts, and then full-text articles were reviewed for relevance to the review. The search resulted in 53 studies. Twenty-one studies met our review criteria. Integrative therapies identified included acupuncture/acupressure, aromatherapy, herbal supplements, hypnosis, and other cognitive behavioral interventions. Our review identified little information on the effectiveness and safety of most integrative therapeutic approaches for the control and management of CINV in children with cancer. However, evidence from adult cancer studies and some pediatric studies identify promising interventions for further testing.
ERIC Educational Resources Information Center
Devine, Elizabeth C.; And Others
1988-01-01
A three-hour, two-stage workshop for staff nurses on providing education and psychological support to 148 patients who had abdominal surgery. After the workshop the patients used fewer sedatives or antiemetics, fewer hypnotics, and were discharged from the hospital on the average half a day sooner. (Author/BJV)
Gauchan, Sabin; Thapa, Chitra; Shakya, Priyanka; Bhattarai, Ramesh; Shakya, Sajal
2014-01-01
Laparoscopic surgeries are known to be associated with a higher incidence of postoperative nausea and vomiting (PONV). Prophylaxis of PONV is usually achieved with a single-dose antiemetic drug administered during the surgical procedure. The aim of this study was to compare the antiemetic efficacy of two different 5-hydroxytryptamine-3 (5HT3) receptor antagonists, ondansetron and granisetron when given prophylactically to patients undergoing laparoscopic cholecystectomy. It was a randomized, double blind study, conducted in 90 patients. Patients were divided into two groups: Group A and Group B with 45 patients in each group. Patients in groupA were given 100 microgram/kg ondansetron intravenously (IV), and patients in Group B were given 40 microgram/kg granisetron. Both the drugs were diluted in 10 ml of 0.9% NaCl and were given at the end of surgery. The standard general anesthetic technique was administered to all the patients. Episodes of nausea, retching and vomiting were assessed during the first 24 hours after anesthesia. There was no statistically significant difference for demographic data and duration of surgery among the two groups (P>0.05). Evaluated nausea and vomiting scores in the first 3 hours period revealed that each of the drugs had a similar antiemetic effect (P>0.05). Between 4-12 hours also the episodes of nausea, retching as well as vomiting were statistically insignificant in both the groups. In the last 12 hours, episodes of nausea, retching and vomiting were significantly higher in ondansetron group. Granisetron, when given prophylactically, resulted in a significantly lower incidence of PONV than ondansetron in the first 24 hours.
Rothwell, M P; Pearson, D; Hunter, J D; Mitchell, P A; Graham-Woollard, T; Goodwin, L; Dunn, G
2011-06-01
To determine if oral oxycodone (OOXY) could provide equivalent postoperative analgesia and a similar side-effect profile to i.v. patient-controlled morphine in patients undergoing elective primary total hip replacement (THR) under spinal anaesthesia. We studied 110 consecutive patients aged 60-85 yr. After operation, patients were randomly allocated to receive either oral controlled- and immediate-release OOXY or i.v. patient-controlled analgesia (IVPCA) with morphine. Both groups received regular co-analgesia and antiemetics. The primary outcome measures were: (i) postoperative pain at rest and movement and (ii) nausea score recorded 12 hourly. The secondary outcome measures were: (i) time to first mobilization, (ii) total amount of opioid consumed, (iii) number of additional antiemetic doses, and (iv) time to analgesic discontinuation. There were no statistically significant differences in the primary outcome measures of pain at rest and movement (P>0.05, 95% confidence intervals -0.41, +0.96) or nausea score (P>0.5). The secondary outcome measures showed no significant difference in the total amount of opioid consumed (102 vs 63 mg; P>0.05) or time to mobilization (24.45 vs 26.6 h, P=0.2). The number of antiemetic doses required in the first 24 h was significantly lower in the OOXY group (1.1 vs 1.4, P<0.05). The time to analgesic discontinuation was significantly shorter in the OOXY group (50.5 vs 56.6 h, P<0.05). Oral analgesia with OOXY was approximately GBP 10 less expensive per patient than IVPCA. Oral analgesia with OOXY after THR offers non-inferior analgesia to IVPCA and may offer some logistical and cost advantages.
Ioroi, Takeshi; Furukawa, Junya; Kume, Manabu; Hirata, Sachi; Utsubo, Yuko; Mizuta, Naomi; Miyake, Hideaki; Fujisawa, Masato; Hirai, Midori
2018-05-01
This study aimed to determine the antiemetic efficacy and safety of palonosetron, aprepitant and dexamethasone in patients with testicular germ cell tumours (TGCTs) receiving 5-day cisplatin-based combination chemotherapy. In this open-label, single-arm, single-centre study, the antiemetic therapy consisted of palonosetron 0.75 mg on day 1, aprepitant 125 mg on day 1 and 80 mg on days 2-7 and dexamethasone 6.6 mg on days 1-7. The primary endpoint was complete response (CR; no vomiting/retching or rescue medication) in the overall period (0-240 h), and secondary endpoints included complete protection (CP; defined as CR and no more than mild nausea) and total control (TC; defined as CR and no nausea). The incidence and severity of nausea were assessed on the basis of the Common Terminology Criteria for Adverse Events v4.0 and a subjective rating scale completed by patients. Twenty-five patients were enrolled and evaluated for safety, and 24 patients were evaluated for efficacy. CR was achieved in 62.5% of patients (95% confidence interval [CI] = 40.6-81.2, p = 0.043) in the overall period. CP and TC were achieved in 62.5% (95% CI = 40.6-81.2) and 25.0% of patients (95% CI = 9.8-46.7), respectively, in the overall period. The primary adverse drug reaction was hiccups (48.0%). The events were expected, and none was grade 3 or 4. The examined combination antiemetic therapy was effective and well-tolerated in patients with TGCTs receiving 5-day cisplatin-based combination chemotherapy.
Vig, Sierra; Seibert, Laurel; Green, Myke R
2014-01-01
The role of olanzapine added to a dopamine antagonist and benzodiazepine for the treatment of refractory chemotherapy-induced nausea and vomiting (CINV) is incompletely characterized in all levels of chemotherapy emetogenicity. This retrospective study evaluated the efficacy of the addition of olanzapine in adults experiencing refractory CINV stratified by chemotherapy emetogenicity. Thirty-three adults who experienced CINV refractory to guideline-recommended prophylaxis and breakthrough antiemetics (dopamine antagonists and benzodiazepines) and received at least one dose of olanzapine 5-10 mg per os were evaluated. Failure was defined as >5 emesis events in 24 h or more than 10 cumulative doses of rescue antiemetics following first olanzapine dose per treatment cycle. Post hoc analyses investigated variables impacting olanzapine efficacy. The addition of olanzapine demonstrated an overall success rate of 70 %. This success rate did not differ between chemotherapy regimens of high versus low-to-moderate emetogenicity (p = 0.79), prophylaxis with serotonin antagonist plus corticosteroid and aprepitant versus serotonin antagonist alone (p = 0.77), or age over 50 versus ≤50 years (p > 0.99). A trend toward greater benefit was seen in women (p = 0.08). The addition of olanzapine to a dopamine antagonist and benzodiazepine demonstrated high efficacy rates for refractory CINV irrespective of chemotherapy emetogenicity. The high success rates among all groups suggests that incomplete resolution of CINV with prophylactic serotonin antagonists and breakthrough dopamine antagonists plus benzodiazepine may benefit from the addition of olanzapine regardless of gender, degree of chemotherapy emetogenicity, number of prophylactic antiemetics, or age. The trend toward greater control of emesis in women merits further investigation.
Does ramosetron reduce postoperative emesis and pain after TKA?
Koh, In Jun; Chang, Chong Bum; Jeon, Young-Tae; Ryu, Jung-Hee; Kim, Tae Kyun
2012-06-01
Current pain management protocols involving many anesthetic and analgesic drugs reportedly provide adequate analgesia after TKA. However, control of emetic events associated with the drugs used in current multimodal pain management remains challenging. We determined (1) whether ramosetron prophylaxis reduces postoperative emetic events; and (2) whether it influences pain levels and opioid consumption in patients managed with a current multimodal pain management protocol after TKA. We randomized 119 patients undergoing TKA to receive either ramosetron (experimental group, n = 60) or no prophylaxis (control group, n = 59). All patients received regional anesthesia, preemptive analgesic medication, continuous femoral nerve block, periarticular injection, and fentanyl-based intravenous patient-controlled analgesia. We recorded the incidence of emetic events, rescue antiemetic requirements, complete response, pain level, and opioid consumption during three periods (0-6, 6-24, and 24-48 hours postoperatively). The severity of nausea was evaluated using a 0 to 10 VAS. The ramosetron group tended to have a lower incidence of nausea with a higher complete response and tended to have less severe nausea and fewer rescue antiemetic requirements during the 6- to 24-hour period. However, the overall incidences of emetic events, rescue antiemetic requirements, and complete response were similar in both groups. We found no differences in pain level or opioid consumption between the two groups. Ramosetron reduced postoperative emetic events only during the 6- to 24-hour postoperative period and did not affect pain relief. More efficient measures to reduce emetic events after TKA should be explored. Level I, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
Prevention of chemotherapy-induced nausea: the role of neurokinin-1 (NK1) receptor antagonists.
Bošnjak, Snežana M; Gralla, Richard J; Schwartzberg, Lee
2017-05-01
Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of cancer patients. The use of 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists (RAs) has reduced the risk of vomiting, but (except for palonosetron) their effect on nausea, especially delayed nausea, is limited. This article reviews the role of NK 1 RAs when combined with 5-HT 3 RA-dexamethasone in CIN prophylaxis. Aprepitant has not shown consistent superiority over a two-drug (ondansetron-dexamethasone) combination in nausea control after cisplatin- or anthracycline-cyclophosphamide (AC)-based highly emetogenic chemotherapy (HEC). Recently, dexamethasone and dexamethasone-metoclopramide were demonstrated to be non-inferior to aprepitant and aprepitant-dexamethasone, respectively, for the control of delayed nausea after HEC (AC/cisplatin), and are now recognized in the guidelines. The potential impact of the new NK 1 RAs rolapitant and netupitant (oral fixed combination with palonosetron, as NEPA) in CIN prophylaxis is discussed. While the clinical significance of the effect on nausea of the rolapitant-granisetron-dexamethasone combination after cisplatin is not conclusive, rolapitant addition showed no improvement in nausea prophylaxis after AC or moderately emetogenic chemotherapy (MEC). NEPA was superior to palonosetron in the control of nausea after HEC (AC/cisplatin). Moreover, the efficacy of NEPA in nausea control was maintained over multiple cycles of HEC/MEC. Recently, NK 1 RAs have been challenged by olanzapine, with olanzapine showing superior efficacy in nausea prevention after HEC. Fixed antiemetic combinations (such as NEPA) or new antiemetics with a long half-life that may be given once per chemotherapy cycle (rolapitant or NEPA) may improve patient compliance with antiemetic treatment.
Sanaati, Fateme; Najafi, Safa; Kashaninia, Zahra; Sadeghi, Masoud
2016-01-01
Chemotherapy-induced nausea and vomiting (CINV) places a significant burden on the patient. Herbal agents are the most commonly complementary therapies used among the public. This study was done to determine the effect of ginger and chamomile capsules on nausea and vomiting in cases undergoing chemotherapy for breast cancer (BC). In a randomized, double-blind and clinical trial study, 65 women with BC undergoing chemotherapy were referred to Breast Cancer Research Center, Tehran, Iran, between May 2013 to June 2014. Regimen for ginger group for 5 days before and 5 days after chemotherapy was: 2 times a day and 500 mg capsules of powdered ginger root in addition to a routine antiemetic regimen consisting of dexamethasone, metoclopramide and aprepitant (DMA) capsules. Chamomile group similarly was: 2 times a day and 500 mg capsules of Matricaria chamomilla extract in addition to a routine antiemetic regimen consisting of DMA capsules. Control group, routine antiemetic regimen consisting of DMA capsules. There were no significant differences between the ginger, chamomile and control groups regarding age. Drugs used for chemotherapy were identical and duration of disease was also matched (1-4 months). Ginger and chamomile were both significantly effective for reducing the frequency of vomiting, there being no significant difference between the ginger and chamomile groups. Moreover, unlike the chamomile, ginger significantly influenced the frequency of nausea. According to the findings of this study, it should be declared that taking ginger capsules (1 g/day) might relieve CINV safely. Nurses dealing directly with cancer patients should be responsible for providing educational programs for patients and their families about how to deal with their drug regimens and associated side effects.
21 CFR 336.50 - Labeling of antiemetic drug products.
Code of Federal Regulations, 2011 CFR
2011-04-01
... labeled for use in adults and for those products that can be and are labeled for use in children under 12... enlargement of the prostate gland.” (ii) For those products that can be and are labeled only for children under 12 years of age. “Do not give this product to children who have a breathing problem such as...
21 CFR 336.50 - Labeling of antiemetic drug products.
Code of Federal Regulations, 2010 CFR
2010-04-01
... years of age. “Do not take this product, unless directed by a doctor, if you have a breathing problem... Section 336.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... under 12 years of age. “Do not give this product to children who have a breathing problem such as...
21 CFR 336.50 - Labeling of antiemetic drug products.
Code of Federal Regulations, 2014 CFR
2014-04-01
... years of age. “Do not take this product, unless directed by a doctor, if you have a breathing problem... under 12 years of age. “Do not give this product to children who have a breathing problem such as... diphenhydramine, including one used on skin”. 1 See § 201.66(b)(4) of this chapter for definition of bullet symbol...
21 CFR 336.50 - Labeling of antiemetic drug products.
Code of Federal Regulations, 2012 CFR
2012-04-01
... years of age. “Do not take this product, unless directed by a doctor, if you have a breathing problem... under 12 years of age. “Do not give this product to children who have a breathing problem such as... diphenhydramine, including one used on skin”. 1 See § 201.66(b)(4) of this chapter for definition of bullet symbol...
21 CFR 336.50 - Labeling of antiemetic drug products.
Code of Federal Regulations, 2013 CFR
2013-04-01
... years of age. “Do not take this product, unless directed by a doctor, if you have a breathing problem... under 12 years of age. “Do not give this product to children who have a breathing problem such as... diphenhydramine, including one used on skin”. 1 See § 201.66(b)(4) of this chapter for definition of bullet symbol...
Veiga-Gil, Leonor; López-Olaondo, Luis; Pueyo, Javier; Callejas, Raquel; Duque, Paula; Carrascosa, Francisco
2015-02-01
In this observational study we reviewed the efficacy and side effects of different antiemetic combinations used in our hospital for postoperative nausea and vomiting (PONV) prophylaxis in high-risk women undergoing highly emetogenic surgery. After reviewing retrospectively the medical records of patients undergoing highly emetogenic elective surgeries under general anaesthesia, we selected 368 women whose Apfel risk score was ≥ 3 and receiving a combination of 2 antiemetics for PONV prophylaxis. We analysed the incidence of PONV at 2, 6, 12 and 24h after surgery, antiemetic rescue requirements, pattern of occurrence of PONV, side effects and level of sedation were also assessed. The main goal was complete response defined as no PONV within 24h after surgery. Ondansetron 4mg i.v. plus dexamethasone 8mg i.v. (O&Dex), haloperidol 1mg i.v. (O&Hal1), haloperidol 2mg i.v. (O&Hal2) or droperidol 1.25mg i.v. (O&Dro) were the combinations most frequently used. The complete response was better in groups O&Dex: 68.5% (CI: 58-78), O&Hal2: 64.1% (CI: 53-74) and O&Dro 63% (CI: 52-73) than in group O&Hal1: 41.3% (CI: 31-52) (p<0,01). Peak incidence of PONV occurred within the 2-6h period. The incidence of side effects was higher in group O&Hal2. In high risk patients for PONV who underwent highly emetogenic surgeries, the efficacy of low-dose haloperidol (1mg) in combination is limited. Higher doses (2mg) are more effective but its use is associated with a high incidence of side effects. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.
Ismail, Samina; Ahmed, Aliya; Hoda, Muhammad Qamarul; Sohaib, Muhammad; Zia-Ur-Rehman
2016-12-01
All laparoscopic cholecystectomy (LC) patients in our hospital setting are admitted overnight. This article assesses the contribution of factors like postoperative nausea and vomiting (PONV), postoperative pain and surgical complications to overnight stay after elective LC. This 1-year observational study included patients having normal liver functions undergoing elective LC before 1400 h. The collected data included patient demographics, co-morbidities, PONV, pain scores, complications, surgical time, anesthesia technique, use of prophylactic antiemetics, analgesics, patient satisfaction and desire to have this surgery as day case or in-patient procedure. From 930 LC done per annum, 45.2 % (430/950) patients were included in this study. Prophylactic antiemetic was given in 91.6 %, intraoperative narcotics in 94.2 % patients and multimodal analgesia in 85.3 %. The mean pain score in the recovery and ward was maintained to <4. In the ward, 99.1 % patients were able to start oral fluids after 6 h and were started on oral non-steroidal anti-inflammatory drugs and paracetamol, and none required parental opioid. The PONV score of more than 2 was observed in only 3.2 % of patients in the ward requiring parenteral antiemetic. Surgical complications in the form of bleeding, visceral injury and bile duct leak were observed in 2 % of patients, which was treated intra-operatively. Satisfaction was observed in 99.3 % and desire to stay overnight in 87.4 % of patients. Factors like postoperative pain, PONV and surgical complications were well managed and were not associated with significant morbidity to justify routine overnight admission. However, majority of the patients desired to stay overnight, which could be improved by counseling and education.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dennis, Kristopher; Zhang Liying; Lutz, Stephen
Purpose: To investigate international patterns of practice in the management of radiation therapy-induced nausea and vomiting (RINV). Methods and Materials: Oncologists prescribing radiation therapy in the United States, Canada, The Netherlands, Australia, New Zealand, Spain, Italy, France, Hong Kong, Singapore, Cyprus, and Israel completed a Web-based survey that was based on 6 radiation therapy-only clinical cases modeled after the minimal-, low-, moderate-, and high-emetic risk levels defined in the antiemetic guidelines of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer. For each case, respondents estimated the risks of nausea and vomiting separately andmore » committed to an initial management approach. Results: In total, 1022 responses were received. Risk estimates and management decisions for the minimal- and high-risk cases varied little and were in line with guideline standards, whereas those for the low- and moderate-risk cases varied greatly. The most common initial management strategies were as follows: rescue therapy for a minimal-risk case (63% of respondents), 2 low-risk cases (56% and 80%), and 1 moderate-risk case (66%); and prophylactic therapy for a second moderate-risk case (75%) and a high-risk case (95%). The serotonin (5-HT){sub 3} receptor antagonists were the most commonly recommended prophylactic agents. On multivariate analysis, factors predictive of a decision for prophylactic or rescue therapy were risk estimates of nausea and vomiting, awareness of the American Society of Clinical Oncology antiemetic guideline, and European Society for Therapeutic Radiology and Oncology membership. Conclusions: Risk estimates and management strategies for RINV varied, especially for low- and moderate-risk radiation therapy cases. Radiation therapy-induced nausea and vomiting are under-studied treatment sequelae. New observational and translational studies are needed to allow for individual
Structural basis of ligand recognition in 5-HT3 receptors
Kesters, Divya; Thompson, Andrew J; Brams, Marijke; van Elk, René; Spurny, Radovan; Geitmann, Matthis; Villalgordo, Jose M; Guskov, Albert; Helena Danielson, U; Lummis, Sarah C R; Smit, August B; Ulens, Chris
2013-01-01
The 5-HT3 receptor is a pentameric serotonin-gated ion channel, which mediates rapid excitatory neurotransmission and is the target of a therapeutically important class of anti-emetic drugs, such as granisetron. We report crystal structures of a binding protein engineered to recognize the agonist serotonin and the antagonist granisetron with affinities comparable to the 5-HT3 receptor. In the serotonin-bound structure, we observe hydrophilic interactions with loop E-binding site residues, which might enable transitions to channel opening. In the granisetron-bound structure, we observe a critical cation–π interaction between the indazole moiety of the ligand and a cationic centre in loop D, which is uniquely present in the 5-HT3 receptor. We use a series of chemically tuned granisetron analogues to demonstrate the energetic contribution of this electrostatic interaction to high-affinity ligand binding in the human 5-HT3 receptor. Our study offers the first structural perspective on recognition of serotonin and antagonism by anti-emetics in the 5-HT3 receptor. PMID:23196367
Alternative Therapies for the Prevention of Postoperative Nausea and Vomiting.
Stoicea, Nicoleta; Gan, Tong J; Joseph, Nicholas; Uribe, Alberto; Pandya, Jyoti; Dalal, Rohan; Bergese, Sergio D
2015-01-01
Postoperative nausea and vomiting (PONV) is a complication affecting between 20 and 40% of all surgery patients, with high-risk patients experiencing rates of up to 80%. Recent studies and publications have shed light on the uses of alternative treatment for PONV through their modulation of endogenous opioid neuropeptides and neurokinin ligands. In addition to reducing PONV, hypnosis was reported to be useful in attenuating postoperative pain and anxiety, and contributing to hemodynamic stability. Music therapy has been utilized to deepen the sedation level and decrease patient anxiety, antiemetic and analgesic requirements, hospital length of stay, and fatigue. Isopropyl alcohol and peppermint oil aromatherapy have both been used to reduce postoperative nausea. With correct training in traditional Chinese healing techniques, acupuncture (APu) at the P6 acupoint has also been shown to be useful in preventing early PONV, postdischarge nausea and vomiting, and alleviating of pain. Electro-acupuncture (EAPu), as with APu, provided analgesic and antiemetic effects through release and modulation of opioid neuropeptides. These non-pharmacological modalities of treatment contribute to an overall patient wellbeing, assisting in physical and emotional healing.
Proceedings: TRIAGE of Irradiated Personnel, 25-27 September 1996
1998-03-01
thermoluminescent dosimeter project group (PG-29) has recommended grani- (TLD) systems accredited by the National Volun- setron as the deployable...individual phylactic antiemetic medications and regimens dosimeter system currently fielded is the high-range were evaluated prior to adoption of...granisetron. photoluminescent AN/PDR-75. This system con- sists of the ruggedized DT-236 wristband dosimeter Two drugs exceeded the criteria (shown below
Huizing, G; Beckett, A H; Segura, J; Bakke, O M
1980-03-01
1. Electron impact and field desorption mass spectrometry is described and discussed for clebopride, a newly developed benzamide with anti-emetic and anti-dopaminergic properties, and for some related compounds. 2. When clebopride was incubated with liver homogenates of rabbits, 4-amino-5-chloro-2-methoxybenzoic acid and N-(4'-piperidyl)-4-amino-5-chloro-2-methoxybenzamide were identified as metabolites.
Chen, Xin-yu; Zhang, Chun-quan; Zhang, Hong; Liu, Wei; Wang, Jun-yan
2010-05-01
To investigate the use and trend of drugs on digestive system in Hangzhou area, under the comprehensive statistics index (CSI). Using the analytical method related to the sum of consumption and CSI, the application of digestive system drugs of different manufacturers in Hangzhou from 2005 to 2007 was analyzed. Other than H2 receptor antagonist, the total consumption of digestive system drugs increased yearly, in terms of the total consumption, the first 4 leading ones were proton pump inhibitors, micro ecology medicines, antiemetic drugs and gastroprokinetic agents. The Laspeyres index of drugs on digestive system increased to different extent. The Laspeyres indices of proton pump inhibitors, probiotics, antiemetic drugs and gastroprokinetic agents were 1.396 50, 1.020 42, 1.728 90, 1.148 50 in 2006 while 2.081 10, 1.217 55, 2.223 50, 1.156 60 in 2007, respectively. Through CSI, the results showed the situation of use and trend of digestive system related drugs in Hangzhou. Factors as rationality, efficiency and costs of the drugs as well as the etiology of the disease were also explored to some degree.
Alternative Therapies for the Prevention of Postoperative Nausea and Vomiting
Stoicea, Nicoleta; Gan, Tong J.; Joseph, Nicholas; Uribe, Alberto; Pandya, Jyoti; Dalal, Rohan; Bergese, Sergio D.
2015-01-01
Postoperative nausea and vomiting (PONV) is a complication affecting between 20 and 40% of all surgery patients, with high-risk patients experiencing rates of up to 80%. Recent studies and publications have shed light on the uses of alternative treatment for PONV through their modulation of endogenous opioid neuropeptides and neurokinin ligands. In addition to reducing PONV, hypnosis was reported to be useful in attenuating postoperative pain and anxiety, and contributing to hemodynamic stability. Music therapy has been utilized to deepen the sedation level and decrease patient anxiety, antiemetic and analgesic requirements, hospital length of stay, and fatigue. Isopropyl alcohol and peppermint oil aromatherapy have both been used to reduce postoperative nausea. With correct training in traditional Chinese healing techniques, acupuncture (APu) at the P6 acupoint has also been shown to be useful in preventing early PONV, postdischarge nausea and vomiting, and alleviating of pain. Electro-acupuncture (EAPu), as with APu, provided analgesic and antiemetic effects through release and modulation of opioid neuropeptides. These non-pharmacological modalities of treatment contribute to an overall patient wellbeing, assisting in physical and emotional healing. PMID:26734609
Acute Radiation Sickness Amelioration Analysis
1994-05-01
Emetic Drugs 16. PRICE CODE Antagonists 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19, SECURITY CLASSIFICATION 20. LIMITATION OF ABSTRACT OF...102 UNCLASSIFIED mcuIw IA IIIcaIIin or Isis PAW CLASSFIED BY: N/A since Unclassified. DECLASSIFY ON: N/A since Unclassified. SECURITY CLASSIFICATION OF...Approximately 2000 documents relevant to the development of the candidate anti-emetic drugs ondansetron (Zofran, Glaxo Pharmaceuticals) and granisetron
TRIAGE of Irradiated Personnel
1996-09-25
Vivo Electron Paramagnetic Resonance, Electron Spin Resonance (EPR, ESR) for In Vivo Dosimetry Under Field Conditions Dr. Harold M. Swartz Dartmouth...Force Medical Center Andrews Air Force Base, MD • Status and Limitations of Physical Dosimetry in the Field Environment David A. Schauer, LCDR, MSC...USN Naval Dosimetry Center Navy Environmental Health Center Detachment Bethesda, MD • NATO Policy and Guidance on Antiemetic Usage Robert Kehlet
Toward drugs derived from cannabis.
Mechoulam, R; Carlini, E A
1978-04-01
Recent work aimed at the introduction of natural and synthetic cannabinoids as drugs is reviewed. Delta1-Tetrahydrocannabinol (delta1-THC) is mainly investigated as a potential drug against glaucoma and asthma, and as an antiemetic agent in cancer chemotherapy. Cannabidiol is being tried in the clinic against epilepsy and as a hypnotic. Numerous synthetic cannabinoids are currently being investigated as analgetics and as sedative-relaxants.
Can We Rely on Pharmacy Claims Databases to Ascertain Maternal Use of Medications during Pregnancy?
Zhao, Jin-Ping; Sheehy, Odile; Gorgui, Jessica; Bérard, Anick
2017-04-03
Administrative databases are increasingly used to measure drug exposure in perinatal pharmacoepidemiology. We aimed to estimate the concordance between records of prescriptions filled in pharmacies and self-reported drug use during pregnancy. Data on self-reported medication use were collected at each trimester of pregnancy among a sub-sample from the Organization of Teratology Information Specialists Antidepressants in Pregnancy Cohort. Women were eligible if they were Quebec resident and provided their pharmacist's contact information. Maternal self-reports were compared with prescriptions filled in pharmacies, which are transferred to pharmaceutical services files of Quebec provincial health plan database (Régie de l'asssurance maladie du Québec). Positive and negative predictive values (PPV and NPV) for medications taken chronically (antidepressants, thyroid hormones), acutely (antibiotics), and as needed (antiemetics, asthma medications) were calculated. Among the 93 participants (mean age = 30.2 ± 3.8 years), 41.9% (n = 39) took at least one antidepressant during pregnancy according to self-reports, and 39.8% (n = 37) according to pharmacy records. Other commonly used drugs were antiemetics (self-reported 22.6%, pharmacy record 24.7%), antibiotics (20.4%, 16.1%), asthma medications (15.1%, 15.1%), and thyroid hormones (10.8%, 8.6%). PPVs and NPVs were: (1) chronic medication: antidepressants PPV = 100% (95% confidence interval [CI], 100-100%), NPV = 96% (95% CI, 92-100%); thyroid hormones PPV = 100% (95% CI, 100-100%), NPV = 98% (95% CI, 95-100%); (2) Acute medication: antibiotics PPV = 87% (95% CI, 70-100%), NPV = 92% (95% CI, 86-98%); (3) as needed medications: antiemetics: PPV = 78% (95% CI, 62-95%), NPV = 96% (95% CI, 91-100%); asthma: PPV = 33% (95% CI, 3-64%), NPV = 99% (95% CI, 97-100%). The high PPV and NPV validate the use of filled prescription data in large databases as a measure of medication exposure. Birth Defects Research 109:423-431, 2017
Hu, Zhihuang; Liang, Wenhua; Yang, Yunpeng; Keefe, Dorothy; Ma, Yuxiang; Zhao, Yuanyuan; Xue, Cong; Huang, Yan; Zhao, Hongyun; Chen, Likun; Chan, Alexandre; Zhang, Li
2016-01-01
Abstract Chemotherapy-induced nausea and vomiting (CINV) is presented in over 30% of cancer patients receiving highly/moderately emetogenic chemotherapy (HEC/MEC). The currently recommended antiemetic therapy is merely based on the emetogenic level of chemotherapy, regardless of patient's individual risk factors. It is, therefore, critical to develop an approach for personalized management of CINV in the era of precision medicine. A number of variables were involved in the development of CINV. In the present study, we pooled the data from 2 multi-institutional investigations of CINV due to HEC/MEC treatment in Asian countries. Demographic and clinical variables of 881 patients were prospectively collected as defined previously, and 862 of them had full documentation of variables of interest. The data of 548 patients from Chinese institutions were used to identify variables associated with CINV using multivariate logistic regression model, and then construct a personalized prediction model of nomogram; while the remaining 314 patients out of China (Singapore, South Korea, and Taiwan) entered the external validation set. C-index was used to measure the discrimination ability of the model. The predictors in the final model included sex, age, alcohol consumption, history of vomiting pregnancy, history of motion sickness, body surface area, emetogenicity of chemotherapy, and antiemetic regimens. The C-index was 0.67 (95% CI, 0.62–0.72) for the training set and 0.65 (95% CI, 0.58–0.72) for the validation set. The C-index was higher than that of any single predictor, including the emetogenic level of chemotherapy according to current antiemetic guidelines. Calibration curves showed good agreement between prediction and actual occurrence of CINV. This easy-to-use prediction model was based on chemotherapeutic regimens as well as patient's individual risk factors. The prediction accuracy of CINV occurrence in this nomogram was well validated by an independent data set
Aromatherapy as treatment for postoperative nausea: a randomized trial.
Hunt, Ronald; Dienemann, Jacqueline; Norton, H James; Hartley, Wendy; Hudgens, Amanda; Stern, Thomas; Divine, George
2013-09-01
Postoperative nausea (PON) is a common complication of anesthesia and surgery. Antiemetic medication for higher-risk patients may reduce but does not reliably prevent PON. We examined aromatherapy as a treatment for patients experiencing PON after ambulatory surgery. Our primary hypothesis was that in comparison with inhaling a placebo, PON will be reduced significantly by aromatherapy with (1) essential oil of ginger, (2) a blend of essential oils of ginger, spearmint, peppermint, and cardamom, or (3) isopropyl alcohol. Our secondary hypothesis was that the effectiveness of aromatherapy will depend upon the agent used. A randomized trial of aromatherapy with patients who reported nausea in the postanesthesia care unit was conducted at one ambulatory surgical center. Eligibility criteria were adult, able to give consent, and no history of coagulation problems or allergy to the aromatherapy agents. Before surgery, demographic and risk factors were collected. Patients with a nausea level of 1 to 3 on a verbal descriptive scale (0-3) received a gauze pad saturated with a randomly chosen aromatherapy agent and were told to inhale deeply 3 times; nausea (0-3) was then measured again in 5 minutes. Prophylactic and postnausea antiemetics were given as ordered by physicians or as requested by the patient. A total of 1151 subjects were screened for inclusion; 303 subjects reporting nausea were enrolled (26.3%), and 301 meeting protocol were analyzed (26.2%). The change in nausea level was significant for the blend (P < 0.001) and ginger (P = 0.002) versus saline but not for alcohol (P < 0.76). The number of antiemetic medications requested after aromatherapy was also significantly reduced with ginger or blend aromatherapy versus saline (P = 0.002 and P < 0.001, respectively). The hypothesis that aromatherapy would be effective as a treatment for PON was supported. On the basis of our results, future research further evaluating aromatherapy is warranted. Aromatherapy is
Tsavaris, N; Kosmas, C; Kopterides, P; Vadiaka, M; Kosmas, N; Skopelitis, H; Karadima, D; Kolliokosta, G; Tzima, E; Loukeris, D; Pagouni, E; Batziou, E; Xyla, V; Koufos, C
2008-03-01
Even though significant progress has been made, chemotherapy-induced emesis remains a challenging problem. Few studies focus on emesis in patients treated with carboplatin and the observation period is limited to the initial 24 h following chemotherapy. Thus, we investigated if tropisetron (T) monotherapy can adequately prevent acute and delayed emesis in non-small-cell lung cancer (NSCLC) patients receiving a moderately emetogenic chemotherapy (MEC) (carboplatin-containing) regimen. Furthermore, we explored the merits of adding dexamethasone (D) or alprazolam (A) to T, especially in the setting of a pre-existing high level of stress. We studied 60 patients with advanced NSCLC receiving carboplatin and taxanes in three consecutive cycles. During the first cycle, patients received 5 mg of T intravenously before chemotherapy and the same dose per os on each of the following 3 days. In the second cycle, T was co-administered with 8 mg of D once a day, while, during the third cycle, T was combined with per os A 0.25 mg every 12 h and continued over the following 3 days. Finally, we evaluated the impact of stress on the anti-emetic response achieved with the previously described regimens. The combination of T + A was superior to T monotherapy and the combination of T + D, regarding the prevention of acute and delayed emesis. Both T + A and T + D combinations led to appetite improvement, while patients receiving T + A experienced sedation more frequently. Interestingly, subgroup analysis revealed that patients without underlying stress obtained no further benefit by the addition of A or D, while both T + A and T + D combinations led to a better anti-emetic response in patients with stress. In conclusion, T monotherapy provides a satisfactory result in controlling nausea and emesis caused by a MEC regimen in patients without stress. However, the addition of D and, mainly, A improves its anti-emetic effect in patients with obvious stress.
Hu, Zhihuang; Liang, Wenhua; Yang, Yunpeng; Keefe, Dorothy; Ma, Yuxiang; Zhao, Yuanyuan; Xue, Cong; Huang, Yan; Zhao, Hongyun; Chen, Likun; Chan, Alexandre; Zhang, Li
2016-01-01
Chemotherapy-induced nausea and vomiting (CINV) is presented in over 30% of cancer patients receiving highly/moderately emetogenic chemotherapy (HEC/MEC). The currently recommended antiemetic therapy is merely based on the emetogenic level of chemotherapy, regardless of patient's individual risk factors. It is, therefore, critical to develop an approach for personalized management of CINV in the era of precision medicine.A number of variables were involved in the development of CINV. In the present study, we pooled the data from 2 multi-institutional investigations of CINV due to HEC/MEC treatment in Asian countries. Demographic and clinical variables of 881 patients were prospectively collected as defined previously, and 862 of them had full documentation of variables of interest. The data of 548 patients from Chinese institutions were used to identify variables associated with CINV using multivariate logistic regression model, and then construct a personalized prediction model of nomogram; while the remaining 314 patients out of China (Singapore, South Korea, and Taiwan) entered the external validation set. C-index was used to measure the discrimination ability of the model.The predictors in the final model included sex, age, alcohol consumption, history of vomiting pregnancy, history of motion sickness, body surface area, emetogenicity of chemotherapy, and antiemetic regimens. The C-index was 0.67 (95% CI, 0.62-0.72) for the training set and 0.65 (95% CI, 0.58-0.72) for the validation set. The C-index was higher than that of any single predictor, including the emetogenic level of chemotherapy according to current antiemetic guidelines. Calibration curves showed good agreement between prediction and actual occurrence of CINV.This easy-to-use prediction model was based on chemotherapeutic regimens as well as patient's individual risk factors. The prediction accuracy of CINV occurrence in this nomogram was well validated by an independent data set. It could
Gastroenteritis Therapies in Developed Countries: Systematic Review and Meta-Analysis.
Freedman, Stephen B; Pasichnyk, Dion; Black, Karen J L; Fitzpatrick, Eleanor; Gouin, Serge; Milne, Andrea; Hartling, Lisa
2015-01-01
Gastroenteritis remains a leading cause of childhood morbidity. Because prior reviews have focused on isolated symptoms and studies conducted in developing countries, this study focused on interventions commonly considered for use in developed countries. Intervention specific, patient-centered outcomes were selected. MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, trial registries, grey literature, and scientific meetings. Randomized controlled trials, conducted in developed countries, of children aged <18 years, with gastroenteritis, performed in emergency department or outpatient settings which evaluated oral rehydration therapy (ORT), antiemetics, probiotics or intravenous fluid administration rate. The study was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Data were independently extracted by multiple investigators. Analyses employed random effects models. 31 trials (4,444 patients) were included. ORT: Compared with intravenous rehydration, hospitalization (RR 0.80, 95%CI 0.24, 2.71) and emergency department return visits (RR 0.86, 95%CI 0.39, 1.89) were similar. Antiemetics: Fewer children administered an antiemetic required intravenous rehydration (RR 0.40, 95%CI 0.26, 0.60) While the data could not be meta-analyzed, three studies reported that ondansetron administration does increase the frequency of diarrhea. Probiotics: No studies reported on the primary outcome, three studies evaluated hospitalization within 7 days (RR 0.87, 95%CI 0.25, 2.98). Rehydration: No difference in length of stay was identified for rapid vs. standard intravenous or nasogastric rehydration. A single study found that 5% dextrose in normal saline reduced hospitalizations compared with normal saline alone (RR 0.70, 95% CI 0.53, 0.92). There is a paucity of patient-centered outcome evidence to support many interventions. Since ORT is a low-cost, non-invasive intervention, it should continue to be
Rowbottom, Leigha; Pasetka, Mark; McDonald, Rachel; Hunyh, Lise; Raman, Srinivas; DeAngelis, Carlo; Chow, Edward
2015-01-01
Radiotherapy-induced nausea and vomiting (RINV) is a toxicity that can occur in 40-80% of individuals who receive radiation treatment. Current guidelines recommend 5-hydroxytryptamine3 receptor antagonists (5-HT3 RAs) for prophylaxis of RINV for moderate and highly emetogenic radiotherapy; however, certain patients may suffer from RINV despite prophylaxis. This report details the case of a 47-year-old female with extensive bony involvement to the spine from breast cancer presenting with lower back pain. To palliate her symptoms, the patient underwent a course of irradiation to the lumbar spine and was prescribed ondansetron as an antiemetic. However, the patient experienced severe nausea and emesis and was subsequently switched to granisetron and aprepitant. The patient completed the remainder of the radiation treatment with no further emesis and minimal nausea, representing the first documented success of granisetron and aprepitant for RINV after failure on ondansetron. In chemotherapy, switching 5-HT3 RAs after failure on the first is successful in preventing chemotherapy-induced nausea and vomiting (CINV), yet this has not been previously reported in radiation. In this patient, granisetron and aprepitant were successful in substantially reducing nausea and preventing further emesis, and may represent an alternative antiemetic regimen for RINV prophylaxis and salvage.
[A Case of Psychogenic Tremor during Awake Craniotomy].
Kujirai, Kazumasa; Kamata, Kotoe; Uno, Toshihiro; Hamada, Keiko; Ozaki, Makoto
2016-01-01
A 31-year-old woman with a left frontal and parietal brain tumor underwent awake craniotomy. Propofol/remifentanil general anesthesia was induced. Following craniotomy, anesthetic administrations ceased. The level of consciousness was sufficient and she was not agitated. However, the patient complained of nausea 70 minutes into the awake phase. Considering the adverse effects of antiemetics and the upcoming surgical strategy, we did not give any medications. Nausea disappeared spontaneously while the operation was suspended. When surgical intervention extended to the left caudate nucleus, involuntary movement, classified as a tremor, with 5-6 Hz frequency, abruptly occurred on her left forearm. The patient showed emotional distress. Tremor appeared on her right forearm and subsequently spread to her lower extremities. Intravenous midazolam and fentanyl could not reduce her psychological stress. Since the tremor disturbed microscopic observation, general anesthesia was induced. Consequently, the tremor disappeared and did not recur. Based on the anatomical ground and the medication status, her involuntary movement was diagnosed as psychogenic tremor. Various factors can induce involuntary movements. In fact, intraoperative management of nausea and vomiting takes priority during awake craniotomy, but we should be reminded that some antiemetics potentially induce involuntary movement that could be caused by surgery around basal ganglia.
Fosaprepitant-induced phlebitis: a focus on patients receiving doxorubicin/cyclophosphamide therapy.
Leal, A D; Kadakia, K C; Looker, S; Hilger, C; Sorgatz, K; Anderson, K; Jacobson, A; Grendahl, D; Seisler, D; Hobday, T; Loprinzi, Charles L
2014-05-01
The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy. A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs, and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given. Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7 % (n=34), while the incidence of aprepitant-associated ISAEs was 2.3 % (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5), and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE. The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy are significant and appreciably higher than what has been previously reported.
Freedman, Orit; Amir, Eitan; Zimmermann, Camilla; Clemons, Mark
2011-03-01
Supportive care interventions can have a substantial impact on side effects of chemotherapy. Consequently, accurate reporting of such interventions is essential when interpreting clinical trial results. This study determined the prevalence and quality of reporting of supportive care treatment for common chemotherapy-induced toxicities in phase III, breast cancer chemotherapy trials. A systematic review of phase III trials of breast cancer trials incorporating chemotherapy published in the last 5 years was undertaken. Trials were identified through MEDLINE, EMBASE, BIOSIS, and the Cochrane Library. Supportive treatments evaluated were use of antiemetics, colony-stimulating growth factors, and antibiotics. Reporting quality was rated as "good", "fair", "poor", or "absent" using predetermined criteria. Sixty-two trials met inclusion criteria. In 41 studies (66%), details regarding prophylactic antiemetic treatment were not provided. Growth factor use was not reported in 20 trials (32%). Instructions for the use of prophylactic antibiotics were absent in 45 trials (72%). There are significant deficiencies in reporting of use of prophylactic supportive care agents in breast cancer trials. Omission of supportive care instructions may impact substantially on patient management and health care system expenditure. Recommendations for the type, dose, and frequency of supportive care drugs should be provided and reported on in trials.
Lorusso, Domenica; Bria, Emilio; Costantini, Anna; Di Maio, Massimo; Rosti, Giovanni; Mancuso, Annamaria
2017-03-01
Chemotherapy side effects (CSE) have a strong impact on patients' quality of life (QOL). To assess patient perceptions of CSE, their impact on QOL and doctor-patient communication regarding these aspects, a survey was conducted among Italian cancer patients. Patients at least 18 years of age, who received chemotherapy, were administered a dedicated questionnaire to assess their point of view on five domains: expectations about CSE and impact on QOL; doctor-patient communication about CSE; treatments to reduce the impact of CSE; sexual life; family relationships/activities and employment. A total of 761 patients participated. CSE had a considerable impact on patient QOL. Nausea/vomiting was the most feared adverse effect before initiating chemotherapy and the one most commonly experienced during treatment. Patients generally reported good doctor-patient communication regarding information about CSE. In almost all cases, the oncologists prescribed an antiemetic treatment, but the incidence of nausea/vomiting was high. Cancer and CSE severely affected sexual life, daily activities and employment. CSE had a strong negative impact on QOL. Good doctor-patient communication is essential. Improving antiemetic strategies may improve QOL. Doctors' ability to inform patients about delicate issues, such as the impact of CSE on sexual life, needs to be improved. © 2016 John Wiley & Sons Ltd.
Prophylactic Diclectin reduces the incidence of postoperative vomiting.
Reeve, Brenda K; Cook, Deborah J; Babineau, Denise; Scholes, L Cory; Buckley, D Norman
2005-01-01
Diclectin(R) (DCL) is an effective antiemetic used for relief of nausea and vomiting in pregnancy. It is unknown whether DCL is effective in the prevention of postoperative nausea and vomiting (PONV). We conducted a randomized, stratified, double-blind placebo-controlled trial to examine the incidence of PONV in women undergoing elective laparoscopic tubal ligation in the day surgery setting. DCL (doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg) was administered orally the night before surgery, the morning of surgery, and upon hospital discharge. We enrolled 146 women in the trial, 127 of whom were included in the effectiveness analysis and 102 of whom were included in the efficacy analysis. We did not detect a difference in the incidence of nausea and vomiting in the first six hours postoperatively after adjusting for additional antiemetics administered. Patients receiving DCL as compared with placebo were significantly less likely to experience vomiting six to 24 hr postoperatively [5/59 (8.5%) vs 14/55 (25.4%), P < 0.017]. Treated patients tended to return to work earlier than those who received placebo (1.74 vs 3.7 days P = NS). Perioperative oral DCL reduces the incidence of postoperative vomiting in women undergoing elective laparoscopic tubal ligation, and may accelerate return to work.
Gupta, Deepak; Mazumdar, Ashish; Stellini, Michael
2014-09-01
Nausea-vomiting is a common and unpleasant phenomenon with numerous underlying mechanisms and pathways that are not always well elucidated. In clinical practice, refractory nausea-vomiting is encountered in several settings. Antiemetic medications may reduce these symptoms but are not always effective in all patients. In the absence of a well-defined optimal strategy for management of nausea-vomiting, the search for better approaches to treat this distressing symptom continues. One of the alternative treatment approaches is a compounded formulation called ABHR gel that is comprised of multiple antiemetic medications and has been shown to be useful for symptomatic relief in some patients with refractory nausea-vomiting. It has been suggested that alternative mechanisms should be explored to explain the perceived efficacy of ABHR gel, because transdermal absorption leading to nil-to-minimal or subtherapeutic blood concentrations of active ingredients does not explain the role of ABHR gel in the treatment of nausea-vomiting. In the current paper, we discuss possible mechanisms that may explain ABHR transdermal gel's efficacy. Compounded ABHR transdermal gel formulation's efficacy in antagonizing nausea-vomiting that has been recently questioned may be explained by alternative mechanisms mediated through the P-6 acupoint stimulation and facial-nasal, cooling-related counterstimulation. © The Author(s) 2013.
Examination of the effectiveness of peppermint aromatherapy on nausea in women post C-section.
Lane, Betty; Cannella, Kathi; Bowen, Cathy; Copelan, David; Nteff, Grace; Barnes, Katrina; Poudevigne, Melanie; Lawson, Jacqueline
2012-06-01
This study examined the effect of peppermint spirits on postoperative nausea in women following a scheduled C-section. A pretest-posttest research design with three groups was used. The peppermint group inhaled peppermint spirits, the placebo aromatherapy control group inhaled an inert placebo, green-colored sterile water, and the standard antiemetic therapy control group received standard antiemetics, usually intravenous ondansetron or promethazine suppositories. Women were randomly assigned to a group on admission to the hospital. If they became nauseated, nurses on the mother-baby unit assessed their nausea (baseline), administered the assigned intervention, and then reassessed participants' nausea 2 and 5 minutes after the initial intervention. Participants rated their nausea using a 6-point nausea scale. Thirty-five participants became nauseated post-operatively. Participants in all three intervention groups had similar levels of nausea at baseline. The nausea levels of participants in the peppermint spirits group were significantly lower than those of participants in the other two groups 2 and 5 minutes after the initial intervention. Peppermint spirits may be a useful adjunct in the treatment of postoperative nausea. This study should be replicated with more participants, using a variety of aromatherapies to treat nausea in participants with different preoperative diagnoses.
Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy.
Smith, Lesley A; Azariah, Fredric; Lavender, Verna T C; Stoner, Nicola S; Bettiol, Silvana
2015-11-12
Cannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs). However, unpleasant adverse effects may limit their widespread use. To evaluate the effectiveness and tolerability of cannabis-based medications for chemotherapy-induced nausea and vomiting in adults with cancer. We identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication. We included randomised controlled trials (RCTs) that compared a cannabis-based medication with either placebo or with a conventional anti-emetic in adults receiving chemotherapy. At least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta-analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI). We included 23 RCTs. Most were of cross-over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti-emetic drugs such as ondansetron. Comparison with placebo People had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence
1979-11-02
patients who are not sensitive tc the effect /action of aminazine. PHARMAGOLOGICAL STUDY. Aethaperazinum - dihydrocdloride of 2-chloro- {[4-(8-hydroxyetnyl...that te new neuroplegic substance has the wide spectrum of activity, similar to the spectrum of the effect /action of aminazina. Page 147. All means of...the aminazine; some DOC = 791 PAGE 3 mans of the peripheral effect /action in aethaperazinus are expressed to a lesser degree. Anti-emetic effect
New Prescriptions for Migraine in the Emergency Department
Lane, Peter L.
1992-01-01
Migraine headache is a common affliction and presenting symptom in the emergency department. Its diagnosis is entirely clinical, and the treating physician should ensure precise diagnosis before commencing therapy. General non-pharmacological measures and oral medications are usually effective in relieving the symptoms. Occasionally, patients with fixed migraines require parenteral therapy. Some medications used for migraine are antiemetic agents, ergot preparations, narcotic agents, phenothiazines (particularly chlorpromazine), and newer selective serotonin agonists. PMID:21221402
Clinical Investigation Program Annual Progress Report.
1983-09-30
Antiemetics (A Phase II Study).(O) ............... 049 79/110 Evaluation of Local Anesthetic Skin Testing and Progressive Challenge in Patients with a History ...Associated with Oat Cell Carcinoma. J Assoc Mil Derm 8, 1982. Grimwood, R.E.: The History and Principles of Immunofluorescence. J Assn Mil Derm 9(1...December, 1981. ""’ PRESENTATIONS: 1.) Kindig, N.B.: D CO correction using PaCO back pressure predicted from venous bloo . Sfresented: Carl E
[Therapeutic use of Cannibis Sativa L. in Arab medicine].
Lozano, I
1997-01-01
Arab scientists were various centuries ahead of our current knowledge of the curative power of hemp (Cannabis sativa L., Cannabaceae). Modern scientific literature ignores their contribution on the subject. We review in this paper the therapeutic uses of the plant in Arabic medicine from the 8th to the 18th century. Arab physicians knew and used its diuretic, anti-emetic, anti-epileptic, anti-inflammatory, pain-killing and antipyretic properties, among others.
Bateman, D Nicholas; Dear, James W; Thanacoody, H K Ruben; Thomas, Simon H L; Eddleston, Michael; Sandilands, Euan A; Coyle, Judy; Cooper, Jamie G; Rodriguez, Aryelly; Butcher, Isabella; Lewis, Steff C; Vliegenthart, A D Bastiaan; Veiraiah, Aravindan; Webb, David J; Gray, Alasdair
2014-02-22
Paracetamol poisoning is common worldwide. It is treated with intravenous acetylcysteine, but the standard regimen is complex and associated with frequent adverse effects related to concentration, which can cause treatment interruption. We aimed to ascertain whether adverse effects could be reduced with either a shorter modified acetylcysteine schedule, antiemetic pretreatment, or both. We undertook a double-blind, randomised factorial study at three UK hospitals, between Sept 6, 2010, and Dec 31, 2012. We randomly allocated patients with acute paracetamol overdose to either the standard intravenous acetylcysteine regimen (duration 20·25 h) or a shorter (12 h) modified protocol, with or without intravenous ondansetron pretreatment (4 mg). Masking was achieved by infusion of 5% dextrose (during acetylcysteine delivery) or saline (for antiemetic pretreatment). Randomisation was done via the internet and included a minimisation procedure by prognostic factors. The primary outcome was absence of vomiting, retching, or need for rescue antiemetic treatment at 2 h. Prespecified secondary outcomes included a greater than 50% increase in alanine aminotransferase activity over the admission value. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov (identifier NCT01050270). Of 222 patients who underwent randomisation, 217 were assessable 2 h after the start of acetylcysteine treatment. Vomiting, retching, or need for rescue antiemetic treatment at 2 h was reported in 39 of 108 patients assigned to the shorter modified protocol compared with 71 of 109 allocated to the standard acetylcysteine regimen (adjusted odds ratio 0·26, 97·5% CI 0·13-0·52; p<0·0001), and in 45 of 109 patients who received ondansetron compared with 65 of 108 allocated placebo (0·41, 0·20-0·80; p=0·003). Severe anaphylactoid reactions were recorded in five patients assigned to the shorter modified acetylcysteine regimen versus 31 who were allocated to the
Tricco, Andrea C; Soobiah, Charlene; Antony, Jesmin; Hemmelgarn, Brenda; Moher, David; Hutton, Brian; Straus, Sharon E
2013-06-28
Serotonin (5-HT3) receptor antagonists are a class of antiemetic medications often used to prevent nausea and vomiting among patients undergoing chemotherapy, radiotherapy or surgery. However, recent studies suggest that these agents might be associated with increased cardiac harm. To examine this further, we are proposing to conduct a systematic review and network meta-analysis on the comparative safety of 5-HT3 receptor antagonists among patients undergoing chemotherapy or surgery. Studies reporting one or more safety outcomes of interest for 5-HT3 receptor antagonists compared with each other, placebo, and/or other anti-emetic agents (for example, benzamides, phenothiazines, butyrophenones, antihistamines, and anticholinergics) among children and adult patients undergoing surgery or chemotherapy will be included. Our primary outcome of interest is arrhythmia. Our secondary outcomes include cardiac death, QT prolongation, PR prolongation, all-cause mortality, nausea, and vomiting. We will include experimental studies, quasi-experimental studies (namely controlled before-after and interrupted time series), and observational studies (namely cohort studies). We will not limit inclusion by publication status, time period, duration of follow-up or language of dissemination.Electronic databases (for example, MEDLINE, EMBASE) will be searched from inception onwards. These main searches will be supplemented by searching for difficult to locate and unpublished studies, such as dissertations, and governmental reports. The eligibility criteria will be pilot-tested and subsequently used to screen the literature search results by two reviewers in duplicate. A similar process will be followed for full-text screening, data abstraction, and risk of bias/methodological quality appraisal. The Cochrane Risk of Bias tool will be used to appraise experimental and quasi-experimental studies, and cohort studies will be assessed using the Newcastle Ottawa Scale. If the data allows
Pre-emptive therapy for severe nausea and vomiting of pregnancy and hyperemesis gravidarum.
Koren, G; Maltepe, Caroline
2004-08-01
Nausea and vomiting of pregnancy (NVP) affects 80% of pregnancies. Its severe form, hyperemesis gravidarum (HG), results in dehydration, electrolyte imbalance, the need for hospitalisation and can, rarely, be fatal. This was a prospective, open-labelled, controlled, interventional study to evaluate the effectiveness of pre-emptive treatment of NVP symptoms in women who experienced severe NVP or HG in their previous pregnancy. Twenty-five women who reported severe symptoms of NVP with or without HG in their previous pregnancy were recruited and counselled to commence the use of antiemetics as soon as they became aware of the present pregnancy, and no later than the beginning of symptoms. They were followed-up prospectively through the index pregnancy for symptoms of NVP, and were counselled continuously as to how to modify antiemetic doses based on symptoms. A comparison group consisted of randomly selected women also counselled by us for NVP, who had also had severe NVP in the previous pregnancy, but who did not call before a planned pregnancy and thus could not be offered pre-emptive therapy. The recruited women commenced pre-emptive drug therapy for NVP before conception or up to 7 weeks' gestation, before the appearance of NVP symptoms in all cases. In comparison to the previous pregnancy, only eight of these 18 women experienced a HG again in the index pregnancy (P = 0.01). The majority of study the women had an improvement in severity of NVP symptoms compared to the previous pregnancy. In the comparison group (n = 35), symptoms in the index pregnancy remained severe in 28 cases (80%), decreased to moderate in six (16.6%) and decreased to mild in five cases (13.9%). There were five cases of HG in the previous pregnancy and three in the index pregnancy. The pre-emptive group was improved significantly compared to the control group (P = 0.01). Pre-emptive symptom management appears to be effective in preventing severe NVP in general, and HG in particular. Women
2014-01-01
Background Craniotomy patients have a high incidence of postoperative nausea and vomiting (PONV). This prospective, randomized, double-blind, multi-center study was performed to evaluate the efficacy of prophylactic ramosetron in preventing PONV compared with ondansetron after elective craniotomy in adult patients. Methods A total of 160 American Society of Anesthesiologists physical status I–II patients aged 19–65 years who were scheduled to undergo elective craniotomy for various intracranial lesions were enrolled in this study. All patients received total intravenous anesthesia (TIVA) with propofol and remifentanil. Patients were randomly allocated into three groups to receive ondansetron (4 mg; group A, n = 55), ondansetron (8 mg; group B, n = 54), or ramosetron (0.3 mg; group C, n = 51) intravenously at the time of dural closure. The incidence of PONV, the need for rescue antiemetics, pain score, patient-controlled analgesia (PCA) consumption, and adverse events were recorded 48 h postoperatively. Results Among the initial 160 patients, 127 completed the study and were included in the final analysis. The incidences of PONV were lower (nausea, 14% vs. 59% and 41%, respectively; P < 0.001; vomiting, P = 0.048) and the incidence of complete response was higher (83% vs. 37% and 59%, respectively; P < 0.001) in group C than in groups A and B at 48 h postoperatively. There were no significant differences in the incidence of PONV or need for rescue antiemetics 0–2 h postoperatively, but significant differences were observed in the incidence of PONV and complete response among the three groups 2–48 h postoperatively. No statistically significant intergroup differences were observed in postoperative pain, PCA consumption, or adverse events. Conclusion Intravenous administration of ramosetron at 0.3 mg reduced the incidence of PONV and rescue antiemetic requirement in craniotomy patients
George, Ronald B; Allen, Terrence K; Habib, Ashraf S
2009-07-01
We performed a systematic review to determine the overall efficacy of serotonin (5-HT3) receptor antagonists for the prevention and treatment of pruritus, nausea, and vomiting in women receiving spinal anesthesia with intrathecal morphine for cesarean delivery. Reports of randomized, controlled trials that compared prophylaxis or treatment of pruritus and/or nausea, and vomiting using one of the 5-HT3 receptor antagonists or placebo in women undergoing cesarean delivery were reviewed. The articles were scored for validity and data were extracted by the authors independently and summarized using relative risks (RR) with 95% confidence intervals (CI). Nine randomized, controlled trials were included in the systematic review. The nine trials had a total of 1152 patients enrolled; 539 received 5-HT3 receptor antagonists, 413 received placebo, and 200 received other antiemetics and were not included in the analysis. The incidence of pruritus was not reduced with 5-HT3 receptor antagonists prophylaxis compared with placebo (80.7% vs 85.8%, RR [95% CI] = 0.94 [0.81-1.09]). However, their use reduced the incidence of severe pruritus and the need for treatment of pruritus (number-needed-to-treat = 12 and 15, respectively). Their use for the treatment of established pruritus showed improved efficacy compared with placebo with a number-needed-to-treat of three. There was a significant reduction in the incidence of postoperative nausea (22.0% vs 33.6%, RR [95% CI] = 0.75[0.58-0.96]) and vomiting (7.7% vs 16.8%, RR [95% CI] = 0.49 [0.30-0.81]), and the need for postoperative rescue antiemetic treatment with the use of 5-HT(3) receptor antagonists when compared with placebo (9% vs 23%, RR [95% CI] = 0.38 [0.21-0.68]). Although prophylactic 5-HT(3) receptor antagonists were ineffective in reducing the incidence of pruritus, they significantly reduced the severity and the need for treatment of pruritus, the incidence of postoperative nausea and vomiting, and the need for rescue
Gastroenteritis Therapies in Developed Countries: Systematic Review and Meta-Analysis
Freedman, Stephen B.; Pasichnyk, Dion; Black, Karen J. L.; Fitzpatrick, Eleanor; Gouin, Serge; Milne, Andrea; Hartling, Lisa
2015-01-01
Context Gastroenteritis remains a leading cause of childhood morbidity. Objective Because prior reviews have focused on isolated symptoms and studies conducted in developing countries, this study focused on interventions commonly considered for use in developed countries. Intervention specific, patient-centered outcomes were selected. Data Sources MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, trial registries, grey literature, and scientific meetings. Study Selection Randomized controlled trials, conducted in developed countries, of children aged <18 years, with gastroenteritis, performed in emergency department or outpatient settings which evaluated oral rehydration therapy (ORT), antiemetics, probiotics or intravenous fluid administration rate. Data Extraction The study was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Data were independently extracted by multiple investigators. Analyses employed random effects models. Results 31 trials (4,444 patients) were included. ORT: Compared with intravenous rehydration, hospitalization (RR 0.80, 95%CI 0.24, 2.71) and emergency department return visits (RR 0.86, 95%CI 0.39, 1.89) were similar. Antiemetics: Fewer children administered an antiemetic required intravenous rehydration (RR 0.40, 95%CI 0.26, 0.60) While the data could not be meta-analyzed, three studies reported that ondansetron administration does increase the frequency of diarrhea. Probiotics: No studies reported on the primary outcome, three studies evaluated hospitalization within 7 days (RR 0.87, 95%CI 0.25, 2.98). Rehydration: No difference in length of stay was identified for rapid vs. standard intravenous or nasogastric rehydration. A single study found that 5% dextrose in normal saline reduced hospitalizations compared with normal saline alone (RR 0.70, 95% CI 0.53, 0.92). Conclusions There is a paucity of patient-centered outcome evidence to support many
Postdural puncture headache: a study with 256 Quincke needle.
Singh, N Ratan; Singh, H Shanti
2010-02-01
The incidence of postdural puncture headache, its severity, time of onset and duration following spinal anaesthesia in female subjects using 25 gauge Quincke needles are discussed in this paper. Postdural puncture headache was seen in only 3% of the cases. The headache appeared mainly on the 1st postoperative day and was associated with nausea and vomiting in one case; and it disappeared by the 2nd to 3rd day following administration of mild analgesics and anti-emetics.
Acute and anticipatory emesis in breast cancer patients.
Fernández-Marcos, A; Martín, M; Sanchez, J J; Rodriguez-Lescure, A; Casado, A; López Martin, J A; Diaz-Rubio, E
1996-09-01
A group of 90 breast cancer patients undergoing chemotherapy were assessed prospectively to estimate the prevalence of acute (post-treatment) and anticipatory emesis in the 1990s. For this purpose, two protocols of chemotherapy were analysed separately: cyclophosphamide/methotrexate/5-fluorouracil (CMF) and 5-fluorouracil/doxorubicin/cyclophosphamide (FAC). All patients were treated with antiemetic therapy, which included one corticoid plus ondansetron (in the FAC regimen), or one corticoid plus thiethylperazine (in the CMF regimen). For at least one cycle of chemotherapy 86.1% and 91.7% patients in the FAC protocol presented vomiting and nausea respectively: 11.1% had anticipatory vomiting and 30.6% had anticipatory nausea. In the CMF protocol, 79.6% had post-chemotherapy vomiting and 71.7% had post-chemotherapy nausea associated with at least one cycle. In this group, 7.4% had anticipatory vomiting and 16.6% had anticipatory nausea. A high proportion of patients suffered anticipatory anxiety in both groups (75% in FAC, 74.1% in CMF). The stimuli most frequently associated with the appearance of anticipatory emesis were olfactory stimuli and cognitive stimuli. In summary, as a result of the advances made in antiemetic control during the last decade, the severity of chemotherapy-induced emesis seems to have significantly decreased, but the prevalence of these symptoms along the course of the treatment still remains high.
Chen, Bo; Hu, Shu-xiang; Liu, Bao-hu; Zhao, Tian-yi; Li, Bo; Liu, Yan; Li, Ming-yue; Pan, Xing-fang; Guo, Yong-ming; Chen, Ze-lin; Guo, Yi
2015-05-12
Many patients experience nausea and vomiting during chemotherapy treatment. Evidence demonstrates that electroacupuncture is beneficial for controlling chemotherapy-induced nausea and vomiting (CINV). However, the acupoint or matching acupoint with the best efficacy for controlling CINV still remains unidentified. This study consists of a randomized controlled trial (RCT) with four parallel arms: a control group and three electroacupuncture groups (one with Neiguan (PC6), one with Zhongwan (CV12), and one with both PC6 and CV12). The control group received standard antiemetic only, while the other three groups received electroacupuncture stimulation with different acupoints besides the standard antiemetic. The intervention is done once daily from the first day (day 1) to the fourth day (day 4) during chemotherapy treatment. The primary outcome measures include frequency of nausea, vomiting and retching. The secondary outcome measures are the grade of constipation and diarrhea, electrogastrogram, assessment of quality of life, assessment of anxiety and depression, and other adverse effects during the chemotherapy. Assessments are scheduled from one day pre-chemotherapy (day 0) to the fifth day of chemotherapy (day 5). Follow-ups are done from day 6 to day 21. The aim of this study is to evaluate the efficacy and safety of electro-acupuncture with different acupoints in the management of CINV. The register number of randomized controlled trial is NCT02195908 . The date of registration was 21 July 2014.
Lee, Won-Suk; Lee, Kwang-Beom; Lim, Soyi; Chang, Young Gin
2015-09-03
Selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are reported to have potent antiemetic effects for postoperative nausea and vomiting (PONV). The purpose of this study was to prospectively evaluate the efficacy of palonosetron, granisetron, and ramosetron for the prevention of PONV in patients undergoing laparoscopic gynecologic surgery. In this prospective, randomized observational study, 105 healthy female patients who were undergoing laparocopic hystectomy under general anaesthesia were enrolled (clinical trial number: NCT01752374, www.clinicaltrials.gov ). Patients were divided into three groups: the palonostron (0.075 mg i.v.; n = 35), the granisetron group (3 mg i.v.; n = 35), and the ramosetron group (0.3 mg i.v.; n = 35). The treatments were given before the end of surgery. The incidence of PONV, severity of nausea/vomiting, and the use of rescue antiemetic requirements during the first 48 h after surgery were evaluated. The overall incidence of PONV was 33.3 % for this series. The number of complete responders at 48 h after the surgery was 21 (60.0 %) for palonosetron, 24 (68.6 %) for granisetron, and 26 (71.4 %) for ramosetron, representing no statistical difference (P = 0.086). There were no significant differences in the overall incidence of postoperative nausea and vomiting and complete responders for palonosetron, granisetron and ramosetron group. NCT01752374 , www.clinicaltrials.gov .
Myotoku, Michiaki; Nakanishi, Akiko; Kanematsu, Miwa; Sakaguchi, Noriko; Hashimoto, Norio; Koyama, Fumiko; Yamaguchi, Seiji; Ikeda, Kenji; Konishi, Hiroki; Hirotani, Yoshihiko
2010-04-01
In February 2002, the palliative care team was established in Ikeda Municipal Hospital to improve palliative care. We investigated changes in the incidences of side effects related to opioids, and evaluated palliative care team activities. Regarding inpatients for whom narcotics were prescribed in our hospital in the years of 2002 (from October 1, 2002 until September 30, 2003), 2004 (from October 1, 2004 until September 30, 2005), and 2006 (from October 1, 2006 until September 30, 2007), we surveyed the rates at which laxatives or antiemetics were prescribed, frequency of defecation/its state before and after the start of narcotic therapy, frequency of nausea/vomiting, and dietary intake. The proportions of patients in whom laxatives were simultaneously prescribed during opioid therapy in 2002, 2004, and 2006 were 43.5%, 78.7%, and 75.6%, respectively. The proportions of those in whom antiemetics were combined with opioids were 45.7%, 78.7%, and 78.0%, respectively. The incidences of constipation were 50.0%, 39.3%, and 37.8%, respectively. Those of nausea/vomiting were 30.4%, 21.3%, and 9.8%, respectively. Those of anorexia were 65.3%, 39.4%, and 15.4%, respectively. These results suggest that palliative care team activities facilitated appropriate drug prescription during opioid therapy, reducing the appearance of side effects, with likelihood of improved quality of life.
Use of Gelatin Sponge Affects Postoperative Morbidity In Cesarean Section Patients.
Özer, Alev; Köstü, Bülent
2017-03-04
BACKGROUND This study aimed to determine the effects of use of a local hemostatic gelatin sponge (GS) on postoperative morbidity in patients undergoing cesarean section (CS). MATERIAL AND METHODS The records of 318 patients who underwent CS surgery were retrospectively evaluated. Group 1 consisted of 59 patients with gelatin sponge (GS) applied, and Group 2 consisted of 259 patients with no GS applied. The groups were compared for time to the first flatus, nausea and vomiting, requirement for anti-emetic drugs, development of postoperative ileus, and the length of hospitalization. RESULTS The patients in Group 1 and Group 2 were statistically similar in mean age, gravida, parity, and body mass index (BMI) (p=0.352, p=0.275, p=0.458, and p=0.814, respectively). No significant difference was determined in the number of patients with nausea, vomiting, anti-emetic drug use, febrile morbidity, and postoperative ileus (p=0.063, p=0.436, p=328, p=0.632, and p=0.179, respectively). Time to the first flatus and length of hospitalization were significantly longer in Group 2 (p<0.001 and p<0.001, respectively). CONCLUSIONS Delay in recovery of bowel motility may be due to the local hypersensitivity reaction caused by GS and/or dislocation of this local hemostat. Women who receive gelatin sponge treatment during CS should be monitored closely for the recovery of postoperative intestinal motility.
Fosaprepitant-induced Phlebitis: A Focus on Patients receiving Doxorubicin/Cyclophosphamide therapy
Leal, A. D.; Kadakia, K. C.; Looker, S.; Hilger, C.; Sorgatz, K.; Anderson, K.; Jacobson, A.; Grendahl, D.; Seisler, D.; Hobday, T.; Loprinzi, C. L.
2014-01-01
Purpose The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy. Methods A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given. Results Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7% (n=34), while the incidence of aprepitant-associated ISAEs was 2.3% (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were: infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5) and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE. Conclusions The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy is significant and appreciably higher than what has been previously reported. PMID:24402411
Postoperative nausea and vomiting (PONV) in outpatient repair of inguinal hernia.
Palumbo, Piergaspare; Usai, Sofia; Amatucci, Chiara; Pulli, Valentina Taurisano; Illuminati, Giulio; Vietri, Francesco; Tellan, Guglielmo
2018-01-01
Nausea and vomiting are among the most frequent complications following anesthesia and surgery. Due to anesthesia seems to be primarily responsible for post operative nausea and vomiting (PONV) in Day Surgery facilities, the aim of the study is to evaluate how different methods of anesthesia could modify the onset of postoperative nausea and vomiting in a population of patients undergoing inguinal hernia repair. Ninehundredten patients, aged between 18 and 87 years, underwent open inguinal hernia repair. The PONV risk has been assessed according to Apfel Score. Local anesthetic infiltration, performed by the surgeon in any cases, has been supported by and analgo-sedation with Remifentanil in 740 patients; Fentanyl was used in 96 cases and the last 74 underwent deep sedation with Propofol . Among the 910 patients who underwent inguinal hernia repair, PONV occurred in 68 patients (7.5%). Among patients presenting PONV, 29 received Remifentanil, whereas 39 received Fentanyl. In the group of patients receiving Propofol, no one presented PONV. This difference is statistically significant (p < .01). Moreover, only 50 patients of the total sample received antiemetic prophylaxis, and amongst these, PONV occurred in 3 subjects. Compared to Remifentanil, Fentanyl has a major influence in causing PONV. Nonetheless, an appropriate antiemetic prophylaxis can significantly reduce this undesirable complication. Key words: Day Surgery, Fentanyl, Inguinal, Hernia repair, Nausea, Vomiting.
Effect of Acupressure on Nausea-Vomiting in Patients With Acute Myeloblastic Leukemia.
Avc, Hatice Sevil; Ovayolu, Nimet; Ovayolu, Özlem
2016-01-01
The aim of this study was to assess the effect of acupressure, applied at P6 (Neiguan) acupuncture point, on chemotherapy-induced nausea and vomiting in patients with acute myeloblastic leukemia. This was a randomized controlled trial conducted on patients with myeloblastic leukemia. A total of 90 patients, who received the same chemotherapy regimen and antiemetic therapy, were included in the study as 30 patients in the control group, 30 patients in the band group, and 30 patients in the pressure group. Although acupressure was applied by placing wristbands at P6 acupuncture point of both wrists in patients of the band group for totally 4 days, acupressure was applied with the use of finger pressure in patients of the pressure group for totally 4 days. No intervention was made in patients of the control group other than the routine antiemetic therapy. The data of the study were collected by using a questionnaire and nausea-vomiting chart. Severity of nausea-vomiting was assessed by using the visual analog scale on this chart. It was determined that the acupressure band applied to the patients included in the study reduced number and severity of nausea-vomiting (P < .05); however, the acupressure applied with pressure did not affect number and severity of nausea-vomiting (P > .05). It was found that the acupressure band was effective for reducing the chemotherapy-induced nausea and vomiting.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Horiot, Jean-Claude
Nausea and vomiting are two of the most distressing side effects of radiotherapy and cytotoxic drugs, which currently are often combined to treat moderately advanced and advanced solid tumors. Inadequate control of these symptoms may result in significant patient suffering and decrease in the patient's quality of life, which has been shown to decrease patients' compliance to treatment, with potential impact on disease outcome. It is, therefore, important that radiation oncologists recognize the need for adequate prophylactic treatment of radiation-induced nausea and vomiting (RINV) to avoid the detrimental effects on patients' quality of life, and optimize chances for cure. Themore » 5-hydroxytryptamine type 3 (5-HT{sub 3})-receptor antagonists have been proved to provide effective antiemetic therapy in patients undergoing highly emetogenic radiotherapy. Nevertheless, several large surveys have shown that optimal treatments are not always used. Hence, a risk exists that waiting for RINV symptoms rather than prescribing prophylactic antiemetic treatment may lead to increased patient suffering, poorer disease control, and less cost-effective therapy options. Prophylactic management with an effective 5-HT{sub 3}-receptor antagonist should offer a better treatment option for patients at high to moderate risk of RINV. Adequate control of RINV should contribute to patient compliance to treatment, improved therapy outcomes, and decreased burdens on nursing and health care resources.« less
Marijuana to prevent nausea and vomiting in cancer patients: a survey of clinical oncologists.
Schwartz, R H; Voth, E A; Sheridan, M J
1997-02-01
Marijuana, if rescheduled by the Drug Enforcement Agency, would be the only Food and Drug Administration (FDA)-approved drug to be administered by smoking. American physicians need timely, factual information about probable usage patterns and potential adverse effects of medical marijuana, and a factual complete review of the literature on the subject. We mailed a survey to 1,500 American clinical oncologists. Of particular interest was whether and how often in the past 24 months these physicians recommended smoked marijuana, synthetic tetrahydrocannabinol, or 5-HT3 (serotonin) antagonists (ondansetron [Zofran], granisetron [Kytril]) for their patients. We also inquired whether and how often the oncologists would prescribe marijuana in the form of cigarettes, were it to be FDA-approved. Completed surveys were received from 1,122 (75%) of the oncologists. The percentages of oncologists who prescribed or recommended selected antiemetics more than five times between 1992 and 1994 were 98% for 5-HT, antagonists, 6% for dronabinol (Marinol), and 1% for smoked marijuana. We also found that 332 (30%) of the oncologist-respondents to this nationwide survey supported rescheduling of marijuana for medical purposes; however, two thirds (67%) of the 332 respondents who were in favor of rescheduling estimated that they would write less than one prescription per month for marijuana cigarettes. A comprehensive literature review failed to provide persuasive evidence to recommend marijuana as a needed antiemetic medicine.
NASA Technical Reports Server (NTRS)
Kohl, Randall Lee
1987-01-01
Orally administered metoclopramide (REGLAN) at doses of 10 or 20 mg, 75 min prior to either stressful linear acceleration (parabolic flight) or cross-coupled accelerative semicircular canal stimulation in a rotating chair was evaluated for its ability to prevent emesis or nausea II, respectively. Although metoclopramide is an effective antiemetic agent that enhances gastric emptying and prevents cancer chemotherapy-induced emesis, it was not possible to demonstrate any significant (p less than 0.05) effects of this drug on motion sickness.
Nickel-Catalyzed Phosphine Free Direct N-Alkylation of Amides with Alcohols.
Das, Jagadish; Banerjee, Debasis
2018-03-16
Herein, we developed an operational simple, practical, and selective Ni-catalyzed synthesis of secondary amides. Application of renewable alcohols, earth-abundant and nonprecious nickel catalyst facilitates the transformations, releasing water as byproduct. The catalytic system is tolerant to a variety of functional groups including nitrile, allylic ether, and alkene and could be extended to the synthesis of bis-amide, antiemetic drug Tigan, and dopamine D2 receptor antagonist Itopride. Preliminary mechanistic studies revealed the participation of a benzylic C-H bond in the rate-determining step.
Craver, Chris; Gayle, Julie; Balu, Sanjeev; Buchner, Deborah
2011-01-01
This study evaluated the rate of uncontrolled chemotherapy-induced nausea and vomiting (CINV) after initiating antiemetic prophylaxis with palonosetron versus other 5-HT₃ receptor antagonists (RAs) in patients diagnosed with hematologic malignancies (lymphoma and leukemia) and receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) in a hospital outpatient setting. Patients aged ≥ 18 years and diagnosed with hematologic malignancies initiating HEC or MEC and antiemetic prophylaxis with palonosetron (Group 1) and other 5-HT₃ RAs (Group 2) for the first time in a hospital outpatient setting between 4/1/2007 and 3/31/2009 were identified from the Premier Perspective Database. Within each cycle, CINV events were identified (in the hospital outpatient, inpatient, and emergency room settings) through ICD-9 codes for nausea, vomiting, and/or volume depletion (from each CT administration day 1 until the end of the CT cycle), or use of rescue medications (day 2 until the end of the CT cycle). Negative binomial distribution generalized linear multivariate regression model estimating the CINV event rate on CT, specific CT cycles, and cancer diagnosis (leukemia/lymphoma)-matched groups in the follow-up period (first of 8 cycles or 6 months) was developed. Of 971 identified patients, 211 initiated palonosetron (Group 1). Group 1 patients comprised of more females [50.2 vs. 41.4%; p = 0.0226], Whites [74.4 vs. 70.4%, and Hispanics [7.6 vs. 6.3%; all races p = 0.0105], received more HEC treatments [89.6 vs. 84.2%; all CT types p = 0.0129], and had more lymphoma diagnosed patients [89.6 vs. 76.3%; all cancer types p = 0.0033] at baseline. After controlling for differences in several demographic and clinical variables, the regression model predicted a 20.4% decrease in CINV event rate per CT cycle for Group 1 versus Group 2 patients. Study limitations include potential lack of generalizability, absence of data on certain
Leal, Alexis D.; Grendahl, Darryl C.; Seisler, Drew K.; Sorgatz, Kristine M.; Anderson, Kari J.; Hilger, Crystal R.; Loprinzi, Charles L.
2015-01-01
Purpose Fosaprepitant is an antiemetic used for chemotherapy-induced nausea and vomiting. We recently reported increased infusion site adverse events (ISAE) in a cohort of breast cancer patients receiving chemotherapy with doxorubicin and cyclophosphamide (AC). In this current study, we evaluated the venous toxicity of fosaprepitant use with non-anthracycline platinum-based antineoplastic regimens. Methods A retrospective review was conducted of the first 81 patients initiated on fosaprepitant among patients receiving highly emetogenic chemotherapy, on or after January 1, 2011 at Mayo Clinic Rochester. None of these regimens included an anthracycline. Data collected included baseline demographics, chemotherapy regimen, type of intravenous access and type, and severity of ISAE. Data from these patients were compared to previously collected data from patients who had received AC. Statistical analysis using χ2 and univariate logistic regression was used to evaluate the association between treatment regimen, fosaprepitant, and risk of ISAE. Results Among these 81 patients, the incidence of ISAE was 7.4 % in the non-anthracycline platinum group. The most commonly reported ISAE were swelling (3 %), extravasation (3 %), and phlebitis (3 %). When stratified by regimen, fosaprepitant was associated with a statistically significant increased risk of ISAE in the anthracycline group (OR 8.1; 95 % CI 2.0–31.9) compared to the platinum group. Conclusions Fosaprepitant antiemetic therapy causes significant ISAE that are appreciably higher than previous reports. Patients receiving platinum-based chemotherapy appear to have less significant ISAE than do patients who receive anthracycline-based regimens. PMID:24964876
Koyuncu, Onur; Turhanoglu, Selim; Ozbakis Akkurt, Cagla; Karcıoglu, Murat; Ozkan, Mustafa; Ozer, Cahit; Sessler, Daniel I; Turan, Alparslan
2015-02-01
To determine whether the new selective binding agent sugammadex causes less postoperative nausea and vomiting (PONV) than the cholinesterase inhibitor neostigmine. Prospective, randomized, double-blinded study. University-affiliated hospital. One hundred American Society of Anesthesiologists physical status 1 and 2 patients scheduled for extremity surgery. Patients were randomly assigned to neostigmine (70 μg/kg) and atropine (0.4 mg per mg neostigmine) or sugammadex 2 mg/kg for neuromuscular antagonism at the end of anesthesia, when 4 twitches in response to train-of-four stimulation were visible with fade. We recorded PONV, recovery parameters, antiemetic consumption, and side effects. Nausea and vomiting scores were lower in the sugammadex patients upon arrival in the postanesthesia care unit (med: 0 [min-max, 0-3] vs med: 0 [min-max, 0-3]; P < .05), but thereafter low and comparable. Postoperative antiemetic and analgesic consumption were similar in each group. Extubation (median [interquartile range], 3 [1-3.25] vs 4 [1-3.25]; P < .001) first eye opening (4 [3-7.25] vs 7 [5-11]; P < .001), and head lift (4 [2-7.25] vs 8 [11-25]; P < .001) in minutes were shorter in patients given sugammadex. Postoperative heart rates were significantly lower in all measured times patients given neostigmine. Nondepolarizing neuromuscular blocking antagonism with sugammadex speeds recovery of neuromuscular strength but only slightly and transiently reduces PONV compared with neostigmine and atropine. Copyright © 2014 Elsevier Inc. All rights reserved.
Comparison of the effects of sugammadex and neostigmine on postoperative nausea and vomiting.
Yağan, Özgür; Taş, Nilay; Mutlu, Tuğçe; Hancı, Volkan
The aim of our study is to compare the effects of sugammadex and neostigmine, used for neuromuscular blockage antagonism, on postoperative nausea and vomiting (PONV). Our study was completed with 98 ASA I-II risk patients undergoing endotracheal intubation under general anesthesia. At the end of the surgery patients were randomly divided into two groups given 2mgkg -1 sugammadex (Group S) or 50μgkg -1 neostigmine plus 0.2mgkg -1 atropine (Group N). Monitoring and recording times were set as 1 hour postoperative and from 1-6, 6-12, and 12-24hours. The anti-emetic amounts administered were recorded. In the first hour postoperative 13 patients in Group N (27%) and 4 in Group S (8%) were observed to have nausea and/or vomiting and the difference was statistically significant (p=0.0016). During the 24 hours of monitoring there was no significant difference in the incidence and severity of PONV (p>0.05), however the number of patients given ondansetron for PONV treatment in Group N was statistically significantly higher than the number in Group S (16 in Group N, 6 in Group S, p<0.011). At the end of our study comparing neostigmine with sugammadex for neuromuscular blockage antagonism, we found use of sugammadex had lower incidence of PONV in the postoperative 1st hour and less anti-emetic use in 24 hours of monitoring. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.
Ullah, Ihsan; Subhan, Fazal; Lu, Zengbing; Chan, Sze Wa; Rudd, John A
2017-04-01
Bacopa monnieri (BM, family Scrophulariaceae) is used in several traditional systems of medicine for the management of epilepsy, depression, neuropathic pain, sleep disorders and memory deficits. The present study investigated the potential of BM methanol (BM-MetFr) and BM n-butanol fractions (BM-ButFr) to reduce chemotherapy-induced emesis in Suncus murinus (house musk shrew). Cisplatin (30 mg/kg, i.p.) reliably induced retching and/or vomiting over a 2 day period. BM-MetFr (10-40 mg/kg, s.c.) and BM-ButFr (5-20 mg/kg, s.c.) antagonized the retching and/or vomiting response by ∼59.4% (p < 0.05) and 78.9% (p < 0.05), respectively, while the 5-HT 3 receptor antagonist, palonosetron (0.5 mg/kg, s.c.), reduced the response by ∼71% (p < 0.05). The free radical scavenger/antioxidant, N-(2-mercaptopropionyl)-glycine (30-300 mg/kg, s.c.) reduced the retching and/or vomiting response occurring on day one non-significantly by 44% (p > 0.05). In conclusion, the n-butanol fractions of BM have anti-emetic activity comparable with palonosetron and MPG. BM may be useful alone or in combination with other anti-emetic drugs for the treatment of chemotherapy-induced emesis in man. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
Formulation and evaluation of bilayer tablets of metoclopramide hydrochloride and diclofenac sodium.
Gattani, Surendra G; Khabiya, Sohan S; Amrutkar, Jitendra R; Kushare, Sachin S
2012-01-01
The main objective of the present research work was to develop a bilayer tablet of metoclopramide hydrochloride (MTH) and diclofenac sodium (DS) in separate layers to avoid incompatibility and thus to maximize the efficacy of both drugs in combination for the effective treatment of migraine headaches. MTH and DS were formulated as immediate and sustained release layers respectively. In vitro dissolution kinetic studies of an optimized (D10) batch of DS in both sustained release layer and bilayer tablet forms show good linearity of regression coefficient 0.9773 (first order equation). The results reveal that an optimized immediate release layer (M5) of MTH and a sustained release layer (D10) of DS might be suitable for the treatment of migraine by sequential release of the two drugs in a bilayer tablet. Migraine is a type of recurring headache of moderate to severe intensity associated with gastrointestinal, neurological, and autonomic symptoms. In migraine, a combination of pretreatment with antiemetics is required for symptomatic treatment, when nausea and vomiting are severe. In our present research, we have selected the metoclopramide hydrochloride (MTH) active ingredient for study because it has an antiemetic effect and is a prokinetic agent. MTH is more effective to counteract gastric stasis associated with migraine, and it enhances the rate of absorption of non-steroidal anti-inflammatory drugs (NSAIDs). In the present investigation we combine MTH and a second active ingredient, diclofenac sodium, as a formulated bilayer tablet to prevent degradation of MTH.
Kim, M-H; Hwang, J-W; Jeon, Y-T; Do, S-H
2012-09-01
Many anti-epileptics cause resistance to non-depolarizing neuromuscular blocking agents, but this has not been reported for valproic acid (VPA). We hypothesized that VPA would increase the rocuronium requirement and that magnesium sulphate (MgSO(4)) may reduce this increase. Fifty-five patients undergoing cerebrovascular surgeries were studied. Subjects were allocated into three groups at a 1:1:1 ratio: Groups VM, VC, and C. Groups VM and VC were given VPA premedication; Group C was not. A rocuronium injection (0.6 mg kg(-1) i.v.) was administered to Group VM, followed by MgSO(4) as a 50 mg kg(-1) i.v. bolus and 15 mg kg(-1) h(-1) infusion. The same volume of 0.9% saline was administered to the other groups. Supplementary rocuronium (0.15 mg kg(-1)) was given whenever the train-of-four count reached 2. Rocuronium requirements (primary outcome), mean arterial pressure (MAP), heart rate (HR), nausea, vomiting, shivering, and use of anti-emetics and nicardipine were compared. Group VC showed the highest rocuronium requirement [mg kg(-1) h(-1): 0.47 (0.08) vs 0.33 (0.12) (Group C), 0.31 (0.07) (Group VM); P<0.001]. MAP, intraoperative HR, nausea, vomiting, shivering, and use of anti-emetics and nicardipine were not significantly different among the groups. Postoperative HR was lower in Group VM than in Group VC. VPA increased the rocuronium requirement, and MgSO(4) infusion attenuated this increase.
Cannabinoids for Symptom Management and Cancer Therapy: The Evidence.
Davis, Mellar P
2016-07-01
Cannabinoids bind not only to classical receptors (CB1 and CB2) but also to certain orphan receptors (GPR55 and GPR119), ion channels (transient receptor potential vanilloid), and peroxisome proliferator-activated receptors. Cannabinoids are known to modulate a multitude of monoamine receptors. Structurally, there are 3 groups of cannabinoids. Multiple studies, most of which are of moderate to low quality, demonstrate that tetrahydrocannabinol (THC) and oromucosal cannabinoid combinations of THC and cannabidiol (CBD) modestly reduce cancer pain. Dronabinol and nabilone are better antiemetics for chemotherapy-induced nausea and vomiting (CINV) than certain neuroleptics, but are not better than serotonin receptor antagonists in reducing delayed emesis, and cannabinoids have largely been superseded by neurokinin-1 receptor antagonists and olanzapine; both cannabinoids have been recommended for breakthrough nausea and vomiting among other antiemetics. Dronabinol is ineffective in ameliorating cancer anorexia but does improve associated cancer-related dysgeusia. Multiple cancers express cannabinoid receptors directly related to the degree of anaplasia and grade of tumor. Preclinical in vitro and in vivo studies suggest that cannabinoids may have anticancer activity. Paradoxically, cannabinoid receptor antagonists also have antitumor activity. There are few randomized smoked or vaporized cannabis trials in cancer on which to judge the benefits of these forms of cannabinoids on symptoms and the clinical course of cancer. Smoked cannabis has been found to contain Aspergillosis. Immunosuppressed patients should be advised of the risks of using "medical marijuana" in this regard. Copyright © 2016 by the National Comprehensive Cancer Network.
Medicinal cannabis: rational guidelines for dosing.
Carter, Gregory T; Weydt, Patrick; Kyashna-Tocha, Muraco; Abrams, Donald I
2004-05-01
The medicinal value of cannabis (marijuana) is well documented in the medical literature. Cannabinoids, the active ingredients in cannabis, have many distinct pharmacological properties. These include analgesic, anti-emetic, anti-oxidative, neuroprotective and anti-inflammatory activity, as well as modulation of glial cells and tumor growth regulation. Concurrent with all these advances in the understanding of the physiological and pharmacological mechanisms of cannabis, there is a strong need for developing rational guidelines for dosing. This paper will review the known chemistry and pharmacology of cannabis and, on that basis, discuss rational guidelines for dosing.
2002-07-01
and T877A intermediary products in the biosynthesis of aldosterone (27). The mutant AR’ production of DOG is up-regulated in a number of disease states...therapy 0O- DOG and as an antiemetic in patients undergoing chemotherapy and/or0.05 ’ -6- Dex o 0.04 -X-OH-F radiation therapy. Our results show that Dex...nonandrogenic activa- therapy; (b) the use of high-dose ketoconazole as second-line hormo- tors of the AR/T877A mutant, an AR mutant frequently found to
Solution behavior of metoclopramide in aqueous-alcoholic solutions at 30°C
NASA Astrophysics Data System (ADS)
Deosarkar, S. D.; Sawale, R. T.; Tawde, P. D.; Kalyankar, T. M.
2016-07-01
Densities (ρ) and refractive indices ( n D) of solutions of antiemetic drug metoclopramide (4-amino-5-chloro- N-(2-(diethylamino)ethyl)-2-methoxybenzamide hydrochloride hydrate) in methanolwater and ethanol-water mixtures of different compositions were measured at 30°C. Apparent molar volume (φv) of the drug was calculated from density data and partial molar volumes (φ v 0 ) were determined from Massons relation. Concentration dependence of nD has been studied to determine refractive indices of solution at infinite dilution ( n D 0 ). Results have been interpreted in terms of solute-solvent interactions.
Astanehe, Arezoo; Temple-Oberle, Claire; Nielsen, Markus; de Haas, William; Lindsay, Robert; Matthews, Jennifer; McKenzie, David C; Yeung, Justin
2018-01-01
Background: The aim of this study was to develop, implement, and evaluate a standardized perioperative enhanced recovery after surgery (ERAS) clinical care pathway in microsurgical abdominal-based breast reconstruction. Methods: Development of a clinical care pathway was informed by the latest ERAS guideline for breast reconstruction. Key features included shortened preoperative fasting, judicious fluids, multimodal analgesics, early oral nutrition, early Foley catheter removal, and early ambulation. There were 3 groups of women in this cohort study: (1) traditional historical control; (2) transition group with partial implementation; and (3) ERAS. Narcotic use, patient-reported pain scores, antiemetic use, time to regular diet, time to first walk, hospital length of stay, and 30-day postoperative complications were compared between the groups. Results: After implementation of the pathway, the use of parenteral narcotics was reduced by 88% (traditional, 112 mg; transition, 58 mg; ERAS, 13 mg; P < 0.0001), with no consequent increase in patient-reported pain. Patients in the ERAS cohort used less antiemetics (7.0, 5.3, 2.2 doses, P < 0.0001), returned to normal diet 19 hours earlier (46, 39, 27 hours, P < 0.0001), and walked 25 hours sooner (75, 70, 50 hours, P < 0.0001). Overall, hospital length of stay was reduced by 2 days in the ERAS cohort (6.6, 5.6, 4.8 days, P < 0.0001), without an increase in rates of major complications (9.5%, 10.1%, 8.3%, P = 0.9). Conclusions: A clinical care pathway in microsurgical breast reconstruction using the ERAS Society guideline promotes successful early recovery. PMID:29464164
Tan, Terry T; Teoh, Wendy H L; Woo, David C M; Ocampo, Cecilia E; Shah, Mukesh K; Sia, Alex T H
2012-02-01
Previous studies examining the efficacy of transversus abdominis plane block after caesarean section have mostly been in parturients under spinal anaesthesia. We postulated that the advantage of performing transversus abdominis plane block after caesarean section might be even more obvious after general anaesthesia, resulting in reduced 24-h consumption of morphine. DESIGN, SETTING, PATIENTS AND INTERVENTIONS: In this single centre, randomised double-blind controlled trial, 40 women who underwent caesarean delivery under general anaesthesia were allocated randomly to receive a transversus abdominis plane block or no block. In those who received the block, 20 ml of levobupivacaine 2.5 mg ml was deposited bilaterally into the transversus abdominis plane under ultrasound guidance using a Sonosite Titan (SonoSite, Bothell, Washington, USA) 7-13 MHz linear transducer at the end of surgery when the patient was still anaesthetised. We recorded patient-controlled intravenous morphine use for 24 h, pain scores at rest and activity, sedation, nausea and vomiting, use of antiemetic medication and overall maternal satisfaction. The primary outcome was 24-h morphine consumption. Patients who received the transversus abdominis plane block used significantly less morphine in 24 h than those in the control group [12.3 (2.6) vs. 31.4 mg (3.1), P<0.001) and had higher satisfaction scores [16 (80%) vs. 5 (25%), P = 0.012). There were no differences between groups in the visual analogue pain scores, sedation level, nausea and vomiting or the use of antiemetic medication. Ultrasound-guided transversus abdominis plane block reduced morphine consumption following caesarean section under general anaesthesia, with increased maternal satisfaction.
Diabetic and Nondiabetic Gastroparesis.
McCallum; Brown
1998-12-01
Nutritional support is essential in treating patients with gastroparesis. Initially, dietary changes should be instituted to reduce extra fat and bulk, and patients should be encouraged to eat frequent small meals with liquid supplementation. Enteral feeding should be introduced in the event of weight loss or persistent vomiting. Medical therapy is usually necessary early in treatment. Cisapride is the initial agent of choice and may be combined with an antiemetic agent, such as promethazine or chlorpromazine or, if side effects occur, ondansetron and granesitron. If cisapride is ineffective or contraindicated, metoclopramide is a reasonable option, though limited by side effects. Erythromycin is useful in the acute treatment of postoperative ileus and hospitalized gastroparetic patients, but its role is limited based on concerns about poor long-term effectiveness and antimicrobial resistance. Once domperidone becomes available in the United States, it will be useful for its promotility and antiemetic qualities. Combination therapy should be considered if monotherapy with cisapride or metoclopramide alone is ineffective. While not yet well studied, combination therapy has the potential to offer dramatic benefit for patients with refractory gastroparesis. Metoclopramide may be added to cisapride for patients with breakthrough symptoms or refractory chronic symptoms. Other combinations include metoclopramide with erythromycin, domperidone with cisapride, and domperidone with erythromycin. In the future, gastric pacing may become an effective option for patients not responding to medical therapy. Total gastrectomy should be performed only for end-stage gastroparesis when all other therapy has failed. Both procedures should be reserved for centers that specialize in severe gastric motility disorders.
Koizumi, Wasaburo; Tanabe, Satoshi; Nagaba, Shizuka; Higuchi, Katsuhiko; Nakayama, Norisuke; Saigenji, Katsunori; Nonaka, Miwa; Yago, Kazuo
2003-12-01
Serotonin receptor antagonists are recommended by the American Society of Clinical Oncology for the prevention of acute and delayed chemotherapy-induced emesis. However, the most effective agent in this class of antiemetic drugs for preventing emesis has not been clearly defined. We therefore performed a double-blind, crossover, randomized, controlled trial comparing the efficacy of granisetron and ramosetron, using patient preference as the primary endpoint. Thirty patients receiving two courses of combined chemotherapy (including > or =60 mg/m(2) cisplatin) for gastric or esophageal cancer were randomly assigned to the granisetron-ramosetron group (treatment phase 1: granisetron, 3 mg; treatment phase 2: ramosetron, 0.3 mg) or the ramosetron-granisetron group (treatment phase 1: ramosetron, 0.3 mg; treatment phase 2: granisetron, 3 mg). All patients received methylprednisolone sodium, 250 mg i.v., during each treatment phase. The efficacy of granisetron and ramosetron was similar in terms of the suppression of emesis and appetite status. However, the majority of patients (19/30, 63.3%) expressed a preference for granisetron, as compared with 9 patients (30.0%) who preferred ramosetron; 2 patients (6.7%) had no preference (chi(2) test: p = 0.008; Fisher's exact test: p = 0.015). (1) A significant proportion of patients prefer granisetron over ramosetron for the prevention of chemotherapy-induced emesis. (2) Granisetron and ramosetron possess similar effectiveness for the suppression of emesis. (3) The variable of 'patient preference' should be accepted as a primary endpoint of antiemetic drug efficacy. Copyright 2003 S. Karger AG, Basel
Gasanova, Irina; Grant, Erica; Way, Megan; Rosero, Eric B; Joshi, Girish P
2013-07-01
Transversus abdominis plane (TAP) block has been shown to provide pain relief after abdominal procedures. However, TAP block combined with multimodal analgesia technique have not been assessed in a randomized controlled trial. This randomized, controlled, observer-blinded study was designed to evaluate the analgesic efficacy of bilateral ultrasound-guided TAP blocks with or without acetaminophen and non-steroidal anti-inflammatory drug (NSAID) combination. Patients undergoing total abdominal hysterectomy were randomized to one of three groups. Group 1 (n = 25) received a TAP block and ketorolac 30 mg, IV at the end of surgery and then ketorolac plus paracetamol 650 mg, orally, every 6 h for 24 h. Group 2 (n = 24) received only TAP block at the end of surgery. Group 3 (n = 25) received ketorolac 30 mg, IV at the end of surgery and then ketorolac plus paracetamol 650 mg, orally, every 6 h for 24 h. All patients received IV-PCA morphine for 24-h, postoperatively. All patients received a standardized general anaesthetic technique and dexamethasone 4 mg and ondansetron 4 mg, IV for antiemetic prophylaxis. There were no statistically significant differences in pain at rest between the groups. However, the pain on coughing (dynamic pain) in Group 1 was significantly less variable, compared with the other two groups (P = 0.012). Opioid consumption and occurrences of nausea, vomiting, and rescue antiemetic were similar in three the groups. The combination of TAP block and acetaminophen and NSAID provided less variability in dynamic pain compared with either treatment alone.
Chan, Carmen W H; Lam, Lai Wah; Li, Chi Kong; Cheung, Jeanny S S; Cheng, Karis K F; Chik, Ki Wai; Chan, Helen Y L; So, Winnie K W; Tang, Winnie P Y
2015-04-01
Childhood cancer patients often suffer from Chemotheraphy-Associated Nausea and Vomiting (CANV). To alleviate CANV, relaxation techniques and patient education were combined to develop a multidimensional psychoeducational intervention package. The aim of this pilot study was to assess the feasibility of the two major components, namely, (1) relaxation, and (2) patient education, of a psychoeducational intervention, prior to the commencement of the main study. A pre-test-post-test control group design was adopted. Twenty patients were allocated equally to the relaxation group (10 participants) and to the educational group (10 participants). Twenty historical matched control cases were identified to form the control groups. Besides, a process evaluation was adopted to assess the feasibility of the study. In relation to episodes of vomiting on day 3, a significant difference was detected from the results (X(2) = 8.54, p = 0.036), in that fewer patients in the relaxation group experienced vomiting. A significant difference was not found in both the use of antiemetics and body weight between the groups. All subjects in the intervention groups adhered to the intervention and completed the questionnaire without difficulty. Patients and parents perceived the intervention as being moderately useful. Although the beneficial effect of relaxation and education in alleviating CANV was not well-supported statistically, the findings from descriptive data suggest that these interventions promoted the intake of antiemetics as a preventive method. Both interventions and instruments were well-received by the patients and also by their parents. Copyright © 2014 Elsevier Ltd. All rights reserved.
Bourdeanu, Laura; Frankel, Paul; Yu, Wai; Hendrix, Gregory; Pal, Sumanta; Badr, Lina; Somlo, George; Luu, Thehang
2012-01-01
Chemotherapy-induced nausea and vomiting (CINV) remain among the most frequently reported distressing side effects associated with anthracycline-based chemotherapy despite significant advances in antiemetic management. The main risk factor for severity of CINV is the emetogenic potential of the chemotherapeutic agents. However, patient-related risk factors have been identified, including genetic makeup. Although studies have noted that ethnicity influences nausea and vomiting in other contexts, there is a paucity of research regarding the impact of ethnicity on CINV. This study was undertaken to evaluate whether Asian women receiving anthracycline-based chemotherapy experience more CINV than non-Asians. A retrospective, comparative, correlational chart review was performed to abstract the relevant variables. Data from a convenience sample of 358 women with breast cancer who received chemotherapy with doxorubicin between 2004 and 2008 at City of Hope in Duarte, California, were evaluated. The sample consisted of Caucasians (45%), Hispanics (27.7%), Asians (19.8%), and African Americans (7.5%). The results indicate that Asian women with breast cancer undergoing anthracycline-based chemotherapy experienced statistically significantly more clinically important CINV than their non-Asian counterparts. The data were collected retrospectively, with a certain population distribution at a specific time. This study provides interesting preliminary evidence that Asian ethnicity plays a role in the development of severe CINV. When managing chemotherapy toxicities in women with breast cancer, health-care providers should tailor therapy to individual risk profiles. Specifically, consideration of antiemetic therapy should accommodate patient characteristics, such as Asian descent. Copyright © 2012 Elsevier Inc. All rights reserved.
Integrating cannabis into clinical cancer care.
Abrams, D I
2016-03-01
Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use. However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use. For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression. Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite. Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy. A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia. Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis. Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating. Human studies should be conducted to address critical questions related to the foregoing effects.
Intra-abdominal saline irrigation at cesarean section: a systematic review and meta-analysis.
Eke, Ahizechukwu Chigoziem; Shukr, Ghadear Hussein; Chaalan, Tina Taissir; Nashif, Sereen Khaled; Eleje, George Uchenna
2016-01-01
The aim of this study was to examine the evidence guiding intraoperative saline irrigation at cesarean sections. We searched "cesarean sections", "pregnancy", "saline irrigation" and "randomized clinical trials" in ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, AJOL, MEDLINE, LILACS and CINAHL from inception of each database to April 2015. The primary outcomes were predefined as intraoperative nausea and emesis. The pooled results were reported as relative risk (RR) with 95% confidence interval (95% CI). Three randomized trials including 862 women were analyzed. Intraoperative saline irrigation was associated with a 68% increased risk of developing intraoperative nausea (RR = 1.68, 95% CI 1.36-2.06), 70% increased risk of developing intraoperative emesis (RR = 1.70, 95% CI 1.28-2.25), 92% increased risk of developing post-operative nausea and 84% increased risk of using anti-emetics post-operatively (RR = 1.84, 95% CI 0.21-2.78) when compared with controls. There were no significant differences between intraoperative saline irrigation and no treatment for post-operative emesis (RR = 1.65, 95% CI 0.74-3.67), estimated blood loss, time to return of gastrointestinal function, postpartum endometritis (RR = 0.95, 95% CI 0.64-1.40), urinary tract infection and wound infection. Intraoperative saline irrigation at cesarean delivery increases intraoperative and post-operative nausea, requiring increasing use of anti-emetics without significant reduction in infectious, intraoperative and postpartum complications. Routine abdominal irrigation at cesarean section is not supported by current data.
Singh, Komal P; Kober, Kord M; Dhruva, Anand A; Flowers, Elena; Paul, Steve M; Hammer, Marilyn J; Cartwright, Frances; Wright, Fay; Conley, Yvette P; Levine, Jon D; Miaskowski, Christine
2018-05-29
Despite current advances in antiemetic treatments, between 19% to 58% of oncology patients experience chemotherapy-induced nausea (CIN). Aims of this post hoc exploratory analysis were to determine occurrence, severity, and distress of CIN and evaluate for differences in demographic and clinical characteristics, symptom severity, stress; and quality of life (QOL) outcomes between oncology patients who did and did not report CIN in the week prior to CTX. Demographic, clinical, symptom, and stress characteristics associated with CIN occurrence were determined. Patients (n=1296) completed questionnaires that provided information on demographic and clinical characteristics, symptom severity, stress, and QOL. Univariate analyses evaluated for differences in demographic and clinical characteristics, symptom severity, stress, and QOL scores between the two patient groups. Multiple logistic regression analysis was used to evaluate for factors associated with nausea group membership. Of the 1296 patients, 47.5% reported CIN. In the CIN group, 15% rated CIN as severe and 23% reported high distress. Factors associated with CIN included: less education; having childcare responsibilities; poorer functional status; higher levels of depression, sleep disturbance, evening fatigue, and intrusive thoughts; as well as receipt of CTX on a 14-day CTX cycle and receipt of an antiemetic regimen that contained serotonin receptor antagonist and steroid. Patients in the CIN group experienced clinically meaningful decrements in QOL. This study identified new factors (e.g., poorer functional status, stress) associated with CIN occurrence. CIN negatively impacted patients' QOL. Pre-emptive and ongoing interventions may alleviate CIN occurrence in high risk patients. Copyright © 2018. Published by Elsevier Inc.
Thalidomide for Control Delayed Vomiting in Cancer Patients Receiving Chemotherapy.
Han, Zhengxiang; Sun, Xuan; Jiang, Guan; Du, Xiuping
2016-11-01
To explore the efficacy and safety of thalidomide for the treatment of delayed vomiting, induced by chemotherapy in cancer patients. Randomized, double-blind controlled study. The Oncology Department of Affiliated Hospital of Xuzhou Medical University, Jiangsu Xuzhou, China, from January 2012 to January 2014. A total of 78 cancer patients, who had delayed vomiting observed from 24 hours to 1 week after chemotherapy, were included in the study. Patients were divided in a treatment group (40 patients, 51.28%) and a control group (38 patients, 48.71%). The treatment group received thalidomide at an oral dose of 100 mg per night; 50 mg was added daily up to a dose of 200 mg per night, if the curative effect was suboptimal and the medicine was tolerated. Both the treatment and the control groups received a drip of 10 mg azasetron 30 minutes before chemotherapy. The control group only proportions of antiemetic effects and adverse reactions were compared using the c2 test. Antiemetic effects and adverse reactions were assessed from Odds Ratios (OR) with 95% Confidence Intervals(95% CI). The effective control rate of delayed vomiting in the treatment group was significantly higher than that in the control group (c2=5.174, p=0.023). No significant difference was found between the two groups in other adverse effects of chemotherapy. Karnofsky scores or the overall self-evaluation of the patients (p>0.05). Thalidomide can effectively control the delayed vomiting of cancer patients receiving chemotherapy and the adverse reactions of the agent can be tolerated.
Itai, Shingo; Suga, Yukio; Hara, Yusuke; Izumi, Kouji; Maeda, Yuji; Kitagawa, Yasuhide; Ishizaki, Junko; Shimada, Tsutomu; Mizokami, Atsushi; Sai, Yoshimichi
2017-01-01
Bladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia. This was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (-)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia. Episodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (-), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (-) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3-223.1). Co-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.
Integrating cannabis into clinical cancer care
Abrams, D.I.
2016-01-01
Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use. However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use. For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression. Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite. Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy. A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia. Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis. Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating. Human studies should be conducted to address critical questions related to the foregoing effects. PMID:27022315
The challenge of international consensus: defining an opioid essential prescription package.
Vignaroli, Ernesto; Wenk, Roberto
2012-09-01
To describe a new strategy that aimed to facilitate opioid prescription for better pain management. The International Association of Hospice and Palliative Care recently develop a single prescription package (drugs and dosing) with one opioid, one laxative, and one antiemetic for the initiation of opioid treatment in cancer pain and other life-threatening conditions, with the intention to facilitate opioid use, improve patient compliance, and reduce adverse effects. The opioid essential prescription package was an international project designed to ensure that opioids are better tolerated by reducing the adverse effects of opioids, which could lead to more sustained improvements in pain management.
Alexander, Amy B; Hanley, Christopher S; Duncan, Mary C; Ulmer, Kyle; Padilla, Luis R
2015-09-01
A 3-yr-old captive-born California sea lion (Zalophus californianus) developed Sarcocystis neurona-induced myositis and rhabdomyolysis that led to acute renal failure. The sea lion was successfully managed with fluid therapy, antiprotozoals, antibiotics, anti-inflammatories, antiemetics, gastroprotectants, and diuretics, but developed severe delayed hypercalcemia, a syndrome identified in humans after traumatic or exertion-induced rhabdomyolysis. Treatment with calcitonin was added to the management, and the individual recovered fully. The case emphasizes that animals with rhabdomyolysis-induced renal failure risk developing delayed hypercalcemia, which may be life threatening, and calcium levels should be closely monitored past the resolution of renal failure.
Koren, Gideon
2013-01-01
The US FDA approval in April 2013 of Diclegis®, the doxylamine-pyridoxine combination for morning sickness, is a major milestone, particularly since it is indicated for use in pregnancy and the FDA has labeled it a pregnancy category A drug the strongest evidence of fetal safety. After thirty years of being orphaned from an FDA-labeled drug for the most common medical condition in pregnancy, American women and their health care providers have a therapeutic solution that is likely to positively impact millions of women each year. This review highlights the milestones of this antiemetic agent over the last 40 years.
Treatment of heartburn and acid reflux associated with nausea and vomiting during pregnancy
Law, Ruth; Maltepe, Caroline; Bozzo, Pina; Einarson, Adrienne
2010-01-01
QUESTION In addition to suffering from nausea and vomiting of pregnancy, which is being treated with antiemetics, some of my pregnant patients complain of heartburn and acid reflux. Should these symptoms also be treated and, if so, which acid-reducing medications are safe for use during pregnancy? ANSWER Increased severity of nausea and vomiting of pregnancy is associated with the presence of heartburn and acid reflux. Antacids, histamine-2 receptor antagonists, and proton pump inhibitors can be used safely during pregnancy, as large studies have been published with no evidence of adverse fetal effects. PMID:20154244
Haloperidol, a Novel Treatment for Cannabinoid Hyperemesis Syndrome.
Witsil, Joanne C; Mycyk, Mark B
Cannabinoid hyperemesis syndrome (CHS) is typically unresponsive to conventional pharmacologic antiemetics, and patients often require excessive laboratory and radiographic testing and hospital admission. We report 4 cases of CHS that failed standard emergency department therapy but improved significantly after treatment with haloperidol. Although the exact mechanism for CHS remains unclear, dysregulation at cannabinoid type 1 seems to play a role. Recent animal data demonstrate complex interactions between dopamine and cannabinoid type 1 signaling, a potential mechanism for haloperidol success in patients with CHS. Our success with haloperidol in these 4 patients warrants further investigation of haloperidol as an emergency department treatment for CHS.
A NEW ANTIEMETIC FOR THE TREATMENT OF NAUSEA AND VOMITING ASSOCIATED WITH ROENTGEN THERAPY
DOE Office of Scientific and Technical Information (OSTI.GOV)
Codiga, V.A.
Thiethylperazine dimaleate was administered orally or rectally in 56 patients for treatment of nausea or vomiting associated with radiation (2000 to 5000 r). The oral form had a quicker onset of action. Fifty patients (89%) experienced satisfactory response with either oral tablets or suppositories, the latter being used when oral tolerance was poor. Only 2 complained of side effects attributable to thiethylperazine dimaleate. One patient experienced transient blurred vision and tinnitus and another noted sialorrhea plus diminished gustatory sensation. In view of the observed high percentage of favorable responses with the drug and its lack of ataractic action, the rolemore » of psychogenic factors in gastrointestinal disturbance associated with roentgen ray therapy would seem to be slight. (H.H.D.)« less
Lorenzutti, A Matías; Martín-Flores, Manuel; Litterio, Nicolás J; Himelfarb, Martín A; Zarazaga, M Pilar
2016-03-01
To evaluate whether maropitant (1 mg kg(-1)) injected subcutaneously (SC), administered simultaneously or 30 minutes prior to intramuscular (IM) administration of morphine (0.5 mg kg(-1)) and acepromazine (0.05 mg kg(-1)), reduces the incidence of salivation, retching and emesis in dogs. Randomized, controlled, prospective clinical trial. Sixty dogs scheduled for an ovariohysterectomy as part of a population control program. Dogs were randomly allocated to be administered maropitant (1 mg kg(-1)) SC simultaneously (group M0) or 30 minutes prior to (group M30) administration of morphine (0.5 mg kg(-1)) and acepromazine (0.05 mg kg(-1)) IM. A control group was administered normal saline (C) at T-30 and T0. Dogs were observed for 30 minutes after morphine-acepromazine administration. The occurrence of vomiting, retching and salivation were recorded, as well as the time to first emesis and the number of emetic events per dog. The occurrence of salivation was not different between the groups. Retching and vomiting occurred significantly less frequently in M30 than in the other two groups (p < 0.02). The number of emetic events was also significantly less for M30 than for the other two groups (p = 0.01). When emesis occurred, the time to the first emetic event was similar among the groups. Maropitant (1 mg kg(-1)) SC reduced the frequency of morphine-induced emesis by as much as 70% when administered 30 minutes in advance. Simultaneous administration of maropitant and morphine-acepromazine produced no measurable effect on the frequency of retching or vomiting. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.
Delayed nausea and vomiting from carboplatin doublet chemotherapy
Waqar, Saiama N.; Mann, Janelle; Baggstrom, Maria Q.; Waqar, Muhammad Atif; Chitneni, Pooja; Williams, Kristina; Gao, Feng; Morgensztern, Daniel; Govindan, Ramaswamy
2016-01-01
Background Delayed nausea and vomiting following administration of carboplatin containing chemotherapy regimen remains a clinically significant problem for patients with cancer despite administration of standard antiemetic prophylaxis comprising of a 5-HT3 antagonist and dexamethasone. We performed a prospective study to define the incidence and risk factors for delayed chemotherapy induced nausea and vomiting (CINV). Methods Previously untreated patients with newly diagnosed cancer scheduled to receive carboplatin containing chemotherapy (AUC 5 or above), but no prophylactic aprepitant were enrolled in the study. The primary endpoint was the incidence of delayed CINV after cycle 1 of chemotherapy. Secondary endpoints included the incidence of CINV with the third chemotherapy cycle and gender differences in incidence of CINV. Patients completed the Functional Living Index Emesis (FLIE) questionnaires 24, 48, 72 and 96 hours after receiving chemotherapy. Telephone interviews were conducted 24–48 hours following chemotherapy to assess the severity and need for breakthrough medications for CINV. Results Between December 2006 and July 2009, 105 patients were enrolled onto this study. Delayed emesis following cycle 1 of carboplatin was observed in 30% of patients. Of these, 14.1%, 22.4% and 23.5% of patients described CINV at 48 hours, 72 hours, and 96 hours respectively. The incidence of delayed CINV following cycle 3 dropped to 12.8%, 14.6% and 16% of patients at 48 hours, 72 hours and 96 hours respectively. No differences were observed in the incidence of CINV between men and women. A total of 20% of patients required use of breakthrough antiemetics with cycle 1. Conclusions Without prophylactic aprepitant administration, 30% of patients receiving carboplatin containing regimen had moderate to severe delayed CINV. PMID:27145068
2010-01-01
Background Dexamethasone has been reported to reduce postoperative symptoms after different surgical procedures. We evaluated the efficacy of preoperative dexamethasone in ameliorating postoperative nausea and vomiting (PONV), and pain after mastectomy. Methods In this prospective, double-blind, placebo-controlled study, 70 patients scheduled for mastectomy with axillary lymph node dissection were analyzed after randomization to treatment with 8 mg intravenous dexamethasone (n = 35) or placebo (n = 35). All patients underwent standardized procedures for general anesthesia and surgery. Episodes of PONV and pain score were recorded on a visual analogue scale. Analgesic and antiemetic requirements were also recorded. Results Demographic and medical variables were similar between groups. The incidence of PONV was lower in the dexamethasone group at the early postoperative evaluation (28.6% vs. 60%; p = 0.02) and at 6 h (17.2% vs. 45.8%; p = 0.03). More patients in the placebo group required additional antiemetic medication (21 vs. 8; p = 0.01). Dexamethasone treatment significantly reduced postoperative pain just after surgery (VAS score, 4.54 ± 1.55 vs. 5.83 ± 2.00; p = 0.004), at 6 h (3.03 ± 1.20 vs. 4.17 ± 1.24; p < 0.0005) and at 12 h (2.09 ± 0.85 vs. 2.54 ± 0.98; p = 0.04). Analgesics were required in more patients of the control group (21 vs. 10; p = 0.008). There were no adverse events, morbidity or mortality. Conclusions Preoperative intravenous dexamethasone (8 mg) can significantly reduce the incidence of PONV and pain in patients undergoing mastectomy with axillary dissection for breast cancer. Trial registration number NCT01116713 PMID:21182781
Fujiwara, Satoe; Terai, Yoshito; Tsunetoh, Satoshi; Sasaki, Hiroshi; Kanemura, Masanori; Ohmichi, Masahide
2015-10-01
There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT₃ receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC. We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT₃ receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT₃ receptor and dexamethasone with/without aprepitant. When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT₃ receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT₃ receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001). The addition of aprepitant therapy was more effective than the control therapy of a 5-HT₃ receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.
Unal, Yusuf; Ozsoylar, Ozgür; Arslan, Mustafa; Sarigüney, Damla; Akçabay, Mehmet
2009-06-01
To compare the administration of sub hypnotic dose of propofol with metoclopramide and placebo in prevention of postoperative nausea and vomiting (PONV) after middle ear surgery. This clinical research was performed in the Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey, between December 2004 and October 2005. Following approval by the hospital ethics committee, 60 adult patients scheduled for a middle ear operation were randomly assigned into 3 groups. The patients in group P received 0.5 mg x kg(-1) propofol; in group M, 0.2 mg x kg(-1) metoclopramide, and in group C, 0.9% saline solution. The number of patients suffering from nausea and vomiting at 0-4, 4-12, and 12-24 hours postoperatively, and additional use of antiemetics was recorded. Comparisons of the data showed that at 0-4th hours, the incidence of vomiting was 25% in group P, 40% in group M, and 75% in group C. The incidence rate of group P was significantly lower than that of group C (p=0.002), and the rate of antiemetics use in group C was higher than that in group P (p=0.028). The Nausea Vomiting Scale scores of group C were also significantly higher than those of group P (p=0.005). There were no significant differences between the values at 4-12 and 12-24 hours. The administration of a sub hypnotic dose of propofol at the end of surgery was found to be at least as effective as metoclopramide in preventing PONV in the early postoperative period in adult patients undergoing middle ear surgery.
The effect of single low-dose dexamethasone on vomiting during awake craniotomy.
Kamata, Kotoe; Morioka, Nobutada; Maruyama, Takashi; Komayama, Noriaki; Nitta, Masayuki; Muragaki, Yoshihiro; Kawamata, Takakazu; Ozaki, Makoto
2016-12-01
Intraoperative vomiting leads to serious respiratory complications that could influence the surgical decision-making process for awake craniotomy. However, the use of antiemetics is still limited in Japan. The aim of this study was to investigate the effect of prophylactically administered single low-dose dexamethasone on the incidence of vomiting during awake craniotomy. The frequency of hyperglycemia was also examined. We conducted a retrospective case review of awake craniotomy for glioma resection between 2012 and 2015. Of the 124 patients, 91 were included in the analysis. Dexamethasone was not used in 43 patients and the 48 remaining patients received an intravenous bolus of 4.95 mg dexamethasone at anesthetic induction. Because of stable operating conditions, no one required conscious sedation throughout functional mapping and tumor resection. Although dexamethasone pretreatment reduced the incidence of intraoperative vomiting (P = 0.027), the number of patients who complained of nausea was comparable (P = 0.969). No adverse events related to vomiting occurred intraoperatively. Baseline blood glucose concentration did not differ between each group (P = 0.143), but the samples withdrawn before emergence (P = 0.018), during the awake period (P < 0.0001) and at the end of surgery (P < 0.0001) showed significantly higher glucose levels in the dexamethasone group. Impaired wound healing was not observed in either group. A single low-dose of dexamethasone prevents intraoperative vomiting for awake craniotomy cases. However, as even a small dose of dexamethasone increases the risk for hyperglycemia, antiemetic prophylaxis with dexamethasone should be administered after careful consideration. Monitoring of perioperative blood glucose concentration is also necessary.
Aksu, Recep; Patmano, Gülçin; Biçer, Cihangir; Emek, Ertan; Çoruh, Aliye Esmaoğlu
We aimed to evaluate the effect of bupivacaine and dexmedetomidine added to bupivacaine used in tranversus abdominis plane (TAP) block on postoperative pain and patient satisfaction in patients undergoing lower abdominal surgery. Patients submitted to lower abdominal surgery were enrolled in the study. After anesthesia induction, ultrasound guided TAP block was performed. TAP block was obtained with 21mL 0.9% saline in Group C (n=31), 20mL 0.5% bupivacaine+1mL saline in Group B (n=31), and 20mL 0.5% bupivacaine+1mL dexmedetomidine (100μg) in Group BD (n=31). Visual analog scale scores were lower in Group BD compared to Group C, at all time points (p<0.05); it was lower in group BD than in group B at 10-24h. In Group B, it was lower than Group C at 2-8h (p<0.05). Total morphine consumption was lower in Group BD compared to other groups and lower in group B than in the controls (p<0.001). Patient satisfaction was higher in Group BD than in other groups and was higher in both study groups than in the controls (p<0.001). Nausea-vomiting scores, antiemetic requirement, or additional analgesic administration were not significant among groups (p>0.05). The addition of dexmedetomidine to bupivacaine on TAP block decreased postoperative pain scores and morphine consumption; it also increased patient satisfaction in patients undergoing lower abdominal surgery. Dexmedetomidine did not have any effect on nausea and vomiting score and antiemetic requirement. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.
Implementation of additional prescribing authorization among oncology pharmacists in Alberta.
Au, Bianca; Dersch-Mills, Deonne; Ghosh, Sunita; Jupp, Jennifer; Chambers, Carole; Cusano, Frances; Danilak, Melanie
2018-01-01
Purpose To describe the practice settings and prescribing practices of oncology pharmacists with additional prescribing authorization. Methods A descriptive, cross-sectional survey of all oncology pharmacists in Alberta was conducted using a web-based questionnaire over four weeks between March and April 2016. Pharmacists were identified from the Cancer Services Pharmacy Directory and leadership staff in Alberta Health Services. Descriptive statistics were used to describe the practice setting, prescribing practices, motivators to apply for additional prescribing authorization, and the facilitators and barriers of prescribing. Logistic regression was used to explore factors associated with having additional prescribing authorization. Results The overall response rate was 41% (71 of 175 pharmacists). Oncology pharmacists with additional prescribing authorization made up 38% of respondents. They primarily worked in urban, tertiary cancer centers, and practiced in ambulatory care. The top 3 clinical activities they participated in were medication reconciliation, medication counseling/education, and ambulatory patient assessment. Respondents thought additional prescribing authorization was most useful for ambulatory patient assessment and follow-up. Antiemetics were prescribed the most often. The median number of prescriptions written in an average week of clinical work was 5. Competence, self-confidence, and the potential impact on patient care/perceived impact on work environment were the strongest facilitators of prescribing. The strongest motivators to apply for additional prescribing authorization were relevancy to practice, the potential for increased efficiency, and advancing the profession. Conclusion The current majority of oncology pharmacist prescribing in Alberta occurs in ambulatory care with a large focus on antiemetic prescribing. Pharmacists found additional prescribing authorization most useful for ambulatory patient assessment and follow-up.
Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block.
Buonanno, Pasquale; Laiola, Anna; Palumbo, Chiara; Spinelli, Gianmario; Servillo, Giuseppe; Di Minno, Raffaele Maria; Cafiero, Tullio; Di Iorio, Carlo
2016-06-01
Sugammadex is a relatively new molecule that reverses neuromuscular block induced by rocuronium. The particular structure of sugammadex traps the cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity. Dexamethasone shares the same steroidal structure with rocuronium. Studies in vitro have demonstrated that dexamethasone interacts with sugammadex, reducing its efficacy. In this study, we investigated the clinical relevance of this interaction and its influence on neuromuscular reversal. In this retrospective case-control study, we analyzed data from 45 patients divided into 3 groups: dexamethasone after induction group (15 patients) treated with 8 mg dexamethasone as an antiemetic drug shortly after induction of anesthesia; dexamethasone before reversal group (15 patients) treated with dexamethasone just before sugammadex injection; and control group (15 patients) treated with 8 mg ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2 mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular relaxation was monitored with a TOF-Watch® system. The control group had a recovery time of 154 ± 54 seconds (mean ± SD), the dexamethasone after induction group 134 ± 55 seconds, and the dexamethasone before reversal group 131 ± 68 seconds. The differences among groups were not statistically significant (P = 0.5141). Our results show that the use of dexamethasone as an antiemetic drug for the prevention of postoperative nausea and vomiting does not interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia in contrast to in vitro studies that support this hypothesis.
Ohnishi, Shunsuke; Watari, Hidemichi; Kanno, Maki; Ohba, Yoko; Takeuchi, Satoshi; Miyaji, Tempei; Oyamada, Shunsuke; Nomura, Eiji; Kato, Hidenori; Sugiyama, Toru; Asaka, Masahiro; Sakuragi, Noriaki; Yamaguchi, Takuhiro; Uezono, Yasuhito; Iwase, Satoru
2017-09-01
Rikkunshito, an herbal medicine, is widely prescribed in Japan for the treatment of anorexia and functional dyspepsia, and has been reported to recover reductions in food intake caused by cisplatin. We investigated whether rikkunshito could improve chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients treated with cisplatin. Patients with uterine cervical or corpus cancer who were to receive cisplatin (50 mg/m² day 1) and paclitaxel (135 mg/m² day 0) as first-line chemotherapy were randomly assigned to the rikkunshito group receiving oral administration on days 0-13 with standard antiemetics, or the control group receiving antiemetics only. The primary endpoint was the rate of complete control (CC: no emesis, no rescue medication, and no significant nausea) in the overall phase (0-120 hours). Two-tailed p<0.20 was considered significant in the planned analysis. The CC rate in the overall phase was significantly higher in the rikkunshito group than in the control group (57.9% vs. 35.3%, p=0.175), as were the secondary endpoints: the CC rate in the delayed phase (24-120 hours), and the complete response (CR) rates (no emesis and no rescue medication) in the overall and delayed phases (63.2% vs. 35.3%, p=0.095; 84.2% vs. 52.9%, p=0.042; 84.2% vs. 52.9%, p=0.042, respectively), and time to treatment failure (p=0.059). Appetite assessed by visual analogue scale (VAS) appeared to be superior in the rikkunshito group from day 2 through day 6. Rikkunshito provided additive effect for the prevention of CINV and anorexia. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology
Predictors for postoperative nausea and vomiting after xenon-based anaesthesia.
Schaefer, M S; Apfel, C C; Sachs, H-J; Stuttmann, R; Bein, B; Tonner, P H; Hein, M; Neukirchen, M; Reyle-Hahn, M; Kienbaum, P
2015-07-01
In contrast to volatile anaesthetics, xenon acts by antagonism at N-methyl-d-aspartate receptors and antagonizes 5-hydroxytryptamine type 3 receptors that mediate nausea and vomiting. Therefore, it is unknown whether the same risk factors for postoperative nausea and vomiting (PONV) after volatile anaesthetics apply to xenon-based anaesthesia. With ethics committee approval and written informed consent, 502 consecutive patients undergoing xenon-based anaesthesia were included in a multicentre prospective observational study. Antiemetic prophylaxis was administered at the discretion of the attending anaesthetists. Postoperative nausea and vomiting and need for antiemetic rescue medication were assessed for 24 h after anaesthesia. Multivariate logistic regression analysis was performed to quantify risk factors for PONV and need for rescue medication. Four hundred and eighty-eight subjects were available for the final analysis. The incidence of PONV in subjects without prophylaxis was lower than expected according to the Apfel Score (28% observed; 42% expected, P<0.001). Independent predictors for PONV were (adjusted odds ratio; 95% confidence interval) female sex (1.76; 1.08-2.89), younger patient age (0.82 per 10 yr; 0.69-0.97), and longer duration of anaesthesia (1.36 per hour; 1.17-1.59). The incidence of PONV was significantly lower than predicted by the Apfel Score. Female sex, younger age, and longer duration of anaesthesia are risk factors for PONV after xenon-based anaesthesia. German Federal Institute for Drugs and Medical Devices number AL-PMS-01/07GER. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
The lesser of two adverse reactions.
Chakraborti, Chayan; Egan, John
2010-01-01
Fundamental to complex systems are interconnected processes involved in providing high-quality patient care. A case study and a root cause analysis (RCA) illustrate a patient safety effort with unintended consequences. A 38-year-old woman presented to the hospital for odynophagia and vomiting. The patient developed Mobitz type 2, second-degree heart block temporally associated with the administration of intravenous ondansetron. RESPONSE TO THE EVENT: An Ishikawa, or fishbone, diagram conducted to enumerate potential contributing factors indicated that a key factor appeared to be an institutional restriction against using intravenous (i.v.) promethazine, which resulted in ondansetron being the only readily available i.v. anti-emetic on formulary. The anesthesia department requested that i.v. promethazine be removed from all operating and recovery room automated medication dispensing machines. The pharmacy department, given the realization that individual departments were taking independent action regarding promethazine, discussed the matter with the medical director, who issued a memo banning the use of i.v. promethazine. An institutional ban on i.v. anti-emetics such as promethazine may have resulted in an increase in the use of ondansetron and contributed to this adverse reaction. The reason to restrict promethazine is not well reported in the literature. In limiting the use of promethazine for patient safety concerns, the inadvertent increase in adverse reactions of the alternative medication, ondansetron, may have been overlooked. The resultant RCA underscores the need for careful cataloguing of adverse medication effects. Stakeholders should anticipate as many "downstream effects" of quality and patient safety improvements as possible. Comprehensive reporting of adverse medication effects will augment the emerging science of patient safety.
Generation Z: Adolescent Xenobiotic Abuse in the 21st Century.
Eggleston, William; Stork, Christine
2015-12-01
NMDA receptor antagonists include the prescription medication ketamine, the illicit xenobiotics PCP, MXE, and other novel PCP analogs, and the OTC medication DXM. The NMDA receptor antagonist most commonly abused by adolescents in the United States is DXM. These xenobiotics cause dissociative effects by non-competitively inhibiting the action of glutamate at the NMDA receptor. Additionally, these agents modulate the actions of monoamine neurotransmitters, agonize opioid receptors, and inhibit nitric oxide synthase. Patients typically present with sympathomimetic and neuropsychiatric clinical manifestations after abuse of NMDA receptor antagonists. Treatment is generally symptomatic and supportive. Interventions include benzodiazepines, propofol, fluids, antiemetics, aggressive cooling, and respiratory support.
[Clebopride in premedication in ambulatory interventions in general anesthesia].
Migliavacca, S; Speranza, R; Cipolla, M; Laveneziana, D
1992-03-01
The authors examine the antiemetic effects of 1 mg clebopride administered iv after surgery, vs a placebo, by making a double blind randomized study on two groups of 40 women comparable by age and weight. The 2 groups of outpatients, admitted for short gynecological surgery, underwent diagnostic uterine curettage. They were anaesthetized with a cocktail of 2.5 mcg/kg fentanyl and 0.25 mg/kg ketamine, on spontaneous respiration. Nausea, vomiting and the other side effects were evaluated 3-6 hours after surgery. Statistically, clebopride proved more effective than placebo against nausea and vomiting (P ranging between 0.05-0.01), with no relevant side effects.
Samuel, Cleo A; Landrum, Mary Beth; McNeil, Barbara J; Bozeman, Samuel R; Williams, Christina D; Keating, Nancy L
2014-09-01
We assessed cancer care disparities within the Veterans Affairs (VA) health care system and whether between-hospital differences explained disparities. We linked VA cancer registry data with VA and Medicare administrative data and examined 20 cancer-related quality measures among Black and White veterans diagnosed with colorectal (n = 12,897), lung (n = 25,608), or prostate (n = 38,202) cancer from 2001 to 2004. We used logistic regression to assess racial disparities for each measure and hospital fixed-effects models to determine whether disparities were attributable to between- or within-hospital differences. Compared with Whites, Blacks had lower rates of early-stage colon cancer diagnosis (adjusted odds ratio [AOR] = 0.80; 95% confidence interval [CI] = 0.72, 0.90), curative surgery for stage I, II, or III rectal cancer (AOR = 0.57; 95% CI = 0.41, 0.78), 3-year survival for colon cancer (AOR = 0.75; 95% CI = 0.62, 0.89) and rectal cancer (AOR = 0.61; 95% CI = 0.42, 0.87), curative surgery for early-stage lung cancer (AOR = 0.50; 95% CI = 0.41, 0.60), 3-dimensional conformal or intensity-modulated radiation (3-D CRT/IMRT; AOR = 0.53; 95% CI = 0.47, 0.59), and potent antiemetics for highly emetogenic chemotherapy (AOR = 0.87; 95% CI = 0.78, 0.98). Adjustment for hospital fixed-effects minimally influenced racial gaps except for 3-D CRT/IMRT (AOR = 0.75; 95% CI = 0.65, 0.87) and potent antiemetics (AOR = 0.95; 95% CI = 0.82, 1.10). Disparities in VA cancer care were observed for 7 of 20 measures and were primarily attributable to within-hospital differences.
Radwan, R W; Gardner, A; Jayamanne, H; Stephenson, B M
2018-03-15
Introduction The open prosthetic repair of inguinal hernias under local anaesthesia (LA) is well established, with the concept of intraoperative 'pre-emptive analgesia' evolving so that patients are as comfortable as possible. We used a peri-incisional LA solution in patients undergoing day-case inguinal hernioplasty under general anaesthesia (GA) and recorded use of analgesia in the immediate postoperative period. Methods In this observational cohort study, 100 consecutive unselected men underwent open inguinal hernia repair as a day case. Of these, 75 underwent repair under GA and 25 with peri-incisional LA solution (equal mixture of 0.5% bupivacaine and 1% lignocaine with 1:200,000 adrenaline). Analgesia prescribed at induction, for maintenance and after cessation of anaesthesia was scored in accordance with the World Health Organization (WHO) analgesic ladder. Results The median age in the GA group was 59 years (range: 25-89 years) and in the GA+LA group, it was 62 years (range: 27-88 years). Of the 100 patients, 82 underwent a mesh plug repair by seven surgeons whereas 18 underwent a flat (Lichtenstein) mesh repair by two surgeons. WHO analgesic induction and postoperative scores were significantly lower in the GA+LA group (p=0.034 and p<0.001 respectively). There was also a significant difference in use of postoperative antiemetics (23% vs 0% in the GA only and GA+LA cohorts respectively, p=0.020). Six patients (8%) in the GA group failed day-case discharge criteria. Conclusions Patients undergoing contemporary day-case GA inguinal hernioplasty with pre-emptive LA solution infiltration require lower levels of postoperative opioid analgesia and antiemetics. These cases are less likely to fail discharge criteria for planned day surgery.
Gandhi, Ranju; Sunder, Rani
2012-01-01
Background: Analgesic efficacy of rectal acetaminophen is variable in different surgical procedures. Little data is available on its efficacy in ophthalmic surgeries. We conducted this prospective, randomized, double blind study to evaluate and compare the efficacy of single high dose and low dose rectal acetaminophen in pediatric ophthalmic surgery over a 24 hour period. Materials and Methods: 135 children scheduled for elective ophthalmic surgery were randomly allocated to one of the three groups, high, low, or control (H, L, or N) and received rectal acetaminophen 40 mg/kg, 20 mg/kg or no rectal drug respectively after induction of general anesthesia. Postoperative observations included recovery score, hourly observational pain score (OPS) up to 8 hours, time to first analgesic demand, and requirement of rescue analgesics and antiemetics over a 24 hour period. Results: Nineteen of 30 (63%) of children in group N required postoperative rescue analgesic versus 5/48 (10%) of group H (P <0.0001) and 10/47 (23%) of group L (P =0.0005) during 24 hour period. Mean time to requirement of first analgesic was 206±185 min in group H, 189±203min in group L, and 196 ±170 min in group N (P=0.985). OPS was significantly lower in group H and L compared to group N during first 8 hours. Requirement of rescue antiemetic was 18.7% in group H as compared to 23% each in group L and group N (P >0.5). Conclusions: Single dose rectal acetaminophen can provide effective postoperative analgesia for pediatric ophthalmic surgery at both high dose (40 mg/kg) and low dose (20 mg/kg) both in early postoperative and over a 24 hour period. PMID:23225924
Ryan, Julie L.; Heckler, Charles E.; Roscoe, Joseph A.; Dakhil, Shaker R.; Kirshner, Jeffrey; Flynn, Patrick J.; Hickok, Jane T.; Morrow, Gary R.
2012-01-01
Purpose Despite the widespread use of antiemetics, nausea continues to be reported by over 70% of patients receiving chemotherapy. Methods In this double blind, multicenter trial, we randomly assigned 744 cancer patients to four arms: 1) placebo, 2) 0.5g ginger, 3) 1.0g ginger, or 4) 1.5g ginger. Nausea occurrence and severity were assessed at a baseline cycle and the two following cycles during which patients were taking their assigned study medication. All patients received a 5-HT3 receptor antagonist antiemetic on Day 1 of all cycles. Patients took three capsules of ginger (250mg) or placebo twice daily for six days starting three days before the first day of chemotherapy. Patients reported the severity of nausea on a 7-point rating scale (“1” = “Not at all Nauseated” and “7” = “Extremely Nauseated”) for Days 1-4 of each cycle. The primary outcomes were to determine the dose and efficacy of ginger at reducing the severity of chemotherapy-induced nausea on Day 1 of chemotherapy. Results A total of 576 patients were included in final analysis (91% female, mean age = 53). Mixed model analyses demonstrated that all doses of ginger significantly reduced acute nausea severity compared to placebo on Day 1 of chemotherapy (p=0.003). The largest reduction in nausea intensity occurred with 0.5g and 1.0g of ginger (p=0.017 and p=0.036, respectively). Anticipatory nausea was a key factor in acute chemotherapy-induced nausea (p<0.0001). Conclusions Ginger supplementation at daily dose of 0.5g-1.0g significantly aids in reduction of the severity of acute chemotherapy-induced nausea in adult cancer patients. PMID:21818642
Fujiwara, Satoe; Tsunetoh, Satoshi; Sasaki, Hiroshi; Kanemura, Masanori; Ohmichi, Masahide
2015-01-01
Objective There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT3 receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC. Methods We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT3 receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT3 receptor and dexamethasone with/without aprepitant. Results When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001). Conclusion The addition of aprepitant therapy was more effective than the control therapy of a 5-HT3 receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen. PMID:26197776
Kwiatkowska, Magdalena; Parker, Linda A; Burton, Page; Mechoulam, Raphael
2004-07-01
The 5-HT3 antagonist, ondansetron (OND), and the cannabinoid, delta9-tetrahydrocannabinol (delta9-THC), have been shown to interfere with emesis; however, their relative and/or combined effectiveness in suppressing vomiting produced by the chemotherapeutic agent, cisplatin, is unknown. To evaluate the potential of: 1) a broad range of doses of delta9-THC and OND to prevent cisplatin-induced vomiting and retching in the Suncus murinus (house musk shrew), 2) combined treatment with ineffective individual doses of delta9-THC and OND to prevent cisplatin-induced vomiting and retching, 3) the CB1 receptor antagonist, SR141716, to reverse the antiemetic effects of OND, and 4) cannabidiol (CBD), the principal non-psychoactive component of marijuana, to reverse cisplatin-induced vomiting in the shrew. Shrews were injected with various doses of OND (0.02-6.0 mg/kg), delta9-THC (1.25-10 mg/kg) and a combination of ineffective doses of each (0.02 mg/kg OND+1.25 mg/kg delta9-THC) prior to being injected with cisplatin (20 mg/kg) which induces vomiting. Shrews were also injected with CBD (5 mg/kg and 40 mg/kg) prior to an injection of cisplatin. OND and delta9-THC both dose-dependently suppressed cisplatin-induced vomiting and retching. Furthermore, a combined pretreatment of doses of the two drugs that were ineffective alone completely suppressed vomiting and retching. CBD produced a biphasic effect, suppressing vomiting at 5 mg/kg and potentiating it at 40 mg/kg. A low dose of the non-intoxicating cannabinoid CBD may be an effective anti-emetic treatment and combined doses of OND and delta9-THC that are ineffective alone suppresses cisplatin-induced emetic reactions in shrews.
Mazzotta, P; Maltepe, C; Navioz, Y; Magee, L A; Koren, G
2000-09-01
Nausea and vomiting of pregnancy (NVP) affects a large proportion of pregnant women. In 1983, Bendectin((R)), the only FDA-approved drug for NVP, was removed from the market by its manufacturer due to legal costs based on claims of teratogenicity, which were subsequently proven to be unsubstantiated. In Canada, a generic form of Bendectin (Diclectin; a doxylamine/pyridoxine combination) has continued to be available, with increasing use over the last few years. To characterize the attitudes, management and consequences of NVP among pregnant women in the USA, where no approved drug for NVP is available, and in Canada, where such a drug is available. Prospective, observational study. Women suffering from NVP (N = 1444) were interviewed, of which 42% were American and 58% were Canadian. The two groups had similar maternal characteristics and a similar distribution of severity of NVP, although among Canadian women the NVP continued for slightly longer. American respondents were treated significantly more often by an obstetrician as their primary caregiver, were more commonly advised by their caregiver to change their diet and/or lifestyle and to use non-pharmacological agents to manage their NVP, and more often perceived anti-emetics as posing an increased risk for malformations (all P < 0.001). Canadian respondents reported a family physician as their primary caregiver significantly more often, were more commonly advised to take anti-emetic medications and perceived their NVP as causing a concern to their unborn (all P < 0.001). American women experienced significantly larger weight loss, more hospitalizations and more time lost from paid work. Lack of an approved drug for symptoms of NVP may be associated with unwarranted and preventable adverse health effects. Because this is an observational study, these associations do not necessarily prove causation.
Li, Wing S; van der Velden, Joanne M; Ganesh, Vithusha; Vuong, Sherlyn; Raman, Srinivas; Popovic, Marko; Lam, Henry; Wong, Kam H; Ngan, Roger K; Burbach, J P Maarten; DeAngelis, Carlo; Xxxx, Rachel McDonald; Chow, Edward
2017-04-01
The aim of this article was to systematically review the efficacy and safety of various antiemetics in prophylaxis of radiation-induced nausea and vomiting (RINV). A literature search of Ovid MEDLINE, EMBASE and Cochrane CENTRAL was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy of prophylaxis for RINV in patients receiving radiotherapy to abdomen/pelvis, including total body irradiation (TBI). Primary endpoints were complete control of nausea and complete control of vomiting during acute and delayed phases. Secondary endpoints included use of rescue medication, quality of life (QoL) and incidence of adverse events. Seventeen RCTs were identified. Among patients receiving radiotherapy to abdomen/pelvis, our meta-analysis showed that prophylaxis with a 5-hydroxytryptamine-3 receptor antagonist (5HT3 RA) was significantly more efficacious than placebo and dopamine receptor antagonists in both complete control of vomiting [OR 0.49; 95% confidence interval (CI): 0.33-0.72 and OR 0.17; 95% CI: 0.05-0.58 respectively] and complete control of nausea (OR 0.43; 95% CI: 0.26-0.70 and OR 0.46; 95% CI: 0.24-0.88 respectively). 5HT3 RAs were also more efficacious than rescue therapy and dopamine receptor antagonists plus dexamethasone. The addition of dexamethasone to 5HT3 RA compared to 5HT3 RA alone provides a modest improvement in prophylaxis of RINV. Among patients receiving TBI, 5HT3 RA was more effective than other agents (placebo, combination of metoclopramide, dexamethasone and lorazepam). 5HT3 RAs are more effective than other antiemetics for prophylaxis of RINV in patients receiving radiotherapy to abdomen/pelvis and TBI. Future RCTs should investigate the efficacy of newer agents such as substance P neurokinin 1 receptor antagonists in addition to 5HT3 RAs in prophylaxis of RINV during both acute and delayed phases.
Darvall, J N; Handscombe, M; Leslie, K
2017-01-01
A novel treatment, chewing gum, may be non-inferior to ondansetron in inhibiting postoperative nausea and vomiting (PONV) in female patients after laparoscopic or breast surgery. In this pilot study, we tested the feasibility of a large randomized controlled trial. We randomized 94 female patients undergoing laparoscopic or breast surgery to ondansetron 4 mg i.v. or chewing gum if PONV was experienced in the postanaesthesia care unit (PACU). The primary outcome was full resolution of PONV, with non-inferiority defined as a difference between groups of <15% in a per protocol analysis. Secondary outcomes were PACU stay duration, anti-emetic rescue use, and acceptability of anti-emetic treatment. The feasibility of implementing the protocol in a larger trial was assessed. Postoperative nausea and vomiting in the PACU occurred in 13 (28%) ondansetron patients and 15 (31%) chewing gum patients (P=0.75). Three chewing gum patients could not chew gum when they developed PONV. On a per protocol basis, full resolution of PONV occurred in five of 13 (39%) ondansetron vs nine of 12 (75%) chewing gum patients [risk difference 37% (6.3-67%), P=0.07]. There was no difference in secondary outcomes between groups. Recruitment was satisfactory, the protocol was acceptable to anaesthetists and nurses, and data collection was complete. In this pilot trial, chewing gum was not inferior to ondansetron for treatment of PONV after general anaesthesia for laparoscopic or breast surgery in female patients. Our findings demonstrate the feasibility of a larger, multicentred randomized controlled trial to investigate this novel therapy. Australian New Zealand Clinical Trials Registry: ACTRN12615001327572. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Gasanova, Irina; Alexander, John; Ogunnaike, Babatunde; Hamid, Cherine; Rogers, David; Minhajuddin, Abu; Joshi, Girish P
2015-11-01
Surgical site infiltration and transversus abdominis plane (TAP) blocks are commonly used to improve pain relief after lower abdominal surgery. This randomized, observer-blinded study was designed to compare the analgesic efficacy of TAP blocks with surgical site infiltration in patients undergoing open total abdominal hysterectomy via a Pfannenstiel incision. Patients were randomized to receive either bilateral ultrasound-guided TAP blocks using bupivacaine 0.5% 20 mL on each side (n = 30) or surgical site infiltration with liposomal bupivacaine 266 mg diluted to 60 mL injected in the preperitoneal, subfascial, and subcutaneous planes (n = 30). The remaining aspects of the perioperative care were standardized. An investigator blinded to the group allocation documented pain scores at rest and with coughing, opioid requirements, nausea, vomiting, and rescue antiemetics in the postanesthesia care unit and at 2, 6, 12, 24, and 48 hours postoperatively. The primary outcome measure was pain scores on coughing at 6 hours postoperatively. One patient in each group was excluded from the analysis because of reoperation within 24 hours in the TAP block group and change of incision type in the infiltration group. The pain scores at rest and with coughing were significantly lower in the surgical site infiltration group at all postoperative time points (P < 0.0001) except at rest in the postanesthesia care unit. The opioid requirements between 24 and 48 hours were significantly lower in the infiltration group (P = 0.009). The nausea scores, occurrence of vomiting, and need for rescue antiemetics were similar. Surgical site infiltration provided superior pain relief at rest and on coughing, as well as reduced opioid consumption for up to 48 hours. Future studies need to compare TAP blocks with liposomal bupivacaine with surgical site infiltration with liposomal bupivacaine.
Min, Byunghun; Hwang, Jin-Young
2018-01-01
Background The preemptive multimodal pain protocols used in total knee arthroplasty (TKA) often cause emesis postoperatively. We investigated whether palonosetron prophylaxis reduces postoperative nausea and vomiting (PONV) in high-risk patients after TKA. Methods We randomized 120 female patients undergoing TKA to receive either palonosetron (0.075 mg, intravenous) or no antiemetic prophylaxis (0.9% saline, control group). All patients were given spinal anesthesia, a continuous femoral nerve block, and fentanyl-based intravenous patient controlled analgesia. Patients undergoing staged bilateral TKA were assigned to one group for the first knee and the other group for the second knee. The overall incidence of PONV, the incidences of both nausea and vomiting, severity of nausea, complete response, requirement for rescue antiemetics, pain level, opioid consumption, and satisfaction scores were evaluated during three periods: 0–2, 2–24, and 24–48 h postoperatively. We also compared PONV and pain between the first and second TKA. Results The incidence of PONV during the first 48 h was lower in the palonosetron group compared with the controls (22 vs. 41%, p = 0.028), especially 2–24 h after surgery, as was the nausea and vomiting respectively. The severity of nausea was lower in the palonosetron group (p = 0.010). The complete response rate (93 vs. 73%, p = 0.016) and satisfaction score (84 ± 12 vs. 79 ± 15, p = 0.032) were higher in the palonosetron group during 2–24 h after surgery. Patients who underwent a second operation complained of more severe pain, and consumed more opioids than those of the first operation. There was no difference in the incidence of PONV between the first and second operations. Conclusions Palonosetron prophylaxis reduced the incidence and severity of PONV in high-risk patients managed with multimodal pain protocol for 48 h, notably 2–24 h after TKA. PMID:29758039
Ryu, Jung-Hee; Jeon, Young-Tae; Min, Byunghun; Hwang, Jin-Young; Sohn, Hye-Min
2018-01-01
The preemptive multimodal pain protocols used in total knee arthroplasty (TKA) often cause emesis postoperatively. We investigated whether palonosetron prophylaxis reduces postoperative nausea and vomiting (PONV) in high-risk patients after TKA. We randomized 120 female patients undergoing TKA to receive either palonosetron (0.075 mg, intravenous) or no antiemetic prophylaxis (0.9% saline, control group). All patients were given spinal anesthesia, a continuous femoral nerve block, and fentanyl-based intravenous patient controlled analgesia. Patients undergoing staged bilateral TKA were assigned to one group for the first knee and the other group for the second knee. The overall incidence of PONV, the incidences of both nausea and vomiting, severity of nausea, complete response, requirement for rescue antiemetics, pain level, opioid consumption, and satisfaction scores were evaluated during three periods: 0-2, 2-24, and 24-48 h postoperatively. We also compared PONV and pain between the first and second TKA. The incidence of PONV during the first 48 h was lower in the palonosetron group compared with the controls (22 vs. 41%, p = 0.028), especially 2-24 h after surgery, as was the nausea and vomiting respectively. The severity of nausea was lower in the palonosetron group (p = 0.010). The complete response rate (93 vs. 73%, p = 0.016) and satisfaction score (84 ± 12 vs. 79 ± 15, p = 0.032) were higher in the palonosetron group during 2-24 h after surgery. Patients who underwent a second operation complained of more severe pain, and consumed more opioids than those of the first operation. There was no difference in the incidence of PONV between the first and second operations. Palonosetron prophylaxis reduced the incidence and severity of PONV in high-risk patients managed with multimodal pain protocol for 48 h, notably 2-24 h after TKA.
Shin, Hyun-Jung; Choi, Eun-Su; Lee, Gwan-Woo; Do, Sang-Hwan
2015-01-01
The adverse effects of spinal anesthesia (SA) include arterial hypotension and bradycardia. The aim of this study was to compare the effects of 2 type 3 serotonin receptor antagonists in SA-induced adverse effects. Specifically, we assessed whether ramosetron was more effective than ondansetron in reducing SA-induced decreases in blood pressure (BP) and heart rate (HR). A total of 117 patients undergoing orthopedic surgery and receiving SA were intravenously administered 0.3 mg of ramosetron (n = 39, group R), 4 mg of ondansetron (n = 39, group O4), or 8 mg of ondansetron (n = 39, group O8). Systolic BP (SBP), diastolic BP (DBP), mean BP (MBP), HR, and the lowest SBP, DBP, MBP, and HR values were measured preoperatively (baseline) and intraoperatively. The incidence of postoperative nausea and vomiting, the need for rescue antiemetics, the amount of patient-controlled analgesia consumption, and pain score in the first 48 hours after surgery were determined. Baseline values did not significantly differ among the 3 groups. After SA, SBP, DBP, MBP, and HR were lower than their baseline values in all 3 groups. The differences between the baseline and the lowest values were significantly less in group R than in groups O4 and O8 with respect to SBP (P < 0.001), DBP (P = 0.001), and MBP (P < 0.001) less in group R than in group O4 with respect to HR (P = 0.032). Intergroup differences were not significant for postoperative nausea and vomiting, the need for rescue antiemetics, patient-controlled analgesia consumption, or pain score. The administration of ramosetron (0.3 mg) significantly attenuated the SA-induced decrease in BP compared with 4 or 8 mg of ondansetron and HR compared with 4 mg of ondansetron.
Aapro, Matti; Karthaus, Meinolf; Schwartzberg, Lee; Bondarenko, Igor; Sarosiek, Tomasz; Oprean, Cristina; Cardona-Huerta, Servando; Hansen, Vincent; Rossi, Giorgia; Rizzi, Giada; Borroni, Maria Elisa; Rugo, Hope
2017-04-01
Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK 1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT 3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study. This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25-120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0-120 h) CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles. Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1-4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles. NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.
Palli, Swetha Rao; Grabner, Michael; Quimbo, Ralph A; Rugo, Hope S
2015-01-01
To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics. This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. We identified 1,832 palonosetron and 2,387 other 5-HT3 RA ("other") patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs.
Palli, Swetha Rao; Grabner, Michael; Quimbo, Ralph A; Rugo, Hope S
2015-01-01
Purpose To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics. Materials and methods This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. Results We identified 1,832 palonosetron and 2,387 other 5-HT3 RA (“other”) patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). Conclusion Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs. PMID:26124681
Samuel, Cleo A.; Landrum, Mary Beth; McNeil, Barbara J.; Bozeman, Samuel R.; Williams, Christina D.
2014-01-01
Objectives. We assessed cancer care disparities within the Veterans Affairs (VA) health care system and whether between-hospital differences explained disparities. Methods. We linked VA cancer registry data with VA and Medicare administrative data and examined 20 cancer-related quality measures among Black and White veterans diagnosed with colorectal (n = 12 897), lung (n = 25 608), or prostate (n = 38 202) cancer from 2001 to 2004. We used logistic regression to assess racial disparities for each measure and hospital fixed-effects models to determine whether disparities were attributable to between- or within-hospital differences. Results. Compared with Whites, Blacks had lower rates of early-stage colon cancer diagnosis (adjusted odds ratio [AOR] = 0.80; 95% confidence interval [CI] = 0.72, 0.90), curative surgery for stage I, II, or III rectal cancer (AOR = 0.57; 95% CI = 0.41, 0.78), 3-year survival for colon cancer (AOR = 0.75; 95% CI = 0.62, 0.89) and rectal cancer (AOR = 0.61; 95% CI = 0.42, 0.87), curative surgery for early-stage lung cancer (AOR = 0.50; 95% CI = 0.41, 0.60), 3-dimensional conformal or intensity-modulated radiation (3-D CRT/IMRT; AOR = 0.53; 95% CI = 0.47, 0.59), and potent antiemetics for highly emetogenic chemotherapy (AOR = 0.87; 95% CI = 0.78, 0.98). Adjustment for hospital fixed-effects minimally influenced racial gaps except for 3-D CRT/IMRT (AOR = 0.75; 95% CI = 0.65, 0.87) and potent antiemetics (AOR = 0.95; 95% CI = 0.82, 1.10). Conclusions. Disparities in VA cancer care were observed for 7 of 20 measures and were primarily attributable to within-hospital differences. PMID:25100422
The management of children with gastroenteritis and dehydration in the emergency department.
Colletti, James E; Brown, Kathleen M; Sharieff, Ghazala Q; Barata, Isabel A; Ishimine, Paul
2010-06-01
Acute gastroenteritis is characterized by diarrhea, which may be accompanied by nausea, vomiting, fever, and abdominal pain. To review the evidence on the assessment of dehydration, methods of rehydration, and the utility of antiemetics in the child presenting with acute gastroenteritis. The evidence suggests that the three most useful predictors of 5% or more dehydration are abnormal capillary refill, abnormal skin turgor, and abnormal respiratory pattern. Studies are conflicting on whether blood urea nitrogen (BUN) or BUN/creatinine ratio correlates with dehydration, but several studies found that low serum bicarbonate combined with certain clinical parameters predicts dehydration. In most studies, oral or nasogastric rehydration with an oral rehydration solution was equally efficacious as intravenous (i.v.) rehydration. Many experts discourage the routine use of antiemetics in young children. However, children receiving ondensetron are less likely to vomit, have greater oral intake, and are less likely to be treated by intravenous rehydration. Mean length of Emergency Department (ED) stay is also less, and very few serious side effects have been reported. In the ED, dehydration is evaluated by synthesizing the historical and physical examination, and obtaining laboratory data points in select patients. No single laboratory value has been found to be accurate in predicting the degree of dehydration and this is not routinely recommended. The evidence suggests that the majority of children with mild to moderate dehydration can be treated successfully with oral rehydration therapy. Ondansetron (orally or intravenously) may be effective in decreasing the rate of vomiting, improving the success rate of oral hydration, preventing the need for i.v. hydration, and preventing the need for hospital admission in those receiving i.v. hydration. Copyright 2010. Published by Elsevier Inc.
A review of nabilone in the treatment of chemotherapy-induced nausea and vomiting
Ware1, Mark A; Daeninck, Paul; Maida, Vincent
2008-01-01
Chemotherapy-induced nausea and vomiting (CINV) in cancer patients places a significant burden on patients’ function and quality of life, their families and caregivers, and healthcare providers. Despite the advances in preventing CINV, a substantial proportion of patients experience persistent nausea and vomiting. Nabilone, a cannabinoid, recently received Food and Drug Administration approval for the treatment of the nausea and vomiting in patients receiving cancer chemotherapy who fail to achieve adequate relief from conventional treatments. The cannabinoids exert antiemetic effects via agonism of cannabinoid receptors (CB1 and CB2). Clinical trials have demonstrated the benefits of nabilone in cancer chemotherapy patients. Use of the agent is optimized with judicious dosing and selection of patients. PMID:18728826
Coluzzi, Flaminia; Mattia, Consalvo
2016-08-01
Granisetron transdermal delivery system (GTDS) is the first 5-HT3 drug to be transdermally delivered and represents a convenient alternative to oral and intravenous antiemetics for the treatment of chemotherapy-induced nausea and vomiting. GTDS is effective and well tolerated in patients receiving multiple-day moderate-to-highly emetogenic chemotherapy. In this setting noninferiority studies showed similar efficacy when GTDS was compared with intravenous and oral granisetron and intravenous palonosetron. GTDS has shown good cardiovascular safety; however, special caution is needed in patients at risk for developing excessive QTc interval prolongation and arrhythmias. So far, GTDS has been investigated for intravenous prevention in comparison with granisetron and palonosetron; however, further prospects open the route to future clinical investigations.
Adjuvant and induction chemotherapy in non-small cell lung cancer.
Pirker, R; Malayeri, R; Huber, H
1999-01-01
About 25%-30% of patients with non-small cell lung cancer can be resected with curative intent. However, systemic relapses occur in up to 70% of these patients. Thus, postoperative adjuvant chemotherapy was evaluated in several randomised trials but the results of these trials were inconclusive with a survival benefit only in some trials. Shortcomings of these trials included low number of patients, poor patient compliance and inadequate chemotherapy protocols. A recent meta-analysis suggested an absolute survival benefit of 5% at five years for postoperative cisplatin-based chemotherapy as compared to surgery alone. Thus adjuvant chemotherapy with both improved chemotherapy protocols and improved anti-emetics is currently re-evaluated in several randomised trials on large patient populations.
Emerging role of thalidomide in the treatment of gastrointestinal bleeding.
McFarlane, Michael; O'Flynn, Lauren; Ventre, Rachel; Disney, Benjamin R
2018-04-01
Thalidomide was initially synthesised in 1954 and marketed as a sedative and antiemetic for morning sickness. It was withdrawn in 1961 due to the realisation that it was teratogenic with over 10 000 children born with congenital abnormalities. Since then it has been used for treatment of dermatological and oncological conditions, including myeloma. In 1994, it was found to have a potent antiangiogenic effect via downregulation of vascular endothelial growth factor (VEGF). This has led to its use in gastrointestinal bleeding, as vascular abnormalities such as angiodysplasia have been found to have elevated VEGF levels. This article will review the current evidence of the use of thalidomide in bleeding associated with gastrointestinal vascular malformations, including angiodysplasia, gastric cancer and radiation-induced proctitis.
Preventing recurrence of severe morning sickness
Koren, Gideon; Maltepe, Caroline
2006-01-01
QUESTION A recent Motherisk article showed that initiating antinauseants even before symptoms start could prevent recurrence of severe morning sickness. In the study described, however, different physicians used different drugs. How can one be sure which drugs work? ANSWER The study of 26 women who had had severe morning sickness during previous pregnancies showed that using antiemetics before symptoms of morning sickness started appeared to prevent recurrence of severe morning sickness in subsequent pregnancies. Physicians in the United States used various antinauseant drugs. Physicians in Canada administered only one drug, the combination of doxylamine-pyridoxine (Diclectin®), to 12 women. Subanalysis of these 12 women revealed that pre-emptive use of doxylamine-pyridoxine significantly decreased the likelihood that severe morning sickness would recur. PMID:17279232
Preventing recurrence of severe morning sickness.
Koren, Gideon; Maltepe, Caroline
2006-12-01
A recent Motherisk article showed that initiating antinauseants even before symptoms start could prevent recurrence of severe morning sickness. In the study described, however, different physicians used different drugs. How can one be sure which drugs work? The study of 26 women who had had severe morning sickness during previous pregnancies showed that using antiemetics before symptoms of morning sickness started appeared to prevent recurrence of severe morning sickness in subsequent pregnancies. Physicians in the United States used various antinauseant drugs. Physicians in Canada administered only one drug, the combination of doxylamine-pyridoxine (Diclectin), to 12 women. Subanalysis of these 12 women revealed that pre-emptive use of doxylamine-pyridoxine significantly decreased the likelihood that severe morning sickness would recur.
Wu, Jyh-I; Lu, Shao-Fong; Chia, Yuan-Yi; Yang, Lin-Cheng; Fong, Wen-Po; Tan, Ping-Heng
2009-11-01
To evaluate the prophylactic use of dexamethasone with sevoflurane in outpatient anorectal surgery. Randomized, controlled study. Operating room and Postanesthesia Care Unit of a general hospital. 60 adult, ASA physical status I and II outpatients undergoing anorectal surgery. Patients were randomized to receive either dexamethasone 5 mg intravenously (IV; Group D; n = 30) or an equal volume of saline (Group S; n = 30) before anesthesia induction. Anesthesia was induced with propofol 2.5 mg.kg(-1), fentanyl two microg.kg(-1), and 2% lidocaine one mg.kg(-1) followed by placement of a Laryngeal Mask Airway. Frequency of postoperative nausea and vomiting (PONV), visual analog scale (VAS) pain scores, and patient satisfaction were recorded. Frequency of PONV and VAS pain scores were significantly lower in Group D than Group S (P < 0.05). The time required for "home readiness" was significantly shorter in Group D than Group S (P < 0.05). The prophylactic administration of 5 mg dexamethasone IV can reduce the frequency of PONV, lower VAS pain scores, facilitate recovery to home readiness, and improve satisfaction in outpatients undergoing anorectal surgery.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Qing; Institute of Clinical Pharmacology, Central South University, Hunan 410078; Guo, Dong
2013-11-15
The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate formore » OCTs and MATEs, in wild-type and Mate1−/− mice. The nephrotoxicity was assessed in the wild-type and Mate1−/− mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1−/− mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT{sub 3}) receptor antagonists, such as ondansetron, should be investigated in patients. - Highlights: • Nephrotoxicity significantly limits clinical use of the
Sabbagh, Heba J; Alamoudi, Najlaa M; Abdulhameed, Fatma Dawood; Innes, Nicola P T; Al-Aama, Jumana Y; Hummaida, Tarig; Almalik, Manal; El Derwi, Douaa A; Mossey, Peter A
2016-07-01
Nonsyndromic orofacial cleft (NSOFC) etiology is multifactorial and heterogeneous. This study aimed to identify environmental risk factors related to NSOFC in the Western Region of Saudi Arabia. A case-control study carried out in seven hospitals in two main cities (Jeddah and Maddina) over 2 years on parents of 112 infants with NSOFC (infants were also examined) and 138 infant controls, matched for age (<18 months), gender, and location, completed a questionnaire on 3-month pregestation and first trimester events. There was significantly increased NSOFC risk with twin pregnancies (P = .01, odds ratio [OR] = 9.5, 95% confidence interval [CI]: 1.15 to 78.4), maternal antibiotic use (P = .021, OR = 2.71, 95% CI: 1.11 to 6.62), antiemetic medication (P = .005, OR = 2.85, 95% CI: 1.3 to 6), severe morning sickness (P = .006, OR = 3.6, 95% CI: 1.34 to 9.65), illness (P = .009, OR = 2.19, 95% CI: 1.17 to 4.08), common cold/flu (P = .003, OR = 3.32, 95% CI: 1.48 to 7.58), Jorak smoking (P = .004, OR = 14.07, 95% CI: 1.55 to 128.1), and passive smoking (P = .05, OR = 2.05, 95% CI: 1.05 to 4.01). Reduced NSOFC risk was found with calcium supplementation (P = .02, OR = 0.32, 95% CI: 0.11 to 0.88), incense use (P = .03, OR = 0.58, 95% CI: 0.34 to 0.98), and maternal drinking water, with Zamzam water (which contains a high concentration of minerals) showing a significant protective effect compared with tap water (P = .01, 95% CI: 0.06 to 0.6) and bottled water (P = .02, 95% CI: 0.03 to 0.57). Twin births, maternal antibiotic use, antiemetic medication, severe morning sickness, common cold/flu, Jorak smoking, and passive smoking were associated with infants born with NSOFC. Calcium supplementation, incense use, and Zamzam water reduced the risk of NSOFC, raising the possibility of community preventive programs.
Kim, Kun Hyung; Kim, Dae Hun; Bae, Ji Min; Son, Gyung Mo; Kim, Kyung Hee; Hong, Seung Pyo; Yang, Gi Young; Kim, Hee Young
2017-01-04
This study aims to assess the feasibility of acupuncture and a Pericardium 6 (PC6) wristband as an add-on intervention of antiemetic medication for the prevention of postoperative nausea and vomiting (PONV) in patients undergoing elective laparoscopic colorectal cancer resection. A total of 60 participants who are scheduled to undergo elective laparoscopic resection of colorectal cancer will be recruited. An enhanced recovery after surgery protocol using standardised antiemetic medication will be provided for all participants. Participants will be equally randomised into acupuncture plus PC6 wristband (Acupuncture), PC6 wristband alone (Wristband), or no acupuncture or wristband (Control) groups using computer-generated random numbers concealed in opaque, sealed, sequentially numbered envelopes. For the acupuncture combined with PC6 wristband group, the embedded auricular acupuncture technique for preoperative anxiolysis and up to three sessions of acupuncture treatments with manual and electrical stimulation within 48 hours after surgery will be provided by qualified Korean medicine doctors. The PC6 wristband will be applied in the Acupuncture and Wristband groups, beginning 1 hour before surgery and lasting 48 hours postoperatively. The primary outcome will be the number of participants who experience moderate or severe nausea, defined as nausea at least 4 out of 10 on a severity numeric rating scale or vomiting at 24 hours after surgery. Secondary outcomes, including symptom severity, participant global assessments and satisfaction, quality of life, physiological recovery, use of medication and length of hospital stay, will be assessed. Adverse events and postoperative complications will be measured for 1 month after surgery. All participants will provide written informed consent. The study has been approved by the institutional review board (IRB). This pilot trial will inform a full-scale randomised trial of acupuncture combined with PC6 stimulation
Gallagher, Lisa M; Gardner, Vickie; Bates, Debbie; Mason, Shelley; Nemecek, Jeanine; DiFiore, Jacquelyn Baker; Bena, James; Li, Manshi; Bethoux, Francois
Music therapy (MT) research has demonstrated positive effects on fatigue, depressed mood, anxiety, and pain in perioperative care areas. However, there has been limited research on the effects of MT for surgical patients on orthopaedic units. The purpose of this study was to understand the impact of MT sessions on post-elective orthopaedic surgery patients' pain, mood, nausea, anxiety, use of narcotics and antiemetics, and length of stay. This was a randomized controlled study with an experimental arm (MT sessions) and a control arm (standard medical care). Patients received MT within 24 hours of admission to the unit, as well as every day of their stay. Same-day pre- and postdata were collected 30 minutes apart for both arms, including patient self-reported mood, pain, anxiety, and nausea. Use of medications and length of stay were gleaned from the electronic medical record. Data were obtained for 163 patients, age 60.5 ± 11.1 years, 56% of whom were male. Joints targeted by surgeries were hips (54%), knees (42%), and shoulders (4%). There were significantly greater changes favoring the MT group on Day 1 (pain, anxiety, and mood), Day 2 (pain, anxiety, mood, and nausea), and Day 3 (pain, anxiety, and mood). Among participants with a pre-pain score of 2 or more on Day 1, a decrease of at least 2 points was noted in 36% of the MT group and 10% of the control group (P < .001). Overall, 73% of MT patients versus 41% of control patients reported improved pain (P < .001). No significant between-group differences in medications or length of stay were noted. We observed greater same-day improvements of pain, emotional status, and nausea with MT sessions, compared to usual care, in patients hospitalized after elective orthopaedic surgeries. Effects on narcotic and antiemetic usage, as well as length of stay, were not observed. More research needs to be conducted to better understand the benefits of MT pre- and post-elective orthopaedic surgery.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jahn, Franziska, E-mail: franziska.jahn@uk-halle.de; Riesner, Anica; Jahn, Patrick
Purpose: To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy–induced nausea and vomiting. Patients and Methods: This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in thismore » period. Results: Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03). Conclusion: This is the first study of an NK1-RA–containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting.« less
Comparison of pain-relieving effects of fentanyl versus ketorolac after eye amputation surgery.
Kim, Jin Hyung; Jang, Sun Young; Kim, Myung Jin; Lee, Sang Yeul; Yoon, Jin Sook
2013-08-01
To investigate the analgesic effect and incidence of postoperative nausea and vomiting (PONV) between the opioid fentanyl and the non-steroidal anti-inflammatory drug ketorolac in patients who underwent eye amputation surgery. Retrospective observational case series. Eighty-two patients underwent evisceration or enucleation surgery by one surgeon over a 2-year period. Fentanyl by intravenous patient-controlled analgesia (IV-PCA) at 20 µg/kg with 12 mg/kg ondansetron or intravenous ketorolac at 2 mg/kg/day was administered to patients at postoperative days 0, 1, and 2. The pain score was measured using an 11-point visual analog scale (VAS). The incidence of severe nausea requiring anti-emetics and the incidence of vomiting were reviewed. The mean postoperative VAS in the fentanyl group was significantly lower than that in the ketorolac group on the day of operation for both types of surgery (p = 0.001 and p = 0.004, respectively). At postoperative days 1 and 2, the mean VAS was not different between the two groups for either surgical type (p > 0.05 for both days). The mean VAS was significantly higher in eviscerated patients than in enucleated patients at postoperative days 0 and 1 in the fentanyl group (p = 0.023 and p = 0.016, respectively). However, this was not observed in the ketorolac group. The incidence of PONV was higher in the fentanyl group than in the ketorolac group, although this was not statistically significant for either surgical type (p > 0.05 for both groups). Fentanyl was more effective as an analgesic than was ketorolac on the day of operation for both surgical types. There was no difference between the two analgesics on postoperative day 1. The analgesic effect of fentanyl in enucleated patients was significantly higher than in eviscerated patients at postoperative days 0 and 1. The use of fentanyl by IV-PCA was associated with greater PONV despite co-administration with anti-emetics, although this finding was not significant.
Comparison of Pain-relieving Effects of Fentanyl versus Ketorolac after Eye Amputation Surgery
Kim, Jin Hyung; Jang, Sun Young; Kim, Myung Jin; Lee, Sang Yeul
2013-01-01
Purpose To investigate the analgesic effect and incidence of postoperative nausea and vomiting (PONV) between the opioid fentanyl and the non-steroidal anti-inflammatory drug ketorolac in patients who underwent eye amputation surgery. Methods Retrospective observational case series. Eighty-two patients underwent evisceration or enucleation surgery by one surgeon over a 2-year period. Fentanyl by intravenous patient-controlled analgesia (IV-PCA) at 20 µg/kg with 12 mg/kg ondansetron or intravenous ketorolac at 2 mg/kg/day was administered to patients at postoperative days 0, 1, and 2. The pain score was measured using an 11-point visual analog scale (VAS). The incidence of severe nausea requiring anti-emetics and the incidence of vomiting were reviewed. Results The mean postoperative VAS in the fentanyl group was significantly lower than that in the ketorolac group on the day of operation for both types of surgery (p = 0.001 and p = 0.004, respectively). At postoperative days 1 and 2, the mean VAS was not different between the two groups for either surgical type (p > 0.05 for both days). The mean VAS was significantly higher in eviscerated patients than in enucleated patients at postoperative days 0 and 1 in the fentanyl group (p = 0.023 and p = 0.016, respectively). However, this was not observed in the ketorolac group. The incidence of PONV was higher in the fentanyl group than in the ketorolac group, although this was not statistically significant for either surgical type (p > 0.05 for both groups). Conclusions Fentanyl was more effective as an analgesic than was ketorolac on the day of operation for both surgical types. There was no difference between the two analgesics on postoperative day 1. The analgesic effect of fentanyl in enucleated patients was significantly higher than in eviscerated patients at postoperative days 0 and 1. The use of fentanyl by IV-PCA was associated with greater PONV despite co-administration with anti-emetics, although this finding
2006-01-01
In July 2003, the Food and Drug Administration approved palonosetron hydrochloride injection for the treatment of chemotherapy-induced nausea and vomiting (CINV). The newest agent in the class of 5-HT3 receptor antagonists (5-HT3RAs), palonosetron differs from other agents in its class by its higher receptor-binding affinity and longer half-life. These pharmacological properties have resulted in improved antiemetic activity in clinical trials, particularly in the treatment of delayed CINV following moderate emetogenic chemotherapy. Based on the results of these clinical studies, palonosetron is the only 5-HT3RA approved for delayed CINV. Palonosetron is given as a single 0.25-mg intravenous dose 30 minutes before the initial dose of chemotherapy. Headache and constipation were the most common adverse events reported with palonosetron therapy. PMID:17106506
Serotonergic mechanisms in emesis
NASA Technical Reports Server (NTRS)
Lucot, J. B.; Crampton, G. H.
1988-01-01
The observation that the cerebrospinal fluid of cats which are susceptible to motion sickness contained lower baseline levels of 5-hydroxyindoleacetic acid, among other constituents, led to the hypothesis that serotonin inhibits emesis. The hypothesis was tested by administration of the serotonin-1A agonists buspirone and 8-OH-DPAT before motion testing in cats susceptible to motion sickness. Both drugs blocked motion sickness in a dose-dependent fashion. To determine if these drugs blocked emesis elicited by other stimuli, they were administered before subcutaneous administration of the alpha-2 noradrenergic agonist, xylazine. Both drugs also blocked xylazine-induced emesis. It was concluded that the stimulation of serotonin-1A receptors inhibits emesis elicited by the two stimuli and that this mechanism may exert a general antiemetic effect.
[Diphenhydramine addiction and detoxification. A systematic review and case report].
Erbe, Sebastian; Bschor, Tom
2013-07-01
In many countries diphenhydramine (DPH) is commonly available over the counter, frequently used, and generally regarded as a harmless drug. It is used as a sedative, antiallergic or antiemetic substance. We present a systematic review of literature search in Pubmed from 1972 to 2012 describing DPH addiction. The literature search in reveals that the addictive potential of DPH can be regarded as proved, based on cases series, eight case reports, a pharmacological overview, one uncontrolled, and one randomized, placebo controlled study. In addition we report a case of an abstinent alcoholic patient treated in our department for DPH-dependency. Especially when treating patients with a history of addiction, physicians should consider and check the possibility of a DPH dependency. © Georg Thieme Verlag KG Stuttgart · New York.
Büttner, Stefan; Koch, Benjamin; Dolnik, Olga; Eickmann, Markus; Freiwald, Tilo; Rudolf, Sarah; Engel, Jürgen; Becker, Stephan; Ronco, Claudio; Geiger, Helmut
2014-01-01
Therapeutic options for Ebola virus disease (EVD) are currently limited to (1) best supportive care, and (2) evolving virus-specific therapies, resulting from decades of analyzing one of the world's deadliest diseases. Supportive care ranges from oral or intravenous rehydration therapy and anti-emetics in developing countries to much more extensive life-support interventions in resource-rich countries. Current EVD-specific therapies attempt to either interfere with the earliest steps of viral replication or to elicit a strong immune response against the virus. An entirely new approach is the extracorporeal elimination of viruses and viral glycoproteins by lectin affinity plasmapheresis. Herein, we report for the first time the successful and safe use of lectin affinity plasmapheresis in a patient with severe Ebola virus disease. © 2015 S. Karger AG, Basel.
Elwood, C; Devauchelle, P; Elliott, J; Freiche, V; German, A J; Gualtieri, M; Hall, E; den Hertog, E; Neiger, R; Peeters, D; Roura, X; Savary-Bataille, K
2010-01-01
Emesis is a common presenting sign in small animal practice. It requires a rational approach to management that is based upon a sound understanding of pathophysiology combined with logical decision making. This review, which assesses the weight of available evidence, outlines the physiology of the vomiting reflex, causes of emesis, the consequences of emesis and the approach to clinical management of the vomiting dog. The applicability of diagnostic testing modalities and the merit of traditional approaches to management, such as dietary changes, are discussed. The role and usefulness of both traditional and novel anti-emetic drugs is examined, including in specific circumstances such as following cytotoxic drug treatment. The review also examines areas in which common clinical practice is not necessarily supported by objective evidence and, as such, highlights questions worthy of further clinical research.
Wang, Chong-Zhi; Qi, Lian-Wen; Yuan, Chun-Su
2015-01-01
Ginger is a commonly used spice and herbal medicine worldwide. Besides its extensive use as a condiment, ginger has been used in traditional Chinese medicine for the management of various medical conditions. In recent years, ginger has received wide attention due to its observed antiemetic and anticancer activities. This paper reviews the potential role of ginger and its active constituents in cancer chemoprevention. The phytochemistry, bioactivity, and molecular targets of ginger constituents, especially 6-shogaol, are discussed. The content of 6-shogaol is very low in fresh ginger, but significantly higher after steaming. With reported anti-cancer activities, 6-shogaol can be served as a lead compound for new drug discovery. The lead compound derivative synthesis, bioactivity evaluation, and computational docking provide a promising opportunity to identify novel anticancer compounds originating from ginger.
Ryu, Jung-Hee; Jeon, Young-Tae; Hwang, Jung-Won; Oh, A-Young; Moon, Ji-Yeon; Ro, Young-Jin; Kim, Chong Soo; Chen, Chen; Apfel, Christian C; Do, Sang-Hwan
2011-09-01
Patients undergoing general anesthesia for laparoscopic cholecystectomy have a high risk of postoperative nausea and vomiting (PONV) with incidences up to 75%. Ramosetron, a serotonin subtype 3 (5-HT(3)) antagonist, has been shown to be effective as an antiemetic after chemotherapy and surgery. Consensus guidelines recommend a combination of antiemetic therapies in high-risk groups. Until now, no published data have been available on the use of combination oral plus intravenous ramosetron. The goal of this prospective, randomized, double-blind study was to compare the efficacy and tolerability of intravenous, oral, and the combination of oral and intravenous ramosetron for PONV prophylaxis in patients undergoing laparoscopic cholecystectomy. Patients scheduled for laparoscopic cholecystectomy were double-randomly allocated to 1 of 3 groups. Patients were randomly allocated to receive either 0.3 mg of intravenous ramosetron (group A), 0.1 mg of oral ramosetron (group B), or the combination of 0.1 mg of oral ramosetron and 0.3 mg of intravenous ramosetron (group C). All patients received standardized balanced anesthesia with desflurane and remifentanil. Postoperative nausea, retching, vomiting, pain, and adverse effects were assessed at 0 to 2, 2 to 24, and 24 to 48 hours after surgery. A total of 124 Korean patients (67 women, 57 men; age range, 25-65 years) were randomized to 1 of 3 study groups (42 in group A [mean age, 49.8 years], 41 in group B [mean age, 47.4 years], and 41 in group C [mean age, 48.9 years]). No statistical differences were observed among the 3 groups with regard to patient characteristics and information on surgery and anesthesia. During postoperative period 0 to 2 hours, complete response occurred in 31 (74%) patients in group A, 27 (66%) in group B, and 37 (90%) in group C. During the postoperative period of 2 to 24 hours, complete response was observed in 36 (86%), 33 (80%), and 40 (98%) patients in groups A, B, and C, respectively; there
Treatment of tension-type headache: from old myths to modern concepts.
Barbanti, P; Egeo, G; Aurilia, C; Fofi, L
2014-05-01
Tension-type headache (TTH) is the second most common human disease, accounting for intense disability, high costs and numerous workdays lost. Tension-type headache is less simple and easy-to-treat than commonly thought. Antidepressants, despite their poor tolerability, are still the first-choice drugs for preventing TTH. The most widely studied non-pharmacological approach to TTH, cognitive-behavioral techniques, effectively relieve pain only in selected patients. The most frequently used and recommended treatments for acute TTH, NSAIDs and paracetamol have scarce efficacy as documented by their low therapeutic gain over placebo in the 2-h pain-free response. Their effectiveness may be increased by a more proper use and by the adjunction of caffeine, antiemetics, myorelaxants or tranquillizers but the risk of medication-overuse headache must be considered. Hence, the need for more effective and tailored treatments in TTH remains.
Drug Interactions in Childhood Cancer
Haidar, Cyrine; Jeha, Sima
2016-01-01
Children with cancer are increasingly benefiting from novel therapeutic strategies and advances in supportive care, as reflected in improvements in both their survival and quality of life. However, the continuous emergence of new oncology drugs and supportive care agents has also increased the possibility of deleterious drug interactions and healthcare providers need to practice extreme caution when combining medications. In this review, we discuss the most common interactions of chemotherapeutic agents with supportive care drugs such as anticonvulsants, antiemetics, uric acid–lowering agents, acid suppressants, antimicrobials, and pain management medications in pediatric oncology patients. As chemotherapy agents interact not only with medications but also with foods and herbal supplements that patients receive during the course of their treatment, we also briefly review such interactions and provide recommendations to avoid unwanted and potentially fatal interactions in children with cancer. PMID:20869315
Sklenář, Zbyněk; Horáčková, Kateřina; Bakhouche, Hana
2014-04-01
In veterinary medicine, extemporaneously prepared drugs can be also used in therapy. In the recent four years the selection of suitable compounds for extemporaneous (magistral) preparation has been expanded and new possibilities for the creation of formulas have appeared. The paper reports on the substances available for compounding that can be used in veterinary medicine, in the pharmacotherapeutic classes antibiotics, antimycotics, antiseptics, corticosteroids, emollients and epithelizing agents, anti-inflammatory drugs, local anesthetics, decongestives, beta-blockers and calcium channel blockers, antiemetics and prokinetics, sedatives and hypnotics. The emphasis has been placed on newly available substances. Examples of suitable magistral formulas are presented that can replace mass-produced drug products which are not readily obtainable. The aim of the paper is to inform pharmacists and veterinarians about new possibilities of drug compounding. compounded preparations extemporaneous preparation compounding of drugs possibilities magistral formulas in veterinary medicine.
Richards, John R; Lapoint, Jeff M; Burillo-Putze, Guillermo
2018-01-01
Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation. Putative mechanisms responsible for the benefit of hot water hydrotherapy are also investigated. An extensive search of PubMed, OpenGrey, and Google Scholar from inception to April 2017 was performed to identify known and theoretical thermoregulatory mechanisms associated with the endocannabinoid system. The searches resulted in 2417 articles. These articles were screened for relevant mechanisms behind capsaicin and heat activation having potential antiemetic effects. References from the selected articles were also hand-searched. A total of 137 articles were considered relevant and included. Capsaicin: Topical capsaicin is primarily used for treatment of neuropathic pain, but it has also been used successfully in some 20 cases of cannabinoid hyperemesis syndrome. The pharmacokinetics and pharmacodynamics of capsaicin as a transient receptor potential vanilloid 1 agonist may explain this effect. Topical capsaicin has a longer half-life than oral administration, thus its potential duration of benefit is longer. Capsaicin and transient receptor potential vanilloid 1: Topical capsaicin binds and activates the transient receptor potential vanilloid 1 receptor, triggering influx of calcium and sodium, as well as release of inflammatory neuropeptides leading to transient burning, stinging, and itching. This elicits
Siddique, R; Hafiz, M G; Rokeya, B; Jamal, C Y; Islam, A
2011-10-01
Effect of ondansetron and granisetron were evaluated in sixty (60) children (age 4-11 years) irrespective of sex, diagnosed case of acute lymphoblastic leukemia (ALL) who received high dose methotrexate and did not receive any antiemetic 24 hours prior to HDMTX. This was a prospective, randomized, double-blind, single center study. Of 60 children, 30 received oral ondansetron (4mg) and rest 30 granisetron (1mg) half an hour before therapy. Drugs were randomly allocated with appropriate code. The patients were followed up from day 1 to day 5 of therapy. Episodes of nausea and vomiting were recorded and scorings was done every 24 hours following chemotherapy. No significant difference was found between two groups according to acute emesis (Day-1) (p=0.053). In day two and day three it was significant (p<0.05). In day four it was significant (p=0.002). Early chemotherapy induced nausea and vomiting (CINV) were controlled 90% in children who received granisetron and 70% in children who received ondansetron. Delayed (Day 2-4) CINV were controlled in 80% of children who received granisetron and 43.4% who received ondansetron (p<0.05). Granisetron group required additional doses only 3.3% cases and ondanseton group 30% cases on the second day (p<0.05). Result was significant between two groups. About 36.7% patients had episodes of nausea on day four of chemotherapy in ondansetron group and it was only 3.3% in granisetron group due to adverse effects of antiemetic drug itself (p=0.001). Maximum episodes of vomiting were found on the second day in ondansetron group 33.3% and in granisetron group 3.3% (p=0.003). Though adverse effects like headache, constipation, abdominal pain and loose motion were common in both group of children but their number was much less in children who received granisetron. On second day of therapy score of nausea and vomiting was maximum in ondansetron and minimum in granisetron treated on day 4 and the result was significant. So, to prevent acute
Tricco, Andrea C; Soobiah, Charlene; Antony, Jesmin; Hemmelgarn, Brenda; Moher, David; Hutton, Brian; Straus, Sharon E
2013-06-28
Patients undergoing surgery or chemotherapy often experience nausea and vomiting. To increase their quality of life and treatment satisfaction, antiemetic medication, such as serotonin receptor antagonists, is often prescribed for patients experiencing these symptoms. However, early warning signs suggest that serotonin receptor antagonists can cause harm, including arrhythmia. Our objective is to identify the most effective interventions that mitigate the risk of adverse cardiac events associated with serotonin receptor antagonists in patients undergoing surgery and chemotherapy through a systematic review and network meta-analysis. We will search electronic databases (for example, MEDLINE, Embase) from inception onwards, as well as dissertations and governmental reports, to identify interventions (for example, telemetry, electrocardiography, electrolyte monitoring) that decrease the cardiac risk associated with serotonin receptor antagonists among surgery and chemotherapy patients. Eligible comparators include placebo or supportive care; eligible study designs are experimental studies (randomized controlled trials (RCTs), quasi-RCTs, non-RCTs), non-experimental studies (interrupted time series, controlled before-and-after studies), and cohort studies. Outcomes of interest include arrhythmia, sudden cardiac death, QT prolongation, PR prolongation, and all-cause mortality. We will include unpublished studies and studies published in languages other than English.Draft inclusion and exclusion criteria will be established and pilot tested amongst the team. Subsequently, two team members will screen the results in duplicate and resolve conflicts through discussion. The same process will be followed to screen full-text articles, data abstraction, and appraise quality or risk of bias. To determine validity of results, experimental and quasi-experimental studies will be assessed using the Cochrane Effective Practice and Organisation of Care (EPOC) Risk of Bias tool, while
Tu, Longlong; Lu, Zengbing; Dieser, Karolina; Schmitt, Christina; Chan, Sze Wa; Ngan, Man P.; Andrews, Paul L. R.; Nalivaiko, Eugene; Rudd, John A.
2017-01-01
Motion sickness occurs under a variety of circumstances and is common in the general population. It is usually associated with changes in gastric motility, and hypothermia, which are argued to be surrogate markers for nausea; there are also reports that respiratory function is affected. As laboratory rodents are incapable of vomiting, Suncus murinus was used to model motion sickness and to investigate changes in gastric myoelectric activity (GMA) and temperature homeostasis using radiotelemetry, whilst also simultaneously investigating changes in respiratory function using whole body plethysmography. The anti-emetic potential of the highly selective histamine H1 receptor antagonists, mepyramine (brain penetrant), and cetirizine (non-brain penetrant), along with the muscarinic receptor antagonist, scopolamine, were investigated in the present study. On isolated ileal segments from Suncus murinus, both mepyramine and cetirizine non-competitively antagonized the contractile action of histamine with pKb values of 7.5 and 8.4, respectively; scopolamine competitively antagonized the contractile action of acetylcholine with pA2 of 9.5. In responding animals, motion (1 Hz, 4 cm horizontal displacement, 10 min) increased the percentage of the power of bradygastria, and decreased the percentage power of normogastria whilst also causing hypothermia. Animals also exhibited an increase in respiratory rate and a reduction in tidal volume. Mepyramine (50 mg/kg, i.p.) and scopolamine (10 mg/kg, i.p.), but not cetirizine (10 mg/kg, i.p.), significantly antagonized motion-induced emesis but did not reverse the motion-induced disruptions of GMA, or hypothermia, or effects on respiration. Burst analysis of plethysmographic-derived waveforms showed mepyramine also had increased the inter-retch+vomit frequency, and emetic episode duration. Immunohistochemistry demonstrated that motion alone did not induce c-fos expression in the brain. Paradoxically, mepyramine increased c-fos in brain
Dental treatment in patients with severe gag reflex using propofol-remifentanil intravenous sedation
Shin, Sooil
2017-01-01
Patients with severe gag reflex (SGR) have difficulty getting the treatment they require in local clinics, and many tend to postpone the start of their treatment. To address this problem, dentists have used behavioral techniques and/or pharmacological techniques for treatment. Among the pharmacological methods available, propofol IV sedation is preferred over general anesthesia because it is a simpler procedure. Propofol in combination with remifentanil is characterized by stable sedative effects and quick recovery, leading to a deep sedation. Remifentanil acts to reduce the pain caused by lipid-soluble propofol on injection. The synergistic effects of propofol-remifentanil include reduction in the total amount of drug required to achieve a desired sedation level and anti-emetic effects. In this case report, we outline how the use of propofol-remifentanil IV sedation enabled us to successfully complete a wide range of dental treatments in a patient with SGR. PMID:28879331
The optimal management of headaches in children and adolescents
Kacperski, Joanne; Kabbouche, Marielle A.; O’Brien, Hope L.; Weberding, Jessica L.
2016-01-01
The recognition of the diagnosis of migraine in children is increasing. Early and aggressive treatment of migraine in this population with the use of over-the-counter medications has proven effective. The off-label use of many migraine-specific medications is often accepted in the absence of sufficient evidenced-based trials. Mild to severe cases of migraine should be treated with nonsteroidal anti-inflammatory drugs, with triptans used in moderate to severe headaches unresponsive to over-the-counter therapy. Rescue medication including dihydroergotamine [DHE] should be used for status migrainosus, preferably in the hospital setting. Antiemetics that have antidopaminergic properties can be helpful in patients with associated symptoms of nausea and vomiting through their action on central migraine generation. Furthermore, patients and families should be educated on nonpharmacologic management such as lifestyle modification and avoidance of triggers that can prevent episodic migraine. PMID:26788131
Shin, Sooil; Kim, Seungoh
2017-03-01
Patients with severe gag reflex (SGR) have difficulty getting the treatment they require in local clinics, and many tend to postpone the start of their treatment. To address this problem, dentists have used behavioral techniques and/or pharmacological techniques for treatment. Among the pharmacological methods available, propofol IV sedation is preferred over general anesthesia because it is a simpler procedure. Propofol in combination with remifentanil is characterized by stable sedative effects and quick recovery, leading to a deep sedation. Remifentanil acts to reduce the pain caused by lipid-soluble propofol on injection. The synergistic effects of propofol-remifentanil include reduction in the total amount of drug required to achieve a desired sedation level and anti-emetic effects. In this case report, we outline how the use of propofol-remifentanil IV sedation enabled us to successfully complete a wide range of dental treatments in a patient with SGR.
Medical use of cannabis: Italian and European legislation.
Zaami, S; Di Luca, A; Di Luca, N M; Montanari Vergallo, G
2018-02-01
This review illustrates some brief considerations of the medical use of cannabis recently issued in Italy. History and uses of cannabis throughout centuries and different countries are illustrated together with a description of botany and active phytocannabinoids. Then, medical use of cannabis anti-pain treatment for patients resistant to conventional therapies is described in case of chronic neuropathic pain, spasticity, for anticinetosic and antiemetic effect in nausea and vomiting caused by chemotherapy, for appetite stimulating effect in cachexia, anorexia, loss of appetite in cancer patients or patients with AIDS and in anorexia nervosa, hypotensive effect in glaucoma resistant to conventional therapies and for reduction of involuntary body and facial movements in Gilles de la Tourette syndrome. Italian most recent legislation on medical cannabis is detailed with some law proposals, also showing the inconsistent legislation within European Union. Some final considerations of future studies are also reported.
Gastroparesis: a review of current and emerging treatment options
Enweluzo, Chijioke; Aziz, Fahad
2013-01-01
Gastroparesis is a motility disorder of the stomach causing delay in food emptying from the stomach without any evidence of mechanical obstruction. The majority of cases are idiopathic. Patients need to be diagnosed properly by formal testing, and the evaluation of the severity of the gastroparesis may assist in guiding therapy. Initially, dietary modifications are encouraged, which include frequent and small semisolid-based meals. Promotility medications, like erythromycin, and antiemetics, like prochlorperazine, are offered for symptom relief. In patients who are refractory to pharmacologic treatment, more invasive options, such as intrapyloric botulinum toxin injections, placement of a jejunostomy tube, or implantation of a gastric stimulator, can be considered. Hemin therapy and gastric electric stimulation are emerging treatment options that are still at different stages of research. Regenerative medicine and stem cell-based therapies also hold promise for gastroparesis in the near future. PMID:24039443
Eiseman, Julie L; Sciullo, Michael; Wang, Hong; Beumer, Jan H; Horn, Charles C
2017-10-01
Several cancer chemotherapies cause nausea and vomiting, which can be dose-limiting. Musk shrews are used as preclinical models for chemotherapy-induced emesis and for antiemetic effectiveness. Unlike rats and mice, shrews possess a vomiting reflex and demonstrate an emetic profile similar to humans, including acute and delayed phases. As with most animals, dosing of shrews is based on body weight, while translation of such doses to clinically equivalent exposure requires doses based on body surface area. In the current study body surface area in musk shrews was directly assessed to determine the Meeh constant (K m ) conversion factor (female = 9.97, male = 9.10), allowing estimation of body surface area based on body weight. These parameters can be used to determine dosing strategies for shrew studies that model human drug exposures, particularly for investigating the emetic liability of cancer chemotherapeutic agents.
Coleman, Morton; Martin, Peter; Ruan, Jia; Furman, Richard; Niesvizky, Ruben; Elstrom, Rebecca; George, Patricia; Leonard, John; Kaufmann, Thomas
2008-03-01
The prednisone, etoposide, procarbazine and cyclophosphamide (PEP-C) oral combination chemotherapy regimen (prednisone 20 mg, cyclophosphamide 50 mg, etoposide 50 mg, and procarbazine 50 mg with an oral anti-emetic) was employed at our center to treat 22 patients with heavily pretreated, recurrent mantle cell lymphoma (MCL). All medications were administered daily until leukocytes fell to <3.0 x 10(9)/L whereupon treatment was withheld until recovery from the nadir. Therapy was then reinstituted on a daily, alternate day, or fractionated basis (e.g. 5 of 7 days) depending on patient tolerance. Doses given per day were held constant. Eighty-two percent achieved an objective response with 46% complete responses and 36% partial responses. Median time on therapy was 17 months. The regimen was well tolerated. Our findings demonstrate that low-dose oral agents administered in combination for continuous, prolonged periods with minimal drug-free intervals (metronomic therapy) may represent a novel, effective, easily tolerated approach to MCL and that this treatment approach warrants further exploration.
Dietary poisoning with Veratrum album--a report of two cases.
Zagler, Bernhard; Zelger, Anton; Salvatore, Carmen; Pechlaner, Christoph; De Giorgi, Franco; Wiedermann, Christian J
2005-02-01
Veratrum album is a poisonous plant that can easily be mistaken for the yellow gentian, Gentiana lutea, used in beverages. Two adult men were brought to the emergency department six hours after drinking gentian spirit. Each presented with nausea and vomiting, preceded by headache, developed within one hour after ingestion, and followed by diarrhea in one of the patients. Vital signs were normal except for heart rates of 42 and 45 beats per minute in the two patients, respectively. Laboratory findings were unremarkable. Electrocardiograms revealed sinus bradycardia. Activated charcoal and antiemetics were given and the patients were admitted for observation of signs of toxicity. The further clinical course was uneventful. Heart rates returned to normal within eight hours after admission. Retrospective investigation of the gentian beverage confirmed that V. album was mistaken for G. lutea. Patients with clinical toxicity following unintentional ingestion of V. album should be kept under observation and generally recover with supportive care.
Cannabinoid Regulation of Acute and Anticipatory Nausea
Rock, Erin M.; Sticht, Martin A.; Limebeer, Cheryl L.; Parker, Linda A.
2016-01-01
Abstract Chemotherapy-induced nausea is one of the most distressing symptoms reported by patients undergoing treatment, and even with the introduction of newer antiemetics such as ondansetron and aprepitant, nausea remains problematic in the clinic. Indeed, when acute nausea is not properly managed, the cues of the clinic can become associated with this distressing symptom resulting in anticipatory nausea for which no effective treatments are available. Clinical trials exploring the potential of exogenous or endogenous cannabinoids to reduce chemotherapy-induced nausea are sparse; therefore, we must rely on the data from pre-clinical rat models of nausea. In this review, we explore the human and pre-clinical animal literature examining the potential for exogenous and endogenous cannabinoid treatments to regulate chemotherapy-induced nausea. The pre-clinical evidence points to a compelling need to evaluate the antinausea potential of cannabidiol, cannabidiolic acid, and treatments that boost the functioning of the endocannabinoid system in human clinical trials. PMID:28861486
Spartinou, Anastasia; Nyktari, Vasileia; Papaioannou, Alexandra
2017-12-01
Chemotherapy induced nausea and vomiting (CINV) are major side effects of chemotherapy and a great burden to patients' quality of life. Serotonin and substance P are the major neurotransmitters involved in the pathophysiology of CINV, but in spite of new antiemetics no completely effective regime exists for its prevention or treatment. Areas covered: In this review the authors provide a detailed description of granisetron's chemistry pharmacokinetics, pharmacodynamics, toxicity and a brief review of clinical trials involving granisetron and the management of CINV. We searched reviews, meta-analysis and randomized controlled trials (Medline, Embase and article reference lists). Expert opinion: According to current literature, granisetron 2 mg orally or 0,01mg/kg (1 mg) intravenously per day, co-administered with dexamethasone and NK-1 antagonists is the recommended regime for highly emetogenic chemotherapy. In the future the role of transdermal and subcutaneous formulations against delayed CINV will be clarified and probably enhance patients' convenience.
Osawa, Hiroshi; Goto, Hiroaki; Myojo, Tomohiro
2013-05-01
Nausea and vomiting are among the most problematic symptoms experienced by patients with cancer who are receiving chemotherapy. 5-hydroxytryptamine 3(5-HT3)-receptor antagonists, NK1 receptor antagonists(aprepitant)and dexamethasone are now the standard therapies for preventing chemotherapy-induced nausea and vomiting(CINV)that follow highly emetogenic chemotherapy, such as cisplatin and anthracycline. However, since it is not cleared which 5-HT3-recepter antagonist is a proper treatment for combined use with aprepitant and dexamethasone, we conducted a questionnaire survey, which used the numerical rating scale(NRS), for comparing palonosetron with granisetron in the same patient. Palonosetron showed a significant improvement of nausea for both acute(within 24 hours)and delayed phase(24-120 hours later), regardless of the type of chemotherapy(cisplatin or anthracycline-based regimen). Furthermore, palonosetron had a tolerable safety profile. Our study suggests that palonosetron-based antiemetic treatment will be a preferred choice for preventing CINV following highly emetogenic chemotherapy.
Ruiz, A; Llácer, J M; Morales, E; Gallardo, V
2004-06-01
Ondansetron is a carbazol with antiemetic properties. It is used primarily to control nausea and vomiting caused by cytotoxic chemotherapy and radiotherapy, as well as in postoperative vomiting in gynecological surgery. Ondansetron has a half-life of approximately 4 h, hence it is a matter of great interest to determine the ideal conditions for the formation of a drug-polymer complex in order to prolong the duration of the therapeutic action. A stability study of the active drug was first carried out on each of the polymers (Aquateric and Aquacoat). The adsorption of ondansetron on the lattices was determined with respect to time, pH and concentration. The results obtained suggest that both polymers are suitable as drug carriers for the controlled-release formulations obtained. We conclude that an acid pH is evidently fundamental in the adsorption process of this drug in the latexes. Moreover, the Aquateric latex would seem to be the best-suited polymer to use as a vehicle for drug delivery.
Ondansetron: design and development of oral pharmaceutical suspensions.
Gallardo Lara, V; Gallardo, M Lopez-Viota; Morales Hernandez, Ma E; Ruiz Martinez, Ma A
2009-02-01
Ondansetron is a carbazol with antiemetic properties that acts as a competitive and selective antagonist for the 5 HT3 serotonin receptors. It is used primarily to control nausea and vomiting caused by cytotoxic chemotherapy and radiotherapy, as well as in postoperative vomiting in gynecological surgery. The main aim of this work was to obtain a stable, long-acting oral suspension of ondansetron. To prolong the action, latexes are used as transport vehicles, specifically we tested, Aquateric, which comprises mainly cellulose acetophthalate. We prepared a complex drug-polymer, and the release profile of ondansetron was evaluated at acid, basic and acid-basic pH. This complex is additioned to a vehicle with xanthan gum and sodium carboxymethylcellulose (CMCNa) as thickeners to retard as much as possible particle sedimentation and thus increase physical stability of the suspension. The results obtained for sediment volume and degree of flocculation suggest that xanthan gum provides the best results, with better organolepticcharacteristics, appearance, physical stability and easy redispersability.
Yalçin, S; Tekuzman, G; Baltali, E; Ozişik, Y; Barişta, I
1999-02-01
In this randomized study, the efficacy of a single dose of three serotonin antagonists were compared in prophylaxis of acute and delayed vomiting induced by moderately emetogenic, single-day chemotherapy in chemotherapy-naïve patients. A total of 54 patients were entered. Eighteen patients received ondansetron, 17 received tropisetron, and 19 received granisetron. Antiemetics were administered as 15-minute intravenous infusion before chemotherapy. Complete control of acute vomiting was achieved in 38.8% with ondansetron, 58.8% with tropisetron, and 73.7% with granisetron. Major response rates were 83.3%, 82.3%, and 89.5%, respectively. For the delayed control of emesis, complete control of delayed vomiting was achieved in 38.8% with ondansetron, 52.9% with tropisetron, and 73.7% with granisetron. The major response rates were 71.8%, 70.5%, and 100%, respectively. The adverse effects were rare and mild in all groups. The authors conclude that there may be clinically important differences among serotonin antagonists used for chemotherapy-induced emesis.
The Analgesic Potential of Cannabinoids
Elikottil, Jaseena; Gupta, Pankaj; Gupta, Kalpna
2013-01-01
Historically and anecdotally cannabinoids have been used as analgesic agents. In recent years, there has been an escalating interest in developing cannabis-derived medications to treat severe pain. This review provides an overview of the history of cannabis use in medicine, cannabinoid signaling pathways, and current data from preclinical as well as clinical studies on using cannabinoids as potential analgesic agents. Clinical and experimental studies show that cannabis-derived compounds act as anti-emetic, appetite modulating and analgesic agents. However, the efficacy of individual products is variable and dependent upon the route of administration. Since opioids are the only therapy for severe pain, analgesic ability of cannabinoids may provide a much-needed alternative to opioids. Moreover, cannabinoids act synergistically with opioids and act as opioid sparing agents, allowing lower doses and fewer side effects from chronic opioid therapy. Thus, rational use of cannabis based medications deserves serious consideration to alleviate the suffering of patients due to severe pain. PMID:20073408
Antitumor action of temozolomide, ritonavir and aprepitant against human glioma cells.
Kast, Richard E; Ramiro, Susana; Lladó, Sandra; Toro, Salvador; Coveñas, Rafael; Muñoz, Miguel
2016-02-01
In the effort to find better treatments for glioblastoma we tested several currently marketed non-chemotherapy drugs for their ability to enhance the standard cytotoxic drug currently used to treat glioblastoma- temozolomide. We tested four antiviral drugs- acyclovir, cidofovir, maraviroc, ritonavir, and an anti-emetic, aprepitant. We found no cytotoxicity of cidofovir and discussed possible reasons for discrepancy from previous findings of others. We also found no cytotoxicity from acyclovir or maraviroc also in contradistinction to predictions. Cytotoxicity to glioma cell line GAMG for temozolomide alone was 14%, aprepitant alone 7%, ritonavir alone 14%, while temozolomide + aprepitant was 19%, temozolomide + ritonavir 34%, ritonavir + aprepitant 64 %, and all three, temozolomide + ritonavir + aprepitant 78%. We conclude that a remarkable synergy exists between aprepitant and ritonavir. Given the long clinical experience with these two well-tolerated drugs in treating non-cancer conditions, and the current median survival of glioblastoma of 2 years, a trial is warranted of adding these two simple drugs to current standard treatment with temozolomide.
RU 24969-induced emesis in the cat - 5-HT1 sites other than 5-HT1A, 5-HT1B or 5-HT1C implicated
NASA Technical Reports Server (NTRS)
Lucot, James B.
1990-01-01
RU 24969 was administered s.c. to cats and found to elicit emesis with a maximally effective dose of 1.0 mg/kg 5-Methoxytryptamine was found to have lower efficacy and to produce a higher incidence of nonspecific effects while trifluoromethylphenylpiperizine (TFMPP) was devoid of emetic effects. The emesis elicited by 1.0 mg/kg of RU 24969 was not altered by pretreatment with phentolamine, haloperidol, yohimbine or (-)-propranolol, indicating that catecholamines played no role in this response. The emesis was prevented by metergoline and methysergide but not by ketanserin, cyproheptadine, mesulergine, ICS 205 930, methiothepin, trimethobenzamide or BMY 7378. An indirect argument is presented that implicates a role for 5-HT1D sites. This conclusion must remain tentative until drugs selective for this site are synthesized and tested. The emesis was also prevented by 8-hydroxy-2-(di-n-propylamine)tetralin (8-OH-DPAT), confirming that this drug has a general antiemetic effect in cats.
Lorenzutti, Augusto M.; Martín-Flores, Manuel; Litterio, Nicolás J.; Himelfarb, Martín A.; Invaldi, Sergio H.; Zarazaga, María P.
2017-01-01
Morphine is widely used as a preanesthetic agent in dogs, but it often produces signs of nausea and vomiting. Maropitant (MRP) and metoclopramide (MCP) prevent emesis attributable to the opioid agent apomorphine in dogs. We evaluated the antiemetic efficacy and the discomfort in response to SQ injection of MRP [1 mg/kg body weight (BW)], MCP (0.5 mg/kg BW), and normal saline (SAL; 0.1 mL/kg BW) administered to 63 dogs, 45 minutes prior to morphine (0.5 mg/kg BW) and acepromazine (0.05 mg/kg BW). Dogs were observed for signs of nausea (ptyalism, lip licking, and increased swallowing) and vomiting for 30 minutes after morphine/acepromazine. The incidence of emesis was 0% for MRP, 38% for MCP, and 71% for SAL (P < 0.001). The incidence of signs of nausea was not different between groups. Discomfort due to injection was higher after MRP (48%), than after MCP (9.8%) and SAL (4.8%) (P < 0.001). PMID:28042152
Lorenzutti, Augusto M; Martín-Flores, Manuel; Litterio, Nicolás J; Himelfarb, Martín A; Invaldi, Sergio H; Zarazaga, María P
2017-01-01
Morphine is widely used as a preanesthetic agent in dogs, but it often produces signs of nausea and vomiting. Maropitant (MRP) and metoclopramide (MCP) prevent emesis attributable to the opioid agent apomorphine in dogs. We evaluated the antiemetic efficacy and the discomfort in response to SQ injection of MRP [1 mg/kg body weight (BW)], MCP (0.5 mg/kg BW), and normal saline (SAL; 0.1 mL/kg BW) administered to 63 dogs, 45 minutes prior to morphine (0.5 mg/kg BW) and acepromazine (0.05 mg/kg BW). Dogs were observed for signs of nausea (ptyalism, lip licking, and increased swallowing) and vomiting for 30 minutes after morphine/acepromazine. The incidence of emesis was 0% for MRP, 38% for MCP, and 71% for SAL ( P < 0.001). The incidence of signs of nausea was not different between groups. Discomfort due to injection was higher after MRP (48%), than after MCP (9.8%) and SAL (4.8%) ( P < 0.001).
Effect of intramuscular clebopride on postoperative nausea and vomiting.
Duarte, D F; Linhares, S; Gesser, N; Pederneiras, S G
1985-01-01
The antiemetic effect of clebopride, a new derivative of the orthopramide group, was compared with that of placebo in 298 women undergoing elective surgery. A group of 150 patients received premedication of 1 mg/kg of meperidine, administered intramuscularly (IM), and a group of 148 patients received premedication of 10 mg of diazepam IM. All patients received 0.5 mg of atropine IM. Anesthesia was induced with thiopental and maintained with halogenated N2O/O2. In a double-blind procedure, clebopride (2 mg) or placebo was injected IM at the end of anesthesia and whenever a patient had a second episode of vomiting. Clebopride appeared to be better than placebo in the prevention of nausea (P less than or equal to 0.05) and vomiting (P less than or equal to 0.001) during the 12-hour observation period. The frequency of side effects was virtually the same in patients given clebopride and patients given placebo.
Dezieck, Laurel; Hafez, Zachary; Conicella, Albert; Blohm, Eike; O'Connor, Mark J; Schwarz, Evan S; Mullins, Michael E
2017-09-01
Cannabinoid hyperemesis syndrome (CHS) is characterized by symptoms of cyclic abdominal pain, nausea, and vomiting in the setting of prolonged cannabis use. The transient receptor potential vanilloid 1 (TRPV1) receptor may be involved in this syndrome. Topical capsaicin is a proposed treatment for CHS; it binds TRPV1 with high specificity, impairing substance P signaling in the area postrema and nucleus tractus solitarius via overstimulation of TRPV1. This may explain its apparent antiemetic effect in this syndrome. We describe a series of thirteen cases of suspected cannabis hyperemesis syndrome treated with capsaicin in the emergency departments of two academic medical centers. A query of the electronic health record at both centers identified thirteen patients with documented daily cannabis use and symptoms consistent with CHS who were administered topical capsaicin cream for symptom management. All 13 patients experienced symptom relief after administration of capsaicin cream. Topical capsaicin was associated with improvement in symptoms of CHS after other treatments failed.
Interventions for nausea and vomiting in early pregnancy
Matthews, Anne; Dowswell, Therese; Haas, David M; Doyle, Mary; O’Mathúna, Dónal P
2014-01-01
Background Nausea, retching and vomiting are very commonly experienced by women in early pregnancy. There are considerable physical and psychological effects on women who experience these symptoms. This is an update of a review of interventions for nausea and vomiting in early pregnancy previously published in 2003. Objectives To assess the effectiveness and safety of all interventions for nausea, vomiting and retching in early pregnancy, up to 20 weeks’ gestation. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 May 2010). Selection criteria All randomised controlled trials of any intervention for nausea, vomiting and retching in early pregnancy. We excluded trials of interventions for hyperemesis gravidarum which are covered by another review. We also excluded quasi-randomised trials and trials using a crossover design. Data collection and analysis Four review authors, in pairs, reviewed the eligibility of trials and independently evaluated the risk of bias and extracted the data for included trials. Main results Twenty-seven trials, with 4041 women, met the inclusion criteria. These trials covered many interventions, including acupressure, acustimulation, acupuncture, ginger, vitamin B6 and several antiemetic drugs. We identified no studies of dietary or other lifestyle interventions. Evidence regarding the effectiveness of P6 acupressure, auricular (ear) acupressure and acustimulation of the P6 point was limited. Acupuncture (P6 or traditional) showed no significant benefit to women in pregnancy. The use of ginger products may be helpful to women, but the evidence of effectiveness was limited and not consistent. There was only limited evidence from trials to support the use of pharmacological agents including vitamin B6, and anti-emetic drugs to relieve mild or moderate nausea and vomiting. There was little information on maternal and fetal adverse outcomes and on psychological, social or economic outcomes. We
Rock, EM; Bolognini, D; Limebeer, CL; Cascio, MG; Anavi-Goffer, S; Fletcher, PJ; Mechoulam, R; Pertwee, RG; Parker, LA
2012-01-01
BACKGROUND AND PURPOSE To evaluate the hypothesis that activation of somatodendritic 5-HT1A autoreceptors in the dorsal raphe nucleus (DRN) produces the anti-emetic/anti-nausea effects of cannabidiol (CBD), a primary non-psychoactive cannabinoid found in cannabis. EXPERIMENTAL APPROACH The potential of systemic and intra-DRN administration of 5-HT1A receptor antagonists, WAY100135 or WAY100635, to prevent the anti-emetic effect of CBD in shrews (Suncus murinus) and the anti-nausea-like effects of CBD (conditioned gaping) in rats were evaluated. Also, the ability of intra-DRN administration of CBD to produce anti-nausea-like effects (and reversal by systemic WAY100635) was assessed. In vitro studies evaluated the potential of CBD to directly target 5-HT1A receptors and to modify the ability of the 5-HT1A agonist, 8-OH-DPAT, to stimulate [35S]GTPγS binding in rat brainstem membranes. KEY RESULTS CBD suppressed nicotine-, lithium chloride (LiCl)- and cisplatin (20 mg·kg−1, but not 40 mg·kg−1)-induced vomiting in the S. murinus and LiCl-induced conditioned gaping in rats. Anti-emetic and anti-nausea-like effects of CBD were suppressed by WAY100135 and the latter by WAY100635. When administered to the DRN: (i) WAY100635 reversed anti-nausea-like effects of systemic CBD, and (ii) CBD suppressed nausea-like effects, an effect that was reversed by systemic WAY100635. CBD also displayed significant potency (in a bell-shaped dose–response curve) at enhancing the ability of 8-OH-DPAT to stimulate [35S]GTPγS binding to rat brainstem membranes in vitro. Systemically administered CBD and 8-OH-DPAT synergistically suppressed LiCl-induced conditioned gaping. CONCLUSIONS AND IMPLICATIONS These results suggest that CBD produced its anti-emetic/anti-nausea effects by indirect activation of the somatodendritic 5-HT1A autoreceptors in the DRN. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this
Linked Orders Improve Safety in Scheduling and Administration of Chemotherapeutic Agents
Whipple, Nancy; Boulware, Joy; Danca, Kala; Boyarin, Kirill; Ginsberg, Eliot; Poon, Eric; Sweet, Micheal; Schade, Sue; Rogala, Jennifer
2010-01-01
The pharmacologic treatment for cancer must adhere to complex, finely orchestrated treatment plans, including not only chemotherapy medications, but pre/post-hydration, anti-emetics, anti-anxiety, and other medications that are given before, during and after chemotherapy doses. The treatment plans specify the medications and dictate precise dosing, frequency, and timing. This is a challenge to most Computerized Physician Order Entry (CPOE), Pharmacy and Electronic Medication Administration record (eMAR) Systems. Medications are scheduled on specific dates, referred to as chemo days, from the onset of the treatment, and precisely timed on the designated chemo day. For patients enrolled in research protocols, the adherence to the defined schedule takes on additional import, since variation is a violation of the protocol. If the oncologist determines that medications must be administered outside the defined constraints, the patient must be un-enrolled from the protocol and the course of therapy is re-written. Pharmacy and eMAR systems utilized in processing chemotherapy medications must be able to support the intricate relationships between each drug defined in the treatment plans. PMID:21347104
Deckers, Nynke; Ruigrok, Catharina A; Verhoeve, Hans Peter; Lourens, Nicky
2018-01-01
The antiemetic maropitant, with metacresol as preservative (Cerenia, Zoetis), has been associated with pain after subcutaneous injection in dogs and cats. Recently, a generic formulation containing benzyl alcohol was authorised (Prevomax, Le Vet). Benzyl alcohol is reported to have local anaesthetic properties and reduce injection pain. This study compared local pain after subcutaneous injection of the two maropitant formulations, administered at approximately 4°C and 25°C, to dogs. Thirty-two healthy beagle dogs were enrolled into a blinded, randomised, cross-over study. Dogs received subcutaneous injections of maropitant injection containing metacresol as preservative and maropitant injection containing benzyl alcohol as preservative, both at approximately 4°C and 25°C, with at least three days in between treatments. Injection pain was evaluated by two blinded observers using a visual analogue scale immediately after injection and a simple descriptive scale at two minutes after injection. In healthy beagle dogs, subcutaneous injection of maropitant with benzyl alcohol is significantly less painful than injection of maropitant with metacresol.
Supportive care in older adults with cancer - An update of research in 2015.
Steer, Christopher B
2016-09-01
The motto of the Multinational Association for Supportive Care in Cancer (MASCC) is "supportive care makes excellent cancer care possible". This is especially important in the care of older adults with cancer. The use of geriatric assessment in this patient population enables targeted supportive care interventions to work alongside appropriate anticancer therapy. It is the opinion of this author that geriatric oncology is mostly about the provision of streamlined, appropriate supportive care. There are many facets of supportive care of patients with cancer that are important regardless of age. These include issues such as the use of appropriate antiemetics, infection management, oral health, nutritional intervention, psychosocial care, and palliative care. This article provides an update on novel yet important supportive care research specifically in older adults with cancer published in peer-reviewed journals in 2015. This year saw important publications in geriatric assessment, psychosocial care, in the information and supportive care needs of older adults and the role of pharmacists and rehabilitation specialists in the geriatric oncology clinic. Copyright © 2016 Elsevier Inc. All rights reserved.
Chen, Kuo-Hsin; Weng, Meng-Tzu; Chou, Yueh-Hung; Lu, Yueh-Feng; Hsieh, Chen-Hsi
2016-03-01
Sorafenib followed by fractionated radiotherapy (RT) has been shown to decrease the phagocytic and candidacidal activities of antifungal agents due to radiosensitization. Moreover, sorafenib has been shown to suppress the immune system, thereby increasing the risk for candida colonization and infection. In this study, we present the 2 hepatocellular carcinoma (HCC) patients suffered from epigastric distress caused by esophageal candidiasis who received sorafenib plus RT. Two patients who had received sorafenib and RT for HCC with bone metastasis presented with hiccups, gastric ulcer, epigastric distress, anorexia, heart burn, and fatigue. Empiric antiemetic agents, antacids, and pain killers were ineffective at relieving symptoms. Panendoscopy revealed diffuse white lesions in the esophagus. Candida esophagitis was suspected. Results of periodic acid-Schiff staining were diagnostic of candidiasis. Oral fluconazole (150 mg) twice daily and proton-pump inhibitors were prescribed. At 2-weak follow-up, esophagitis had resolved and both patients were free of gastrointestinal symptoms. Physicians should be aware that sorafenib combined with RT may induce an immunosuppressive state in patients with HCC, thereby increasing their risk of developing esophagitis due to candida species.
Phytochemistry and Pharmacology of Berberis Species
Mokhber-Dezfuli, Najmeh; Saeidnia, Soodabeh; Gohari, Ahmad Reza; Kurepaz-Mahmoodabadi, Mahdieh
2014-01-01
The genus Berberis (Berberidaceae) includes about 500 species worldwide, some of which are widely cultivated in the north-eastern regions of Iran. This genus consists of spiny deciduous evergreen shrubs, characterized by yellow wood and flowers. The cultivation of seedless barberry in South Khorasan goes back to two hundred years ago. Medicinal properties for all parts of these plants have been reported, including: Antimicrobial, antiemetic, antipyretic, antioxidant, anti-inflammatory, anti-arrhythmic, sedative, anti-cholinergic, cholagogic, anti-leishmaniasis, and anti-malaria. The main compounds found in various species of Berberis, are berberine and berbamine. Phytochemical analysis of various species of this genus revealed the presence of alkaloids, tannins, phenolic compounds, sterols and triterpenes. Although there are some review articles on Berberis vulgaris (as the most applied species), there is no review on the phytochemical and pharmacological activities of other well-known species of the genus Berberis. For this reason, the present review mainly focused on the diverse secondary metabolites of various species of this genus and the considerable pharmacological and biological activities together with a concise story of the botany and cultivation. PMID:24600191
Nuclear and radiological terrorism: continuing education article.
Anderson, Peter D; Bokor, Gyula
2013-06-01
Terrorism involving radioactive materials includes improvised nuclear devices, radiation exposure devices, contamination of food sources, radiation dispersal devices, or an attack on a nuclear power plant or a facility/vehicle that houses radioactive materials. Ionizing radiation removes electrons from atoms and changes the valence of the electrons enabling chemical reactions with elements that normally do not occur. Ionizing radiation includes alpha rays, beta rays, gamma rays, and neutron radiation. The effects of radiation consist of stochastic and deterministic effects. Cancer is the typical example of a stochastic effect of radiation. Deterministic effects include acute radiation syndrome (ARS). The hallmarks of ARS are damage to the skin, gastrointestinal tract, hematopoietic tissue, and in severe cases the neurovascular structures. Radiation produces psychological effects in addition to physiological effects. Radioisotopes relevant to terrorism include titrium, americium 241, cesium 137, cobalt 60, iodine 131, plutonium 238, califormium 252, iridium 192, uranium 235, and strontium 90. Medications used for treating a radiation exposure include antiemetics, colony-stimulating factors, antibiotics, electrolytes, potassium iodine, and chelating agents.
Wu, Si-Jia; Xiong, Xian-Ze; Lin, Yi-Xin; Cheng, Nan-Sheng
2013-02-01
Our purpose was to assess the prophylactic antiemetic effects of ondansetron versus granisetron for laparoscopic cholecystectomy. We searched Medline, Cochrane Central Register of Controlled Trials, PubMed, Embase, Science Citation Index Expanded, Foreign Medical Journal Full-Text Service, China National Knowledge Infrastructure Whole Article Database, Chinese Biomedical Database, and the Google Scholar. We calculated the risk ratio (RR) with 95% confidence interval (CI) for dichotomous data. The χ(2) test and I(2) value were used to assess heterogeneity. The merged early incidence of postoperative nausea and vomiting (PONV) in ondansetron group (42.9%) was higher than granisetron group (34.3%) (RR = 1.25, 95% CI, 0.82-1.92, P=0.31, I(2) = 48%). The merged total incidence of PONV in ondansetron group (38.7%) was higher than granisetron group (34.2%) (RR = 1.13, 95% CI, 0.82-1.56, P = 0.46, I(2) = 39%), although these differences were not statistically significant. Ondansetron is equivalent to granisetron for preventing early and total incidence of PONV after laparoscopic cholecystectomy.
Quan, Xiang; Zhu, Bo; Ye, Tie-hu
2011-08-01
To compare the efficacy of ondansetron and granisetron in the prevention of postoperative nausea and vomiting (PONV) in high-risk patients. Totally 200 patients with three key risk factors for PONV (female, non-smoking and postoperative opioid use) were equally randomized into ondansetron group and granisetron group. Ondansetron (4 mg) or granisetron (3 mg) was intravenously administered upon the completion of surgery. The episodes of nausea and vomiting were observed for 24 hours after surgery. A significantly greater proportion of patients in granisetron group achieved a complete response (i.e., no PONV or rescue medication) during the first 24 hours postoperatively versus those in ondansetron group (62.6% vs. 46.9%, respectively; P=0.048). There were no significant differences in terms of postoperative nausea incidences (42.9% vs. 34.3%, respectively), postoperative vomiting incidences (25.5% vs. 20.2%, respectively) and postoperative rescue anti-emetics incidences (19.4% vs. 15.2%, respectively) (P>0.05). Granisetron is more effective than ondansetron in preventing PONV in high-risk patients during the first 24 hours postoperatively.
Crawford, Sue E.; Ramani, Sasirekha; Tate, Jacqueline E.; Parashar, Umesh D.; Svensson, Lennart; Hagbom, Marie; Franco, Manuel A.; Greenberg, Harry B.; O’Ryan, Miguel; Kang, Gagandeep; Desselberger, Ulrich; Estes, Mary K.
2017-01-01
Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children <5 years of age. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases. PMID:29119972
Biopharmaceutical potentials of Prosopis spp. (Mimosaceae, Leguminosa).
Henciya, Santhaseelan; Seturaman, Prabha; James, Arthur Rathinam; Tsai, Yi-Hong; Nikam, Rahul; Wu, Yang-Chang; Dahms, Hans-Uwe; Chang, Fang Rong
2017-01-01
Prosopis is a commercially important plant genus, which has been used since ancient times, particularly for medicinal purposes. Traditionally, Paste, gum, and smoke from leaves and pods are applied for anticancer, antidiabetic, anti-inflammatory, and antimicrobial purposes. Components of Prosopis such as flavonoids, tannins, alkaloids, quinones, or phenolic compounds demonstrate potentials in various biofunctions, such as analgesic, anthelmintic, antibiotic, antiemetic, microbial antioxidant, antimalarial, antiprotozoal, antipustule, and antiulcer activities; enhancement of H + , K + , ATPases; oral disinfection; and probiotic and nutritional effects; as well as in other biopharmaceutical applications, such as binding abilities for tablet production. The compound juliflorine provides a cure in Alzheimer disease by inhibiting acetylcholine esterase at cholinergic brain synapses. Some indirect medicinal applications of Prosopis spp. are indicated, including antimosquito larvicidal activity, chemical synthesis by associated fungal or bacterial symbionts, cyanobacterial degradation products, "mesquite" honey and pollens with high antioxidant activity, etc. This review will reveal the origins, distribution, folk uses, chemical components, biological functions, and applications of different representatives of Prosopis. Copyright © 2016. Published by Elsevier B.V.
Severe acute copper sulphate poisoning: a case report.
Sinkovic, Andreja; Strdin, Alenka; Svensek, Franci
2008-03-01
As copper sulphate pentahydrate (CSP) is a common compound used in agriculture and industry, chronic occupational exposures to CSP are well known, but acute poisoning is rare in the Western world. This case report describes acute poisoning of a 33-year-old woman who attempted suicide by ingesting an unknown amount of CSP. On admission to the hospital, she had symptoms and signs of severe hemorrhagic gastroenteritis, dehydration, renal dysfunction and methaemoglobinaemia with normal serum copper level. Therapy included early gastric lavage, fluid replacement, vasoactive drugs, furosemide, antiemetic drugs, ranitidine, and antidotes methylene blue and 2,3-dimercaptopropane-1-sulphonate (DMPS). However, the patient developed severe intravascular haemolysis, acute severe hepatic and renal failure, as well as adrenal insufficiency. After prolonged, but successful hospital treatment, including haemodialysis and IV hydrocortisone, the patient was discharged with signs of mild renal and liver impairment. Our conclusion is that in severe cases of copper poisoning early supportive measures are essential. In addition, antidotes such as methylene blue for methaemoglobinaemia and chelating agent such as DMPS improve morbidity and survival of severely poisoned victims.
Targeting tachykinin receptors in neuroblastoma.
Henssen, Anton G; Odersky, Andrea; Szymansky, Annabell; Seiler, Marleen; Althoff, Kristina; Beckers, Anneleen; Speleman, Frank; Schäfers, Simon; De Preter, Katleen; Astrahanseff, Kathy; Struck, Joachim; Schramm, Alexander; Eggert, Angelika; Bergmann, Andreas; Schulte, Johannes H
2017-01-03
Neuroblastoma is the most common extracranial tumor in children. Despite aggressive multimodal treatment, high-risk neuroblastoma remains a clinical challenge with survival rates below 50%. Adding targeted drugs to first-line therapy regimens is a promising approach to improve survival in these patients. TACR1 activation by substance P has been reported to be mitogenic in cancer cell lines. Tachykinin receptor (TACR1) antagonists are approved for clinical use as an antiemetic remedy since 2003. Tachykinin receptor inhibition has recently been shown to effectively reduce growth of several tumor types. Here, we report that neuroblastoma cell lines express TACR1, and that targeting TACR1 activity significantly reduced cell viability and induced apoptosis in neuroblastoma cell lines. Gene expression profiling revealed that TACR1 inhibition repressed E2F2 and induced TP53 signaling. Treating mice harboring established neuroblastoma xenograft tumors with Aprepitant also significantly reduced tumor burden. Thus, we provide evidence that the targeted inhibition of tachykinin receptor signaling shows therapeutic efficacy in preclinical models for high-risk neuroblastoma.
Schwach-Abdellaoui, Khadija; Moreau, Marinette; Schneider, Marc; Boisramć, Bernard; Gurny, Robert
2002-11-06
In animal health care, current therapeutic regimens for gastrointestinal disorders require repeated oral or parenteral dosage forms of anti-emetic agents. However, fluctuations of plasma concentrations produce severe side effects. The aim of this work is to develop a subcutaneous and biodegradable controlled release system containing metoclopramide (MTC). Semi-solid poly(ortho ester)s (POE) prepared by a transesterification reaction between trimethyl orthoacetate and 1,2,6,-hexanetriol were investigated as injectable bioerodible polymers for the controlled release of MTC. MTC is present in the polymeric matrix as a solubilised form and it is released rapidly from the POE by erosion and diffusion because of its acidic character and its high hydrosolubility. If a manual injection is desired, only low molecular weight can be used. However, low molecular weight POEs release the drug rapidly. In order to extend polymer lifetime and decrease drug release rate, a sparingly water-soluble base Mg(OH)(2) was incorporated to the formulation. It was possible to produce low molecular weight POE that can be manually injected and releasing MTC over a period of several days.
Acute cholestatic hepatitis caused by amoxicillin/clavulanate
Beraldo, Daniel Oliveira; Melo, Joanderson Fernandes; Bonfim, Alexandre Vidal; Teixeira, Andrei Alkmim; Teixeira, Ricardo Alkmim; Duarte, André Loyola
2013-01-01
Amoxicillin/clavulanate is a synthetic penicillin that is currently commonly used, especially for the treatment of respiratory and cutaneous infections. In general, it is a well-tolerated oral antibiotic. However, amoxicillin/clavulanate can cause adverse effects, mainly cutaneous, gastrointestinal, hepatic and hematologic, in some cases. Presented here is a case report of a 63-year-old male patient who developed cholestatic hepatitis after recent use of amoxicillin/clavulanate. After 6 wk of prolonged use of the drug, he began to show signs of cholestatic icterus and developed severe hyperbilirubinemia (total bilirubin > 300 mg/L). Diagnostic investigation was conducted by ultrasonography of the upper abdomen, serum tests for infection history, laboratory screening of autoimmune diseases, nuclear magnetic resonance (NMR) of the abdomen with bile duct-NMR and transcutaneous liver biopsy guided by ultrasound. The duration of disease was approximately 4 mo, with complete resolution of symptoms and laboratory changes at the end of that time period. Specific treatment was not instituted, only a combination of anti-emetic (metoclopramide) and cholestyramine for pruritus. PMID:24379601
Acute cholestatic hepatitis caused by amoxicillin/clavulanate.
Beraldo, Daniel Oliveira; Melo, Joanderson Fernandes; Bonfim, Alexandre Vidal; Teixeira, Andrei Alkmim; Teixeira, Ricardo Alkmim; Duarte, André Loyola
2013-12-14
Amoxicillin/clavulanate is a synthetic penicillin that is currently commonly used, especially for the treatment of respiratory and cutaneous infections. In general, it is a well-tolerated oral antibiotic. However, amoxicillin/clavulanate can cause adverse effects, mainly cutaneous, gastrointestinal, hepatic and hematologic, in some cases. Presented here is a case report of a 63-year-old male patient who developed cholestatic hepatitis after recent use of amoxicillin/clavulanate. After 6 wk of prolonged use of the drug, he began to show signs of cholestatic icterus and developed severe hyperbilirubinemia (total bilirubin > 300 mg/L). Diagnostic investigation was conducted by ultrasonography of the upper abdomen, serum tests for infection history, laboratory screening of autoimmune diseases, nuclear magnetic resonance (NMR) of the abdomen with bile duct-NMR and transcutaneous liver biopsy guided by ultrasound. The duration of disease was approximately 4 mo, with complete resolution of symptoms and laboratory changes at the end of that time period. Specific treatment was not instituted, only a combination of anti-emetic (metoclopramide) and cholestyramine for pruritus.
Zuurman, Lineke; Passier, Paul C C M; de Kam, Marieke L; Kleijn, Huub J; Cohen, Adam F; van Gerven, Joop M A
2010-11-01
An ideal drug for outpatient treatments under conscious sedation would have both sedative and analgesic properties. CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties of intravenous Org 26828. In addition, pharmacokinetics, amnestic properties, postural stability, and behavioural and cardiovascular effects were studied. Midazolam intravenous 0.1 mg/kg and placebo were used as controls. The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose. No effects were observed after doses up to 0.3 μg/kg of Org 26828. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 26828 at 3 and 6 μg/kg, the observed sedation was considerably less than after midazolam. Doses higher than the maximum tolerated dose of 1 μg/kg of Org 26828 caused unpleasant central nervous system effects (anxiety, paranoia, hallucinations). Therefore, Org 26828 is not suitable for providing sedation for outpatient surgical procedures.
Steinbach, Jaclyn R; MacGuire, Jamus; Chang, Shu; Dierks, Elizabeth; Roble, Gordon S
2018-06-01
Retrospective analysis of post-operative vomiting (POV) in non-human primates at our institution was 11%. Based on this additional risk factor for post-operative complications, we aimed to eliminate or decrease POV by adding an antiemetic, maropitant citrate, to the pre-medication protocol. Retrospective and prospective data were collected over a 5-year period from 46 macaques of two species during 155 procedures. Additionally, blood was collected from five Macaca mulatta to perform a pharmacokinetic analysis. A 1 mg/kg subcutaneous dose of maropitant given pre-operatively significantly decreased POV. Findings indicated post-neurosurgical emesis in Macaca fasicularis was significantly greater than in Macaca mulatta. Pharmacokinetic analysis of maropitant in Macaca mulatta determined the mean maximum plasma concentration to be 113 ng/mL. Maropitant administration prior to anesthesia for neurosurgeries decreased our incidence of POV to 1%. The plasma concentration reaches the proposed plasma level for clinical efficacy approximately 20 minutes after administration. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
The use of emergency contraception in Australasian emergency departments.
Millar, J R; Leach, D S; Maclean, A V; Kovacs, G T
2001-09-01
To review the prescribing of emergency contraception by emergency departments in Australasia and compare it with other providers. A postal questionnaire was sent to the director of each of the 79 Australasian College for Emergency Medicine accredited emergency departments in Australasia inquiring about the availability and prescribing habits for emergency contraception within each department. Of the 79 emergency departments, 69 (87.3%) responded to the questionnaire and were aware of the 'emergency contraception regimen'. The majority of departments prescribed appropriately (56%) and only one department did not arrange adequate follow up. Anti-emetics are always used by 45 departments (78.9%). Discussion of future contraceptive needs at the time of presentation was only undertaken by 25 departments (43.9%). Written clinical guidelines for emergency contraception were present in 28 departments (40.6%). Emergency departments are accessed by patients requesting contraception following unprotected intercourse or contraceptive failure. The prescribing of emergency contraception in Australasian emergency departments is comparable with other providers but substantial improvements could be made. Suggestions to assist this improvement include written clinical guidelines and patient information and purpose-made medication packs.
Risk factors of patients with and without postoperative nausea (PON).
Dienemann, Jacqueline; Hudgens, Amanda N; Martin, Dana; Jones, Holly; Hunt, Ronald; Blackwell, Richard; Norton, H James; Divine, George
2012-08-01
This purpose of this analysis was to study risk factors of postoperative nausea (PON) and their strength. Data were obtained during the screening phase of a controlled clinical trial of aromatherapy for PON. In a sample of 1151 postsurgical subjects, 301 (26.2%) reported PON. Significant risk factors identified in the order of odds ratios for nausea were female gender, gastrointestinal surgery, use of volatile anesthesia gases, history of PON, history of motion sickness, and use of opioids after surgery. Although still over 1.0, the risk factors of length of surgery over 1 hour and gynecologic surgery had the lowest odds ratios. Likelihood of nausea increased significantly with the number of significant risk factors (P<.0001). Administration of preventive antiemetic medication also increased with the number of significant risk factors (P<.0001). Among 301 subjects reporting nausea, 49 (16.28%) received preventive medication. Despite prevention efforts, PON remains a substantial side effect for many surgical patients. Copyright © 2012 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.
Inhaled peppermint oil for postop nausea in patients undergoing cardiac surgery.
Briggs, Patricia; Hawrylack, Helen; Mooney, Ruth
2016-07-01
Postoperative nausea is a common occurrence that is very uncomfortable for patients and may result in complications including pain, strain at the surgical site, aspiration, and possible dehiscence. Antiemetics used to manage the nausea cause many adverse reactions, such as dysrhythmias and/or drowsiness resulting in an unwillingness to ambulate or perform deep-breathing exercises. Previous studies have reported a decrease in nausea following the use of peppermint oil. Researchers obtained informed consent from 123 patients for this study; 34 (28%) of them experienced nausea and were offered a nasal inhaler that contained peppermint oil. The average nausea rating before the use of peppermint oil was 3.29 (SD, 1.0) on a scale of 0 to 5, with 5 being the greatest nausea. Two minutes later, the average nausea rating was 1.44 (SD, 1.3). Using paired t-tests, these differences were found to be statistically significant (P = 0.000). The researchers concluded that peppermint oil inhalation is a viable first-line treatment for nausea in postoperative cardiac surgery patients.
Sites, Debra S; Johnson, Nancy T; Miller, Jacqueline A; Torbush, Pauline H; Hardin, Janis S; Knowles, Susan S; Nance, Jennifer; Fox, Tara H; Tart, Rebecca Creech
2014-02-01
With little scientific evidence to support use of aromatherapy for postoperative nausea and/or vomiting (PONV) symptoms, this study evaluated controlled breathing with peppermint aromatherapy (AR) and controlled breathing alone (CB) for PONV relief. A single blind randomized control trial design was used. On initial PONV complaint, symptomatic subjects received either CB (n = 16) or AR (n = 26) intervention based on randomization at enrollment. A second treatment was repeated at 5 minutes if indicated. Final assessment occurred 10 minutes post initial treatment. Rescue medication was offered for persistent symptoms. Among eligible subjects, PONV incidence was 21.4% (42/196). Gender was the only risk factor contributing to PONV symptoms (P = .0024). Though not statistically significant, CB was more efficacious than AR, 62.5% versus 57.7%, respectively. CB can be initiated without delay as an alternative to prescribed antiemetics. Data also support use of peppermint AR in conjunction with CB for PONV relief. Copyright © 2014 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.
Treatment of nausea and vomiting in terminally ill cancer patients.
Glare, Paul A; Dunwoodie, David; Clark, Katherine; Ward, Alicia; Yates, Patsy; Ryan, Sharon; Hardy, Janet R
2008-01-01
Nausea and vomiting is a common and distressing symptom complex in patients with far-advanced cancer, affecting up to 60% of individuals at some stage of their illness. The current approach to the palliative care of patients with nausea and vomiting is based on identifying the cause, understanding its pathophysiology and knowing the pharmacology of the drugs available for its amelioration. The following six main syndromes are identified: gastric stasis, biochemical, raised intracranial pressure, vestibular, mechanical bowel obstruction and ileus. A careful history, focused physical examination and appropriate investigations are needed to elucidate the syndrome and its cause, so that therapy is rational. Drugs are the mainstay of treatment in terminal cancer, and the main classes of antiemetic agents are prokinetics, dopamine antagonists, antihistamines, anticholinergics and serotonin antagonists. Dexamethasone and octreotide are also used, especially in bowel obstruction. Non-drug measures are important in relieving the associated distress. Patients should be able to die comfortably, without tubes. Despite decades of practice affirming this approach, the evidence base is weak and well designed studies are urgently needed.
Gastroparesis Updates on Pathogenesis and Management
Liu, Nanlong; Abell, Thomas
2017-01-01
Gastroparesis (Gp) is a chronic disease that presents with clinical symptoms of early satiety, bloating, nausea, vomiting, and abdominal pain. Along with these symptoms, an objective finding of delayed gastric emptying, along with a documented absence of gastric outlet obstruction, are required for diagnosis. This article focuses on updates in the pathogenesis and management of Gp. Recent studies on full thickness biopsies of Gp patients have shed light on the complex interactions of the central, autonomic, and enteric nervous systems, which all play key roles in maintaining normal gut motility. The management of Gp has evolved beyond prokinetics and antiemetics with the use of gastric electrical stimulators (GES). In addition, this review aims to introduce the concept of gastroparesis-like syndrome (GLS). GLS helps groups of patients who have the cardinal symptoms of Gp but have a normal or rapid emptying test. Recent tests have shown that patients with Gp and GLS have similar pathophysiology, benefit greatly from GES placement, and likely should be treated in a similar manner. PMID:28535580
Liu, Wai M; Fowler, Daniel W; Dalgleish, Angus G
2010-11-01
Cannabinoids, the active components of the cannabis plant, have some clinical merit both as an anti-emetic and appetite stimulant in cachexic patients. Recently, interest in developing cannabinoids as therapies has increased following reports that they possess anti-tumour properties. Research into cannabinoids as anti-cancer agents is in its infancy, and has mainly focussed on the pro-apoptotic effects of this class of agent. Impressive anti-cancer activities have been reported; actions that are mediated in large part by disruptions to ubiquitous signalling pathways such as ERK and PI3-K. However, recent developments have highlighted a putative role for cannabinoids as anti-inflammatory agents. Chronic inflammation has been associated with neoplasia for sometime, and as a consequence, reducing inflammation as a way of impacting cancer presents a new role for these compounds. This article reviews the ever-changing relationship between cannabinoids and cancer, and updates our understanding of this class of agent. Furthermore, the relationship between chronic inflammation and cancer, and how cannabinoids can impact this relationship will be described.
[Quebec Pregnancy Cohort: prevalence of medication use during gestation and pregnancy outcomes].
Bérard, Anick; Sheehy, Odile
2014-01-01
Many women are exposed to medications during pregnancy. The Quebec Pregnancy Cohort (QPC) is a prospective population-based cohort which includes all data on pregnancies and children between January 1997 and December 2008. We linked four administrative databases in Quebec, Canada: RAMQ (medical and pharmaceutical), MED-ECHO (hospitalizations), ISQ (births/deaths), and MELS (Ministry of Education). Pregnancies included were covered by the Quebec prescription drug insurance plan (36% of women aged 15-45 years) from 12 months prior until the end of pregnancy. We analyzed 97,680 pregnancies. Prevalence of medication use was 74% pre-pregnancy, 56% during pregnancy, and 80% post-pregnancy. Most frequently used medications during pregnancy were antibiotics (47%), antiemetic drugs (23%), and non-steroïdal anti-inflammatory drugs (NSAIDs) [17%]. Medication users were more likely to have spontaneous abortions, preterm births, children with congenital malformations and postpartum depression than non-users (p<0.01). Medications are commonly used during pregnancy. The QPC is a powerful tool for perinatal pharmacoepidemiological research. © 2014 Société Française de Pharmacologie et de Thérapeutique.
Perioperative Acupuncture and Related Techniques
Chernyak, Grigory V.; Sessler, Daniel I.
2005-01-01
Acupuncture and related techniques are increasingly practiced in conventional medical settings, and the number of patients willing to use these techniques is increasing. Despite more than 30 years of research, the exact mechanism of action and efficacy of acupuncture have not been established. Furthermore, most aspects of acupuncture have yet to be adequately tested. There thus remains considerable controversy about the role of acupuncture in clinical medicine. Acupuncture apparently does not reduce volatile anesthetic requirement by a clinically important amount. However, preoperative sedation seems to be a promising application of acupuncture in perioperative settings. Acupuncture may be effective for postoperative pain relief but requires a high level of expertise by the acupuncture practitioner. Acupuncture and related techniques can be used for treatment and prophylaxis of postoperative nausea and vomiting in routine clinical practice in combination with, or as an alternative to, conventional antiemetics when administered before induction of general anesthesia. Summary Statement: The use of acupuncture for perioperative analgesia, nausea and vomiting, sedation, anesthesia, and complications is reviewed. PMID:15851892
Butler, Kristina; Yi, John; Wasson, Megan; Klauschie, Jennifer; Ryan, Debra; Hentz, Joseph; Cornella, Jeffrey; Magtibay, Paul; Kho, Roseanne
2017-05-01
After vaginal surgery, oral and parenteral narcotics are used commonly for pain relief, and their use may exacerbate the incidence of sedation, nausea, and vomiting, which ultimately delays convalescence. Previous studies have demonstrated that rectal analgesia after surgery results in lower pain scores and less intravenous morphine consumption. Belladonna and opium rectal suppositories may be used to relieve pain and minimize side effects; however, their efficacy has not been confirmed. We aimed to evaluate the use of belladonna and opium suppositories for pain reduction in vaginal surgery. A prospective, randomized, double-blind, placebo-controlled trial that used belladonna and opium suppositories after inpatient or outpatient vaginal surgery was conducted. Vaginal surgery was defined as (1) vaginal hysterectomy with uterosacral ligament suspension or (2) posthysterectomy prolapse repair that included uterosacral ligament suspension and/or colporrhaphy. Belladonna and opium 16A (16.2/60 mg) or placebo suppositories were administered rectally immediately after surgery and every 8 hours for a total of 3 doses. Patient-reported pain data were collected with the use of a visual analog scale (at 2, 4, 12, and 20 hours postoperatively. Opiate use was measured and converted into parenteral morphine equivalents. The primary outcome was pain, and secondary outcomes included pain medication, antiemetic medication, and a quality of recovery questionnaire. Adverse effects were surveyed at 24 hours and 7 days. Concomitant procedures for urinary incontinence or pelvic organ prolapse did not preclude enrollment. Ninety women were randomly assigned consecutively at a single institution under the care of a fellowship-trained surgeon group. Demographics did not differ among the groups with mean age of 55 years, procedure time of 97 minutes, and prolapse at 51%. Postoperative pain scores were equivalent among both groups at each time interval. The belladonna and opium group used a
Qian, Weibin; Cai, Xinrui; Wang, Yingying; Zhang, Xinying; Zhao, Hongmin; Qian, Qiuhai; Yang, Zhihong; Liu, Zhantao; Hasegawa, Junichi
2016-06-01
Gingerol, the generic term for pungent constituents in ginger, has been used for treating vomiting in China. We are going to investigate the mechanisms of inhibitive effect of gingerol on cisplatin-induced pica behaviour by studying on both peripheral and central levels, and the effects of gingerol on homeostasis of dopamine (DA) transmission: dopamine D2 receptor (D2R), dopamine transporter (DAT) and tyrosine hydroxylase (TH). The antiemetic effect of gingerol was investigated on a vomiting model in rats induced by cisplatin 3 mg·kg(-1) intraperitoneal injection (i.p.). Rats were randomly divided into the normal control group (C), simple gingerol control group (CG), cisplatin control group (V), cisplatin + metoclopramide group (M), cisplatin + low-dose gingerol group (GL), cisplatin + middle-dose gingerol group (GM) and cisplatin + high-dose gingerol group (GH). In observation period, rats in Groups C and V were pretreated with sterile saline 3 mL i.g.; rats in Group CG were pretreated with gingerol 40 mg·kg(-1) i.g.; rats in Group M were pretreated with metoclopramide 2.5 mg·kg(-1) i.g.; rats in Groups GL, GM and GH were pretreated with gingerol 10, 20 and 40 mg·kg(-1) i.g. for 3 days, respectively. Cisplatin (3 mg·kg(-1), i.p.) was administered one time after each treatment with the antiemetic agent or its vehicle except the Groups C and CG. The distribution of D2R, DAT and TH in the area postrema and ileum were measured by immunohistochemistry and quantitated based on the image analysis, and the expression of DAT and TH in the area postrema and ileum were measured by RT-PCR. The weights of kaolin eaten of the remaining rats were observed in every 6 h continuously for 72 h. The weight of kaolin eaten in rats induced by cisplatin was significantly reduced by pretreatment with gingerol in a dose-dependent manner during the 0-24 h and 24-72 h periods (P < 0.05). Gingerol markedly improved gastric emptying induced by cisplatin in a dose-dependent manner (P < 0
Peixoto, A J; Peixoto Filho, A J; Leães, L F; Celich, M F; Barros, M A
2000-10-01
We conducted a prospective, randomized, double-blind clinical trial comparing droperidol 1.25 mg intravenously (i.v.) (group 1, n = 30), ondansetron 4 mg i.v. (group 2, n = 30), or both (group 3, n = 30) in the prevention of postoperative nausea and vomiting (PONV) in the first 24 h following major gynaecological procedures under combined general and epidural anaesthesia. PONV was analysed by a linear nausea/vomiting score, incidence of nausea and vomiting, and the need for antiemetic rescue. Our results showed a similar incidence of nausea and vomiting in all groups (G1 33%, G2 40%, G3 43%). However, when comparisons were made according to the time of assessment, combination therapy resulted in significantly lower PONV than droperidol in the first hour (0% vs. 13%, P < 0.05) and second hour (0% vs. 13%, P < 0.05), and than ondansetron on the first hour (0% vs. 13%, P < 0.05). A trend persisted up to the fourth hour but was not statistically significant in either group. In conclusion, droperidol and ondansetron are effective agents in the prevention of PONV, and their combination seems to provide slightly better results than either drug alone.
Wangnamthip, Suratsawadee; Chinachoti, Thitima; Amornyotin, Somchai; Wongtangman, Karuna; Sukantarat, Numphung; Noitasaeng, Papiroon
2016-05-01
The incidence of postoperative nausea and vomiting (PONV) after intrathecal morphine is high. Ramosetron is a 5-HT₃ antagonist that has been shown to reduce PONV in general anesthesia. The objective of this study was to evaluate the efficacy of Ramosetron in preventing PONV MATERIAL AND METHOD: 165 patients undergoing elective gynecological surgery under spinal anesthesia were randomly allocated to two groups: the Ramosetron group (0.1 mg orally, n = 82), and the placebo group (oral corn starch, n = 83). The incidence of PONV severity of nausea and use of rescue antiemetic during the first 24 hour after surgery were evaluated. The incidence of PONV was significantly lower in the Ramosetron group compared with the placebo group (24.4% vs. 44.6%, number needed to treat (NNT) = 5.0). The severity of nausea was significantly lower in the Ramosetron group compared with the placebo group (20.7% vs. 39.8%, NNT = 6.0) in the 24 hour period. Oral Ramosetron 0.1 mg was more effective than placebo in PONV prevention and reduced the incidence of moderate to severe nausea after intrathecal morphine in the first 24 hour after gynecological surgery.
A novel lipid nanoemulsion system for improved permeation of granisetron.
Doh, Hea-Jeong; Jung, Yunjin; Balakrishnan, Prabagar; Cho, Hyun-Jong; Kim, Dae-Duk
2013-01-01
A new lipid nanoemulsion (LNE) system containing granisetron (GRN) was developed and its in vitro permeation-enhancing effect was evaluated using Caco-2 cell monolayers. Particle size, polydispersity index (PI) and stability of the prepared GRN-loaded LNE systems were also characterized. The mean diameters of prepared LNEs were around 50 nm with PI<0.2. Developed LNEs were stable at 4°C in the dark place over a period of 12 weeks. In vitro drug dissolution and cytotoxicity studies of GRN-loaded LNEs were performed. GRN-loaded LNEs exhibited significantly higher drug dissolution than GRN suspension at pH 6.8 for 2h (P<0.05). In vitro permeation study in Caco-2 cell monolayers showed that the LNEs significantly enhanced the drug permeation compared to GRN powder. The in vivo toxicity study in the rat jejunum revealed that the prepared GRN-loaded LNE was as safe as the commercial formulation (Kytril). These results suggest that LNE could be used as a potential oral liquid formulation of GRN for anti-emetic treatment on the post-operative and chemotherapeutic patients. Copyright © 2012 Elsevier B.V. All rights reserved.
Shima, Yasuo; Yamaguchi, Kensei; Miyata, Yoshinori; Hyodo, Ichinosuke; Yagi, Yasuo; Honke, Yoshifumi
2004-09-01
Terminally ill cancer patients with complicated bowel obstructions often have poor quality of life (QOL) due to gastrointestinal symptoms such as nausea and vomiting. Many of these patients are inoperable because of poor general conditions, and half of these patients can't be managed by conventional antiemetics. There are many reports indicating octreotide is effective for these patients. In the present study, 13 patients (5 patients without a nasogastric tube and 8 patients with) were administered octreotide at 300 microg/day by 24 hours continuous subcutaneous infusion. Among the effectively evaluable 10 cases, 6 cases (60.0%) were assessed as effective according to the efficacy criteria based on the JCOG toxicity scale. In the 6 cases who had nasogastric tubes, the nasogastric aspirates decreased from 890 ml (550-1,950) to 480 ml (180-1,790). Vomiting was successfully controlled after the removals of nasogastric tubes in 4 out of 6 cases (66.7%), regarding safety, 2 out of 13 cases (15.4%) showed an excess of liver enzymes but no clinically suspected adverse effect was observed. Octreotide is effective and well tolerated in terminally ill cancer patients with malignant bowel obstruction.
Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma.
Poklepovic, Andrew; Youssefian, Leena E; Youseffian, Leena; Winning, Mary; Birdsell, Christine A; Crosby, Nancy A; Ramakrishnan, Viswanathan; Ernstoff, Marc S; Roberts, John D
2013-08-01
Preclinical studies in human melanoma cell lines and murine xenograft tumor models suggest that the proteasome inhibitor bortezomib enhances the activity of the cytotoxic agent dacarbazine. We performed a phase I trial of bortezomib and dacarbazine in melanoma, soft tissue sarcoma, and amine precursor uptake and decarboxylation tumors. The primary objective was to identify recommended phase II doses for the combination. Bortezomib and dacarbazine were both administered intravenously once weekly. All patients received prophylactic antiemetics. Dose escalation proceeded using a standard 3 + 3 design. Response was assessed according to NCI RECIST v1.0. Twenty eight patients were enrolled to six dose levels. Bortezomib 1.6 mg/m(2) and dacarbazine 580 mg/m(2) are the recommended phase II weekly doses. The combination was generally well tolerated. Among 15 patients with melanoma there was one durable complete response in a patient with an exon-11 cKIT mutation, and one partial response. Among 12 patients with soft tissue sarcoma there was one partial response. Bortezomib 1.6 mg/m(2) and dacarbazine 580 mg/m(2) administered intravenously once weekly is well tolerated and has at least minimal activity in melanoma and soft tissue sarcoma.
Rock, Erin M; Boulet, Nathalie; Limebeer, Cheryl L; Mechoulam, Raphael; Parker, Linda A
2016-09-05
We aimed to investigate the potential anti-emetic and anti-nausea properties of targeting the cannabinoid 2 (CB2) receptor. We investigated the effect of the selective CB2 agonist, HU-308, on lithium chloride- (LiCl) induced vomiting in Suncus murinus (S. murinus) and conditioned gaping (nausea-induced behaviour) in rats. Additionally, we determined whether these effects could be prevented by pretreatment with AM630 (a selective CB2 receptor antagonist/inverse agonist). In S. murinus, HU-308 (2.5, 5mg/kg, i.p.) reduced, but did not completely block, LiCl-induced vomiting; an effect that was prevented with AM630. In rats, HU-308 (5mg/kg, i.p.) suppressed, but did not completely block, LiCl-induced conditioned gaping to a flavour; an effect that was prevented by AM630. These findings are the first to demonstrate the ability of a selective CB2 receptor agonist to reduce nausea in animal models, indicating that targeting the CB2 receptor may be an effective strategy, devoid of psychoactive effects, for managing toxin-induced nausea and vomiting. Copyright © 2016 Elsevier B.V. All rights reserved.
Myotoku, Michiaki; Murayama, Yoko; Nakanishi, Akiko; Hashimoto, Norio; Koyama, Fumiko; Irishio, Keiko; Kawaguchi, Syunichi; Yamaguchi, Seiji; Ikeda, Kenji; Hirotani, Yoshihiko
2008-02-01
We established the Terminal Care Study Group, consisting of physicians, pharmacists, and nurses, in September 2001, and developed the group into the Palliative Care Team. We have surveyed the state of concomitant medications immediately before and at the beginning of opioid usage (except injections) to assess the role of the Palliative Care Team. The survey period was 3 years from October 1, 2002 to September 30, 2005. While the frequency of the prescription of non-steroidal anti-inflammatory drugs (NSAIDs), laxatives, or antiemetics before the beginning of opioid administration did not differ significantly among the 3 periods, that at the beginning of opioid administration increased significantly in 2003 compared with 2002, and increased further in 2004. Many of the drugs used were those that were recommended in our cancer pain management program. Thus, the activities of the Palliative Care Team are considered to have led to proper measures for the control of the major adverse effects of opioids such as constipation and nausea/vomiting in addition to pain control in accordance with the WHO's pain ladder, and also contributed to improvements of the patients' QOL.
Anaesthesia for the paediatric outpatient.
Jöhr, Martin; Berger, Thomas M
2015-12-01
The aim of this review was to discuss recent developments in paediatric anaesthesia, which are particularly relevant to the practitioner involved in paediatric outpatient anaesthesia. The use of a pharmacological premedication is still a matter of debate. Several publications are focussing on nasal dexmedetomidine; however, its exact place has not yet been defined. Both inhalational and intravenous anaesthesia techniques still have their advocates; for diagnostic imaging, however, propofol is emerging as the agent of choice. The disappearance of codeine has left a breach for an oral opioid and has probably worsened postoperative analgesia following tonsillectomy. In recent years, a large body of evidence for the prevention of postoperative agitation has appeared. Alpha-2-agonists as well as the transition to propofol play an important role. There is now some consensus that for reasons of practicability prophylactic antiemetics should be administered to all and not only to selected high-risk patients. Perfect organization of the whole process is a prerequisite for successful paediatric outpatient anaesthesia. In addition, the skilled practitioner is able to provide a smooth anaesthetic, minimizing complications, and, finally, he has a clear concept for avoiding postoperative pain, agitation and vomiting.
[Methods of preventing phlebitis induced by infusion of fosaprepitant].
Kohno, Emiko; Kanematsu, Sayaka; Okazaki, Satoshi; Ogata, Makoto; Kanemitsu, Meiko; Yamashita, Hiromi; Syuntou, Kaori; Sekita, Masako; Nishioka, Ryoko; Yoshida, Hideyuki
2015-03-01
At our hospital, we use aprepitant for nausea and vomiting when administering highly emetic anticancer agents, according to "Guidelines for the Appropriate Use of Antiemetic Agents" given by the Japan Society of Clinical Oncology. We initiated the intravenous administration of fosaprepitant for better compliance compared with aprepitant; however, we observed phlebitis after the infusion of fosaprepitant. Therefore, we investigated measures to reduce phlebitis associated with the infusion of fosaprepitant. For the first premedication, fosaprepitant (150 mg) was dissolved in 100 mL of saline and administered for 30 minutes; 1 of 2 patients showed grade 4 phlebitis. For the modified premedication, fosaprepitant, dexamethasone, and 5- HT(3) antagonist were dissolved in 100 mL of saline and administered for 30 minutes. The modified premedication was administered to a total of 27 patients; 5 patients developed mild phlebitis (grade 1), but infusion could be continued by treating their phlebitis with a hot pack. We used a combination of dexamethasone and 5-HT(3) antagonist with fosaprepitant as a modified premedication in order to avoid drug-induced vascular damage, which resulted in the pH decreasing to 6.20-7.55 (close to neutral) and a shorter infusion time.
Pavlovian conditioning of nausea and vomiting.
Stockhorst, Ursula; Steingrueber, Hans-Joachim; Enck, Paul; Klosterhalfen, Sibylle
2006-10-30
Cancer patients undergoing cytotoxic drug treatment often experience side-effects, the most distressing being nausea and vomiting. Despite antiemetic drugs, 25-30% of the chemotherapy patients report these side-effects when being re-exposed to the stimuli that usually signal the chemotherapy session and its drug infusion. These symptoms are called anticipatory nausea and anticipatory vomiting. The present paper summarizes the evidence that anticipatory vomiting is acquired by Pavlovian conditioning, and, consequently, may be alleviated by conditioning techniques. To explore the mechanisms that induce and alleviate conditioned nausea and vomiting further, a conditioned nausea model was established in healthy humans using body rotation as the nausea-inducing treatment. The validity of this motion sickness model to examine conditioning mechanisms in the acquisition and alleviation of conditioned nausea was demonstrated. Cortisol and tumor-necrosis factor-alpha were elevated as endocrine and immunological correlates of nausea. Data in the rotation-induced motion sickness model indicated that gender is an important moderator variable to be considered in further studies. The paper concludes with a review of applications of the demonstrated conditioning principles as interventions to ameliorate distressing anticipatory nausea or anticipatory vomiting in cancer patients undergoing chemotherapy.
Valbenazine for the treatment of tardive dyskinesia.
Müller, Thomas
2017-12-01
Chronic intake of typical neuroleptics or centrally acting dopamine receptor blocking antiemetics may cause onset of tardive syndromes. Various types exist. One of them is tardive dyskinesia, characterised by often stigmatising, purposeless, rapid, repetitive, stereotypic, involuntary movements of face, limbs or trunk. Effective symptomatic drug treatment options beyond application of tetrabenazine are rare. Tetrabenazine is usually administered three times daily due to the short half life of this agent. Areas covered: This narrative review discusses the value of valbenazine for the treatment of tardive dyskinesia as a therapeutic alternative to tetrabenazine. Expert commentary: Valbenazine is a selective inhibitor of vesicular monoamine transporter 2, which is metabolized to (+)-alpha-dihydrotetrabenazine. Valbenazine and particularly its metabolite inhibit vesicular monoamine transporter 2 function. Once daily intake of valbenazine ameliorated the severity of tardive dyskinesia. The chiral purity of valbenazine circumvents generation of the (-)alpha and (+) and (-)beta dihydrotetrabenazine metabolites of tetrabenazine or deutetrabenazine. Valbenazine and its metabolite do not antagonize postsynaptic monoamine receptors in contrast to the tetrabenazine formulations. Therefore one may hypothesize that fewer and less severe motor and psychopathological side effects will occur during valbenazine long term application compared with tetrabenazine or deutretrabenazine.
Rolapitant: A Review in Chemotherapy-Induced Nausea and Vomiting.
Heo, Young-A; Deeks, Emma D
2017-10-01
Oral rolapitant (Varubi™; Varuby ® ), a long-acting neurokinin-1 (NK 1 ) receptor antagonist (RA), is indicated in the USA and EU as part of an antiemetic regimen to prevent delayed chemotherapy-induced nausea and vomiting (CINV) in adults receiving highly or moderately emetogenic chemotherapy (HEC or MEC). In randomized, phase III trials, a single oral dose of rolapitant 180 mg was effective in preventing delayed CINV compared with placebo, when each was used in combination with a 5-HT 3 RA plus dexamethasone, in adults receiving their first course of HEC or MEC. The benefits of rolapitant were maintained over multiple cycles of chemotherapy. The tolerability profile of rolapitant is similar to that of placebo and consistent with that of other NK 1 RAs. However, rolapitant differs from other existing NK 1 RAs in that it does not interact with CYP3A4, thereby negating the need for dexamethasone dose adjustments and potentially making rolapitant a more suitable option for patients receiving CYP3A4 substrates. Thus, oral rolapitant is an effective and well tolerated NK 1 RA that expands the treatment options for preventing delayed CINV in adults receiving HEC or MEC.
Occurrence, biological activity and metabolism of 6-shogaol.
Kou, Xingran; Wang, Xiaoqi; Ji, Ruya; Liu, Lang; Qiao, Yening; Lou, Zaixiang; Ma, Chaoyang; Li, Shiming; Wang, Hongxin; Ho, Chi-Tang
2018-03-01
As one of the main bioactive compounds of dried ginger, 6-shogaol has been widely used to alleviate many ailments. It is also a major pungent flavor component, and its precursor prior to dehydration is 6-gingerol, which is reported to be responsible for the pungent flavor and biological activity of fresh ginger. Structurally, gingerols including 6-gingerol have a β-hydroxyl ketone moiety and is liable to dehydrate to generate an α,β-unsaturated ketone under heat and/or acidic conditions. The conjugation of the α,β-unsaturated ketone skeleton in the chemical structure of 6-shogaol explicates its higher potency and efficacy than 6-gingerol in terms of antioxidant, anti-inflammatory, anticancer, antiemetic and other bioactivities. Research on the health benefits of 6-shogaol has been conducted and results have been reported recently; however, scientific data are scattered due to a lack of systematic collection. In addition, action mechanisms of the preventive and/or therapeutic actions of 6-shogaol remain obscurely non-collective. Herein, we review the preparations, biological activity and mechanisms, and metabolism of 6-shogaol as well as the properties of 6-shogaol metabolites.
Tsuchiya, Yo; Fujita, Rina; Saitou, Akae; Wajima, Nanako; Aizawa, Fuyuka; Iinuma, Akane
2014-01-01
[6]-Gingerol possesses a variety of beneficial pharmacological and therapeutic properties, including anti-carcinogenic, anti-inflammatory, and anti-emetic activities. Although [6]-gingerol is known to regulate the contraction of the intestine, its effect on intestinal ion transport is unclear. The aim of this study was to examine the role of [6]-gingerol in the regulation of electrogenic ion transport in the rat intestine by measuring the transmural potential difference (ΔPD). [6]-Gingerol induced significant positive ΔPD when administered to the serosal but not mucosal side of the colon, ileum, and jejunum; the highest effect was detected in the colon at a concentration of 10 μM. [6]-Gingerol-induced increase in ΔPD was suppressed by ouabain, an inhibitor of Na(+)/K(+)-ATPase, whereas no effect was observed in response to bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(-) co-transporter. In addition, ΔPD induction by [6]-gingerol was greatly diminished by capsazepine, an inhibitor of the capsaicin receptor TRPV1. These results suggest that [6]-gingerol induced the electrogenic absorption of sodium in the rat colon via TRPV1.
Ginger-Mechanism of action in chemotherapy-induced nausea and vomiting: A review.
Marx, Wolfgang; Ried, Karin; McCarthy, Alexandra L; Vitetta, Luis; Sali, Avni; McKavanagh, Daniel; Isenring, Liz
2017-01-02
Despite advances in antiemetic therapy, chemotherapy-induced nausea and vomiting (CINV) still poses a significant burden to patients undergoing chemotherapy. Nausea, in particular, is still highly prevalent in this population. Ginger has been traditionally used as a folk remedy for gastrointestinal complaints and has been suggested as a viable adjuvant treatment for nausea and vomiting in the cancer context. Substantial research has revealed ginger to possess properties that could exert multiple beneficial effects on chemotherapy patients who experience nausea and vomiting. Bioactive compounds within the rhizome of ginger, particularly the gingerol and shogaol class of compounds, interact with several pathways that are directly implicated in CINV in addition to pathways that could play secondary roles by exacerbating symptoms. These properties include 5-HT 3 , substance P, and acetylcholine receptor antagonism; antiinflammatory properties; and modulation of cellular redox signaling, vasopressin release, gastrointestinal motility, and gastric emptying rate. This review outlines these proposed mechanisms by discussing the results of clinical, in vitro, and animal studies both within the chemotherapy context and in other relevant fields. The evidence presented in this review indicates that ginger possesses multiple properties that could be beneficial in reducing CINV.
NASA Astrophysics Data System (ADS)
Nasution, E. Z. J.; Tafsin, M.; Hanafi, N. D.
2018-02-01
Red ginger contains high antioxidants and have anti -inflamatory properties. Ginger also has the ability to treat kimiatif, antiemetic, antinausea, and antiparasitik. The aim of this experiment was identified the response of red ginger in broilers were infected by Eimeria tenella. This research used Completely Randomized Design (CRD) with 5 treatments and 4 replications. Eimeria tenella were infected by 10.000 oocysts / head and red ginger solution were aplicated with 1% concentration. The treatments consist of KP (positive control), KO (coccidiostat), K1 (red ginger powder), K2 (extracted red ginger by ethanol) and K3 (extracted red ginger by water) . The results showed that the treatment of red ginger was significant effect (P<0.05) to lower oocyst production in broilers were infected by Eimeria tenella. The comparison between extracted red ginger by ethanol is better than by water or in powder form to decreased. The utilization of red ginger showed the percentage of heterophile and eosinophile close to normal when compared with positive control. Assesment of caecum lesion score was not significant (P>0.05) different effect between all the treatments. It is concluded that the treatment by red ginger better than coccidiostat and positive control.
Zhong, Weixia; Chebolu, Seetha; Darmani, Nissar A
2016-04-01
Cytoplasmic calcium (Ca(2+)) mobilization has been proposed to be an important factor in the induction of emesis. The selective sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor thapsigargin, is known to deplete intracellular Ca(2+) stores, which consequently evokes extracellular Ca(2+) entry through cell membrane-associated channels, accompanied by a prominent rise in cytosolic Ca(2+). A pro-drug form of thapsigargin is currently under clinical trial as a targeted cancer chemotherapeutic. We envisioned that the intracellular effects of thapsigargin could cause emesis and planned to investigate its mechanisms of emetic action. Indeed, thapsigargin did induce vomiting in the least shrew in a dose-dependent and bell-shaped manner, with maximal efficacy (100%) at 0.5 mg/kg (i.p.). Thapsigargin (0.5 mg/kg) also caused increases in c-Fos immunoreactivity in the brainstem emetic nuclei including the area postrema (AP), nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMNX), as well as enhancement of substance P (SP) immunoreactivity in DMNX. In addition, thapsigargin (0.5 mg/kg, i.p.) led to vomit-associated and time-dependent increases in phosphorylation of Ca(2+)/calmodulin kinase IIα (CaMKIIα) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) in the brainstem. We then explored the suppressive potential of diverse chemicals against thapsigargin-evoked emesis including antagonists of: i) neurokinin-1 receptors (netupitant), ii) the type 3 serotonin receptors (palonosetron), iii) store-operated Ca(2+) entry (YM-58483), iv) L-type Ca(2+) channels (nifedipine), and v) SER Ca(2+)-release channels inositol trisphosphate (IP3Rs) (2-APB)-, and ryanodine (RyRs) (dantrolene)-receptors. In addition, the antiemetic potential of inhibitors of CaMKII (KN93) and ERK1/2 (PD98059) were investigated. All tested antagonists/blockers attenuated emetic parameters to varying degrees except palonosetron, however a combination of non
Min, Kyeong T; Koo, Bon N; Kang, Jeong W; Bai, Sun Joon; Ko, Sung R; Cho, Zang-Hee
2003-08-01
Nausea and vomiting are the most frequently reported side-effects by patients who are given general anesthesia perioperatively and patients with cancer who undergo chemotherapy or radiotherapy. Serotonin (5-hydroxytryptamine, 5HT) type 3A receptor (5HT(3A) receptor) is known to mediate nausea and vomiting and its antagonists have been used effectively to prevent and/or reduce the incidence and severity of nausea and vomiting. However, the adverse effects on cardiac function, such as QT interval prolongation, limit their routine use by these patients. This study was designed to elucidate the effect of ginseng saponins on the recombinant 5HT(3A) receptor expressed in the xenopus oocyte. After in vitro transcription of the recombinant human 5HT(3A) receptor in the Xenopus laevis oocyte, we examined Panax ginseng saponins (total saponin [TS], panaxadiol saponin [PD] fraction, panaxatriol saponin [PT] fraction, and ginsenoside-Rb1 and -Rg1) for their ability to inhibit current flow through the 5HT(3A) receptor using the voltage-clamp technique. All saponin fractions (TS, PD, PT fraction, as well as ginsenoside-Rb1 and -Rg1) inhibited the peak current induced by the agonist 5HT on the 5HT(3A) receptor in a concentration-dependent, reversible, and voltage-independent manner. The PT fraction inhibited 5HT-induced currents in 5HT(3A) receptor more than the PD fraction; meanwhile, there was a similar degree of inhibition between ginsenoside-Rg1 and -Rb1, the main substitutes of PT fraction and PD saponin fractions, respectively. These results indicate that ginseng saponins, especially PT fraction, have substantial inhibitory effects on the recombinant 5HT(3A) receptor, suggesting that some of the specific types of ginsenoside might have an antagonistic action against 5HT(3A) receptor related to nausea and vomiting.
Andrew, Inga M; Waterfield, Kerry; Hildreth, Anthony J; Kirkpatrick, Graeme; Hawkins, Colette
2009-12-01
The objective of this study was to quantify the impact of standardized assessment and management tools on patient symptom scores in cancer-induced anorexia cachexia syndrome (ACS) using a within-group study design. Baseline assessments included the Patient Generated Subjective Global Assessment (PG-SGA) tool and an amended Symptoms and Concerns Checklist (SCC). Symptom management strategies, written for this project, were instigated. Follow-up SCC scores were collected at 2 and 4 weeks. Forty out of 79 patients referred were recruited; 29/79 (36.7%) were too unwell or had died prior to consent. At baseline, the PG-SGA tool revealed 250 active symptoms associated with ACS. Total PG-SGA score was above 9 for all patients. Predominant interventions involved simple dietary advice and prescription of artificial saliva, mouthwash and prokinetic antiemetics. Median total SCC score improved sequentially from 11 at baseline, to 7 and 4 at first and second review, respectively (visit 1 to 2, p = 0.001; visit 1 to 3, p < 0.001; and visit 2 to 3, p = 0.02). We conclude that patients with ACS are recognised late in their disease and have a considerable burden of active symptoms. A structured approach to assessment and management has a significant impact on symptom burden.
One Plant, Many Uses: A Review of the Pharmacological Applications of Morinda citrifolia.
Torres, Mylena Andréa Oliveira; de Fátima Braga Magalhães, Isadora; Mondêgo-Oliveira, Renata; de Sá, Joicy Cortez; Rocha, Alessandra Lima; Abreu-Silva, Ana Lucia
2017-07-01
Morinda citrifolia, also known as noni, is commonly used in popular medicine in Brazil. Many parts of the noni tree are utilized in such practices, including the roots, leaves and seeds. Through a search of online databases, the present article reviews 92 research studies on the biological actions of M. citrifolia. The paper will discuss the therapeutic effects of noni and its compounds in a variety of forms of presentation, focusing on studies that support its traditional use. A large and diverse number of properties were identified, which were divided into immunostimulatory, antitumor, antidiabetic, anti-obesity, antibacterial and anti-septic, antifungal, antiviral, leishmanicidal, antiinflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, antiangiogenic, antiemetic and anti-nausea, anti-gastric ulcer and oesophagitis, anthelmintic, antimutagenic, antipsychotic, anxiolytic, photoprotective, anti-wrinkle and periodontal tissue regeneration activities. While it was concluded that although M. citrifolia is widely and successfully used for the treatment or prevention of various diseases, it should be consumed carefully, and only after exhaustive studies into its chemical constituents and mechanisms of action, both in in vitro and in vivo models, as well as clinical trials. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
Fujii, Y; Tanaka, H; Toyooka, H
1996-12-01
Dexamethasone decreases chemotherapy-induced emesis when added to antiemetic regimens. This study was designed to compare the effectiveness of granisetron and dexamethasone with granisetron alone in the prevention of post-operative vomiting after strabismus repair, tonsillectomy with or without adenoidectomy in children. In a randomized, double-blind study, 60 healthy children, 4-10 yr of age, received either granisetron 40 micrograms.kg-1 and saline (Group S) or granisetron 40 micrograms.kg-1 and dexamethasone 4 mg (Group D) iv immediately after the induction of anaesthesia. All subjects received anaesthetics consisting of sevoflurane and nitrous oxide in oxygen Postoperative pain was treated with acetaminophen pr or pentazocine iv. Postoperatively, during the first 24 hr after anaesthesia, the frequencies of retching and vomiting, and the incidence of adverse events were recorded by nursing staff. There were no differences between the treatment groups with regard to demographics, surgical procedure, anaesthetic administered or analgesics used for postoperative pain. The frequency of the symptoms was 27% and 7% in Groups S and D, respectively (P < 0.05). The incidence of adverse events was comparable in the two groups. The prophylactic administration of granisetron and dexamethasone was more effective than granisetron alone in the prevention of postoperative vomiting in paediatric subjects undergoing strabismus repair, tonsillectomy and adenoidectomy.
Effect of Herbal Therapy to Intensity Chemotherapy-Induced Nausea and Vomiting in Cancer Patients.
Montazeri, Akram Sadat; Raei, Mehdi; Ghanbari, Atefeh; Dadgari, Ali; Montazeri, Azam Sadat; Hamidzadeh, Azam
2013-01-01
Background: Chemotherapy-induced nausea and vomiting are the most important complications for cancer patients as its prevalence has been reported to be about 54-96 percent. ginger has been used for medicinal purposes including nausea and vomiting in traditional Persian, Chinese and Indian pharmacopoeia. Objectives: The objective of this study was to evaluate the efficacy of complimentary ginger among cancer patients experiencing nausea and vomiting. Material and Methods: A randomized cross-over clinical trial was carried out on patients under chemotherapy treatment for at least 2 episodes of chemotherapy and at least 2 episodes of previous experience of nausea and vomiting. Subjects of this study received 2 different complementary regimes with 250mg ginger capsule in regime A and placebo capsule in regime B. subjects of the study were crossed over to receive the other regime during the two cycles of chemotherapy. Results: Findings of the study indicated that subjects receiving ginger showed significant reduction in frequency and intensity of nausea and vomiting compared to placebo receiving subjects. Conclusions: According to finding of this study, in accordance to most of other researches, ginger is an effective agent to reduce chemotherapy-induced nausea and vomiting. However, there are some researches supporting ginger as a moderate antiemetic agent among cancerous patients under chemotherapy. PMID:24693415
Hu, Guanying; Peng, Cheng; Xie, Xiaofang; Zhang, Sanyin; Cao, Xiaoyu
2017-01-01
Patchouli alcohol (PA), a tricyclic sesquiterpene, is one of the critical bioactive ingredients and is mainly isolated from aerial part of Pogostemon cablin (known as guanghuoxiang in China) belonging to Labiatae. So far, PA has been widely applied in perfume industries. This review was written with the use of reliable information published between 1974 and 2016 from libraries and electronic researches including NCKI, PubMed, Reaxys, ACS, ScienceDirect, Springer, and Wiley-Blackwell, aiming at presenting comprehensive outline of security, pharmacokinetics, and bioactivities of PA and at further providing a potential guide in exploring the PA and its use in various medical fields. We found that PA maybe was a low toxic drug that was acquired numerously through vegetable oil isolation and chemical synthesis and its stability and low water dissolution were improved in pharmaceutics. It also possessed specific pharmacokinetic characteristics, such as two-compartment open model, first-order kinetic elimination, and certain biometabolism and biotransformation process, and was shown to have multiple biological activities, that is, immunomodulatory, anti-inflammatory, antioxidative, antitumor, antimicrobial, insecticidal, antiatherogenic, antiemetic, whitening, and sedative activity. However, the systematic evaluations of preparation, pharmaceutics, toxicology, pharmacokinetics, and bioactivities underlying molecular mechanisms of action also required further investigation prior to practices of PA in clinic.
Safety and side effects of cannabidiol, a Cannabis sativa constituent.
Bergamaschi, Mateus Machado; Queiroz, Regina Helena Costa; Zuardi, Antonio Waldo; Crippa, José Alexandre S
2011-09-01
Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were "cannabinoids", "cannabidiol" and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.
Kokubun, Hideya; Uezono, Yasuhito; Matoba, Motohiro
2014-04-01
In Europe and the United States, D9-tetrahydrocannabinol(THC, dronabinol), one of the psychoactive constituents of cannabis, has been used for both its anti-emetic and orexigenic effects in cancer patient receiving chemotherapy.However, dronabinol has not yet been launched in the market in Japan.In the future, it is necessary to ascertain the pharmacokinetics of dronabinol in cancer paitient.Therefore, we developed an HPLC procedure using electrochemical detection(ECD)for quan- titation of the concentrations of dronabinol in blood.An eluent of 50mM KH2PO4/CH3CN(9:16)was used as the mobile phase.The column was used the XTerra®RP18, and the voltage of the electrochemical detector in dronabinol was set at 400 mV.As a result, the calibration curve was linear in the range of 10 ng/mL to 100 ng/mL(y=964.85x -3,419, r=0.997).The lower limit of quantification was 0.5 ng/mL(S/N=3).The relative within-runs and between-runs standard deviations for the assay dronabinol were less than 4.7%. The method reported here is superior to previously reported methods in cancer patient.
Complementary Health Approaches Used in the Intensive Care Unit.
Erdoğan, Zeynep; Atik, Derya
Intensive care units are care centers where, in order to provide the maximum benefit to individuals whose life is in danger, many lifesaving technological tools and devices are present, and morbidity and mortality rates are high. In the intensive care unit, when classic treatments fail or become unbearable because of side effects, complementary methods have been suggested to be the best alternative. Complementary health approaches are methods that are used both for the continuation and the improvement of the well-being of an individual and as additions to medical treatments that are based on a holistic approach. These applications are especially helpful in the treatment of the stresses, anxieties, and other symptoms of unstable patients in the intensive care unit who do not tolerate traditional treatment methods well, increasing their psychological and physiological well-being, helping them sleep and rest. In intensive care patients, in order to decrease the incidence of postoperative atrial fibrillation, antiemetic and medicine needs, mechanical ventilation duration, and the intensity of the disease as well as to cope with symptoms such as pain, anxiety, physiological parameters, dyspnea, and sleep problems, body-mind interventions such as massage, reflexology, acupressure, aromatherapy, music therapy, energy therapies (healing touch, therapeutic touch, the Yakson method), and prayer are used as complementary health approaches.
França, Monique Sedlmaier; Usón, Pedro Luiz Serrano; Antunes, Yuri Philippe Pimentel Vieira; Prado, Bernard Lobato; Donnarumma, Carlos del Cistia; Mutão, Taciana Sousa; Rodrigues, Heloisa Veasey; del Giglio, Auro
2015-01-01
ABSTRACT Objective: To assess adherence of the prescribing physicians in a private cancer care center to the American Society of Clinical Oncology guideline for antiemetic prophylaxis, in the first cycle of antineoplastic chemotherapy. Methods: A total of 139 chemotherapy regimens, of 105 patients, were evaluated retrospectively from 2011 to 2013. Results: We observed 78% of non-adherence to the guideline rate. The main disagreements with the directive were the prescription of higher doses of dexamethasone and excessive use of 5-HT3 antagonist for low risk emetogenic chemotherapy regimens. On univariate analysis, hematological malignancies (p=0.005), the use of two or more chemotherapy (p=0.05) and high emetogenic risk regimes (p=0.012) were factors statistically associated with greater adherence to guidelines. Treatment based on paclitaxel was the only significant risk factor for non-adherence (p=0.02). By multivariate analysis, the chemotherapy of high emetogenic risk most correlated with adherence to guideline (p=0.05). Conclusion: We concluded that the adherence to guidelines is greater if the chemotherapy regime has high emetogenic risk. Educational efforts should focus more intensely on the management of chemotherapy regimens with low and moderate emetogenic potential. Perhaps the development of a computer generated reminder may improve the adherence to guidelines. PMID:26154543
Rhabdomyolysis secondary to interaction between atorvastatin and fusidic acid
Saeed, Nabeel Tahir Muhammad; Azam, Mohammad
2009-01-01
A 48-year-old ill-looking man presented with nausea and vomiting. He had been on fusidic acid 500 mg three times a day and linezolid 600 mg twice a day for 2 weeks for right knee methicillin-resistant Staphylococcus aureus infection post right knee arthroscopy performed a month previously. He had been on atorvastatin 40 mg daily and Aspirin 75 mg once a day for a year. His investigations showed elevated creatine phosphokinase (CPK) (759 IU/litre) and transaminases (aspartate transaminase (AST) 58 IU/litre and alanine transaminase (ALT) 123 IU/litre). Atorvastatin was discontinued and the patient was treated with intravenous fluids, a proton pump inhibitor, antiemetics and discharged with follow-up in 2 days for repeat blood results. The patient presented 5 days later with rhabdomyolysis and acute hepatitis. His antibiotics (fusidic acid and linezolid) were stopped. The patient was managed conservatively with intravenous fluids and was transferred for possible dialysis but did not need it. After 3 weeks investigations showed normal urea, creatinine, electrolytes, CPK and liver function tests suggesting earlier rise in transaminases secondary to muscle damage rather than liver. The patient had intensive physiotherapy and his mobility improved, and he was discharged home. The case was reported to pharmacovigilance services. PMID:21918658
[Pneumocystis Pneumonia during Adjuvant Chemotherapy for Advanced Colon Cancer - A Case Report].
Fujiwara, Yushi; Lee, Shigeru; Kishida, Satoru; Hashiba, Ryoya; Gyobu, Ken; Osugi, Harushi
2015-11-01
We report a case of pneumocystis pneumonia (PCP) during adjuvant chemotherapy for advanced sigmoid colon cancer. A 70-year-old Japanese man was referred to our hospital after complaining of bloody stools. He was diagnosed with advanced sigmoid colon cancer, T2N2aM1b, Stage IV B. After 3 cycles of mFOLFOX6 plus panitumumab as first-line chemotherapy, he received FOLFIRI plus bevacizumab as second-line chemotherapy because of progressive disease. Aprepitant and steroids were administered as antiemetic agents for a short period during each chemotherapy session. During the 2 cycle of FOLFIRI plus bevacizumab, he developed a high fever without respiratory symptoms. Chest CT revealed ground-glass opacities in both the lungs. We first treated him with antibiotics (PIPC/TAZ plus GRNX), suspecting bacterial pneumonia. However, based on the elevation of serum b -D-glucan (148 pg/mL), we diagnosed PCP and initiated SMX/TMP in addition to PIPC/TAZ. The inflammation promptly decreased, and follow-up chest CT revealed the disappearance of the ground-glass opacities. If a patient develops a fever or respiratory symptoms during a course of chemotherapy, we should consider the possibility of PCP and perform careful examinations.
Supportive therapy in medical therapy of head and neck tumors
Link, Hartmut
2012-01-01
Fever during neutropenia may be a symptom of severe life threatening infection, which must be treated immediately with antibiotics. If signs of infection persist, therapy must be modified. Diagnostic measures should not delay treatment. If the risk of febrile neutropenia after chemotherapy is ≥20%, then prophylactic therapy with G-CSF is standard of care. After protocols with a risk of febrile neutropenia of 10–20%, G-CSF is necessary, in patients older than 65 years or with severe comorbidity, open wounds, reduced general condition. Anemia in cancer patients must be diagnosed carefully, even preoperatively. Transfusions of red blood cells are indicated in Hb levels below 7–8 g/dl. Erythropoiesis stimulating agents (ESA) are recommended after chemotherapy only when hemoglobin levels are below 11 g/dl. The Hb-level must not be increased above 12 g/dl. Anemia with functional iron deficiency (transferrin saturation <20%) should be treated with intravenous iron, as oral iron is ineffective being not absorbed. Nausea or emesis following chemotherapy can be classified as minimal, low, moderate and high. The antiemetic prophylaxis should be escalated accordingly. In chemotherapy with low emetogenic potential steroids are sufficient, in the moderate level 5-HT3 receptor antagonists (setrons) are added, and in the highest level Aprepitant as third drug. PMID:23320053
Hausel, J; Nygren, J; Thorell, A; Lagerkranser, M; Ljungqvist, O
2005-04-01
A carbohydrate-rich drink (CHO) has been shown to reduce preoperative discomfort. It was hypothesized that it may also reduce postoperative nausea and vomiting (PONV). Patients undergoing elective laparoscopic cholecystectomy under inhalational anaesthesia (127 women and 45 men; mean(s.d.) 48(15) years) were randomized to either preoperative fasting, intake of CHO (50 kcal/100 ml, 290 mOsm/kg) or placebo. The non-fasting groups were double-blinded; patients ingested 800 ml of liquid on the evening before surgery and 400 ml 2 h before anaesthesia. Nausea and pain scores on a visual analogue scale (VAS) and episodes of PONV were recorded up to 24 h after surgery. The incidence of PONV was lower in the CHO than in the fasted group between 12 and 24 h after surgery (P = 0.039). Nausea scores in the fasted and placebo groups were higher after operation than before admission to hospital (P = 0.018 and P < 0.001 respectively), whereas there was no significant change in the CHO group. No intergroup differences in VAS scores were seen. The use of anaesthetics, opioids, antiemetics and intravenous fluids was similar in all groups. CHO may have a beneficial effect on PONV 12-24 h after laparoscopic cholecystectomy.
Hu, Guanying; Xie, Xiaofang; Cao, Xiaoyu
2017-01-01
Patchouli alcohol (PA), a tricyclic sesquiterpene, is one of the critical bioactive ingredients and is mainly isolated from aerial part of Pogostemon cablin (known as guanghuoxiang in China) belonging to Labiatae. So far, PA has been widely applied in perfume industries. This review was written with the use of reliable information published between 1974 and 2016 from libraries and electronic researches including NCKI, PubMed, Reaxys, ACS, ScienceDirect, Springer, and Wiley-Blackwell, aiming at presenting comprehensive outline of security, pharmacokinetics, and bioactivities of PA and at further providing a potential guide in exploring the PA and its use in various medical fields. We found that PA maybe was a low toxic drug that was acquired numerously through vegetable oil isolation and chemical synthesis and its stability and low water dissolution were improved in pharmaceutics. It also possessed specific pharmacokinetic characteristics, such as two-compartment open model, first-order kinetic elimination, and certain biometabolism and biotransformation process, and was shown to have multiple biological activities, that is, immunomodulatory, anti-inflammatory, antioxidative, antitumor, antimicrobial, insecticidal, antiatherogenic, antiemetic, whitening, and sedative activity. However, the systematic evaluations of preparation, pharmaceutics, toxicology, pharmacokinetics, and bioactivities underlying molecular mechanisms of action also required further investigation prior to practices of PA in clinic. PMID:28421121
VMAT2 inhibitors for the treatment of tardive dyskinesia.
Scorr, Laura M; Factor, Stewart A
2018-06-15
Tardive dyskinesia (TD) is an often disabling hyperkinetic movement disorder caused by exposure to dopamine receptor blocking agents. Although initially thought to most commonly occur with typical antipsychotics, the incidence is likely similar with atypical antipsychotics and antiemetics such as metoclopramide. Increased prescribing of these agents as well as low rates of remission have contributed to a rising prevalence of TD. Although this condition was described nearly 60 years ago, it is only within the past year that two novel therapeutic agents were FDA approved. Characterization of the VMAT2 inhibitor tetrabenazine, which was identified as a therapeutic agent for TD in older clinical trials, has yielded two distinct pharmacologic strategies to optimize response. The first strategy, used to create deutetrabenazine, employed deuterization of tetrabenazine to stabilize the pharmacokinetics and eliminate high peak plasma levels. The second strategy was the creation of a prodrug, valbenazine, for the two most active isoforms of tetrabenazine that also resulted in more stable pharmacokinetics and eliminated peak plasma levels. Both agents have been demonstrated to be effective and safe for the treatment of TD in multicenter, controlled trials and their development has led to a resurgence of interest in the characterization and treatment of this movement disorder. Copyright © 2018 Elsevier B.V. All rights reserved.
Valbenazine granted breakthrough drug status for treating tardive dyskinesia.
Müller, Thomas
2015-06-01
The chronic use and high dosing of typical neuroleptics or centrally acting dopamine receptor blocking antiemetics predispose patients to the onset of tardive syndromes. One particular subtype, tardive dyskinesia, is characterized by rapid, repetitive, stereotypic, involuntary movements of the face, limbs or trunk. The inhibition of the vesicular monoamine transporter system, using tetrabenazine therapy, improves the severity of tardive dyskinesia. But there are also drawbacks to tetrabenazine treatment, such as a fluctuating response and the need for frequent intake due to its rapid metabolism. Clinical research on the potentially more efficacious and easier to use tetrabenazine analogs is already under way. One of them is valbenazine, the purified parent drug of the (+)-α-isomer of tetrabenazine. The FDA lowered approval hurdles for valbenazine due to a successful Phase II trial, which showed a distinctive improvement in tardive dyskinesia symptoms during valbenazine administration. This resurgence in the clinical research of tardive syndrome therapy is most welcome. This author notes that the putative long-term side effects of valbenazine should carefully be investigated in the future via naturalistic observational trials. Furthermore, valbenazine may also support the onset of symptoms, such as Parkinsonism and depression, with chronic administration, as it, to a certain extent, shares the mode of action of tetrabenazine.
Ganie, Showkat Ahmad; Yadav, Surender Singh
2014-01-01
Holoptelea integrifolia (Ulmaceae) is a versatile medicinal plant used in various indigenous systems of medicine for curing routine healthcare maladies. It is traditionally used in the treatment and prevention of several ailments like leprosy, inflammation, rickets, leucoderma, scabies, rheumatism, ringworm, eczema, malaria, intestinal cancer, and chronic wounds. In vitro and in vivo pharmacological investigations on crude extracts and isolated compounds showed antibacterial, antifungal, analgesic, antioxidant, anti-inflammatory, anthelmintic, antidiabetic, antidiarrhoeal, adaptogenic, anticancer, wound healing, hepatoprotective, larvicidal, antiemetic, CNS depressant, and hypolipidemic activities. Phytochemical analysis showed the presence of terpenoids, sterols, saponins, tannins, proteins, carbohydrates, alkaloids, phenols, flavonoids, glycosides, and quinines. Numerous compounds including Holoptelin-A, Holoptelin-B, friedlin, epifriedlin, β-amyrin, stigmasterol, β-sitosterol, 1, 4-napthalenedione, betulin, betulinic acid, hexacosanol, and octacosanol have been identified and isolated from the plant species. The results of several studies indicated that H. integrifolia may be used as an effective therapeutic remedy in the prevention and treatment of various ailments. However, further studies on chemical constituents and their mechanisms in exhibiting certain biological activities are needed. In addition, study on the toxicity of the crude extracts and the compounds isolated from this plant should be assessed to ensure their eligibility to be used as source of modern medicines. PMID:24949441
Tremor analysis separates Parkinson's disease and dopamine receptor blockers induced parkinsonism.
Shaikh, Aasef G
2017-05-01
Parkinson's disease, the most common cause of parkinsonism is often difficult to distinguish from its second most common etiology due to exposure to dopamine receptor blocking agents such as antiemetics and neuroleptics. Dual axis accelerometry was used to quantify tremor in 158 patients with parkinsonism; 62 had Parkinson's disease and 96 were clinically diagnosed with dopamine receptor blocking agent-induced parkinsonism. Tremor was measured while subjects rested arms (resting tremor), outstretched arms in front (postural tremor), and reached a target (kinetic tremor). Cycle-by-cycle analysis was performed to measure cycle duration, oscillation amplitude, and inter-cycle variations in the frequency. Patients with dopamine receptor blocker induced parkinsonism had lower resting and postural tremor amplitude. There was a substantial increase of kinetic tremor amplitude in both disorders. Postural and resting tremor in subjects with dopamine receptor blocking agent-induced parkinsonism was prominent in the abduction-adduction plane. In contrast, the Parkinson's disease tremor had equal amplitude in all three planes of motion. Tremor frequency was comparable in both groups. Remarkable variability in the width of the oscillatory cycles suggested irregularity in the oscillatory waveforms in both subtypes of parkinsonism. Quantitative tremor analysis can distinguish Parkinson's disease from dopamine receptor blocking agent-induced parkinsonism.
Laparoscopic gastric plication: technical report.
El-Geidie, Ahmed; Gad-el-Hak, Nabil
2014-01-01
Laparoscopic gastric plication is an emerging restrictive bariatric procedure but still lacks standardization of the technique. The aim of this study was to apply a standardized, modified 3-port approach to laparoscopic gastric plication to improve outcomes. The modified laparoscopic gastric plication technique was applied for 63 morbidly obese patients between March 2010 and January 2013. There were 9 men and 54 women, with a mean age of 34.2 years (range 20-48 years) and a mean body mass index of 38.9 kg/m(2) (range 32-65 kg/m(2)). There were no deaths, no conversion to laparotomy, no reoperation, and no readmission. Percent excess weight loss was 41%, 52%, and 60% at 3, 6, and 12 months, respectively. There were no major complications reported in our study, but prolonged early postoperative nausea and vomiting occurred in 3 of 63 (4.8%) patients who had been successfully treated with proton pump inhibitors and antiemetics. Our initial experience showed that the 4-bite technique starting 2 cm below the angle of His with tight calibration of the gastric tube for obese patients is feasible, effective, and well tolerated, with a low frequency of major problems. Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
First-choice therapy for dogs presenting with diarrhoea in clinical practice.
German, A J; Halladay, L J; Noble, P-J M
2010-11-20
Computerised referral histories were reviewed for dogs admitted to the University of Liverpool Small Animal Teaching Hospital between January 2000 and December 2008 with diarrhoea among the clinical signs. A total of 371 cases presenting to the referring veterinary surgeon were included in the study, and information was compiled regarding signalment, clinical signs and treatment given at the initial consultation. Various breeds, ages and sexes were represented. Antibacterials were used in 263 (71 per cent) cases, steroids in 71 (19 per cent) cases and miscellaneous antidiarrhoeal products (including probiotics, prebiotics, adsorbents and antimotility drugs) in 98 (26 per cent) cases. Other drugs used included antiemetics (48 of 371 [13 per cent] cases), gastric protectants (37 of 371 [10 per cent] cases) and sulfasalazine (26 of 371 [7 per cent] cases). Antibacterial administration was positively associated with hyperthermia (odds ratio [OR]=2.97, P=0.012) and anorexia (OR=2.17, P=0.0075), but negatively associated with both weight loss (OR=0.55, P=0.036) and tenesmus (OR=0.43, P=0.035). In contrast, use of antidiarrhoeal products was positively associated with the presence of faecal mucus (OR=1.77, P=0.043), and negatively associated with vomiting (OR=0.57, P=0.025) and weight loss (OR=0.52, P=0.033).
Swamy, Mallappa Kumara; Sinniah, Uma Rani
2015-05-12
Pogostemon cablin Benth. (patchouli) is an important herb which possesses many therapeutic properties and is widely used in the fragrance industries. In traditional medicinal practices, it is used to treat colds, headaches, fever, nausea, vomiting, diarrhea, abdominal pain, insect and snake bites. In aromatherapy, patchouli oil is used to relieve depression, stress, calm nerves, control appetite and to improve sexual interest. Till now more than 140 compounds, including terpenoids, phytosterols, flavonoids, organic acids, lignins, alkaloids, glycosides, alcohols, aldehydes have been isolated and identified from patchouli. The main phytochemical compounds are patchouli alcohol, α-patchoulene, β-patchoulene, α-bulnesene, seychellene, norpatchoulenol, pogostone, eugenol and pogostol. Modern studies have revealed several biological activities such as antioxidant, analgesic, anti-inflammatory, antiplatelet, antithrombotic, aphrodisiac, antidepressant, antimutagenic, antiemetic, fibrinolytic and cytotoxic activities. However, some of the traditional uses need to be verified and may require standardizing and authenticating the bioactivity of purified compounds through scientific methods. The aim of the present review is to provide comprehensive knowledge on the phytochemistry and pharmacological activities of essential oil and different plant extracts of patchouli based on the available scientific literature. This information will provide a potential guide in exploring the use of main active compounds of patchouli in various medical fields.
Anderson, Lynn A; Gross, Jeffrey B
2004-02-01
To determine whether aromatherapy can reduce postoperative nausea, the investigators studied 33 ambulatory surgery patients who complained of nausea in the PACU. After indicating the severity of nausea on a 100-mm visual analogue scale (VAS), subjects received randomized aromatherapy with isopropyl alcohol, oil of peppermint, or saline (placebo). The vapors were inhaled deeply through the nose from scented gauze pads held directly beneath the patients' nostrils and exhaled slowly through the mouth. Two and 5 minutes later, the subjects rated their nausea on the VAS. Overall nausea scores decreased from 60.6 +/- 4.3 mm (mean +/- SE) before aromatherapy to 43.1 +/- 4.9 mm 2 minutes after aromatherapy (P <.005), and to 28.0 +/- 4.6 mm 5 minutes after aromatherapy (P < 10(-6)). Nausea scores did not differ between the treatments at any time. Only 52% of the patients required conventional intravenous (IV) antiemetic therapy during their PACU stay. Overall satisfaction with postoperative nausea management was 86.9 +/- 4.1 mm and was independent of the treatment group. Aromatherapy effectively reduced the perceived severity of postoperative nausea. The fact that a saline "placebo" was as effective as alcohol or peppermint suggests that the beneficial effect may be related more to controlled breathing patterns than to the actual aroma inhaled.
White, Mary; Zacharin, Margaret R; Werther, George A; Cameron, Fergus J
2016-02-01
Massive insulin overdose may be associated with unpredictable and prolonged hypoglycemia. Concerns surrounding the potential provocation of insulin release from beta cells have previously prevented the use of intravenous glucagon as an adjunct to infusion of dextrose in this situation. We describe the case of a 15-yr-old boy with type 1 diabetes mellitus (T1DM) who presented with profound hypoglycemia following an overdose of an unknown quantity of premixed insulin. Owing to an increasing dextrose requirement and a dependence on hourly intramuscular glucagon injections, a continuous intravenous infusion of glucagon was commenced which successfully avoided the requirement for central venous access or concentrated dextrose infusion. Nausea was managed with anti-emetics. Intramuscular and subcutaneous glucagon is effective in the management of refractory and severe hypoglycemia in youth with both T1DM and hyperinsulinism. Concerns regarding the precipitation of rebound hypoglycemia with the use of intravenous glucagon do not relate to those with T1DM. This treatment option may be a useful adjunct in the management of insulin overdose in youth with T1DM and may avoid the requirement for invasive central venous access placement. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Iwanaga, Y; Miyashita, N; Saito, T; Morikawa, K; Itoh, Z
1996-06-01
The novel benzamide derivative itopride was assayed for its effect on gastrointestinal motility in conscious dogs when it was administered intraduodenally (i.d.). Gastrointestinal motility was measured by means of chronically implanted force transducers, and itopride at a dose of 10 mg/kg, i.d. or more increased the gastric contractile force during the digestive state. Intraduodenal cisapride, domperidone and metoclopramide also stimulated gastric motility, and their threshold doses were 1, 3 and 1 mg/kg, respectively. Dopamine infusion (1 mg/kg/hr, i.v.) caused the postprandial gastric motility to disappear, but it was immediately restored by itopride at a dose of 3 mg/kg, i.d. With itopride at 1 and 3 mg/kg, i.d., acetylcholine (0.05 mg/kg/min)-induced contractions were greatly enhanced. In addition to its gastric stimulation, itopride at doses of 10-100 mg/kg, p.o. inhibited apomorphine (0.1 mg/kg, s.c.)-induced vomiting in dogs. In conclusion, intraduodenal itopride stimulates gastric motility through both anti-dopaminergic and anti-acetylcholinesterase actions. Its gastroprokinetic threshold dose was as large as 3-10 times those of cisapride, domperidone and metoclopramide. These findings suggest that itopride is an orally active gastroprokinetic with a moderate anti-emetic action.
Acute migraine in the Emergency Department: extending European principles of management.
Martelletti, Paolo; Farinelli, Ivano; Steiner, Timothy J
2008-10-01
The World Health Organization (WHO) placed migraine 19th among all causes of disability (12th in women) measured in years of healthy life lost to disability (YLD). The importance of headache disorders, particularly of the primary forms, is established by their distribution worldwide, their duration (the majority being life-long conditions) and their imposition of both disability and life-style restrictions among large numbers of people. For these reasons, headache disorders should represent a public-health priority. In the Emergency Department (ED), as elsewhere, migraine is often under-diagnosed-and under-treated when it is diagnosed. The result is likely to be failure of treatment. Particular attention to diagnosis is needed in ED patients with acute headache, since there is a higher probability of secondary headache due to underlying pathologies. According to European principles of management, acute migraine treatment generally is stepwise. Of the two main steps, the first relies on symptomatic medication, preferably NSAIDs with or without antiemetics. The second step uses specific therapies, usually triptans. Modifications to routine practice are appropriate in the ED. Parenteral administration of symptomatic therapies is a preferred first choice, whilst immediate resort to triptans may be appropriate, and achieve better outcomes, in patients with severe headache and diagnostic confirmation of migraine.
Nishimura, Junichi; Satoh, Taroh; Fukunaga, Mutsumi; Takemoto, Hiroyoshi; Nakata, Ken; Ide, Yoshihito; Fukuzaki, Takayuki; Kudo, Toshihiro; Miyake, Yasuhiro; Yasui, Masayoshi; Morita, Shunji; Sakai, Daisuke; Uemura, Mamoru; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Ohno, Yuko; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Nezu, Riichiro; Doki, Yuichiro; Mori, Masaki
2015-07-01
The oral neurokinin-1 antagonist aprepitant is recommended in several guidelines for preventing chemotherapy-induced nausea & vomiting (CINV) due to highly emetogenic cancer chemotherapy. Little is known about the feasibility and safety of aprepitant in patients treated with oxaliplatin. In this multicentre, open label, randomised, phase 3 trial, we recruited patients with colorectal cancer who underwent an oxaliplatin-based chemotherapy. Patients were centrally randomised in a 1:1 ratio to the control group (5-HT3-receptor antagonist+dexamethasone) or aprepitant group (5-HT3-receptor antagonist+dexamethasone+aprepitant or fosaprepitant) in the first course. All patients were treated with aprepitant/fosaprepitant therapy in the second course. The primary end-point was the proportion of patients with no emesis. A total of 413 patients entered this clinical trial from 25 centres in Japan. Significantly more patients in the aprepitant group achieved no vomiting overall and delayed phase than those in the control group (95.7% versus 83.6%, and 95.7% versus 84.7%, respectively). The aprepitant group also had statistically significantly higher percentages of no significant nausea, complete response and complete protection than the control group overall. In the control group, the percentages of no vomiting were higher in the second cycle than in the first cycle. The incidence of vomiting occurred day 7 or later was significantly higher in the control group compared with the aprepitant group. Other adverse events were not significant between the groups. The aprepitant therapy was more effective than the control therapy for prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen. Copyright © 2015 Elsevier Ltd. All rights reserved.
Efficacy of Liposomal Bupivacaine Infiltration on the Management of Total Knee Arthroplasty.
Sakamoto, Bryan; Keiser, Shelly; Meldrum, Russell; Harker, Gene; Freese, Andrew
2017-01-01
Liposomal bupivacaine is a novel extended-duration anesthetic that has recently been used for local infiltration in total knee arthroplasty (TKA). Athough liposomal bupivacaine is widely used, it is unknown if the benefits justify the cost in the veteran population at our institution. To evaluate a change in practice: the effect of local infiltration of liposomal bupivacaine on perioperative outcomes in patients undergoing primary TKA. A retrospective cohort study was conducted among patients who underwent primary TKA at a Veterans Affairs Medical Center before (March 3, 2013-March 2, 2014) and after (March 3, 2014-March 2, 2015) the implementation of liposomal bupivacaine for local infiltration in TKA. Drug utilization evaluation of liposomal bupivacaine for local infiltration in TKA. Use of opioids after discharge from the postanesthesia care unit. Among 199 patients, those who received liposomal bupivacaine after primary TKA (mean [SD] age, 65.3 [6.9] years; 93 males and 5 females) had a reduced median opioid use in the first 24 hours after surgery compared with those who did not receive liposomal bupivacaine (mean [SD] age, 64.9 [8.4] years; 95 males and 6 females; [intravenous morphine equivalents, 12.50 vs 22.50 mg; P = .001]). The use of patient-controlled analgesia was also reduced among patients who received liposomal bupivacaine vs those who did not (49 vs 91; P < .001). A reduction in the use of antiemetics was observed in the first 24 hours after surgery (13 vs 34; P = .001) and in the postanesthesia care unit among those who received liposomal bupivacaine vs those who did not (4 vs 20; P = .001). The number of patients in the postanesthesia care unit with no pain was improved among those who received liposomal bupivacaine vs those who did not (44 vs 19; P < .001). Although median (interquartile range) pain scores in the postanesthesia care unit were improved among patients who received liposomal bupivacaine vs those who did not (4
Reis, Cristiane Moreira; Dos Santos, Andrezza Gouvêa; de Jesus Souza, Paula; Reis, Adriano Max Moreira
2017-07-01
To determine the frequency and the factors associated with the use of potentially inappropriate medications (PIMs) by older adults with cancer at an onco-haematology ambulatory clinic of a teaching hospital in Brazil. Patients aged 60years or older (n=160) subjected to parenteral antineoplastic chemotherapy from May to December 2015 and treated with one or more medications in the ambulatory clinic were interviewed. Data on medications, comorbidities, oncological diagnosis, and functional status were recorded. Functionality was determined using the Vulnerable Elders Survey (VES-13). PIMs were determined using the 2015 Beers Criteria. Logistic regression was used to determine the factors associated with the use of PIMs. A total of 78 (48.1%) older adults used at least one PIM. The PIMs to be avoided by older adults were proton pump inhibitors (33.3%), antiemetics (10.5%), long-acting benzodiazepines (10.5%), and antidepressants (7.6%). Multivariate analysis indicated that PIMs were associated with the use of five or more medications (odds ratio, 3.14; 95% confidence interval, 1.4-6.6), after adjusting for the number of medications, number of comorbidities, depression, and arthritis/arthrosis. The frequency of use of PIMs by older adults at the investigated ambulatory clinic was high. Polypharmacy was positively associated with the use of PIMs. Copyright © 2017 Elsevier Ltd. All rights reserved.
In vitro percutaneous absorption enhancement of granisetron by chemical penetration enhancers.
Zhao, Nanxi; Cun, Dongmei; Li, Wei; Ma, Xu; Sun, Lin; Xi, Honglei; Li, Li; Fang, Liang
2013-04-01
Granisetron (GRN), a potent antiemetic agent, is frequently used to prevent nausea and vomiting induced by cancer cytotoxic chemotherapy and radiation therapy. As part of our efforts to further modify the physicochemical properties of this market drug, with the ultimate goal to formulate a better dosage form for GRN, this work was carried out to improve its permeability in vitro. The permeation behavior of GRN in isopropyl myristate (IPM) was investigated across excised rabbit abdominal skin and the enhancing activities of three novel O-acylmenthol derivatives synthesized in our laboratory as well as five well-known chemical enhancers were evaluated. It was found that the steady-state flux of granisetron free base (GRN-B) was about 26-fold higher than that of granisetron hydrochloride (GRN-H). The novel enhancer, 2-isopropyl-5-methylcyclohexyl heptanoate (M-HEP), was observed to provide the most significant enhancement for the absorption of GRN-B. When incorporated in the donor solution with the optimal enhancer M-HEP, the steady-state flux of GRN-B increased from (196.44 ± 12.03) μg·cm⁻²·h⁻¹ to (1044.95 ± 71.99) μg·cm⁻²·h⁻¹ (P < 0.01). These findings indicated that the application of chemical enhancers was an effective approach to increase the percutaneous absorption of GRN in vitro.
Erhan, Yamac; Erhan, Elvan; Aydede, Hasan; Yumus, Okan; Yentur, Alp
2008-06-01
Laparoscopic cholecystectomies are associated with an appreciably high rate of postoperative nausea and vomiting (PONV). This study was designed to compare the effectiveness of ondansetron, granisetron, and dexamethasone for the prevention of PONV in patients after laparoscopic cholecystectomy. A total of 80 American Society of Anesthesiologists (ASA) physical class I-II patients scheduled for laparoscopic cholecystectomy were included in this randomized, double blind, placebo-controlled study. All patients received a similar standardized anesthesia and operative treatment. Patients were randomly divided into four groups (n = 20 each). Group 1, consisting of control patients, received 0.9% NaCl; group 2 patients received ondansetron 4 mg i.v.; group 3 patients received granisetron 3 mg i.v.; and group 4 patients received dexamethasone 8 mg i.v., all before the induction of anesthesia. Both nausea and vomiting were assessed during the first 24 h after the procedure. The total incidence of PONV was 75% with placebo, 35% with ondansetron, 30% with granisetron, and 25% with dexamethasone. The incidence of PONV was significantly less frequent in groups receiving antiemetics (p < 0.05). The differences between dexamethasone, granisetron, and ondansetron were not significant. Prophylactic dexamethasone 8 mg i.v. significantly reduced the incidence of PONV in patients undergoing laparoscopic cholecystectomy. Dexamethasone 8 mg was as effective as ondansetron 4 mg and granisetron 3 mg, and it was more effective than placebo.
Granisetron Extended-Release Injection: A Review in Chemotherapy-Induced Nausea and Vomiting.
Deeks, Emma D
2016-12-01
An extended-release (ER) subcutaneously injectable formulation of the first-generation 5-HT 3 receptor antagonist granisetron is now available in the USA (Sustol ® ), where it is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide combination chemotherapy regimens in adults. Granisetron ER is administered as a single subcutaneous injection and uses an erosion-controlled drug-delivery system to allow prolonged granisetron release. Primary endpoint data from phase III studies after an initial cycle of chemotherapy indicate that, when used as part of an antiemetic regimen, granisetron ER injection is more effective than intravenous ondansetron in preventing delayed CINV following highly emetogenic chemotherapy (HEC); is noninferior to intravenous palonosetron in preventing both acute CINV following MEC or HEC and delayed CINV following MEC; and is similar, but not superior, to palonosetron in preventing delayed CINV following HEC. The benefits of granisetron ER were seen in various patient subgroups, including those receiving anthracycline plus cyclophosphamide-based HEC, and (in an extension of one of the studies) over multiple MEC or HEC cycles. Granisetron ER injection is generally well tolerated, with an adverse event profile similar to that of ondansetron or palonosetron. Thus, granisetron ER injection expands the options for preventing both acute and delayed CINV in adults with cancer receiving MEC or anthracycline plus cyclophosphamide-based HEC.
Tsuji, Daiki; Kim, Yong-Il; Taku, Keisei; Nakagaki, Shigeru; Ikematsu, Yoshito; Tsubota, Hiromi; Maeda, Masato; Hashimoto, Naoya; Kimura, Masayuki; Daimon, Takashi
2012-05-01
A single 3 mg or 40 μg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 μg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p < 0.01 for non-inferiority). This study showed that 1 mg granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.
5-Lipoxygenase Inhibition of the Fructus of Foeniculum vulgare and Its Constituents
Lee, Je Hyeong; Lee, Dong Ung; Kim, Yeong Shik; Kim, Hyun Pyo
2012-01-01
The fruits of Foeniculum vulgare (Foeniculi Fructus) have been widely used in Chinese medicine as an antiemetic, ameliorating stomach ailments and as an analgesic. In order to establish its potential for antiallergic use, inhibitory actions of the fruiton 5-lipoxgenase (5-LOX) and β-hexosaminidase release were evaluated. The 70% ethanol extract of this plant material (FR) considerably inhibited 5-LOX-catalyzed leukotriene production from A23187-induced rat basophilic leukemia (RBL)-1 cells. The IC50 was 3.2 μg/ml. From this extract, 12 major compounds including sabinene, fenchone, γ-terpinene, α-pinene, limonene, p-anisylacetone, p-anisylaldehyde, estragole (4-allylanisole), trans-anethole, scopoletin, bergapten and umbelliferone were isolated. And it was found that several terpene derivatives including γ-terpinene and fenchone as well as phenylpropanoid, trans-anethole, showed considerable inhibitory action of 5-LOX. In particular, the IC50 of trans-anethole was 51.6 μ M. In contrast, FR and the isolated compounds did not show considerable inhibitory activity on the degranulation reaction of β-hexosaminidase release from antigen-treated RBL-2H3 cells. Against arachidonic acid-induced ear edema in mice, FR and trans-anethole showed significant inhibition by oral administration at doses of 100-400 mg/kg. In conclusion, FR and several major constituents are 5-LOX inhibitors and they may have potential for treating 5-LOX-related disorders. PMID:24116283
Di Renzo, Nicola; Montanini, Antonella; Mannina, Donato; Dondi, Alessandra; Muci, Stefania; Mancuso, Salvatrice; De Paolis, M Rosaria; Plati, Caterina; Stelitano, Caterina; Patti, Catia; Olivieri, Attilio; Liardo, Eliana; Buda, Gabriele; Cantaffa, Renato; Federico, Massimo
2011-10-01
The control of nausea and vomiting induced by chemotherapy is paramount for overall treatment success in cancer patients. Antiemetic therapy during chemotherapy in lymphoma patients generally consists of anti-serotoninergic drugs and dexamethasone. The aim of this trial was to evaluate the efficacy of a single dose of palonosetron, a second-generation serotonin type 3 (5-HT(3)) receptor antagonist, in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy (MEC) containing steroids. Patients received a single intravenous bolus of palonosetron (0.25 mg) before administration of chemotherapy. Complete response (CR) defined as no vomiting and no rescue therapy during overall phase (0-120 h) was the primary endpoint. Complete control (CC) defined as CR and only mild nausea was a secondary endpoint. Eighty-six evaluable patients entered in the study. A CR was observed in 74 patients (86.0%) during the overall phase; the CR during the acute (0-24 h) and delayed (24-120 h) phases was 90.7% and 88.4%, respectively. CC was 89.5% during the acute and 84.9% during the delayed phase; the overall CC was 82.6%. This was the first trial, which demonstrated the efficacy of a single dose of palonosetron in control CINV in patients with aggressive non-Hodgkin's lymphoma receiving MEC regimen containing steroids.
Promethazine affects autonomic cardiovascular mechanisms minimally
NASA Technical Reports Server (NTRS)
Brown, T. E.; Eckberg, D. L.
1997-01-01
Promethazine hydrochloride, Phenergan, is a phenothiazine derivative with antihistaminic (H1), sedative, antiemetic, anticholinergic, and antimotion sickness properties. These properties have made promethazine a candidate for use in environments such as microgravity, which provoke emesis and motion sickness. Recently, we evaluated carotid baroreceptor-cardiac reflex responses during two Space Shuttle missions 18 to 20 hr after the 50 mg intramuscular administration of promethazine. Because the effects of promethazine on autonomic cardiovascular mechanisms in general and baroreflex function in particular were not known, we were unable to exclude a possible influence of promethazine on our results. Our purpose was to determine the ground-based effects of promethazine on autonomic cardiovascular control. Because of promethazine's antihistaminic and anticholinergic properties, we expected that a 50-mg intramuscular injection of promethazine would affect sympathetically and vagally mediated cardiovascular mechanisms. Eight healthy young subjects, five men and three women, were studied at rest in recumbency. All reported drowsiness as a result of the promethazine injection; most also reported nervous excitation, dry mouth, and fatigue. Three subjects had significant reactions: two reported excessive anxiety and one reported dizziness. Measurements were performed immediately prior to injection and 3.1 +/- 0.1 and 19.5 +/- 0.4 hr postinjection. We found no significant effect of promethazine on resting mean R-R interval, arterial pressure, R-R interval power spectra, carotid baroreflex function, and venous plasma catecholamine levels.
Early clinical outcomes following laparoscopic inguinal hernia repair.
Tolver, Mette Astrup
2013-07-01
Laparoscopic inguinal hernia repair (TAPP) has gained increasing popularity because of less post-operative pain and a shorter duration of convalescence compared with open hernia repair technique (Lichtenstein). However, investigation of duration of convalescence with non-restrictive recommendations, and a procedure-specific characterization of the early clinical outcomes after TAPP was lacking. Furthermore, optimization of the post-operative period with fibrin sealant versus tacks for fixation of mesh, and the glucocorticoid dexamethasone versus placebo needed to be investigated in randomized clinical trials. The objective of this PhD thesis was to characterize the early clinical outcomes after TAPP and optimize the post-operative period. The four studies included in this thesis have investigated duration of convalescence and procedure-specific post-operative pain and other early clinical outcomes after TAPP. Furthermore, it has been shown that fibrin sealant can improve the early post-operative period compared with tacks, while dexamethasone showed no advantages apart from reduced use of antiemetics compared with placebo. Based on these findings, and the existing knowledge, 3-5 days of convalescence should be expected when 1 day of convalescence is recommended and future studies should focus on reducing intraabdominal pain after TAPP. Fibrin sealant can optimize the early clinical outcomes but the risk of hernia recurrence and chronic pain needs to be evaluated. Dexamethasone should be investigated in higher doses.
Haj-Mirzaian, Arya; Amiri, Shayan; Amini-Khoei, Hossein; Rahimi-Balaei, Maryam; Kordjazy, Nastaran; Olson, Carl O; Rastegar, Mojgan; Naserzadeh, Parvaneh; Marzban, Hassan; Dehpour, Ahmad Reza; Hosseini, Mir-Jamal; Samiei, Elika; Mehr, Shahram Ejtemaei
2016-06-01
Tropisetron, a 5-HT3 receptor antagonist widely used as an antiemetic, has been reported to have positive effects on mood disorders. Adolescence is a critical period during the development of brain, where exposure to chronic stress during this time is highly associated with the development of depression. In this study, we showed that 4 weeks of juvenile social isolation stress (SIS) provoked depressive-like behaviors in male mice, which was associated with disruption of mitochondrial function and nitric oxide overproduction in the cortical areas. In this study, tropisetron (5mg/kg) reversed the negative behavioral effects of SIS in male mice. We found that the effects of tropisetron were mediated through mitigating the negative activity of inducible nitric oxide synthase (iNOS) on mitochondrial activity. Administration of aminoguanidine (specific iNOS inhibitor, 20mg/kg) augmented the protective effects of tropisetron (1mg/kg) on SIS. Furthermore, l-arginine (nitric oxide precursor, 100mg/kg) abolished the positive effects of tropisetron. These results have increased our knowledge on the pivotal role of mitochondrial function in the pathophysiology of depression, and highlighted the role of 5-HT3 receptors in psychosocial stress response during adolescence. Finally, we observed that tropisetron alleviated the mitochondrial dysfunction through decreased nitrergic system activity in the cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.
Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea.
De Jonghe, Bart C; Holland, Ruby A; Olivos, Diana R; Rupprecht, Laura E; Kanoski, Scott E; Hayes, Matthew R
2016-01-01
While chemotherapy-induced nausea and vomiting are clinically controlled in the acute (<24 h) phase following treatment, the anorexia, nausea, fatigue, and other illness-type behaviors during the delayed phase (>24 h) of chemotherapy are largely uncontrolled. As the hindbrain glucagon-like peptide-1 (GLP-1) system contributes to energy balance and mediates aversive and stressful stimuli, here we examine the hypothesis that hindbrain GLP-1 signaling mediates aspects of chemotherapy-induced nausea and reductions in feeding behavior in rats. Specifically, hindbrain GLP-1 receptor (GLP-1R) blockade, via 4th intracerebroventricular (ICV) exendin-(9-39) injections, attenuates the anorexia, body weight reduction, and pica (nausea-induced ingestion of kaolin clay) elicited by cisplatin chemotherapy during the delayed phase (48 h) of chemotherapy-induced nausea. Additionally, the present data provide evidence that the central GLP-1-producing preproglucagon neurons in the nucleus tractus solitarius (NTS) of the caudal brainstem are activated by cisplatin during the delayed phase of chemotherapy-induced nausea, as cisplatin led to a significant increase in c-Fos immunoreactivity in NTS GLP-1-immunoreactive neurons. These data support a growing body of literature suggesting that the central GLP-1 system may be a potential pharmaceutical target for adjunct anti-emetics used to treat the delayed-phase of nausea and emesis, anorexia, and body weight loss that accompany chemotherapy treatments. Copyright © 2015 Elsevier Inc. All rights reserved.
Martin, Ana Carolina B M; Fuzer, Angelina M; Becceneri, Amanda B; da Silva, James Almada; Tomasin, Rebeka; Denoyer, Delphine; Kim, Soo-Hyun; McIntyre, Katherine A; Pearson, Helen B; Yeo, Belinda; Nagpal, Aadya; Ling, Xiawei; Selistre-de-Araújo, Heloisa S; Vieira, Paulo Cézar; Cominetti, Marcia R; Pouliot, Normand
2017-09-22
There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin ( Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo . We show that [10]-gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro . In addition, [10]-gingerol is well tolerated in vivo , induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients.
Stillbirth risk factors according to timing of exposure.
Dodds, Linda; King, Will D; Fell, Deshayne B; Armson, B Anthony; Allen, Alexander; Nimrod, Carl
2006-08-01
The purpose of the present study is to identify risk factors for stillbirth and explore hypotheses about the cause of stillbirth based on the time in gestation when exposures occur. Relationships between lifestyle factors, pregnancy conditions, medication use, and occupation on risk for stillbirth were examined within a population-based case-control study. Women who had a stillbirth and a random sample of women who had a live birth between 1999 and 2001 were identified through perinatal databases in Nova Scotia and Eastern Ontario, Canada. Exposure data were collected for each month of pregnancy and analyzed within trimesters. Case-control data were converted to case-cohort data, and hazard ratios (HRs) and 95% confidence intervals (CIs) were determined from Cox proportional hazards models. This study included 105 stillbirth cases and 389 live-birth controls. Fertility treatment in the present pregnancy was associated with increased risk for stillbirth (adjusted HR, 4.0; 95% CI, 1.4-11.6). Smoking during the first trimester also was associated with increased risk for stillbirth (adjusted HR, 2.4; 95% CI, 1.2-4.9). Other risk factors included antiemetic use during the first trimester, second-trimester antibiotic use, low family income, and age older than 35 years. Risk factors identified in this study concur with findings of previous studies and support the importance of early pregnancy exposures on stillbirth risk.
Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs.
Valverde, Alexander; Cantwell, Shauna; Hernández, Jorge; Brotherson, Celeste
2004-01-01
To evaluate the anti-emetic properties of acepromazine in dogs receiving opioids as pre-anesthetic medication. Randomized prospective clinical study. One hundred and sixteen dogs (ASA I or II), admitted for elective surgical procedures. The dogs were a mixed population of males and females, purebreds and mixed breeds, 0.25-13.4 years of age, weighing 1.8-57.7 kg. A prospective clinical trial in which the dogs were randomly assigned to one of three groups. All groups received acepromazine (0.05 mg kg(-1) intramuscularly (i.m.)). Group I received acepromazine 15 minutes prior to opioid administration. Group II received acepromazine in combination with the opioid. Group III received acepromazine 15 minutes after opioid administration. One of three different opioids was administered i.m. to each dog: morphine sulfate at 0.5 mg kg(-1); hydromorphone hydrochloride at 0.1 mg kg(-1); or oxymorphone hydrochloride at 0.075 mg kg(-1). Dogs receiving acepromazine before the opioid (group I) had a significantly lower incidence of vomiting (18%) than dogs in groups II (45%) and III (55%). The degree of sedation was significantly lower in the dogs receiving the combination of acepromazine and the opioid (group II) than in dogs receiving the opioid as the first drug (group III). Acepromazine administered 15 minutes before the opioid lowers the incidence of vomiting induced by opioids.
Becceneri, Amanda B.; da Silva, James Almada; Tomasin, Rebeka; Denoyer, Delphine; Kim, Soo-Hyun; McIntyre, Katherine A.; Pearson, Helen B.; Yeo, Belinda; Nagpal, Aadya; Ling, Xiawei; Selistre-de-Araújo, Heloisa S.; Vieira, Paulo Cézar
2017-01-01
There is increasing interest in the use of non-toxic natural products for the treatment of various pathologies, including cancer. In particular, biologically active constituents of the ginger oleoresin (Zingiber officinale Roscoe) have been shown to mediate anti-tumour activity and to contribute to the anti-inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger. Here we report on the inhibitory properties of [10]-gingerol against metastatic triple negative breast cancer (TNBC) in vitro and in vivo. We show that [10]-gingerol concentration-dependently induces apoptotic death in mouse and human TNBC cell lines in vitro. In addition, [10]-gingerol is well tolerated in vivo, induces a marked increase in caspase-3 activation and inhibits orthotopic tumour growth in a syngeneic mouse model of spontaneous breast cancer metastasis. Importantly, using both spontaneous and experimental metastasis assays, we show for the first time that [10]-gingerol significantly inhibits metastasis to multiple organs including lung, bone and brain. Remarkably, inhibition of brain metastasis was observed even when treatment was initiated after surgical removal of the primary tumour. Taken together, these results indicate that [10]-gingerol may be a safe and useful complementary therapy for the treatment of metastatic breast cancer and warrant further investigation of its efficacy, either alone or in combination with standard systemic therapies, in pre-clinical models of metastatic breast cancer and in patients. PMID:29069785
Marx, Wolfgang; McCarthy, Alexandra L; Ried, Karin; McKavanagh, Dan; Vitetta, Luis; Sali, Avni; Lohning, Anna; Isenring, Elisabeth
2017-08-12
Ginger supplementation could be an effective adjuvant treatment for chemotherapy-induced nausea (CIN). The aim of this clinical trial was to address significant methodological limitations in previous trials. Patients (N = 51) were randomly allocated to receive either 1.2 g of standardised ginger extract or placebo per day, in addition to standard anti-emetic therapy, during the first three cycles of chemotherapy. The primary outcome was CIN-related quality of life (QoL) measured with the Functional Living Index- Emesis (FLIE) questionnaire. Secondary outcomes included acute and delayed nausea, vomiting, and retching as well as cancer-related fatigue, nutritional status, and CIN and vomiting-specific prognostic factors. Over three consecutive chemotherapy cycles, nausea was more prevalent than vomiting (47% vs. 12%). In chemotherapy Cycle 1, intervention participants reported significantly better QoL related to CIN ( p = 0.029), chemotherapy-induced nausea and vomiting (CINV)-related QoL ( p = 0.043), global QoL ( p = 0.015) and less fatigue ( p = 0.006) than placebo participants. There were no significant results in Cycle 2. In Cycle 3, global QoL ( p = 0.040) and fatigue ( p = 0.013) were significantly better in the intervention group compared to placebo. This trial suggests adjuvant ginger supplementation is associated with better chemotherapy-induced nausea-related quality of life and less cancer-related fatigue, with no difference in adverse effects compared to placebo.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Law, Amy; Kennedy, Thomas; Pellitteri, Phillip
2007-12-01
Purpose: To report long-term data from a prospective trial of subcutaneous (s.c.) amifostine in patients who received chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Methods and Materials: Patients {>=}18 years of age with previously untreated Stage III/IV SCCHN received fractionated radiotherapy, 1.8-2.0 Gy/day, 5 days per week, to a total dose of 70-72 Gy, plus weekly paclitaxel (40 mg/m{sup 2}) and carboplatin (100 mg/m{sup 2}) administered intravenously (i.v.) for 6 weeks. All patients received 500 mg s.c. amifostine 30-60 min before radiotherapy with antihistamine and antiemetic prophylaxis. Results: Twenty patients were evaluable (median age, 55 years).more » The incidence of Grade 2 xerostomia was 42% and 29% at 12 and 18 months, respectively; there were no reports of Grade {>=}3 xerostomia. Grade {>=}3 mucositis occurred in 30% of patients, with median time to resolution of 12.5 weeks (range, 5-17 weeks). Survival estimates at 1 and 2 years were 95% and 71%, respectively. All patients experienced Grade 2 weight loss; 7 patients (35%) experienced Grade {<=}2 nausea/vomiting. There were no reports of Grade {>=}3 amifostine-related adverse events. Conclusions: Subcutaneous amifostine was well tolerated by patients receiving chemoradiotherapy for SCCHN, with lower rates of nausea/vomiting than reported in trials with i.v. amifostine. Xerostomia and mucositis rates were similar to those reported in trials with i.v. amifostine.« less
Thyrotoxicosis after a massive levothyroxine ingestion in a 3-year-old patient.
Hays, Hannah L; Jolliff, Heath A; Casavant, Marcel J
2013-11-01
Most children with exploratory levothyroxine ingestions remain asymptomatic or suffer only minor effects, and most patients can be managed in the home or with supportive care in the hospital. We present a case of a 3-year-old girl who was found after a witnessed massive ingestion of levothyroxine. The patient was initially seen in an emergency department and discharged in stable condition, only to return 4 days after ingestion with thyrotoxicosis, hypertension, tachycardia, 24 hours of persistent vomiting, and clinical and laboratory evidence of dehydration. On the day of hospital admission, her thyroid-stimulating hormone was 0.018 µIU/mL (reference range, 0.6-4.5 µIU/mL); free T4 (tetraiodothyronine) was greater than 6.0 ng/dL (reference range, 0.7-2.1 ng/dL); and T3 (triiodothyronine) total was 494 ng/dL (reference range, 100-200 ng/dL). During a 3-day hospital admission, she was managed with supportive care, including intravenous fluid rehydration and antiemetics, and was ultimately discharged in good condition. The patient was followed up until 2 months after ingestion and remained asymptomatic. Although most exploratory levothyroxine ingestions suffer little to no clinical effects, serious symptoms can occur. Because serious symptoms can occur in a delayed fashion, it is important for clinicians to give proper anticipatory guidance regarding home symptom monitoring, follow-up, and reasons to return to the emergency department when patients present for medical evaluation.
Chemotherapy-induced nausea and vomiting in routine practice: a European perspective.
Glaus, Agnes; Knipping, Cornelia; Morant, Rudolf; Böhme, Christel; Lebert, Burkhard; Beldermann, Frank; Glawogger, Bernhard; Ortega, Paz Fernandez; Hüsler, André; Deuson, Robert
2004-10-01
The aim of this study was to evaluate the occurrence of chemotherapy-induced nausea and vomiting (CINV) and its effect on patients' ability to carry out daily life activities following moderately to highly emetogenic, first-cycle chemotherapy in routine practice in cancer centers of four different European countries. This was a prospective, cross-sectional, nonrandomized, self-assessment study in 249 patients enrolled from cancer centers in Spain, Austria, Germany, and Switzerland. The study population consisted of 78% women, with a mean age of 54. Breast, lung, and ovarian cancers made up 75% of all cancers in the study. Patients received a mean of 2.0 chemotherapy agents and 2.5 antiemetic drugs. A total of 450 emetic episodes experienced by 243 patients was recorded over 5 days following chemotherapy, with an average of 1.8 episodes per patient (range: 0-28). A higher percentage of patients (38%) suffered from delayed compared to acute emesis (13%). Between 42% and 52% of all patients suffered from nausea (visual analogue scale > or = 5 mm) on any one day, peaking at day 3. Using the Functional Living Index for Emesis (FLIE) questionnaire, 75% of patients with nausea and 50% with vomiting reported a negative impact of these conditions on performance of daily living. CINV remains a significant problem in routine practice, particularly in the delayed phase posttreatment. Overall, CINV had a negative impact on patients' daily life.
Li, Xihao; Blondino, Frank E; Hindle, Michael; Soine, William H; Byron, Peter R
2005-10-13
Perphenazine (a potent antiemetic) was aerosolized using capillary aerosol generator to generate respirable condensation aerosols from drug in propylene glycol (PG) solutions, by pumping the liquids through a heated capillary tube. The study characterized the stability of perphenazine during and following aerosol generation. The stability-indicating HPLC method (C-8 column with a mobile phase of 52% 0.01 M pH 3.0 acetate buffer+48% acetonitrile) also enabled the study of perphenazine stability in solution under acidic, basic, oxidizing and photolysing conditions. An LC-MS (ESI+) method was used to characterize the degradation products. Perphenazine was found to be stable in acidic and basic conditions, while perphenazine sulfoxide was the major product formed in dilute peroxide solutions. Two photo-degradation products were formed in PG that were tentatively identified by LC-MS; one of these was synthesized and confirmed to be 2-[4-(3-phenothiazin-10-yl-propyl)-piperazino]-ethanol. Both photolysis products showed that aromatic dechlorination had occurred and one appeared to also result from interaction with the solvent. Within an aerosolization energy window of 84-95 J, fine particle aerosols were generated from perphenazine PG formulations with no significant degradation. Small amounts of degradation products were produced in all samples during aerosolization at elevated (non-optimal) energies. These were largely consistent with those seen to result from oxidation and photolysis in solution, showing that oxidation and dehalogenation appeared to be the main degradation pathways followed when the CAG system was overheated.
Lee, O H; Choi, G J; Kang, H; Baek, C W; Jung, Y H; Woo, Y C; Oh, J; Park, Y H
2017-01-01
Sugammadex is a new agent that reverses neuromuscular blockade by aminosteroid neuromuscular blocker. This retrospective study compared the effects of sugammadex on post-operative nausea and vomiting (PONV) with those of a pyridostigmine-glycopyrrolate mixture. We reviewed the electronic medical records of 7179 patients who had received fentanyl-based, intravenous, patient-controlled analgesia (IV-PCA) at Chung-Ang University Hospital between January 1, 2010 and December 31, 2015. We categorized the patients into two groups on the basis of the type of reversal agent to neuromuscular blockade that was used: a traditional reversal agent (pyridostigmine-glycopyrrolate mixture; Group R; n = 7059) and sugammadex (Group S; n = 120). The propensity score matching method was then used to select 408 subjects in Group R and 115 subjects in Group S; on the basis of their covariates, these subjects were then matched with a counterpart in the other group. After propensity score matching, the two groups were well balanced with respect to all baseline covariates. In Group S, the numeric rating scale of nausea on day 0, as well as the number of patients who vomited on day 0, was lower than that in group R. Furthermore, Group S used fewer rescue antiemetics on day 0 and had a higher complete response on day 0. Sugammadex might be more beneficial for PONV compared to pyridostigmine-glycopyrrolate mixture for patients who have received opioid-based IV-PCA. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Pianta, Timothy J; Pickering, John W; Succar, Lena; Chin, Melvin; Davidson, Trent; Buckley, Nicholas A; Mohamed, Fahim; Endre, Zoltan H
2017-01-01
Plasma cystatin C (pCysC) may be superior to serum creatinine (sCr) as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI) after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1), and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague-Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls. In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16-34%)], relative increases were ≥ 50% in 9 patients (35%) for pCysC compared with 2 (8%) for sCr (p = 0.04) and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC), but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion. In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy. © 2017 The Author(s)Published by S. Karger AG, Basel.
Morinda citrifolia Linn. for prevention of postoperative nausea and vomiting.
Prapaitrakool, Sunisa; Itharat, Arunporn
2010-12-01
To be a preliminary, prospective, randomized double blinded, placebo-controlled trial to evaluate the efficacy of Morinda citrifolia Linn or noni for the prevention of postoperative nausea and vomiting (PONV) in patients considered high risk for PONV after various types of surgery. The plant extract was prepared by boiling of dried noni fruit (maturity stage 3-4) then evaporated under standard procedure and processed into capsules. The doses were 150 mg, 300 mg and 600 mg which are equivalent to 5, 10 and 20 g of dried noni fruit, respectively. One hundred patients of ASA physical status I or II, aged 18-65 years, and considered at risk for PONV, were randomized to receive 150, 300, 600 mg of noni extract or a placebo orally 1 hours before surgery. Standard general anesthetic technique and postoperative analgesia were employed. Significantly fewer patients who had received the 600 mg noni extract experienced nausea during the first 6 hours compared to the placebo group (48% for the 600 mg noni group and 80% for the placebo group, p-value = 0.04). The incidence of PONV in other time periods was not statistically different for all three noni doses compared to the placebo group. No side effects were reported in all groups. Morinda citrifolia Linn. has an antiemetic property and prophylactic noni extract at 600 mg (equivalent to 20g of dried noni fruit or scopoletin 8.712 microg) effectively reduces the incidence of early postoperative nausea (0-6 hours).
Javadi-Paydar, Mehrak; Zakeri, Marjan; Norouzi, Abbas; Rastegar, Hossein; Mirazi, Naser; Dehpour, Ahmad Reza
2012-01-06
Granisetron, a serotonin 5-HT(3) receptor antagonist, widely used as an antiemetic drug following chemotherapy, has been found to improve learning and memory. In this study, effects of granisetron on spatial recognition memory and fear memory and the involvement of nitric oxide (NO) have been determined in a Y-maze and passive avoidance test. Granisetron (3, 10mg/kg, intraperitoneally) was administered to scopolamine-induced memory-impaired mice prior to acquisition, consolidation and retrieval phases, either in the presence or in the absence of a non-specific NO synthase inhibitor, l-NAME (3, 10mg/kg, intraperitoneally); a specific inducible NO synthase (iNOS) inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750 mg/kg). It is demonstrated that granisetron improved memory acquisition in a dose-dependent manner, but it was ineffective on consolidation and retrieval phases of memory. The beneficial effect of granisetron (10mg/kg) on memory acquisition was significantly reversed by l-NAME (10mg/kg) and aminoguanidine (100mg/kg); however, l-arginine (750 mg/kg) did not potentiate the effect of sub-effective dose of granisetron (3mg/kg) in memory acquisition phase. It is concluded that nitric oxide is probably involved in improvement of memory acquisition by granisetron in both spatial recognition memory and fear memory. This article is part of a Special Issue entitled The Cognitive Neuroscience. Copyright © 2011 Elsevier B.V. All rights reserved.
The Rise, Fall and Subsequent Triumph of Thalidomide: Lessons Learned in Drug Development
Rehman, Waqas; Arfons, Lisa M.; Lazarus, Hillard M.
2011-01-01
Perhaps no other drug in modern medicine rivals the dramatic revitalization of thalidomide. Originally marketed as a sedative, thalidomide gained immense popularity worldwide among pregnant women because of its effective anti-emetic properties in morning sickness. Mounting evidence of human teratogenicity marked a dramatic fall from grace and led to widespread social, legal and economic ramifications. Despite its tragic past thalidomide emerged several decades later as a novel and highly effective agent in the treatment of various inflammatory and malignant diseases. In 2006 thalidomide completed its remarkable renaissance becoming the first new agent in over a decade to gain approval for the treatment of plasma cell myeloma. The catastrophic collapse yet subsequent revival of thalidomide provides important lessons in drug development. Never entirely abandoned by the medical community, thalidomide resurfaced as an important drug once the mechanisms of action were further studied and better understood. Ongoing research and development of related drugs such as lenalidomide now represent a class of irreplaceable drugs in hematological malignancies. Further, the tragedies associated with this agent stimulated the legislation which revamped the FDA regulatory process, expanded patient informed consent procedures and mandated more transparency from drug manufacturers. Finally, we review recent clinical trials summarizing selected medical indications for thalidomide with an emphasis on hematologic malignancies. Herein, we provide a historic perspective regarding the up-and-down development of thalidomide. Using PubMed databases we conducted searches using thalidomide and associated keywords highlighting pharmacology, mechanisms of action, and clinical uses. PMID:23556097
Yen Pik Sang, Fleur D; Billar, Jessica P; Golding, John F; Gresty, Michael A
2003-01-01
Behavioral countermeasures for motion sickness would be advantageous because of the side effects of antiemetic drugs, but few alternative treatments are available. The objective of this study was to compare the effectiveness of controlling breathing and listening to a music audiotape designed to reduce motion sickness symptoms, on increasing tolerance to motion-induced nausea. Twenty-four healthy subjects were exposed to nauseogenic Coriolis stimulation on a rotating turntable under three conditions: whilst focusing on controlling breathing; listening to a music audiotape; or without intervention (control). The three conditions were performed by each subject according to a replicated factorial design at 1-week intervals at the same time of day. Ratings of motion sickness were obtained every 30 seconds. Once a level of mild nausea was reached subjects commenced controlling breathing or listened to the music audiotape. Motion was stopped after the onset of moderate nausea. Mean (+/- SD) motion exposure time in minutes tolerated before the onset of moderate nausea was significantly longer (p <.01) for controlling breathing (10.7 +/- 5.6 min) and longer (p <.01) for music (10.4 +/- 5.6 min) compared with control (9.2 +/- 5.9 min). Both controlling breathing and the music audiotape provided significant protection against motion sickness and with similar effectiveness. These nonpharmacologic countermeasures are only half as effective as standard doses of anti-motion sickness drugs, such as oral scopolamine; however, they are easy to implement and free of side effects.
Struthers, Jason D; Robl, Nick; Wong, Valerie M; Kiupel, Matti
2018-06-01
Gastrinoma, an infrequent diagnosis in middle-aged dogs, occurs with nonspecific gastrointestinal morbidity. Laboratory tests can yield a presumptive diagnosis, but definitive diagnosis depends on histopathology and immunohistochemistry. We describe a malignant pancreatic gastrinoma with lymph node metastases and corresponding Zollinger-Ellison syndrome in a Mexican gray wolf ( Canis lupus baileyi) and review this endocrine neoplasm in domestic dogs. A 12-y-old, captive, male Mexican gray wolf developed inappetence and weight loss. Abdominal ultrasonography revealed a thickened duodenum and peritoneal effusion. Two duodenal perforations were noted on exploratory celiotomy and were repaired. Persisting clinical signs led to a second celiotomy that revealed a mesenteric mass, which was diagnosed histologically as a neuroendocrine carcinoma. During the following 16 mo, the wolf received a combination of H 2 -receptor antagonists, proton-pump inhibitors, gastroprotectants, and anti-emetics, but had recurrent episodes of anorexia, nausea, acid reflux, and remained underweight. Worsening clinical signs and weakness prompted euthanasia. The antemortem serum gastrin concentration of 414 ng/L (reference interval: 10-40 ng/L) corroborated hypergastrinemia. Autopsy revealed a mass expanding the right pancreatic limb; 3 parapancreatic mesenteric masses; duodenal ulcers; focal duodenal perforation with septic fibrinosuppurative peritonitis; chronic-active ulcerative esophagitis; and poor body condition. The pancreatic mass was diagnosed histologically as a neuroendocrine carcinoma and the parapancreatic masses as lymph node metastases. Immunohistochemistry of the pancreatic mass was positive for gastrin and negative for glucagon, insulin, pancreatic polypeptide, serotonin, somatostatin, and vasoactive intestinal peptide.
Berger, Richard A; Sanders, Sheila A; Thill, Elizabeth S; Sporer, Scott M; Della Valle, Craig
2009-06-01
Advancements in the surgical approach, anesthetic technique, and the initiation of rapid rehabilitation protocols have decreased the duration of hospitalization and subsequent length of recovery following elective total hip arthroplasty. We assessed the feasibility and safety of outpatient total hip arthroplasty in 150 consecutive patients. A comprehensive perioperative anesthesia and rehabilitation protocol including preoperative teaching, regional anesthesia, and preemptive oral analgesia and antiemetic therapy was implemented around a minimally invasive surgical technique. A rapid rehabilitation pathway was started immediately after surgery and patients had the option of being discharged to home the day of surgery if standard discharge criteria were met. All 150 patients were discharged to home the day of surgery, at which time 131 patients were able to walk without assistive devices. Thirty-eight patients required some additional intervention outside the pathway to resolve nausea, hypotension, or sedation prior to discharge. There were no readmissions for pain, nausea, or hypotension yet there was one readmission for fracture and nine emergency room evaluations in the three month perioperative period. This anesthetic and rehabilitation protocol allowed outpatient total hip arthroplasty to be routinely performed in these consecutive patients undergoing primary total hip arthroplasty. With current reimbursement approaches the modest savings to the hospital in length of stay may be outweighed by the additional costs of personnel, thereby making this outpatient system more expensive to implement. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
The feasibility and perioperative complications of outpatient knee arthroplasty.
Berger, Richard A; Kusuma, Sharat K; Sanders, Sheila A; Thill, Elizabeth S; Sporer, Scott M
2009-06-01
The duration of hospitalization and subsequent length of recovery after elective knee arthroplasty have decreased. We hypothesized same-day discharge following either a unicompartmental (UKA) or total knee arthroplasty (TKA) in an unselected group of patients would not result in a higher perioperative complication rate than standard-length hospitalization when following a comprehensive perioperative clinical pathway, including preoperative teaching, regional anesthesia, preemptive oral analgesia, preemptive antiemetics, and a rapid rehabilitation protocol. We prospectively followed 111 of all 121 patients who had primary knee arthroplasty completed by noon and who agreed to be followed prospectively; 25 had UKA and 86 TKA. Of the 111 patients, 104 (94%, 24 with UKA and 80 with TKA) met discharge criteria and were discharged directly to home the day of surgery. Nausea requiring additional treatment before discharge was the most common reason for a delay in discharge. There were four (3.6%) readmissions (all with TKA) and one emergency room visit without readmission (in a patient with a TKA) within the first week after surgery, while there were four subsequent readmissions (3.6%) and one additional emergency room visit without readmission within three months of surgery, all among patients undergoing TKA. There were no deaths, cardiac events, or pulmonary complications during this study. Outpatient knee arthroplasty surgery is feasible in a large percentage of patients yet early readmissions may be decreased with a prolonged hospitalization. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
Sarpong, Kathryn J; Lukowski, Jennifer M; Knapp, Cassandra G
2017-11-01
OBJECTIVE To determine mortality rates and prognostic factors for dogs with parvoviral enteritis receiving outpatient treatment. DESIGN Retrospective case series and case-control study. ANIMALS 130 client-owned dogs with a diagnosis of parvoviral enteritis between August 1, 2012, and January 31, 2015, that were treated with outpatient care. PROCEDURES Medical records were reviewed and data extracted regarding dog age, body weight, breed, and vaccination history; treatments administered; and short-term (≥ 3 day) outcome (determined via telephone call with owner). Treatments were administered according to clinician preference. Mortality rates were calculated overall and for various signalment and treatment groupings and compared. RESULTS 97 (75%) dogs survived and 33 (25%) dogs failed to survive for ≥ 3 days after initial diagnosis of parvoviral enteritis. Compared with distributions in the general hospital population, Chihuahuas, German Shepherd Dogs, pit bull-type dogs, and males were overrepresented. No significant difference was identified between survivors and nonsurvivors regarding age, body weight, or sex. Dogs prescribed a caloric supplement fed every 2 to 4 hours had a mortality rate of 19% (16/85). Most of these dogs had also received fluids administered SC, an antiemetic, and antimicrobials. CONCLUSIONS AND CLINICAL RELEVANCE Clinicians should note the 25% mortality rate of the dogs with parvoviral enteritis that received outpatient care in this study setting when discussing treatment options with owners of affected dogs who are financially unable to pursue hospitalization.
Geiger, Friedemann; Wolfgram, Levke
2013-04-20
Emesis and nausea are side effects induced by chemotherapy. These effects lead to enormous stress and strain on cancer patients. Further consequences may include restrictions in quality of life, cachexia or therapy avoidance. Evidence suggests that cancer patients develop the side effects of nausea and vomiting in anticipation of chemotherapy. Contextual cues such as smell, sounds or even the sight of the clinic may evoke anticipatory nausea and vomiting prior to infusion. Anticipatory nausea and vomiting are problems that cannot be solved by administration of antiemetica alone.The purpose of the proposed randomized placebo-controlled trial is to use an overshadowing technique to prevent anticipatory nausea and vomiting and to decrease the intensity and duration of post-treatment nausea and vomiting. Furthermore, the effect on anxiety, adherence and quality of life will be evaluated. Fifty-two pediatric cancer patients will be evenly assigned to two groups: an experimental group and a control group. The participants, hospital staff and data analysts will be kept blinded towards group allocation. The experimental group will receive during three chemotherapy cycles a salient piece of candy prior to every infusion, whereas the control group will receive flavorless placebo tablets. If an effectiveness of the overshadowing technique is proven, implementation of this treatment into the hospitals' daily routine will follow. The use of this efficient and economic procedure should aid a reduced need for antiemetics. Current Controlled Trials ISRCTN30242271/
A brief review of current scientific evidence involving aromatherapy use for nausea and vomiting.
Lua, Pei Lin; Zakaria, Noor Salihah
2012-06-01
The objective of this study was to compile existing scientific evidence regarding the effects of essential oils (EOs) administered via inhalation for the alleviation of nausea and vomiting. CINAHL, PubMed, and EBSCO Host and Science Direct databases were searched for articles related to the use of EOs and/or aromatherapy for nausea and vomiting. Only articles using English as a language of publication were included. Eligible articles included all forms of evidence (nonexperimental, experimental, case report). Interventions were limited to the use of EOs by inhalation of their vapors to treat symptoms of nausea and vomiting in various conditions regardless of age group. Studies where the intervention did not utilize EOs or were concerned with only alcohol inhalation and trials that combined the use of aromatherapy with other treatments (massage, relaxations, or acupressure) were excluded. Five (5) articles met the inclusion criteria encompassing trials with 328 respondents. Their results suggest that the inhaled vapor of peppermint or ginger essential oils not only reduced the incidence and severity of nausea and vomiting but also decreased antiemetic requirements and consequently improved patient satisfaction. However, a definitive conclusion could not be drawn due to methodological flaws in the existing research articles and an acute lack of additional research in this area. The existing evidence is encouraging but yet not compelling. Hence, further well-designed large trials are needed before confirmation of EOs effectiveness in treating nausea and vomiting can be strongly substantiated.
Rubenstein, Edward B; Slusher, Barbara S; Rojas, Camilo; Navari, Rudolph M
2006-01-01
Nausea and vomiting are considered to be among the most distressing consequences of cytotoxic chemotherapies. Currently, there are several novel 5-HT(3) receptor antagonists for the treatment of chemotherapy-induced nausea and vomiting (CINV), including ondansetron, granisetron, and dolasetron. These agents provide significant improvement in the management of acute emesis but are ineffective at preventing delayed emesis. In 2003, a new 5-HT(3) receptor antagonist, palonosetron HCL (Aloxi), was introduced to the U.S. market. Palonosetron was found to be effective in preventing delayed CINV. Indeed, palonosetron was the first and only 5-HT(3) receptor antagonist approved by the FDA for the prevention of both acute and delayed CINV. More recently, studies on the role of substance P in the emetic process led to the development of aprepitant (Emend) for the prevention of delayed emesis in combination with 5-HT(3) receptor antagonists. Despite these major advances, CINV remains uncontrolled in some patients. Current efforts are focused on treating refractory emesis and include both the clinical evaluation of compounds marketed for other indications and the preclinical evaluation of novel molecules targeting other transmitters in the emetic pathway. Ongoing work in pharmacogenomics has postulated several candidate genes that could be involved in emetic sensitivity and responsiveness to antiemetic therapy. Investigations into the pharmacogenomics of CINV may someday be able to aid in the identification of high risk patients and patients unlikely to respond to conventional therapies.
Therapeutic potential of cannabis in pain medicine.
Hosking, R D; Zajicek, J P
2008-07-01
Advances in cannabis research have paralleled developments in opioid pharmacology whereby a psychoactive plant extract has elucidated novel endogenous signalling systems with therapeutic significance. Cannabinoids (CBs) are chemical compounds derived from cannabis. The major psychotropic CB delta-9-tetrahydrocannabinol (Delta(9)-THC) was isolated in 1964 and the first CB receptor (CB(1)R) was cloned in 1990. CB signalling occurs via G-protein-coupled receptors distributed throughout the body. Endocannabinoids are derivatives of arachidonic acid that function in diverse physiological systems. Neuronal CB(1)Rs modulate synaptic transmission and mediate psychoactivity. Immune-cell CB(2) receptors (CB(2)R) may down-regulate neuroinflammation and influence cyclooxygenase-dependent pathways. Animal models demonstrate that CBRs play a fundamental role in peripheral, spinal, and supraspinal nociception and that CBs are effective analgesics. Clinical trials of CBs in multiple sclerosis have suggested a benefit in neuropathic pain. However, human studies of CB-mediated analgesia have been limited by study size, heterogeneous patient populations, and subjective outcome measures. Furthermore, CBs have variable pharmacokinetics and can manifest psychotropism. They are currently licensed as antiemetics in chemotherapy and can be prescribed on a named-patient basis for neuropathic pain. Future selective peripheral CB(1)R and CB(2)R agonists will minimize central psychoactivity and may synergize opioid anti-nociception. This review discusses the basic science and clinical aspects of CB pharmacology with a focus on pain medicine.
Sanger, Gareth J
2004-04-01
NK1 and NK3 receptors do not appear to play significant roles in normal GI functions, but both may be involved in defensive or pathological processes. NK1 receptor antagonists are antiemetic, operating via vagal sensory and motor systems, so there is a need to study their effects on other gastro-vagal functions thought to play roles in functional bowel disorders. Interactions between NK1 receptors and enteric nonadrenergic, noncholinergic motorneurones suggest a need to explore the role of this receptor in disrupted colonic motility. NK1 receptor antagonism does not exert consistent analgesic activity in humans, but similar studies have not been carried out against pain of GI origin, where NK1 receptors may have additional influences on mucosal inflammatory or "irritant" processes. NK3 receptors mediate certain disruptions of intestinal motility. The activity may be driven by tachykinins released from intrinsic primary afferent neurones (IPANs), which induce slow EPSP activity in connecting IPANs and hence, a degree of hypersensitivity within the enteric nervous system. The same process is also proposed to increase C-fibre sensitivity, either indirectly or directly. Thus, NK3 receptor antagonists inhibit intestinal nociception via a "peripheral" mechanism that may be intestine-specific. Studies with talnetant and other selective NK3 receptor antagonists are, therefore, revealing an exciting and novel pathway by which pathological changes in intestinal motility and nociception can be induced, suggesting a role for NK3 receptor antagonism in irritable bowel syndrome.
Identifying mechanism-of-action targets for drugs and probes
Gregori-Puigjané, Elisabet; Setola, Vincent; Hert, Jérôme; Crews, Brenda A.; Irwin, John J.; Lounkine, Eugen; Marnett, Lawrence; Roth, Bryan L.; Shoichet, Brian K.
2012-01-01
Notwithstanding their key roles in therapy and as biological probes, 7% of approved drugs are purported to have no known primary target, and up to 18% lack a well-defined mechanism of action. Using a chemoinformatics approach, we sought to “de-orphanize” drugs that lack primary targets. Surprisingly, targets could be easily predicted for many: Whereas these targets were not known to us nor to the common databases, most could be confirmed by literature search, leaving only 13 Food and Drug Administration—approved drugs with unknown targets; the number of drugs without molecular targets likely is far fewer than reported. The number of worldwide drugs without reasonable molecular targets similarly dropped, from 352 (25%) to 44 (4%). Nevertheless, there remained at least seven drugs for which reasonable mechanism-of-action targets were unknown but could be predicted, including the antitussives clemastine, cloperastine, and nepinalone; the antiemetic benzquinamide; the muscle relaxant cyclobenzaprine; the analgesic nefopam; and the immunomodulator lobenzarit. For each, predicted targets were confirmed experimentally, with affinities within their physiological concentration ranges. Turning this question on its head, we next asked which drugs were specific enough to act as chemical probes. Over 100 drugs met the standard criteria for probes, and 40 did so by more stringent criteria. A chemical information approach to drug-target association can guide therapeutic development and reveal applications to probe biology, a focus of much current interest. PMID:22711801
Probing the interaction of the phytochemical 6-gingerol from the spice ginger with DNA.
Haris, Poovvathingal; Mary, Varughese; Sudarsanakumar, Chellappanpillai
2018-07-01
6-Gingerol [5-hydroxy-1-(4-hydroxy-3-methoxyphenyl) decan-3-one], the bio-active ingredient of the popular Indian spice ginger (Zingiber officinale Roscoe), is well-known for its pharmacological and physiological actions. The potent antioxidant, antiemetic, antiulcer, antimicrobial, analgesic, hypoglycemic, antihypertensive, antihyperlipidemic, immunostimulant, anti-inflammatory, cardiotonic, and cancer prevention activities of 6-Gingerol has been investigated and explored. 6-Gingerol is a good candidate for the treatment of various cancers including prostrate, pancreatic, breast, skin, gastrointestinal, pulmonary, and renal cancer. In this study we report for the first time the molecular recognition of 6-Gingerol with calf thymus DNA (ctDNA) through experimental and molecular modeling techniques confirming a minor groove binding mode of 6-Gingerol with ctDNA. Fluorescence and UV-vis spectroscopic studies confirm the complex formation of 6-gingerol with ctDNA. The energetics and thermodynamics of the interaction of 6-Gingerol with ctDNA was explored by Isothermal Titration Calorimetry (ITC) and Differential Scanning Calorimetry (DSC). The ctDNA helix melting upon 6-Gingerol binding was examined by melting temperature T m analysis. Further the electrophoretic mobility shift assay confirms a possible groove binding of 6-Gingerol with ctDNA. Molecular docking and Molecular dynamics (MD) studies provide a detailed understanding on the interaction of 6-Gingerol binding in the minor groove of DNA which supports experimental results. Copyright © 2018. Published by Elsevier B.V.
Amato, Laura; Minozzi, Silvia; Mitrova, Zuzana; Parmelli, Elena; Saulle, Rosella; Cruciani, Fabio; Vecchi, Simona; Davoli, Marina
2017-01-01
low risk of bias. The large majority (80%) of the comparisons were with placebo; only 8 studies included patients with cancer receiving chemotherapy comparing cannabis with other antiemetic drugs. Concerning the efficacy of cannabis (compared with placebo) in patients with multiple sclerosis, confidence in the estimate was high in favour of cannabis for spasticity (numerical rating scale and visual analogue scale, but not the Ashworth scale) and pain. For chronic and neuropathic pain (compared with placebo), there was evidence of a small effect; however, confidence in the estimate is low and these results could not be considered conclusive. There is uncertainty whether cannabis, including extracts and tinctures, compared with placebo or other antiemetic drugs reduces nausea and vomiting in patients with cancer requiring chemotherapy, although the confidence in the estimate of the effect was low or very low. In the included studies, many adverse events were reported and none of the studies assessed the development of abuse or dependence. there is incomplete evidence of the efficacy and safety of medical use of cannabis in the clinical contexts considered in this review. Furthermore, for many of the outcomes considered, the confidence in the estimate of the effect was again low or very low. To give conclusive answers to the efficacy and safety of cannabis used for medical purposes in the clinical contexts considered, further studies are needed, with higher quality, larger sample sizes, and possibly using the same diagnostic tools for evaluating outcomes of interest.
Hatoum, Hind T; Lin, Swu-Jane; Buchner, Deborah; Cox, David
2012-05-01
The aim of this study was to compare the risk of chemotherapy-induced nausea and vomiting (CINV) events for various 5-HT(3) RAs in patients who received moderately (MEC) or highly emetogenic chemotherapy (HEC) by evaluating hospital or emergency department (ED) admissions. PharMetrics claims database was used to identify patients diagnosed with breast cancer (BC) who were initiated on cyclophosphamide-based adjuvant chemotherapy or with lung cancer (LC) initiated on carboplatin-based or cisplatin-based chemotherapy between 2005 and 2008. Patients were stratified in two groups: those initiated and maintained on palonosetron versus those treated with any other 5-HT(3) RA regimens in the 6-month post first chemotherapy. Risk for CINV events, identified by ICD-9-CM for nausea, vomiting, and/or dehydration, were estimated using logistic regressions, controlling for age, gender, comorbidity, and total chemotherapy doses or days. Of the 4,868 cyclophosphamide-treated BC, 5,414 carboplatin-treated LC, and 1,692 cisplatin-treated LC identified, there were 1,864 BC (38.5%), 1,806 carboplatin-treated LC (33.4%), and 390 cisplatin-treated LC (23.0%) in the palonosetron-only group. Palonosetron-only group had significantly lower probability of CINV events associated with ED/hospital admissions in all three cohorts (3.5% vs. 6.3% in BC, 9.5% vs. 13.8% in carboplatin-treated LC, and 16.4% vs. 22.6% in cisplatin-treated LC, all at p < 0.05). Logistic regressions found palonosetron-only group had significantly lower risk of CINV events (odds ratios = 0.550, 0.653, and 0.689 in BC, carboplatin-treated LC and cisplatin-treated LC, respectively, p < 0.05). Patients with lung or breast cancer receiving MEC or HEC had significantly lower risk of CINV events associated with hospital/ED admissions if initiated and maintained on palonosetron relative to patients receiving 5-HT(3) RA regimens.
Accidental intoxication with Veratrum album.
Grobosch, T; Binscheck, T; Martens, F; Lampe, D
2008-01-01
A 49-year-old man consumed two glasses (approximately 2 x 20 mL) of a beverage containing yellow gentian (Gentiana lutea). Shortly after ingestion, he developed nausea, vomiting, and oral paraesthesia. On admission to the hospital he suffered from severe bradycardia (35 beats/min) and hypotension (50/30 mm Hg), and he was treated with activated charcoal, antiemetics (metoclopramide, ondansetron), atropine, and intravenous electrolytic solution. The initial suspicion of Veratrum poisoning could be confirmed by identifying protoveratrines A (ProA) and protoveratrine B (ProB) in a sample from the beverage as well as in the patients serum by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS). The yellow-colored beverage contained 25% ethanol (by headspace gas chromatography), 20.4 mg/L ProA, and 13.7 mg/L ProB. The serum concentration of ProA was 1162 ng/L and ProB was 402 ng/L. Veratridine, cevadine, and jervine were not detected, neither in the beverage nor in the serum sample. The lower limits of quantitation for all compounds is 10 microg/L (S/N > 10, beverage) and 100 ng/L (S/N > 10, serum). After treatment, the patient completely recovered from the symptoms within 24 h and was discharged from the hospital. The analytical method described was developed for the simultaneous identification and quantitation of five Veratrum alkaloids. The method is based on a liquid-liquid extraction followed by LC-MS-MS analysis. The time needed for analysis was 6 min.
Lanier, Steven T; Lewis, Kevin C; Kendall, Mark C; Vieira, Brittany L; De Oliveira, Gildasio; Nader, Anthony; Kim, John Y S; Alghoul, Mohammed
2018-03-01
The authors' study represents the first level I evidence to assess whether intraoperative nerve blocks improve the quality of recovery from immediate tissue expander/implant breast reconstruction. A prospective, randomized, double-blinded, placebo-controlled clinical trial was conducted in which patients undergoing immediate tissue expander/implant breast reconstruction were randomized to either (1) intraoperative intercostal and pectoral nerve blocks with 0.25% bupivacaine with 1:200,000 epinephrine and 4 mg of dexamethasone or (2) sham nerve blocks with normal saline. The 40-item Quality of Recovery score, pain score, and opioid use in the postoperative period were compared statistically between groups. Power analysis ensured 80 percent power to detect a 10-point (clinically significant) difference in the 40-item Quality of Recovery score. Forty-seven patients were enrolled. Age, body mass index, laterality, mastectomy type, and lymph node dissection were similar between groups. There were no statistical differences in quality of recovery, pain burden as measured by visual analogue scale, opioid consumption, antiemetic use, or length of hospital stay between groups at 24 hours after surgery. Mean global 40-item Quality of Recovery scores were 169 (range, 155 to 182) for the treatment arm and 165 (range, 143 to 179) for the placebo arm (p = 0.36), indicating a high quality of recovery in both groups. Although intraoperative nerve blocks can be a safe adjunct to a comprehensive postsurgical recovery regimen, the authors' results indicate no effect on overall quality of recovery from tissue expander/implant breast reconstruction. Therapeutic, I.
Acute Organoaxial gastric volvulus: A massive problem with a twist-case report.
Al Daoud, Fadi; Daswani, Gul Sachwani; Perinjelil, Vinu; Nigam, Tina
2017-01-01
Gastric volvulus (GV) is a rare and life threatening condition if not treated promptly or wrongly diagnosed. The main complication of gastric volvulus is foregut obstruction. The extreme rotation can cut off blood supply to the stomach and even distal organs, which can lead to ischemia and necrosis of the affected area. We report a case of a 41yo female that complained of severe abdominal pain, nausea and vomiting for approximately 3days after eating a large meal. The patient didn't have any flatus or bowel movements in the last 24h. CT of the abdomen and pelvis showed a dilatation of the stomach and esophageal hernia. Laparotomy confirmed an organoaxial volvulus at the level of the antrum and body of the stomach. Gastropexy was implemented and the stomach fixed to the posterior abdominal wall to prevent recurrence. GV may have a significant related morbidity and mortality rate. It can be missed easily on diagnosis. The presence of vomiting not responding to initial antiemetic treatment, as well as, the presence of a hiatal hernia on the imaging studies should trigger our thinking of gastric volvulus, regardless of the stable appearance of the patient. Chronic GV can manifests as atypical chest, abdomen and gastro intestinal symptoms. We recommend that everyone with these atypical symptoms seek medical attention to rule out GV. Early diagnosis and treatment will reduce the risk of developing chronic gastric volvulus to acute gastric volvulus. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Salazar, Elizabeth G; Li, Yimei; Fisher, Brian T; Rheingold, Susan R; Fitzgerald, Julie; Seif, Alix E; Huang, Yuan-Shung; Bagatell, Rochelle; Aplenc, Richard
2016-08-01
Although inferior outcomes of children with Down syndrome (DS) and acute lymphoid leukaemia (ALL) are established, national supportive care patterns for these patients are unknown. A validated retrospective cohort of paediatric patients diagnosed with ALL from 1999 to 2011 was assembled from the US Pediatric Health Information System (PHIS) database to examine organ toxicity, sepsis, and resource utilization in children with and without DS. Among 10699 ALL patients, 298 had DS-ALL (2·8%). In a multivariate model, DS was associated with increased risk of cardiovascular (odds ratio [OR] 2·0, 95% confidence interval [CI] 1·6-2·7), respiratory (OR 2·1, 95% CI: 1·6-2·9), neurologic (OR 3·4, 95% CI 1·9-6·2), and hepatic (OR 1·4, 95% CI 1·0-1·9) dysfunction and sepsis (OR 1·8, 95% CI: 1·4-2·4). Children with DS-ALL used significantly more respiratory support, insulin, and anti-infectives, including broad-spectrum Gram-positive agents, quinolones, and azoles. They used significantly fewer analgesics and antiemetics compared to non-DS-ALL children. Ultimately, this study confirms the increased risk of infectious and end-organ toxicity in children with DS-ALL and quantifies important differences in resource utilization between children with DS and non-DS ALL. These findings highlight the importance of investigating the impact of these care variations and developing specific supportive care guidelines for this population. © 2016 John Wiley & Sons Ltd.
Gerónimo-Pardo, M
2014-01-01
To describe the frequency of dose notification of antiinfectives for systemic use in clinical cases published in Revista Española de Anestesiología y Reanimación. Review of individualized clinical cases published in the sections «Clinical case» or «Letter to the Editor» of the above mentioned journal from year 2010 to 2012, and identification of the drugs and their therapeutic regimens cited in such publications, being dose notification the main variable. Drugs have been classified according to the Anatomical Therapeutic Chemical Classification System. One thousand one hundred and thirty-five drugs cited 1,317 times were identified in 167 articles describing the clinical pictures of 182 patients, 73 of the citations (5.6%) regarding to drugs belonging to group J (Antiinfectives for systemic use) which were divided into perioperative prophylaxis (n=15) and active treatment (n=58). Doses were scarcely notified for group J drugs as a whole (27.4%), but especially for active treatment (17.2%) compared to perioperative prophylaxis (66.7%), percentage which was similar to those more classical anesthetic drugs (fentanyl: 86.6%; remifentanil: 70.5%; sevoflurane: 78%; propofol: 79%; rocuronium:79.6%; cisatracurium: 68.4%) or even for antiemetics (ondansetron: 92.3%; dexamethasone: 84.6%). Quality of case reports could be improved by including dose notification for antiinfective agents. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.
Tian, Weihua; Wang, Zhiqiang; Zhou, Juntian; Zhang, Shucai; Wang, Jinghui; Chen, Qiang; Huang, Cheng; Pan, Liangxi; Zhang, Lili; Huang, Jianjin; Shen, Hong; Lin, Tongyu
2011-03-01
The objective of this study was to compare the efficacy and tolerability of palonosetron and granisetron in a Chinese population receiving highly emetogenic cisplatin-based chemotherapy or moderately emetogenic chemotherapy. Patients were stratified by chemotherapy with cisplatin (yes/no) and then randomly assigned to receive either palonosetron (0.25 mg i.v.) in the first cycle followed by granisetron (3 mg i.v.) in the second cycle or vice versa. The primary efficacy endpoint was the proportion of patients with complete response 0-24 h post-chemotherapy administration. The proportions of patients with complete response 24-120 and 0-120 h following chemotherapy were also compared. Of the 144 patients randomized, 36 (25%) received 60-80 mg/m(2) cisplatin; 66 of 72 patients in the palonosetron to granisetron group and 56 of 72 patients in the granisetron to palonosetron group completed treatment with both antiemetics. The efficacy and safety analyses included 128 palonosetron treatments and 138 granisetron treatments. Palonosetron consistently produced numerically higher complete response rates than granisetron in the acute phase (0-24 h, 71.09 vs. 65.22%), the delayed phase (24-120 h, 60.16 vs. 55.80%), and overall (0-120 h, 53.13 vs. 50.00%) though the differences were not significant. Both palonosetron and granisetron were well tolerated. Palonosetron was well tolerated and effective in preventing acute and delayed chemotherapy-induced nausea and vomiting in a Chinese population. When used as monotherapy, 0.25-mg palonosetron was not inferior to 3-mg granisetron for preventing vomiting following highly or moderately emetogenic chemotherapy.
Eguchi, Kenji; Shinkai, Tetsu; Tamura, Tomohide; Ohe, Yuichiro; Nisio, Masato; Kunikane, Hiroshi; Arioka, Hitoshi; Karato, Atsuya; Nakashima, Hajime; Sasaki, Yasutsuna; Tajima, Kinuko; Tada, Noriko; Saijo, Nagahiro
1994-01-01
We carried out a randomized, single‐blind, cross‐over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high‐dose metoclopramide plus dexamethasone (HDMP + Dx). Fifty‐four patients with primary or metastatic lung cancer, given single‐dose cisplatin (> 80 mg/m2) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD=4.3) and 0,1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN + Dx groups, respectively (P=0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively (P= 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2–5, but it was not statistically significant. Twenty‐four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP + Dx. In the HDMP + Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and IS patients (43%) had constipation in the GRN+Dx group (P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed. PMID:7829401
Jain, Virendra; Mitra, Jayanta K; Rath, Girija P; Prabhakar, Hemanshu; Bithal, Parmod K; Dash, Hari H
2009-07-01
Postoperative nausea and vomiting (PONV) are frequent and distressing complications after neurosurgical procedures. We evaluated the efficacy of ondansetron and granisetron to prevent PONV after supratentorial craniotomy. In a randomized double-blind, placebo controlled trial, 90 adult American Society of Anesthesiologists I, II patients were included in the study. A standard anesthesia technique was followed. Patients were divided into 3 groups to receive either placebo (saline), ondansetron 4 mg, or granisetron 1 mg intravenously at the time of dural closure. After extubation, episodes of nausea and vomiting were noted for 24 hours postoperatively. Statistical analysis was performed using chi2 test and 1-way analysis of variance. Demographic data, duration of surgery, intraoperative fluids and analgesic requirement, and postoperative pain (visual analog scale) scores were comparable in all 3 groups. It was observed that the incidence of vomiting in 24 hours, severe emetic episodes, and requirement of rescue antiemetics were less in ondansetron and granisetron groups as compared with placebo (P<0.001). Both the study drugs had comparable effect on vomiting. However, the incidence of nausea was comparable in all 3 groups (P=0.46). A favorable influence on the patient satisfaction scores, and number needed to prevent emesis was seen in the 2 drug groups. No significant correlation was found between neurosurgical factors (presence of midline shift, mass effect, pathologic diagnosis of tumor, site of tumor) and the occurrence of PONV. We conclude that ondansetron 4 mg and granisetron 1 mg are comparably effective at preventing emesis after supratentorial craniotomy. However, neither drugs prevented nausea effectively.
Motohashi, Shinya; Hori, Katsuhito; Ono, Takaaki; Ohnishi, Kazunori; Kawakami, Junichi
2012-01-01
Granisetron is a selective 5-hydroxy tryptamine3 receptor antagonist and widely used for chemotherapy-induced nausea and vomiting (CINV). Recommended dose of intravenous granisetron in the USA and Europe has been set at 0.01 mg/kg (1 mg/body) in the antiemetic treatment guidelines established by the American Society of Clinical Oncology and National Comprehension Cancer Network. In contrast, the approved dose in Japan is 0.04 mg/kg (3 mg/body). Randomized controlled trials (RCTs) which compared 1 mg/body with 3 mg/body of intravenous granisetron for CINV had been reported in Japan. In these RCTs, however, hematological malignancy patients were excluded. We performed observational retrospective study to compare 1 mg/body with 3 mg/body of intravenous granisetron for the prevention of CINV and adverse events in hematological malignancy patients. Number of the patients and chemotherapy courses were 15 and 30 in the 1 mg/body group, and 15 and 27 in the 3 mg/body group, respectively. No nausea rates in the 1 and 3 mg/body group were 83% and 89% of courses, respectively. No vomiting rates in the 1 and 3 mg/body group were 97% and 100% of courses, respectively. The incidences of constipation in the 1 and 3 mg/body group were 34% and 45% of courses, respectively. Anaphylaxis and headache did not occur in both groups. Our findings suggested that 1 mg/body of intravenous granisetron can prevent from CINV in hematological malignancy patients, as well as 3 mg/body.
Granisetron transdermal system improves refractory nausea and vomiting in gastroparesis.
Simmons, Kellie; Parkman, Henry P
2014-06-01
Symptoms of gastroparesis include nausea and vomiting, which can markedly diminish quality of life. Nausea and vomiting can also make treatment with oral antiemetics problematic. Our aim was to determine whether treatment-resistant nausea and vomiting in patients with gastroparesis improve after granisetron transdermal patch (GTP) therapy. In an open-label pilot study, patients with gastroparesis and symptoms of nausea and vomiting refractory to conventional treatment were treated with GTP. After 2 weeks, patients were asked to assess their therapeutic response using the Clinical Patient Grading Assessment Scale (CPGAS; +7 = completely better; 0 = no change; -7 = very considerably worse). Responders were defined as CPGAS score >0, non-responders as ≤0. Patients (n = 36) were treated with GTP. Of these 36 patients, one patient discontinued treatment due to the GTP not adhering to the skin. Of the remaining 35 patients, 18 improved, 15 remained the same, and two worsened. The average CPGAS score was +1.8 ± 0.4 (SEM) (P < 0.05 vs 0). Of the 18 patients with improvement, the average CPGAS score was +3.7 ± 0.3 (SEM), corresponding to "somewhat" to "moderately better" improvement in nausea/vomiting. Side effects occurred in nine patients: four developed constipation, three patients had skin rash, and two reported headaches. GTP was moderately effective in reducing refractory symptoms of nausea and/or vomiting from gastroparesis in 50% of patients. Mild side effects were reported by 25% of patients. GTP may be an effective treatment for nausea and vomiting in gastroparesis, and further study is warranted.
Fujii, Y.; Tanaka, H.; Ito, M.
2001-01-01
BACKGROUND/AIMS—Postoperative vomiting occurs frequently after strabismus surgery in children. Granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, is effective for the prevention of vomiting following paediatric strabismus surgery. Ramosetron, another new antagonist of 5-hydroxytryptamine type 3 receptor, has more potent and longer acting properties than granisetron against cisplatin induced emesis. This study was undertaken to compare the efficacy and safety of granisetron and ramosetron for the prevention of vomiting following strabismus surgery in children. METHODS—In a randomised, double blinded manner 80 children, aged 4-10 years, received intravenously granisetron 40 µg/kg or ramosetron 6 µg/kg (n=40 each) at the end of surgery. A standard general anaesthetic technique and postoperative analgesia were used. Emetic episodes and safety assessment were performed during the first 24 hours and the next 24 hours after anaesthesia. RESULTS—The percentage of patients who were emesis free during 0-24 hours after anaesthesia was 85% with granisetron and 90% with ramosetron, respectively (p = 0.369); the corresponding rate during 24-48 hours after anaesthesia was 70% and 95% (p = 0.003). No clinically serious adverse events caused by the study drug were observed in any of the groups. CONCLUSION—Prophylactic antiemetic therapy with ramosetron is comparable with granisetron for the prevention of vomiting during 0-24 hours after anaesthesia in children undergoing strabismus surgery. During 24-48 hours after anaesthesia, ramosetron is more effective than granisetron for prophylaxis against postoperative vomiting. PMID:11371485
Keat, Chan Huan; Phua, Gillian; Abdul Kassim, Mohd Shainol; Poh, Wong Kar; Sriraman, Malathi
2013-01-01
The purpose of this study is to examine the risk of uncontrolled chemotherapy-induced nausea and vomiting (CINV) among patients receiving low emetogenic chemotherapy (LEC) with and without granisetron injection as the primary prophylaxis in addition to dexamethasone and metochlopramide. This was a single-centre, prospective cohort study. A total of 96 patients receiving LEC (52 with and 42 without granisetron) were randomly selected from the full patient list generated using the e-Hospital Information System (e-His). The rates of complete control (no CINV from days 1 to 5) and complete response (no nausea or vomiting in both acute and delayed phases) were identified through patient diaries which were adapted from the MASCC Antiemesis Tool (MAT). Selected covariates including gender, age, active alcohol consumption, morning sickness and previous chemotherapy history were controlled using the multiple logistic regression analyses. Both groups showed significant difference with LEC regimens (p<0.001). No differences were found in age, gender, ethnic group and other baseline characteristics. The granisetron group indicated a higher complete response rate in acute emesis (adjusted OR: 0.1; 95%CI 0.02-0.85; p=0.034) than did the non-granisetron group. Both groups showed similar complete control and complete response rates for acute nausea, delayed nausea and delayed emesis. Granisetron injection used as the primary prophylaxis in LEC demonstrated limited roles in CINV control. Optimization of the guideline-recommended antiemetic regimens may serve as a less costly alternative to protect patients from uncontrolled acute emesis.
Sharma, Radhika; Kamboj, Sunil; Singh, Gursharan; Rana, Vikas
2016-03-10
The present investigation was aimed to prepare orally disintegrating films (ODFs) containing aprepitant (APT), an antiemetic drug employing pullulan as film forming agent, tamarind pectin as wetting agent and liquid glucose as plasticizer and solubiliser. The ODFs were prepared using solvent casting method. The method was optimized employing 3(2) full factorial design considering proportion of pullulan: tamarind pectin and concentration of liquid glucose as independent variables and disintegration time, wetting time, folding endurance, tensile strength and extensibility as dependent variables. The optimized ODF was evaluated for various physicochemical, mechanical, drug release kinetics and bioavailability studies. The results suggested prepared film has uniform film surface, non-sticky and disintegrated within 18s. The in-vitro release kinetics revealed more than 87% aprepitant was released from optimized ODF as compared to 85%, 49%, and 12% aprepitant release from marketed formulation Aprecap, micronized aprepitant and non micronized aprepitant, respectively. The results of animal preference study indicated that developed aprepitant loaded ODFs are accepted by rabbits as food material. Animal pharmacokinetic (PK) study showed 1.80, 1.56 and 1.36 fold enhancement in relative bioavailability for aprepitant loaded ODF, Aprecap and micronized aprepitant respectively, in comparison with non-micronized aprepitant. Overall, the solubilised aprepitant when incorporated in the form of aprepitant loaded ODF showed enhanced bioavailability as compared to micronized/non-micronized aprepitant based oral formulations. These findings suggested that aprepitant loaded ODF could be effective for antiemesis during cancer chemotherapy. Copyright © 2016 Elsevier B.V. All rights reserved.
Yang, Hyun; Seon, Jein; Sung, Pil Soo; Oh, Jung Suk; Lee, Hae Lim; Jang, Bohyun; Chun, Ho Jong; Jang, Jeong Won; Bae, Si Hyun; Choi, Jong Young; Yoon, Seung Kew
2017-11-01
To test the hypothesis that prophylactic administration of dexamethasone alleviates postembolization syndrome (PES) after transarterial chemoembolization for the treatment of hepatocellular carcinoma (HCC). This prospective, randomized, double-blinded, placebo-controlled trial was conducted in a single center from August 2015 to June 2016. A total of 88 patients with intermediate-stage HCC were enrolled. After randomization, 44 patients were assigned to the dexamethasone group and the other 44 to the control group. In the dexamethasone group, 12 mg of intravenous dexamethasone was administered before chemoembolization. Nausea, vomiting, fever, pain, and alanine aminotransferase level elevation were evaluated after chemoembolization had been performed with the use of Lipiodol and doxorubicin. The incidences of PES were 78.0% in the dexamethasone group and 97.5% in the control group (P = .008). Mean hospitalization times after chemoembolization were 2.7 days ± 1.44 in the dexamethasone group and 2.9 days ± 1.83 in the control group (P = .553). Mean doses of antiemetic and analgesic agents were lower in the dexamethasone group than the control group (0.2 ± 0.58 vs 1.0 ± 1.89 [P = .029] and 0.6 ± 0.97 vs 1.92 ± 2.54 [P = .006], respectively). Prophylactic administration of dexamethasone was a significant factor that influences PES occurrence after chemoembolization (odds ratio = 10.969, P = .027). This study demonstrates that the prophylactic administration of dexamethasone before chemoembolization is an effective way to reduce PES. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.
McBride, Ali; Bonafede, Machaon; Cai, Qian; Princic, Nicole; Tran, Oth; Pelletier, Corey; Parisi, Monika; Patel, Manish
2017-10-01
The economic burden of metastatic pancreatic cancer (mPC) is substantial while treatment options are limited. Little is known about the treatment patterns and healthcare costs among mPC patients who initiated first-line gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-P + G) and FOLFIRINOX. The MarketScan® claims databases were used to identify adults with ≥2 claims for pancreatic cancer, 1 claim for a secondary malignancy, completed ≥1 cycle of nab-P + G or FOLFIRINOX during 4/1/2013 and 3/31/2015, and had continuous plan enrollment for ≥6 months pre- and 3 months after the first-line treatment. Duration of therapy, per patient per month (PPPM) costs of total healthcare, mPC-related treatment, and supportive care were measured during first-line therapy. 550 mPC patients met selection criteria (nab-P + G, n = 294; FOLFIRINOX, n = 256). There was no difference in duration of therapy (p = 0.60) between nab-P + G and FOLFIRINOX. Compared with FOLFIRINOX, patients with nab-P + G had higher chemotherapy drug costs but lower treatment administration costs and supportive care costs (all p < 0.01). Patients treated with nab-P + G (vs FOLFIRINOX) had similar treatment duration but lower costs of outpatient prescriptions, treatment administration and supportive care. Lower supportive care costs in the nab-P + G cohort were mainly driven by lower utilization of pegfilgrastim and anti-emetics.
Kim, Joon Yub; Song, Seong Hun; Cho, Jae Ho; Cho, Hyung Rae
2017-01-01
Hypotensive anesthesia is crucial during arthroscopic shoulder surgery to reduce bleeding and allow for clear visibility. The aim of this study was to compare the clinical efficacy of continuous infusion of remifentanil, nicardipine, and remifentanil plus nicardipine to control hypotensive anesthesia in arthroscopic shoulder surgery. For this study, we enrolled 45 consecutive patients who were scheduled to have arthroscopic rotator cuff repair surgery and randomly allocated them into remifentanil (group R, n = 15), nicardipine (group N, n = 15), and remifentanil plus nicardipine (group RN, n = 15) groups. During the surgeries, these drugs were administered with continuous infusion. We analyzed the mean arterial pressure (MAP) and heart rate during surgery, stay time in the recovery room, visual analogue scale (VAS) scores, use of antiemetics in the recovery room, and postoperative blood urea nitrogen and creatinine changes. The VAS score in the recovery room was higher for group R (mean 5.6, SD 1.4) than for groups N (mean 3.9, SD 0.9) and RN (mean 4.0, SD 1.1; p = 0.000). There were no statistical differences regarding other clinical variables among the three groups (all p > 0.05) except for MAP at 120 min of surgery between groups N and RN (N: 84.67 (SD 10.7) mmHg, RN: 65.4 (SD 9.2) mmHg, p = 0.027). The continuous infusion of remifentanil plus nicardipine appeared to be advantageous for maintaining hypotensive anesthesia until 120 min of arthroscopic shoulder surgery without rebound pain in a postanesthesia care unit.
Abdel Messih, Hanaa A; Ishak, Rania A H; Geneidi, Ahmed S; Mansour, Samar
2017-06-01
The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience. TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3 × 2 2 -level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (Y 1 ), vesicle size (Y 2 ), polydispersity index (Y 3 ), and zeta potential (Y 4 ) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug-excipient interactions, and vesicle stability were also investigated. The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (p < 0.01). The ethosomal vesicles were unilamellar with a nearly spherical shape. EPC-based ethosomes proved good stability. The study suggests the applicability of statistical modeling as a promising tool for prediction of ethosomal characteristics. The ethanolic vesicles were considered as novel potential nanocarriers for accentuated transdermal TRO delivery.
Management strategies in the treatment of neonatal and pediatric gastroenteritis
Ciccarelli, Simona; Stolfi, Ilaria; Caramia, Giuseppe
2013-01-01
Acute gastroenteritis, characterized by the onset of diarrhea with or without vomiting, continues to be a major cause of morbidity and mortality in children in mostly resource-constrained nations. Although generally a mild and self-limiting disease, gastroenteritis is one of the most common causes of hospitalization and is associated with a substantial disease burden. Worldwide, up to 40% of children aged less than 5 years with diarrhea are hospitalized with rotavirus. Also, some microorganisms have been found predominantly in resource-constrained nations, including Shigella spp, Vibrio cholerae, and the protozoan infections. Prevention remains essential, and the rotavirus vaccines have demonstrated good safety and efficacy profiles in large clinical trials. Because dehydration is the major complication associated with gastroenteritis, appropriate fluid management (oral or intravenous) is an effective and safe strategy for rehydration. Continuation of breastfeeding is strongly recommended. New treatments such as antiemetics (ondansetron), some antidiarrheal agents (racecadotril), and chemotherapeutic agents are often proposed, but not yet universally recommended. Probiotics, also known as “food supplement,” seem to improve intestinal microbial balance, reducing the duration and the severity of acute infectious diarrhea. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Society of Paediatric Infectious Diseases guidelines make a stronger recommendation for the use of probiotics for the management of acute gastroenteritis, particularly those with documented efficacy such as Lactobacillus rhamnosus GG, Lactobacillus reuteri, and Saccharomyces boulardii. To date, the management of acute gastroenteritis has been based on the option of “doing the least”: oral rehydration-solution administration, early refeeding, no testing, no unnecessary drugs. PMID:24194646
Pharmaceutical services in a Mexican pain relief and palliative care institute
Escutia Gutiérrez, Raymundo; Cortéz Álvarez, César R.; Álvarez Álvarez, Rosa M.; Flores Hernández, Jorge LV.; Gutiérrez Godínez, Jéssica; López Y López, José G.
Neither the purchase nor the distribution of pharmaceuticals in hospitals and community pharmacies in Mexico is under the care of pharmacists. Some are under control of physicians. This report presents the results of the implementation of somef pharmaceutical services for the Jalisco Pain Relief, and Palliative Care Institute (Palia Institute), under the direction of the Secretary of Health, Government of Jalisco. The services implemented were drug distribution system, Drug Information Service, Pharmacovigilance Program, and home pharmacotherapy follow-up pilot program for patients with advanced illness, with the ultimate using the appropriate medication. The drug distribution system included dispensing of opioid pain medications, antidepressants, anticonvulsants, NSAIDs, anxiolytic drugs, steroid drugs, laxatives, and anti-emetics. The frequently used drugs were morphine sulfate (62%), amitriptyline (6.4%), and dextropropoxyphene (5.8%). The Drug Information Service answered 114 consultations, mainly asked by a physician (71%) concerned with adverse drug reactions and contraindications (21%). The pharmacovigilance program identified 146 suspected adverse drug reactions and classified them reasonably as possible (27%), probable (69%), and certain (4%). These were attributed mainly to pregabalin and tramadol. The home pharmacotherapy follow-up pilot program cared patients with different cancer diagnoses and drug-related problems (DRP), which were identified and classified (according to second Granada Consensus) for pharmaceutical intervention as DRP 1 (5%), DRP 2 (10%), DRP 3 (14%), DRP 4 (19%), DRP 5 (24%), or DRP 6 (28%). This report provides information concerning the accurate use of medication and, above all, an opportunity for Mexican pharmacists to become an part of health teams seeking to resolve drug-related problems. PMID:25170355
Chaparro, Luis Enrique; Clarke, Hance; Valdes, Paola A; Mira, Mauricio; Duque, Lorena; Mitsakakis, Nicholas
2012-12-01
Multimodal analgesia increases the chance of successful discharge and pain control after surgery, and pregabalin is being promoted as an effective analgesic, based on placebo-controlled studies. We investigated whether adding pregabalin improved pain control and reduced opioid requests when it was added to a multimodal analgesic regimen for cosmetic surgery. One hundred and ten women who underwent same-day cosmetic surgery were randomized to receive oral pregabalin, 75 mg q12 h for five consecutive days starting the night before surgery, or identical placebos. Participants, outcomes assessors, and the statistician were blinded. The primary outcome was postoperative numerical movement-evoked pain scores at 2, 24, 48, 72, and 96 h after surgery. The secondary outcomes included pain scores at rest; incidence of moderate to severe pain; and analgesic and antiemetic requirements; as well as the incidence of nausea, vomiting, and somnolence. Based on 99 patients who completed the study, we found no difference between the groups in the primary outcome; 72 h after surgery, movement-evoked median pain scores were <4/10 in both groups. We found no differences in opioid requirements (p = 0.95) or anti-inflammatory requirements (p = 0.45), and no difference in opioid-related adverse events. Perioperative pregabalin 75 mg twice a day does not increase benefit when it is added to an already multimodal analgesic regimen for patients undergoing cosmetic surgery. Several factors could explain our findings, including the possibility of publication bias in the current literature.
Dupuis, L Lee; Kelly, Kara M; Krischer, Jeffrey P; Langevin, Anne-Marie; Tamura, Roy N; Xu, Ping; Chen, Lu; Kolb, E Anders; Ullrich, Nicole J; Sahler, Olle Jane Z; Hendershot, Eleanor; Stratton, Ann; Sung, Lillian; McLean, Thomas W
2018-03-15
Chemotherapy-induced nausea and vomiting remain common, distressing side effects of chemotherapy. It has been reported that acupressure prevents chemotherapy-induced nausea in adults, but it has not been well studied in children. In this multicenter, prospective, randomized, single-blind, sham-controlled trial, the authors compared acute-phase nausea severity in patients ages 4 to 18 years who were receiving highly emetic chemotherapy using standard antiemetic agents combined with acupressure wrist bands, the most common type of acupressure, versus sham bands. Patients wore acupressure or sham bands continuously on each day of chemotherapy and for up to 7 days afterward. Chemotherapy-induced nausea severity in the delayed phase and chemotherapy-induced vomiting control in the acute and delayed phases also were compared. Of the 187 patients randomized, 165 contributed nausea severity assessments during the acute phase. Acupressure bands did not reduce the severity of chemotherapy-induced nausea in the acute phase (odds ratio [OR], 1.33; 95% confidence limits, 0.89-2.00, in which an OR <1.00 favored acupressure) or in the delayed phase (OR, 1.23; 95% CL, 0.75-2.01). Furthermore, acupressure bands did not improve daily vomiting control during the acute phase (OR, 1.57; 95% CL, 0.95-2.59) or the delayed phase (OR, 0.84; 95% CL, 0.45-1.58). No serious adverse events were reported. Acupressure bands were safe but did not improve chemotherapy-induced nausea or vomiting in pediatric patients who were receiving highly emetic chemotherapy. Cancer 2018;124:1188-96. © 2017 American Cancer Society. © 2017 American Cancer Society.
Nilsson, Andreas; Kalman, Sigga; Sonesson, Lena Karin; Arvidsson, Anders; Sjöberg, Folke
2011-01-01
The aim of this study was to evaluate pain relief for patients with burns during rest and mobilization with morphine according to a standard protocol for patient-controlled analgesia (PCA). Eighteen patients with a mean (SD) burned TBSA% of 26 (20) were studied for 10 days. Using a numeric rating scale (NRS, 0 = no pain and 10 = unbearable pain), patients were asked to estimate their acceptable and worst experienced pain by specifying a number on a scale and at what point they would like additional analgesics. Patients were allowed free access to morphine with a PCA pump device. Bolus doses were set according to age, (100 - age)/24 = bolus dose (mg), and 6 minutes lockout time. Degrees of pain, morphine requirements, doses delivered and demanded, oral intake of food, and antiemetics given were used as endpoints. Acceptable pain (mean [SD]) was estimated to be 3.8 (1.3) on the NRS, and additional treatment was considered necessary at scores of 4.3 (1.6) or more. NRS at rest was 2.7 (2.2) and during mobilization 4.7 (2.6). Required mean morphine per day was 81 (15) mg, and the number of doses requested increased during the first 6 days after the burn. The authors found no correlation between dose of morphine required and any other variables. Background pain can be controlled adequately with a standard PCA protocol. During mobilization, the pain experienced was too intense, despite having the already high doses of morphine increased. The present protocol must be refined further to provide analgesia adequate to cover mobilization as well.
Cannabidiol in humans-the quest for therapeutic targets.
Zhornitsky, Simon; Potvin, Stéphane
2012-05-21
Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients. A systematic search was performed in the electronic databases PubMed and EMBASE using the key word "cannabidiol". Both monotherapy and combination studies (e.g., CBD + ∆9-THC) were included. A total of 34 studies were identified: 16 of these were experimental studies, conducted in healthy subjects, and 18 were conducted in clinical populations, including multiple sclerosis (six studies), schizophrenia and bipolar mania (four studies), social anxiety disorder (two studies), neuropathic and cancer pain (two studies), cancer anorexia (one study), Huntington's disease (one study), insomnia (one study), and epilepsy (one study). Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of ∆9-THC. Moreover, some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and/or intensify ∆9-THC-induced effects, whereas others suggest that it may inhibit ∆9-THC-induced effects. Finally, preliminary clinical trials suggest that high-dose oral CBD (150-600 mg/d) may exert a therapeutic effect for social anxiety disorder, insomnia and epilepsy, but also that it may cause mental sedation. Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed.
Brettner, Florian; Janitza, Silke; Prüll, Kathrin; Weninger, Ernst; Mansmann, Ulrich; Küchenhoff, Helmut; Jovanovic, Alexander; Pollwein, Bernhard; Chappell, Daniel; Zwissler, Bernhard; von Dossow, Vera
2016-01-01
Postoperative nausea and vomiting (PONV) is one of the most common and distressing complications after general anesthesia and surgery, with young non-smoking females receiving postoperative opioids being high-risk patients. This register-based study aims to evaluate the effect of low-dose haloperidol (0.5 mg intravenously) directly after induction of general anesthesia to reduce the incidence of PONV in the postoperative anesthesiological care unit (PACU). Multivariable regression models were used to investigate the association between low-dose haloperidol and the occurrence of PONV using a patient registry containing 2,617 surgical procedures carried out at an university hospital. Haloperidol 0.5 mg is associated with a reduced risk of PONV in the total collective (adjusted odds ratio = 0.75, 95% confidence interval: [0.56, 0.99], p = 0.05). The results indicate that there is a reduced risk in male patients (adjusted odds ratio = 0.45, 95% confidence interval: [0.28, 0.73], p = 0.001) if a dose of 0.5 mg haloperidol was administered while there seems to be no effect in females (adjusted odds ratio = 1.02, 95% confidence interval: [0.71, 1.46], p = 0.93). Currently known risk factors for PONV such as female gender, duration of anesthesia and the use of opioids were confirmed in our analysis. This study suggests that low-dose haloperidol has an antiemetic effect in male patients but has no effect in female patients. A confirmation of the gender-specific effects we have observed in this register-based cohort study might have major implications on clinical daily routine.
Gaffigan, Matthew E; Bruner, David I; Wason, Courtney; Pritchard, Amy; Frumkin, Kenneth
2015-09-01
Emergency Department (ED) headache patients are commonly treated with neuroleptic antiemetics like metoclopramide. Haloperidol has been shown to be effective for migraine treatment. Our study compared the use of metoclopramide vs. haloperidol to treat ED migraine patients. A prospective, double-blinded, randomized control trial of 64 adults aged 18-50 years with migraine headache and no recognized risks for QT-prolongation. Haloperidol 5 mg or metoclopramide 10 mg was given intravenously after 25 mg diphenhydramine. Pain, nausea, restlessness (akathisia), and sedation were assessed with 100-mm visual analog scales (VAS) at baseline and every 20 min, to a maximum of 80 min. The need for rescue medications, side effects, and subject satisfaction were recorded. QTc intervals were measured prior to and after treatment. Follow-up calls after 48 h assessed satisfaction and recurrent or persistent symptoms. Thirty-one subjects received haloperidol, 33 metoclopramide. The groups were similar on all VAS measurements, side effects, and in their satisfaction with therapy. Pain relief averaged 53 mm VAS over both groups, with equal times to maximum improvement. Subjects receiving haloperidol required rescue medication significantly less often (3% vs. 24%, p < 0.02). Mean QTcs were equal and normal in the two groups and did not change after treatment. In telephone follow-up, 90% of subjects contacted were "happy with the medication" they had received, with haloperidol-treated subjects experiencing more restlessness (43% vs. 10%). Intravenous haloperidol is as safe and effective as metoclopramide for the ED treatment of migraine headaches, with less frequent need for rescue medications. Published by Elsevier Inc.
Chiu, Chih-Wen; Lee, Tsung-Chieh; Hsu, Po-Chi; Chen, Chia-Yun; Chang, Shun-Chang; Chiang, John Y; Lo, Lun-Chien
2015-06-09
Dizziness and vertigo account for roughly 4% of chief symptoms in the emergency department (ED). Pharmacological therapy is often applied for these symptoms, such as vestibular suppressants, anti-emetics and benzodiazepines. However, every medication is accompanied with unavoidable side-effects. There are several research articles providing evidence of acupuncture treating dizziness and vertigo but few studies of acupuncture as an emergent intervention in ED. We performed a pilot cohort study to evaluate the efficacy and safety of acupuncture in treating patients with dizziness and vertigo in ED. A total of 60 participants, recruited in ED, were divided into acupuncture and control group. Life-threatening conditions or central nervous system disorders were excluded to ensure participants' safety. The clinical effect of treating dizziness and vertigo was evaluated by performing statistical analyses on data collected from questionnaires of Dizziness Handicap Inventory (DHI), Visual Analog Scale (VAS) of dizziness and vertigo, and heart rate variability (HRV). The variation of VAS demonstrated a significant decrease (p-value: 0.001 and p-value: 0.037) between two groups after two different durations: 30 mins and 7 days. The variation of DHI showed no significant difference after 7 days. HRV revealed a significant increase in high frequency (HF) in the acupuncture group. No adverse event was reported in this study. Acupuncture demonstrates a significant immediate effect in reducing discomforts and VAS of both dizziness and vertigo. This study provides clinical evidence on the efficacy and safety of acupuncture to treat dizziness and vertigo in the emergency department. ClinicalTrials.gov ID: NCT02358239 . Registered 5 February 2015.
[Vertigo and dizziness in the emergency room].
Zwergal, A; Möhwald, K; Dieterich, M
2017-06-01
Vertigo and dizziness are among the most common chief complaints in the emergency department. Etiologies can be categorized into three subgroups: neurootological (vestibular), medical (especially cardiovascular, metabolic), and psychiatric disorders. The diagnostic approach in the emergency department is based on a systematic analysis of case history (type, time course of symptoms, modulating factors, associated symptoms), clinical examination of the vestibular, ocular motor, and cerebellar systems (head impulse test, nystagmus, skew deviation, positioning maneuver, test of gait and stance), as well as a basal monitoring (vital signs, 12-lead ECG, blood tests). For differentiation of peripheral and central etiologies in acute vestibular syndrome, the HINTS exam (head impulse test, nystagmus, test of skew) and examination of smooth pursuit and saccades should be applied. Nonselective use of neuroimaging is not indicated due to a low diagnostic yield. Cranial imaging should be done in the following constellations: (1) detection of focal neurological or central ocular motor and vestibular signs on clinical exam, (2) acute abasia with only minor ocular motor signs, (3) presence of various cardiovascular risk factors, (4) headache of unknown quality as an accompanying symptom. Besides the symptomatic therapy of vertigo and dizziness with antiemetics or analgesics, further diagnostic differentiation is urgent to guide proper treatment. Examples are the acute therapy in cerebral ischemia, the execution of positioning maneuvers in benign paroxysmal positional vertigo, the use of corticosteroids in acute unilateral vestibulopathy, as well as the readjustment of metabolic homeostasis in medical disorders.
Therapeutic potential of monoacylglycerol lipase inhibitors.
Mulvihill, Melinda M; Nomura, Daniel K
2013-03-19
Marijuana and aspirin have been used for millennia to treat a wide range of maladies including pain and inflammation. Both cannabinoids, like marijuana, that exert anti-inflammatory action through stimulating cannabinoid receptors, and cyclooxygenase (COX) inhibitors, like aspirin, that suppress pro-inflammatory eicosanoid production have shown beneficial outcomes in mouse models of neurodegenerative diseases and cancer. Both cannabinoids and COX inhibitors, however, have untoward effects that discourage their chronic usage, including cognitive deficits and gastrointestinal toxicity, respectively. Recent studies have uncovered that the serine hydrolase monoacylglycerol lipase (MAGL) links the endocannabinoid and eicosanoid systems together through hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) to provide the major arachidonic acid (AA) precursor pools for pro-inflammatory eicosanoid synthesis in specific tissues. Studies in recent years have shown that MAGL inhibitors elicit anti-nociceptive, anxiolytic, and anti-emetic responses and attenuate precipitated withdrawal symptoms in addiction paradigms through enhancing endocannabinoid signaling. MAGL inhibitors have also been shown to exert anti-inflammatory action in the brain and protect against neurodegeneration through lowering eicosanoid production. In cancer, MAGL inhibitors have been shown to have anti-cancer properties not only through modulating the endocannabinoid-eicosanoid network, but also by controlling fatty acid release for the synthesis of protumorigenic signaling lipids. Thus, MAGL serves as a critical node in simultaneously coordinating multiple lipid signaling pathways in both physiological and disease contexts. This review will discuss the diverse (patho)physiological roles of MAGL and the therapeutic potential of MAGL inhibitors in treating a vast array of complex human diseases. Copyright © 2012 Elsevier Inc. All rights reserved.
Systemic lupus erythematosus pancreatitis: an uncommon presentation of a common disease.
Rodriguez, Eduardo A; Sussman, Daniel A; Rodriguez, Vanessa R
2014-11-17
Acute pancreatitis is uncommon in systemic lupus erythematosus (SLE). When recognized early and properly treated with IV steroids and hydration, the course may be benign, as exemplified in the following report. A 21-year-old woman with history of SLE and stage IV lupus nephritis, was admitted to the Sergio Bernales Hospital ICU (Lima, Peru), complaining of worsening epigastric pain radiating to the back, and nausea and vomiting for 1 week. She denied prior cholelithiasis, alcohol use, or recent medication changes. On examination, she was tachycardic and normotensive, with a slightly distended abdomen and epigastric tenderness on deep palpation, without signs of peritoneal irritation. Laboratory results demonstrated leukocytosis without left shift, creatinine of 2.26 mg/dL, amylase of 750 U/L, and lipase of 1038 U/L. Liver chemistries, calcium, lactic acid, triglycerides, and IgG4 were normal and alcohol level was undetectable. Ultrasound did not show cholelithiasis, biliary sludge, or common bile duct dilation. CT of the abdomen showed pancreas head (parenchyma) stranding with uniform enhancement consistent with interstitial pancreatitis. Despite receiving IV fluids, opiates, anti-emetics, and nothing by mouth, her clinical condition deteriorated, prompting the use of IV methylprednisolone. After completing 1 week of IV steroids, she was transferred to the medical floor clinically improved. The patient was discharged with an oral steroid taper and complete resolution of symptoms. After ruling out common causes, such as hepatobiliary pathology or toxin-related insults like alcohol, hypercalcemia, hypertriglyceridemia or medications, steroids may be used in SLE pancreatitis because they might improve the overall prognosis.
Devrim, Burcu; Dinç, Erdal; Bozkir, Asuman
2014-01-01
Diphenhydramine hydrochloride (DPH), a histamine H1-receptor antagonist, is widely used as antiallergic, antiemetic and antitussive drug found in many pharmaceutical preparations. In this study, a new reconstitutable syrup formulation of DPH was prepared because it is more stable in solid form than that in liquid form. The quantitative estimation of the DPH content of a reconstitutable syrup formulation in the presence of pharmaceutical excipients, D-sorbitol, sodium citrate, sodium benzoate and sodium EDTA is not possible by the direct absorbance measurement. Therefore, a signal processing approach based on continuous wavelet transform was used to determine the DPH in the reconstitutable syrup formulations and to eliminate the effect of excipients on the analysis. The absorption spectra of DPH in the range of 5.0-40.0 μg/mL were recorded between 200-300 nm. Various wavelet families were tested and Biorthogonal1.1 continuous wavelet transform (BIOR1.1-CWT) was found to be optimal signal processing family to get fast and desirable determination results and to overcome excipient interference effects. For a comparison of the experimental results obtained by partial least squares (PLS) and principal component regression (PCR) methods were applied to the quantitative prediction of DPH in the mentioned samples. The validity of the proposed BIOR1.1-CWT, PLS and PCR methods were achieved analyzing the prepared samples containing the mentioned excipients and using standard addition technique. It was observed that the proposed graphical and numerical approaches are suitable for the quantitative analysis of DPH in samples including excipients.
Pirat, Arash; Tuncay, Senay F; Torgay, Adnan; Candan, Selim; Arslan, Gulnaz
2005-11-01
In this study we compared the efficacy of orally disintegrating tablets (ODT) and IV ondansetron for preventing spinal morphine-induced pruritus and postoperative nausea and vomiting (PONV) in healthy young male patients. Patients who received bupivacaine with 0.20 mg morphine for spinal anesthesia were randomly assigned to the ODT group (ODT ondansetron 8 mg, n = 50), the IV group (4 mg ondansetron IV, n = 50), or the placebo group (n = 50). Each individual was assessed for pruritus, postoperative nausea and vomiting, and pain at 0, 2, 6, 12, 18, and 24 h after surgery using three distinct visual analog scales. The frequencies of postoperative nausea and vomiting and frequencies of requirement for rescue antiemetic and antipruritic were recorded. There were no significant differences among the three groups with respect to incidence or severity of PONV or postoperative pain visual analog scale scores. The incidences of pruritus in the ODT (56%) and IV (66%) groups were significantly different from that in the placebo group (86%) (P < 0.02 for both). Only the ODT group had significantly lower mean pruritus visual analog scale scores at 0, 2, 6, and 12 h postsurgery than the placebo group (P < 0.023 for all). The frequency of requirement for rescue antipruritic was significantly less in the ODT group than the placebo group (P = 0.013). Both ODT ondansetron 8 mg and IV ondansetron 4 mg are more effective than placebo for preventing spinal morphine-induced pruritus, but neither form of this agent reduces spinal morphine-induced postoperative nausea and vomiting in this patient group.
Chau, Destiny F; Reddy, Arundathi; Breheny, Patrick; Young, Anna Rebecca; Ashford, Eric; Song, Megan; Zhang, Christina; Taylor, Tammy; Younes, Abbas; Vazifedan, Turaj
2017-01-01
Background and Aims: Post-operative vomiting (POV) in children remains a significant clinical problem. This prospective study aims to investigate the applicability of well-established adult early post-operative nausea and vomiting (PONV) risk factors on paediatric POV after adenotonsillectomies under regulated anaesthetic conditions. Methods: After Institutional Review Board approval, 213 children aged 3–10-year-old were enrolled. The participants had pre-operative questionnaires completed, followed protocolised anaesthetic plans and had saliva analysed for cotinine. The primary outcomes were POV as correlated with age, gender, family or personal history of PONV, motion sickness history, opioid use, surgical time, anaesthetic time and environmental tobacco smoke (ETS) exposure, as assessed by cotinine levels and questionnaire reports. Data on analgesics, antiemetics and POV incidence before post-anaesthesia care unit discharge were collected. Statistical analysis was done through multiple logistic regression. Results: A total of 200 patients finalised the study. Early POV occurred in 32%. Family history of PONV (odds ratio [OR] = 5.3, P < 0.01) and motion sickness history (OR = 4.4, P = 0.02) were highly significant risk factors. Age reached borderline statistical significance (OR = 1.4, P = 0.05). None of the other factors reached statistical significance. Conclusion: Early POV occurs frequently in paediatric patients undergoing adenotonsillectomies. In this paediatric-aged group, the incidence of POV was affected by the family history of PONV, and history of motion sickness. Age, female gender, opioid use, surgical and anaesthetic times did not affect the incidence of POV. ETS exposure, as assessed by cotinine levels and questionnaire reports, had no protective effect on early paediatric POV. PMID:29307901
OnabotulinumtoxinA Injections for the Treatment of Cyclic Vomiting Syndrome.
Hayes, William J; Weisensee, Laurie A; Kappes, John A; Dalton, Shawn M; Lemon, Michael D
2015-05-01
Cyclic vomiting syndrome (CVS) is a disorder characterized by episodes of nausea and vomiting lasting 1 to 5 days, followed by asymptomatic periods. The etiology and pathophysiology of CVS are unknown, but CVS shares similar characteristics to those of migraine headaches. Tricyclic antidepressants have the most evidence and are generally effective for prophylaxis of further episodes in patients with CVS. Second-line pharmacotherapies typically target specific comorbid symptoms or conditions and may include antiepileptic or antimigraine drugs, benzodiazepines, antispasmodics, proton pump inhibitors, antiemetics, and analgesics. OnabotulinumtoxinA (ONABoNT-A) injections have not been studied in the population with CVS but are regarded as a pharmacotherapeutic option for migraine headaches. We describe a 45-year-old woman with a 5-year history of CVS who had failed previous typical prophylactic migraine and CVS pharmacotherapies and was referred to the neurology clinic for management of both of these conditions. On review, the neurologist noted a correlation of the patient's headaches with her CVS symptoms. ONABoNT-A injections were started at 155 units intramuscularly every 12 weeks for her migraine headaches, which also dramatically improved her CVS. The main adverse effect reported by the patient was numbness and weakness in her left shoulder after the injections, which are symptoms consistent with ONABoNT-A injection use; however, these symptoms typically resolved a few days later. Regarded as a pharmacotherapeutic option for migraine headache prophylaxis, ONABoNT-A injections have demonstrated modest efficacy in preventing migraine headaches. Clinicians should be aware that ONABoNT-A injections may also have a role in the prophylaxis of CVS. © 2015 Pharmacotherapy Publications, Inc.
2012-01-01
Background Despite its high incidence among children under the age of five, little is known about the burden of pediatric gastroenteritis outside the medical setting. The objective of this study was to describe the burden of acute gastroenteritis among children residing in the United Arab Emirates, including those not receiving medical care. Methods A quantitative cross-sectional survey of 500 parents of children under 5 years of age who had suffered from acute gastroenteritis the preceding three months was conducted in the cities of Abu Dhabi and Al Ain. Data collected included respondent characteristics, disease symptoms, medical care sought, and parental expenditures and work loss. Data were analyzed using parametric and non-parametric statistical methods. Results Vomiting and diarrhea episodes lasted on average between 3 and 4 days. Overall, 87% of parents sought medical care for their children; 10% of these cases required hospitalization with an average length of stay of 2.6 days. When medical care was sought, the average parental cost per gastroenteritis episode was US$64, 4.5 times higher than with home care only (US$14). Nearly 60% of this difference was attributable to co-payments and medication use: 69% of children used oral rehydration solution, 68% antiemetics, 65% antibiotics and 64% antidiarrheals. Overall, 38 parents missed work per 100 gastroenteritis episodes for an average of 1.4 days. Conclusions Given its high incidence, pediatric gastroenteritis has an important financial and productivity impact on parents in the United Arab Emirates. To reduce this impact, efforts should be made both to prevent acute gastroenteritis and to optimize its treatment. PMID:22708988
Morimoto, Yoshihito; Takei, Hidefumi; Tachibana, Keisei; Nakazato, Yoko; Tanaka, Ryota; Nagashima, Yasushi; Watanabe, Kazuhiro; Seki, Reisuke; Shinohara, Takao; Kondo, Haruhiko
2018-01-01
Adjuvant cisplatin-vinorelbine chemotherapy has been shown to be effective in patients with completely resected non-small cell lung cancer (NSCLC) in several Phase III trials, but not yet in the Japanese population. Pharmacists are expected to assist patients with completion of adjuvant chemotherapy. The aim of this retrospective study was to evaluate the compliance with and safety of adjuvant cisplatin-vinorelbine chemotherapy in Japanese patients and to evaluate the contribution of pharmacists to completion of treatment. Thirty-four patients with NSCLC who received adjuvant cisplatin-vinorelbine chemotherapy at Kyorin University Hospital between January 2006 and June 2015 were reviewed. The treatment schedule comprised cisplatin 80 mg/m 2 on day 1 and vinorelbine 25 mg/m 2 on days 1 and 8 every 3 weeks. Four 3-week cycles were planned. A pharmacist provided guidance to all patients and monitored them for adverse effects thereafter. The pharmacist intervened with advice to doctors as necessary. The 4 cycles were administered in 67.6% of cases. There were no treatment-related deaths. The main grade 3 or 4 toxicities were neutropenia (76.5%) and anorexia (38.2%). The most common reason for discontinuation and dose reduction was anorexia. There were 56 instances of pharmacist intervention. In total, 96.4% of the pharmacist interventions were implemented by doctors, which included administration of an antiemetic on 15 occasions and hot fomentation for prevention of vasculitis on 7 occasions. Adjuvant cisplatin-vinorelbine chemotherapy was tolerated by most patients but was discontinued because of adverse events in some. Pharmacist intervention aids completion of planned chemotherapy and management of treatment-related adverse events.
New Onset Migraine Associated With a Civilian Burn Pit.
Chalela, Julio A
2017-05-01
Deployed service members exposed to burn pit smoke can experience a multitude of symptoms. Respiratory symptoms after burn pit smoke exposure are well recognized, but neurologic symptoms are less well recognized. There are reports of migraines triggered by odors but no specific reports of new onset migraines triggered by exposure to burn pit smoke. Clinicians encountering patients with new onset migraines in the deployed setting face the dilemma of evacuating the patients to perform neuroimaging or keeping them in theatre. Retrospective case series study and review of the literature. Three patients with new onset headache after exposure to open burn pit smoke are described. The headaches met established criteria to be classified as migraine with aura in two patients and migraine without aura in one patient. The migraines were triggered by exposure to the burn pit smoke and relieved by avoidance of the smoke. The patients did not have history of migraine and had normal neurological examinations. Computed tomography performed in one patient and optic nerve insonation performed in all three patients were normal. The patients responded well to triptans and antiemetic medicines. Nociceptive odors can trigger classic migraines in adults without prior history of migraine. The temporal association between exposure to the odor and the development of the headache, the absence of abnormalities on neurologic examination, and the response to triptans help establish the diagnosis. Activation of the trigeminal system leading to release of pain-related neuropeptides may mediate the migrainous symptoms. Evacuation for advanced neuroimaging or specialized consultation can be avoided if the above-mentioned criteria are met. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.
Fast-track surgery for uncomplicated appendicitis in children: a matched case-control study.
Cundy, Thomas P; Sierakowski, Kyra; Manna, Alexandra; Cooper, Celia M; Burgoyne, Laura L; Khurana, Sanjeev
2017-04-01
Standardized post-operative protocols reduce variation and enhance efficiency in patient care. Patients may benefit from these initiatives by improved quality of care. This matched case-control study investigates the effect of a multidisciplinary criteria-led discharge protocol for uncomplicated appendicitis in children. Key protocol components included limiting post-operative antibiotics to two intravenous doses, avoidance of intravenous opioid analgesia, prompt resumption of diet, active encouragement of early ambulation and nursing staff autonomy to discharge patients that met assigned criteria. The study period was from August 2015 to February 2016. Outcomes were compared with a historical control group matched for operative approach. Outcomes for 83 patients enrolled to our protocol were compared with those of 83 controls. There was a 29.2% reduction in median post-operative length of stay in our protocol-based care group (19.6 versus 27.7 h; P < 0.001). The rate of discharges within 24 h improved from 12 to 42%. There was no significant difference in complication rate (4.8 versus 7.2%; P = 0.51). Mean oral morphine dose equivalent per kilogram requirement was less than half (46%) that of control group patients (P < 0.001). Mean number of ondansetron doses was also significantly lower. Projected annual direct cost savings following protocol implementation was AUD$77 057. Implementation of a criteria-led discharge protocol at our hospital decreased length of stay, reduced variation in care, preserved existing low morbidity, incurred substantial cost savings, and safely rationalized opioid and antiemetic medication. These protocols are inexpensive and offer tangible benefits that are accessible to all health care settings. © 2016 Royal Australasian College of Surgeons.
Prevention and treatment of the gastric symptoms of radiation sickness
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dubois, A.; Fiala, N.; Boward, C.A.
1988-09-01
Currently available treatments for radiation-induced nausea and vomiting either are ineffective or reduce performance. The new antiemetic and gastrokinetic agent zacopride was tested in rhesus monkeys to assess its behavioral toxicity and its ability to inhibit radiation-induced emesis. Zacopride (intragastric, 0.3 mg/kg) or a placebo was given blindly and randomly in the basal state and 15 min before a whole-body 800 cGy 60Co gamma-radiation dose (except for the legs which were partially protected to permit survival of some bone marrow). We determined (1) gastric emptying rates; (2) the presence and frequency of retching and vomiting; and (3) the effect ofmore » zacopride on the performance of a visual discrimination task in nonirradiated subjects. No vomiting, retching, or decreased performance was observed after either placebo or zacopride in the control state. Following irradiation plus placebo, 70 emeses were observed in 5 of 6 monkeys, and 353 retches were observed in all 6 monkeys. In contrast, only 1 emesis was observed in 1 of 6 monkeys and 173 retches were seen in 4 of 6 monkeys after irradiation plus zacopride (P less than 0.01). Zacopride also significantly inhibited radiation-induced suppression of gastric emptying. When given after the first vomiting episode in a separate group of irradiated monkeys, zacopride completely prevented any subsequent vomiting. The present results demonstrate that intragastric administration of zacopride significantly inhibited radiation-induced retching, vomiting, and suppression of gastric emptying in rhesus monkeys and did not cause detectable behavioral side effects when given to nonradiated monkeys. This observation has important implications in the treatment of radiation sickness.« less
Chowdhary, Rajani; Pai, Roopa S; Singh, Gurinder
2013-01-01
Introduction: The present investigation was to develop a polypill of 6-mercaptopurine and metoclopramide. A polypill with delayed release granules of an anticancer and immediate release mucoadhesive tablet of antiemetic may result in the reduction of emesis caused by oral chemotherapy. Materials and Methods: 6-Mercaptopurine granules were prepared by wet granulation process. Chitosan, hydroxypropyl methylcellulose, and ethylcellulose were used as individually as delayed release polymers. Seven granule formulations (F1-F7) were prepared and evaluated for flow properties and drug content. Immediate release mucoadhesive tablets of metoclopramide were prepared by direct compression technique using pectin and PVPK-40 as mucoadhesive polymers. Three formulations of pectin (L1-L3) and three formulations of PVPK40 (M1-M3) were prepared using lactose, magnesium stearate, and mannitol and talc as diluent and glidant, respectively. Tablets were evaluated for weight variation, hardness, friability, drug content, ex vivo mucoadhesion time, and in vitro dissolution studies. Results: Formulation F2, F4, F5, and F7 showed maximum drug content. Formulation F7 exhibited the drug release up to 2 h and was selected as the best delayed release formulation. All formulations of metoclopramide showed good drug content ranging from 97.6 % to 100.6%. Formulation M2 among tablets prepared with PVP exhibited desired mucoadhesion time of 15.33 min which prolongs the duration of drug release in gastric pouch of the male Wistar rats. Both the selected formulations F7 and M2 were filled into body of capsule size 0 and capsule was evaluated for technological properties. Conclusion: It may be concluded that polypill released the metoclopramide immediately prior to 6-mercaptopurine. PMID:24350042
Evaluation of anticonvulsant and nootropic effect of ondansetron in mice.
Jain, S; Agarwal, N B; Mediratta, P K; Sharma, K K
2012-09-01
The role of serotonin receptors have been implicated in various types of experimentally induced seizures. Ondansetron is a highly selective 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonist used as antiemetic agent for chemotherapy-, and radiotherapy-induced nausea and vomiting. The present study was carried out to examine the effect of ondansetron on electroshock, pentylenetetrazole (PTZ)-induced seizures and cognitive functions in mice. Ondansetron was administered intraperitoneally (i.p.) at doses of 0.5, 1.0 and 2.0 mg/kg (single dose) to observe its effect on the increasing current electroshock seizure (ICES) test and PTZ-induced seizure test. In addition, a chronic study (21 days) was also performed to assess the effects of ondansetron on electroshock-induced convulsions and cognitive functions. The effect on cognition was assessed by elevated plus maze and passive avoidance paradigms. Phenytoin (25 mg/kg, i.p.) was used as a standard anticonvulsant drug and piracetam (200 mg/kg) was administered as a standard nootropic drug. The results were compared with an acute study, wherein it was found that the administration of ondansetron (1.0 and 2.0 mg/kg) significantly raised the seizure-threshold current as compared to control group in the ICES test. Similar results were observed after chronic administration of ondansetron. In PTZ test, ondansetron in all the three tested doses failed to show protective effect against PTZ-induced seizure test. Administration of ondansetron for 21 days significantly decreased the transfer latency (TL) and prolonged the step-down latency (SDL). The results of present study suggest the anticonvulsant and memory-enhancing effect of ondansetron in mice.
Oral hygiene products and acidic medicines.
Hellwig, E; Lussi, A
2006-01-01
Acidic or EDTA-containing oral hygiene products and acidic medicines have the potential to soften dental hard tissues. The low pH of oral care products increases the chemical stability of some fluoride compounds, favors the incorporation of fluoride ions in the lattice of hydroxyapatite and the precipitation of calcium fluoride on the tooth surface. This layer has some protective effect against an erosive attack. However, when the pH is too low or when no fluoride is present these protecting effects are replaced by direct softening of the tooth surface. Xerostomia or oral dryness can occur as a consequence of medication such as tranquilizers, anti-histamines, anti-emetics and anti-parkinsonian medicaments or of salivary gland dysfunction e.g. due to radiotherapy of the oral cavity and the head and neck region. Above all, these patients should be aware of the potential demineralization effects of oral hygiene products with low pH and high titratable acids. Acetyl salicylic acid taken regularly in the form of multiple chewable tablets or in the form of headache powder as well chewing hydrochloric acids tablets for treatment of stomach disorders can cause erosion. There is most probably no direct association between asthmatic drugs and erosion on the population level. Consumers, patients and health professionals should be aware of the potential of tooth damage not only by oral hygiene products and salivary substitutes but also by chewable and effervescent tablets. Additionally, it can be assumed that patients suffering from xerostomia should be aware of the potential effects of oral hygiene products with low pH and high titratable acids.
Pharmacokinetics and repolarization effects of intravenous and transdermal granisetron.
Mason, Jay W; Selness, Daniel S; Moon, Thomas E; O'Mahony, Bridget; Donachie, Peter; Howell, Julian
2012-05-15
The need for greater clarity about the effects of 5-HT(3) receptor antagonists on cardiac repolarization is apparent in the changing product labeling across this therapeutic class. This study assessed the repolarization effects of granisetron, a 5-HT(3) receptor antagonist antiemetic, administered intravenously and by a granisetron transdermal system (GTDS). In a parallel four-arm study, healthy subjects were randomized to receive intravenous granisetron, GTDS, placebo, or oral moxifloxacin (active control). The primary endpoint was difference in change from baseline in mean Fridericia-corrected QT interval (QTcF) between GTDS and placebo (ddQTcF) on days 3 and 5. A total of 240 subjects were enrolled, 60 in each group. Adequate sensitivity for detection of QTc change was shown by a 5.75 ms lower bound of the 90% confidence interval (CI) for moxifloxacin versus placebo at 2 hours postdose on day 3. Day 3 ddQTcF values varied between 0.2 and 1.9 ms for GTDS (maximum upper bound of 90% CI, 6.88 ms), between -1.2 and 1.6 ms for i.v. granisetron (maximum upper bound of 90% CI, 5.86 ms), and between -3.4 and 4.7 ms for moxifloxacin (maximum upper bound of 90% CI, 13.45 ms). Day 5 findings were similar. Pharmacokinetic-ddQTcF modeling showed a minimally positive slope of 0.157 ms/(ng/mL), but a very low correlation (r = 0.090). GTDS was not associated with statistically or clinically significant effects on QTcF or other electrocardiographic variables. This study provides useful clarification on the effect of granisetron delivered by GTDS on cardiac repolarization. ©2012 AACR.
Kitayama, Hiromitsu; Tsuji, Yasushi; Sugiyama, Junko; Doi, Ayako; Kondo, Tomohiro; Hirayama, Michiaki
2015-12-01
Although palonosetron (PALO) and NK1 receptor antagonist both reduce chemotherapy-induced nausea and vomiting, no comparison trial in moderately emetogenic chemotherapy (MEC) had been reported. The purpose of this study was to find out which drug combinations are preferable for patients receiving MEC. Chemotherapy-naive patients receiving MEC were randomized to two groups; group A first received PALO therapy [PALO plus 1-day dexamethasone (DEX)], and group B first received fosaprepitant (FAPR) therapy [FAPR, granisetron (GRAN), and DEX]. Patients were re-allocated to the other therapy, respectively, for the second cycle of chemotherapy. We administered intravenous PALO (0.75 mg) and DEX (9.9 mg) to the PALO therapy group, and FAPR (150 mg), DEX (4.95 mg), and GRAN (3 mg) to the FAPR therapy group, on Day 1. Complete response (CR) was the primary endpoint; complete control (CC), total control (CT), and the therapy chosen by the patients for their third and following cycles of antiemetic therapy were the secondary endpoints. We evaluated CR, CC, and TC in the acute phase, in the delayed phase, and over the whole period. A total of 35 patients and 70 cycles of therapy was evaluable for analysis. No significant difference was found at all evaluation points. Overall CR rates for PALO and FAPR therapy were 74 vs 69 % (P = 0.567), CC rates 66 vs 69 % (P = 0.521), and TC rates 46 vs 60 % (P = 0.235), respectively. Patients also showed no clear preference for their third and following cycles of chemotherapy, choosing both regimens almost equally often (PALO 10 vs FAPR 13). PALO and 1-day DEX is almost equivalent to FAPR, GRAN, and DEX for MEC.
Mu, Linjing; Müller Herde, Adrienne; Rüefli, Pascal M; Sladojevich, Filippo; Milicevic Sephton, Selena; Krämer, Stefanie D; Thompson, Andrew J; Schibli, Roger; Ametamey, Simon M; Lochner, Martin
2016-11-16
Serotonin-gated ionotropic 5-HT 3 receptors are the major pharmacological targets for antiemetic compounds. Furthermore, they have become a focus for the treatment of irritable bowel syndrome (IBS) and there is some evidence that pharmacological modulation of 5-HT 3 receptors might alleviate symptoms of other neurological disorders. Highly selective, high-affinity antagonists, such as granisetron (Kytril) and palonosetron (Aloxi), belong to a family of drugs (the "setrons") that are well established for clinical use. To enable us to better understand the actions of these drugs in vivo, we report the synthesis of 8-fluoropalonosetron (15) that has a binding affinity (K i = 0.26 ± 0.05 nM) similar to the parent drug (K i = 0.21 ± 0.03 nM). We radiolabeled 15 by nucleophilic 18 F-fluorination of an unsymmetrical diaryliodonium palonosetron precursor and achieved the radiosynthesis of 1-(methyl- 11 C)-N-granisetron ([ 11 C]2) through N-alkylation with [ 11 C]CH 3 I, respectively. Both compounds [ 18 F]15 (chemical and radiochemical purity >95%, specific activity 41 GBq/μmol) and [ 11 C]2 (chemical and radiochemical purity ≥99%, specific activity 170 GBq/μmol) were evaluated for their utility as positron emission tomography (PET) probes. Using mouse and rat brain slices, in vitro autoradiography with both [ 18 F]15 and [ 11 C]2 revealed a heterogeneous and displaceable binding in cortical and hippocampal regions that are known to express 5-HT 3 receptors at significant levels. Subsequent PET experiments suggested that [ 18 F]15 and [ 11 C]2 are of limited utility for the PET imaging of brain 5-HT 3 receptors in vivo.
Treating nausea and vomiting in palliative care: a review
Glare, Paul; Miller, Jeanna; Nikolova, Tanya; Tickoo, Roma
2011-01-01
Nausea and vomiting are portrayed in the specialist palliative care literature as common and distressing symptoms affecting the majority of patients with advanced cancer and other life-limiting illnesses. However, recent surveys indicate that these symptoms may be less common and bothersome than has previously been reported. The standard palliative care approach to the assessment and treatment of nausea and vomiting is based on determining the cause and then relating this back to the “emetic pathway” before prescribing drugs such as dopamine antagonists, antihistamines, and anticholinergic agents which block neurotransmitters at different sites along the pathway. However, the evidence base for the effectiveness of this approach is meager, and may be in part because relevance of the neuropharmacology of the emetic pathway to palliative care patients is limited. Many palliative care patients are over the age of 65 years, making these agents difficult to use. Greater awareness of drug interactions and QTc prolongation are emerging concerns for all age groups. The selective serotonin receptor antagonists are the safest antiemetics, but are not used first-line in many countries because there is very little scientific rationale or clinical evidence to support their use outside the licensed indications. Cannabinoids may have an increasing role. Advances in interventional gastroenterology are increasing the options for nonpharmacological management. Despite these emerging issues, the approach to nausea and vomiting developed within palliative medicine over the past 40 years remains relevant. It advocates careful clinical evaluation of the symptom and the person suffering it, and an understanding of the clinical pharmacology of medicines that are available for palliating them. PMID:21966219
Assessment of Hospital Pharmacy Preparedness for Mass Casualty Events
Awad, Nadia I.; Cocchio, Craig
2015-01-01
Objectives: To assess the preparedness of hospital pharmacies in New Jersey to provide pharmaceutical services in mass casualty scenarios. Methods: An electronic cross-sectional survey was developed to assess the general knowledge of available resources and attitudes toward the preparedness of the pharmacy department. Results: Out of 60 invitations to participate, 18 surveys (30%) were completed. Respondents practiced at community hospitals (12, 66.6%) with no trauma center designation (11, 67.4%) that served more than 500 licensed beds (five, 29.4%). Six respondents (35.3%) indicated that 75,000 to 100,000 patients visited their emergency departments annually. Seventeen sites (94.4%) reported the existence of an institutional disaster preparedness protocol; 10 (55.5%) indicated that there is a specific plan for the pharmacy department. Most respondents (10, 55.5%) were unsure whether their hospitals had an adequate supply of analgesics, rapid sequence intubation agents, vasopressors, antiemetics, respiratory medications, ophthalmics, oral antimicrobials, and chemical-weapon-specific antidotes. Five (27.7%) agreed that the pharmacy disaster plan included processes to ensure care for patients already hospitalized, and four (22.2%) agreed that the quantity of medication was adequate to treat patients and hospital employees if necessary. Medication stock and quantities were determined based on national or international guidelines at three (16.6%) institutions surveyed. Conclusion: This survey demonstrates a lack of general consensus regarding hospital pharmacy preparedness for mass casualty scenarios despite individualized institutional protocols for disaster preparedness. Standardized recommendations from government and/or professional pharmacy organizations should be developed to guide the preparation of hospital pharmacy departments for mass casualty scenarios. PMID:25859121
Lam, Annie; Kiyak, Asuman; Gossett, Allison M; McCormick, Lawrence
2009-10-01
To describe the health conditions, dental problems, and use of xerogenic medications among dental patients in adult day health (ADH) centers. Cross-sectional descriptive study. ADH centers in King County, Washington. ADH clients who were patients of a mobile dental service. Pharmacist-conducted chart reviews and in-person medication reviews with patients. Demographic description, mean numbers of medical and dental problems, medications, xerogenic medications used per subject, and identification of xerogenic medications by therapeutic class. At five sites, 97 patients were interviewed (average age 73.8 +/- 11.8 years, 61% female); ethnicities included: Asian-American (37.1%), Caucasian (30.9%), Russian (29%), and African-American (3%). Mean numbers of chronic health problems, medications, and xerogenic medications per patient were 5.2 +/- 2.7, 10.9 +/- 4.4, and 3.3 +/- 1.8, respectively. Antidepressants were the most commonly used xerogenic medication, followed by antipsychotics, antiemetics, analgesics, and antihistamines. Among 74 patients who received dental treatment, 33 (44.6%) wore dentures. Among 58 patients with teeth, a mean number of 2.8 dental problems per patient was identified. Dental caries (51.7%) was the most prevalent problem, followed by periodontitis (29.3%), soft tissue lesions (10.3%), gingivitis (5.2%), and candidiasis (3.4%). Multiple systemic diseases, use of multiple xerogenic medications, and poor oral health were prevalent among the ADH clients in this study. However, self-reports of dry mouth were unrelated to number of xerogenic medications or oral conditions. Further research is needed to determine the association between self-reported dry mouth, chronic health conditions, use of xerogenic medications, tooth loss, and/or denture use.
Fernández-Ruiz, Javier; Sagredo, Onintza; Pazos, M Ruth; García, Concepción; Pertwee, Roger; Mechoulam, Raphael; Martínez-Orgado, José
2013-01-01
Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ9-tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ9-tetrahydrocannabinol, i.e. CB1 and CB2 receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB2 receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels. PMID:22625422
2013-01-01
Background Levomepromazine is an antipsychotic drug that is used clinically for a variety of distressing symptoms in palliative and end-of-life care. We undertook a systematic review based on the question “What is the published evidence for the use of levomepromazine in palliative symptom control?”. Methods To determine the level of evidence for the use of levomepromazine in palliative symptom control, and to discover gaps in evidence, relevant studies were identified using a detailed, multi-step search strategy. Emerging data was then scrutinized using appropriate assessment tools, and the strength of evidence systematically graded in accordance with the Oxford Centre for Evidence-Based Medicine’s ‘levels of evidence’ tool. The electronic databases Medline, Embase, Cochrane, PsychInfo and Ovid Nursing, together with hand-searching and cross-referencing provided the full research platform on which the review is based. Results 33 articles including 9 systematic reviews met the inclusion criteria: 15 on palliative sedation, 8 regarding nausea and three on delirium and restlessness, one on pain and six with other foci. The studies varied greatly in both design and sample size. Levels of evidence ranged from level 2b to level 5, with the majority being level 3 (non-randomized, non-consecutive or cohort studies n = 22), with the quality of reporting for the included studies being only low to medium. Conclusion Levomepromazine is widely used in palliative care as antipsychotic, anxiolytic, antiemetic and sedative drug. However, the supporting evidence is limited to open series and case reports. Thus prospective randomized trials are needed to support evidence-based guidelines. PMID:23331515
das Dores Graciano Silva, Maria; Martins, Maria Auxiliadora Parreiras; de Gouvêa Viana, Luciana; Passaglia, Luiz Guilherme; de Menezes, Renata Rezende; de Queiroz Oliveira, João Antonio; da Silva, Jose Luiz Padilha; Ribeiro, Antonio Luiz Pinho
2018-06-06
Adverse drug events (ADEs) can seriously compromise the safety and quality of care provided to hospitalized patients, requiring the adoption of accurate methods to monitor them. We sought to prospectively evaluate the accuracy of the triggers proposed by the Institute for Healthcare Improvement (IHI) for identifying ADEs. A prospective study was conducted in a public university hospital, in 2015, with patients ≥18 years. Triggers proposed by IHI and clinical alterations suspected to be ADEs were searched daily. The number of days in which the patient was hospitalized was considered as unit of measure to evaluate the accuracy of each trigger. Three hundred patients were included in this study. Mean age was 56.3 years (standard deviation (SD) 16.0), and 154 (51.3%) were female. The frequency of patients with ADEs was 24.7% and with at least one trigger was 53.3%. From those patients who had at least one trigger, the most frequent triggers were antiemetics (57.5%) and "abrupt medication stop" (31.8%). Triggers' sensitivity ranged from 0.3 to11.8 % and the positive predictive value ranged from 1.2 to 27.3%. Specificity and negative predictive value were greater than 86%. Most patients identified by the presence of triggers did not have ADEs (64.4%). No triggers were identified in 40 (38.5%) ADEs. IHI Trigger Tool did not show good accuracy in detecting ADEs in this prospective study. The adoption of combined strategies could enhance effectiveness in identifying patient safety flaws. Further discussion might contribute to improve trigger usefulness in clinical practice. This article is protected by copyright. All rights reserved.
Update on the chemopreventive effects of ginger and its phytochemicals.
Baliga, Manjeshwar Shrinath; Haniadka, Raghavendra; Pereira, Manisha Maria; D'Souza, Jason Jerome; Pallaty, Princy Louis; Bhat, Harshith P; Popuri, Sandhya
2011-07-01
The rhizomes of Zingiber officinale Roscoe (Zingiberaceae), commonly known as ginger, is one of the most widely used spice and condiment. It is also an integral part of many traditional medicines and has been extensively used in Chinese, Ayurvedic, Tibb-Unani, Srilankan, Arabic, and African traditional medicines, since antiquity, for many unrelated human ailments including common colds, fever, sore throats, vomiting, motion sickness, gastrointestinal complications, indigestion, constipation, arthritis, rheumatism, sprains, muscular aches, pains, cramps, hypertension, dementia, fever, infectious diseases, and helminthiasis. The putative active compounds are nonvolatile pungent principles, namely gingerols, shogaols, paradols, and zingerone. These compounds are some of the extensively studied phytochemicals and account for the antioxidant, anti-inflammatory, antiemetic, and gastroprotective activities. A number of preclinical investigations with a wide variety of assay systems and carcinogens have shown that ginger and its compounds possess chemopreventive and antineoplastic effects. A number of mechanisms have been observed to be involved in the chemopreventive effects of ginger. The cancer preventive activities of ginger are supposed to be mainly due to free radical scavenging, antioxidant pathways, alteration of gene expressions, and induction of apoptosis, all of which contribute towards decrease in tumor initiation, promotion, and progression. This review provides concise information from preclinical studies with both cell culture models and relevant animal studies by focusing on the mechanisms responsible for the chemopreventive action. The conclusion describes directions for future research to establish its activity and utility as a human cancer preventive and therapeutic drug. The above-mentioned mechanisms of ginger seem to be promising for cancer prevention; however, further clinical studies are warranted to assess the efficacy and safety of ginger.
Bielefeldt, Klaus
2014-06-01
Dyspeptic symptoms are common with most patients suffering functional disorders that remain a therapeutic challenge for medical practitioners. Within the last three decades, gastric infection, altered motility, and hypersensitivity have gained and lost traction in explaining the development of functional dyspepsia. Considering these shifts, the aim of this review was to analyze changing understanding of and approaches to dyspepsia over a longer time period. Monographs, textbooks, and articles published during the last three centuries show that our understanding of normal gastric function has improved dramatically. With increased insight came new ideas about disease mechanisms, diagnostic options, and treatments. Despite shifts over time, the importance of functional abnormalities was recognized early on and explained in the context of societal influences and stressors, anxieties, and biological influences, thus resembling the contemporary biopsychosocial model of illness. Symptoms were often attributed to changes in secretion, motility, and sensation or perception with technological innovation often influencing proposed mechanisms and treatments. Many of the principles or even agents applied more than a century ago are still part of today's approach. This includes acid suppression, antiemetics, analgesics, and even non-pharmacologic therapies, such as gastric decompression or electrical stimulation of the stomach. This historical information does not only help us understand how we arrived at our current state of knowledge and standards of care, it also demonstrates that enthusiastic adoption of various competing explanatory models and the resulting treatments often did not survive the test of time. In view of the benign prognosis of dyspepsia, the data may function as a call for caution to avoid the potential harm of overly aggressive approaches or treatments with a high likelihood of adverse effects.
Spoletini, G; Kennedy, M; Flint, L; Graham, T; Etherington, C; Shaw, N; Whitaker, P; Denton, M; Clifton, I; Peckham, D
2018-04-13
The increased prevalence of multi-drug resistant strains of P.aeruginosa and allergic reactions among adult patients with cystic fibrosis (CF) limits the number of antibiotics available to treat pulmonary exacerbations. Fosfomycin, a unique broad spectrum bactericidal antibiotic, might offer an alternative therapeutic option in such cases. To describe the clinical efficacy, safety and tolerability of intravenous fosfomycin in combination with a second anti-pseudomonal antibiotic to treat pulmonary exacerbations in adult patients with CF. A retrospective analysis of data captured prospectively, over a 2-years period, on the Unit electronic medical records for patients who received IV fosfomycin was performed. Baseline characteristics in the 12 months prior treatment, lung function, CRP, renal and liver function and electrolytes at start and end of treatment were retrieved. 54 patients received 128 courses of iv fosfomycin in combination with a second antibiotic, resulting in improved FEV1 (0.94 L vs 1.24 L, p < 0.01) and reduced CRP (65 mg/L vs 19.3 mg/L, p < 0.01). Renal function pre- and post-treatment remained stable. 4% (n = 5) of courses were complicated with AKI at mid treatment, which resolved at the end of the course. Electrolyte supplementation was required in 18% of cases for potassium and magnesium and 7% for phosphate. Nausea was the most common side effects (48%), but was well controlled with anti-emetics. Antibiotic regimens including fosfomycin appear to be clinically effective and safe. Fosfomycin should, therefore, be considered as an add-on therapy in patients who failed to respond to initial treatment and with multiple drug allergies. Copyright © 2018. Published by Elsevier Ltd.
Malaviya, Anand Narayan
2017-02-01
The aim of this study was to investigate the effect of caffeine on the symptoms of methotrexate (MTX) intolerance in patients with RA. The follow-up patients with RA seen over a period of 11 months were included in this work. The degree of MTX intolerance, if present, was classified as 'moderate' and 'severe'. Those with intolerance were advised caffeine (coffee or dark chocolate) synchronised with the MTX dose. The effect was assessed as 'very good', 'good' or 'none'. Among 855 patients seen during this period, 313 (36.6 %) did not have any MTX intolerance, 542 (63.4 %) patients had some degree of MTX intolerance, 422 (77.8 %; 49.3 % of the total patients) had 'minimal' intolerance not requiring any intervention. The remaining 120 (22.1 %) of the 542 (14 % of the total 855) patients had 'moderate' or 'severe' MTX intolerance. Among these, 55 % had complete relief of symptoms and were able to continue taking the advised dose of MTX; 13.3 % had partial improvement and continued taking MTX but only with antiemetics; 7.5 % were minimally better but were somehow managing; 10 % were complete caffeine failure without any relief; 14.2 % did not like caffeine (coffee or dark chocolate) and did not want to take it. Caffeine relieved the symptoms of MTX intolerance in 55 % and partial relief in 13 % of the patients. A significant number of patients did not like to take caffeine (coffee or dark chocolate). It is of note that northern part of India is primarily a tea-drinking population where coffee is not a favourite drink.
Optimal management of severe nausea and vomiting in migraine: improving patient outcomes
Láinez, Miguel JA; García-Casado, Ana; Gascón, Francisco
2013-01-01
Migraine is a common and potentially disabling disorder for patients, with wide-reaching implications for health care services, society, and the economy. Nausea and vomiting during migraine attacks are common symptoms that affect at least 60% of patients suffering from migraines. These symptoms are often more disabling than the headache itself, causing a great burden on the patient’s life. Nausea and vomiting may delay the use of oral abortive medication or interfere with oral drug absorption. Therefore, they can hinder significantly the management and treatment of migraine (which is usually given orally). The main treatment of pain-associated symptoms of migraine (such as nausea and vomiting) is to stop the migraine attack itself as soon as possible, with the effective drugs at the effective doses, seeking if necessary alternative routes of administration. In some cases, intravenous antiemetic drugs are able to relieve a migraine attack and associated symptoms like nausea and vomiting. We performed an exhaustive PubMed search of the English literature to find studies about management of migraine and its associated symptoms. Search terms were migraine, nausea, and vomiting. We did not limit our search to a specific time period. We focused on clinical efficacy and tolerance of the various drugs and procedures based on data from human studies. We included the best available studies for each discussed drug or procedure. These ranged from randomized controlled trials for some treatments to small case series for others. Recently updated books and manuals on neurology and headache were also consulted. We herein review the efficacy of the different approaches in order to manage nausea and vomiting for migraine patents. PMID:24143125
Assessing national provision of care: variability in bariatric clinical care pathways.
Telem, Dana A; Majid, Saniea F; Powers, Kinga; DeMaria, Eric; Morton, John; Jones, Daniel B
2017-02-01
The American Society for Metabolic and Bariatric Surgery (ASMBS) Quality Improvement and Patient Safety (QIPS) Committee hypothesized that collecting and sharing clinical pathways could provide a valuable resource to new and existing bariatric programs. To shed light on the variability in practice patterns across the country by analyzing pathways. United States Centers of Excellence METHODS: From June 2014 to April 2015, clinical pathways pertaining to preoperative, intraoperative, and postoperative management of bariatric patients were solicited from the ASMBS executive council (EC), QIPS committee members, and state chapter presidents. Pathways were de-identified and then analyzed based on predetermined metrics pertaining to preoperative, intraoperative, and postoperative care. Concordance and discordance were then analyzed. In total, 31 pathways were collected; response rate was 80% from the EC, 77% from the QIPS committee, and 21% from state chapter presidents. The number of pathways sent in ranged from 1 to 10 with a median of 3 pathways per individual or institution. The majority of pathways centered on perioperative care (80%). Binary assessment (presence or absence) of variables found a high concordance (defined by greater than 65% of pathways accounting for that parameter) in only 6 variables: nutritional evaluation, psychological evaluation, intraoperative venous thromboembolism (VTE) prophylaxis, utilization of antiemetics in the postoperative period, a dedicated pain pathway, and postoperative laboratory evaluation. There is considerable national variation in clinical pathways among practicing bariatric surgeons. Most pathways center on Metabolic and Bariatric Surgery Accredited Quality Improvement Program (MBSAQIP) accreditation parameters, patient satisfaction, or Surgical Care Improvement Protocol (SCIP) measures. These pathways provide a path toward standardization of improved care. Copyright © 2016. Published by Elsevier Inc.
Bhukal, Ishwar; Srinivas, N.; Solanki, Sohan Lal; Yaddanapudi, L. N.; Jain, Amit
2012-01-01
Background: The purpose of this study was to evaluate the effect of two different volume of crystalloid given intraoperatively on postoperative nausea and vomiting (PONV). Materials and Methods: Eighty adult patients of either sex belonging to ASA I and II class undergoing elective surgeries under general anesthesia for 1–2 h were studied in this prospective, randomized double blinded study. First group (group L) (n=40) received normal saline 4 mL/kg and second group (group H) (n=40) received 10 mL/kg of normal saline. This was in excess of the fasting requirement of the patients. No propofol or antiemetic drugs were given. PONV was evaluated by verbal descriptive score (VDS) [0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = unbearable]. Ondansetron (4 mg i.v.) was given if VDS score was 3 or more. Results: The median immediate PONV score was 2 and 1 in group L and H, respectively. The median 2 h PONV score in group L was 3 and in group H was 1. The median 6 h PONV score in group L was 3 and in group H was 1. The 24 h median postoperative PONV score was 1 and 0 in group L and H, respectively. In all these period of time the differences were statistically significant. The incidence of vomiting was more in group L [72.5% (29/40)] than in group H [30% (12/40)]. This was statistically significant (P=0.0003). Conclusion: From the current study it was concluded that patients who received larger volume of crystalloid intraoperatively have lesser incidence of PONV. PMID:25885496
Fakhfouri, Gohar; Mousavizadeh, Kazem; Mehr, Sharam Ejtemaei; Dehpour, Ahmad Reza; Zirak, Mohammad Reza; Ghia, Jean-Eric; Rahimian, Reza
2015-12-01
5-HT3 receptor antagonists are extensively used as efficacious agents in counteracting chemotherapy-induced emesis. Recent investigations have shed light on other potential effects (analgesic, anxiolytic, and anti-psychotic). Some studies have reported neuroprotective properties for the 5-HT3 receptor antagonists in vitro and in vivo. When administered to Aβ-challenged rat cortical neurons, 5-HT3 receptor antagonists substantially abated apoptosis, elevation of cytosolic Ca(2), glutamate release, reactive oxygen species (ROS) generation, and caspase-3 activity. In addition, in vivo studies show that 5-HT3 receptor antagonists possess, alongside their anti-emetic effects, notable immunomodulatory properties in CNS. We found that pretreatment with tropisetron significantly improved neurological deficits and diminished leukocyte transmigration into the brain, TNF-α level, and brain infarction in a murine model of embolic stroke. Our recent investigation revealed that tropisetron protects against Aβ-induced neurotoxicity in vivo through both 5-HT3 receptor-dependent and -independent pathways. Tropisetron, in vitro, was found to be an efficacious inhibitor of the signaling pathway leading to the activation of pro-inflammatory NF-κB, a transcription factor pivotal to the upregulation of several neuroinflammatory mediators in brain. This mini review summarizes novel evidence concerning effects of 5-HT3 antagonists and their possible mechanisms of action in ameliorating neurodegenerative diseases including Alzheimer, multiple sclerosis, and stroke. Further, we discuss some newly synthesized 5-HT3 receptor antagonists with dual properties of 5-HT3 receptor blockade/alpha-7 nicotinic receptor activator and their potential in management of memory impairment. Since 5-HT3 receptor antagonists possess a large therapeutic window, they can constitute a scaffold for design and synthesis of new neuroprotective medications.
Chow, Ronald; Warr, David G; Navari, Rudolph M; Tsao, May; Popovic, Marko; Chiu, Leonard; Milakovic, Milica; Lam, Henry; DeAngelis, Carlo
2018-05-23
Chemotherapy-induced nausea and vomiting (CINV) continues to be a common side effect of systemic anticancer therapy, decreasing quality of life and increasing resource utilization. The aim of this meta-analysis was to investigate the comparative efficacy and safety of palonosetron relative to other 5-HT 3 RAs. A literature search was carried out in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Full-text references were then screened and included in this meta-analysis if they were an RCT and had adequate data regarding one of the five primary endpoints-complete response (CR), complete control (CC), no emesis, no nausea, or no rescue medications. A total of 24 RCTs were included in this review. Palonosetron was statistically superior to other 5-HT 3 RAs for 10 of the 19 assessed endpoints. Only one endpoint-emesis in the overall phase-had noticeable more favorable data for palonosetron to the point that it approached the 10% risk difference (RD) threshold as specified by the MASCC/ESMO antiemetic panel; another two endpoints (CR in the overall phase and nausea in the delayed phase) approached the 10% threshold. Palonosetron seems to be more efficacious and safe than other 5-HT 3 RAs-statistically superior in 10 of 19 endpoints. It is, however, only clinically significant in one endpoint and approached clinically significant difference in another two endpoints. Within the limits of this meta-analysis, our results indicate that palonosetron may not be as superior in efficacy and safety as reported in a previous meta-analysis, and supports the recent MASCC/ESMO, ASCO, and NCCN guidelines in not generally indicating palonosetron as the 5-HT 3 RA of choice.
Gastrografin in Prolonged Postoperative Ileus: A Double-blinded Randomized Controlled Trial.
Vather, Ryash; Josephson, Rachel; Jaung, Rebekah; Kahokehr, Arman; Sammour, Tarik; Bissett, Ian
2015-07-01
To investigate the therapeutic value of Gastrografin in shortening duration of prolonged postoperative ileus (PPOI) after elective colorectal surgery. Gut wall edema is central to the pathogenesis of PPOI. Hyperosmotic, orally administered, water-soluble contrast media such as Gastrografin are theoretically capable of mitigating this edema. A double-blinded, placebo-controlled, randomized trial was conducted. Participants were allocated to receive 100 mL of Gastrografin (Exposure Group) or flavored distilled water (Control Group) administered enterally. Other aspects of management were standardized. Resolution of PPOI was assessed 12-hourly. Eighty patients were randomized equally, with 5 in the Exposure Group and 4 in the Control Group excluded from analysis. Participants were evenly matched at baseline. Mean duration of PPOI did not differ between Exposure and Control Groups (83.7 vs 101.3 hours; P = 0.191). When considering individual markers of PPOI resolution, Gastrografin did not affect time to resolution of nausea and vomiting (64.5 vs 74.3 hours; P = 0.404) or consumption of oral diet (75.8 vs 90.0 hours; P = 0.297). However, it accelerated time to flatus or stool (18.9 vs 32.7 hours; P = 0.047) and time to resolution of abdominal distension (52.8 vs 77.7 hours; P = 0.013). There were no significant differences between groups in nasogastric output; analgesia, antiemetic, or fluid requirement; complications; or length of stay. Gastrografin is not clinically useful in shortening an episode of PPOI characterized by upper and lower gastrointestinal symptoms. It may however be of therapeutic benefit in the subset of PPOI patients who display lower gastrointestinal symptoms exclusively after surgery.
Rapoport, Bernardo; Schwartzberg, Lee; Chasen, Martin; Powers, Dan; Arora, Sujata; Navari, Rudolph; Schnadig, Ian
2016-04-01
Rolapitant, a novel neurokinin-1 receptor antagonist (RA), was shown to protect against delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in randomized, double-blind trials. This analysis explored the efficacy and safety of rolapitant in preventing CINV over multiple cycles of MEC or HEC. Patients in one phase III MEC, one phase II HEC, and two phase III HEC clinical trials were randomized to receive oral rolapitant (180 mg) or placebo in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Regardless of response in cycle 1, patients could continue the same antiemetic treatment for up to six cycles. On days 6-8 of each subsequent chemotherapy cycle, patients reported the incidence of emesis and/or nausea interfering with normal daily life. Post hoc analyses of pooled safety and efficacy data from the four trials were performed for cycles 2-6. Significantly more patients receiving rolapitant than control reported no emesis or interfering nausea (combined measure) in cycles 2 (p = 0.006), 3 (p < 0.001), 4 (p = 0.001), and 5 (p = 0.021). Over cycles 1-6, time-to-first emesis was significantly longer with rolapitant than with control (p < 0.001). The incidence of treatment-related adverse events during cycles 2-6 was similar in rolapitant (5.5%) and control (6.8%) arms. No cumulative toxicity was observed. Over multiple cycles of MEC or HEC, rolapitant provided superior CINV protection and reduced emesis and nausea interfering with daily life compared with control and remained well tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Robin, Elisabeth M; Pey, Pascaline B; de Fornel-Thibaud, Pauline; Moissonnier, Pierre H M; Freiche, Valérie
2018-02-01
CASE DESCRIPTION A 10-year-old spayed female Rottweiler was referred for evaluation because of a 2-month history of regurgitation and weight loss, despite no apparent change in appetite. The dog had received antiemetic and antacid treatment, without improvement. CLINICAL FINDINGS Physical examination revealed a low body condition score (2/5), but other findings were unremarkable. Diffuse, global esophageal dilatation was noted on plain thoracic radiographs, and normal motility was confirmed through videofluoroscopic evaluation of swallowing. Transhepatic ultrasonographic and CT examination revealed a circumferential, intraparietal lesion in the distal portion of the esophagus causing distal esophageal or cardial subobstruction and no metastases. Incisional biopsy of the lesion was performed, and findings of histologic examination supported a diagnosis of esophageal leiomyoma. TREATMENT AND OUTCOME In view of numerous possible complications associated with esophageal surgery, the decision was made to palliatively treat the dog by transcardial placement of a self-expanding, covered, nitinol esophageal stent under endoscopic guidance. Two weeks after stent placement, radiography revealed complete migration of the stent into the gastric lumen. Gastrotomy was performed, and the stent was replaced and fixed in place. Twenty-four months after initial stent placement, the dog had a healthy body condition and remained free of previous clinical signs. CLINICAL RELEVANCE Diffuse benign muscular neoplasia should be considered as a differential diagnosis for acquired esophageal dilatation in adult and elderly dogs. In the dog of this report, transcardial stent placement resulted in resolution of the clinical signs, with no apparent adverse effect on digestive function. The described procedure could be beneficial for nonsurgical treatment of benign esophageal tumors in dogs.
Cannabidiol in Humans—The Quest for Therapeutic Targets
Zhornitsky, Simon; Potvin, Stéphane
2012-01-01
Cannabidiol (CBD), a major phytocannabinoid constituent of cannabis, is attracting growing attention in medicine for its anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, up to this point, a comprehensive literature review of the effects of CBD in humans is lacking. The aim of the present systematic review is to examine the randomized and crossover studies that administered CBD to healthy controls and to clinical patients. A systematic search was performed in the electronic databases PubMed and EMBASE using the key word “cannabidiol”. Both monotherapy and combination studies (e.g., CBD + ∆9-THC) were included. A total of 34 studies were identified: 16 of these were experimental studies, conducted in healthy subjects, and 18 were conducted in clinical populations, including multiple sclerosis (six studies), schizophrenia and bipolar mania (four studies), social anxiety disorder (two studies), neuropathic and cancer pain (two studies), cancer anorexia (one study), Huntington’s disease (one study), insomnia (one study), and epilepsy (one study). Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of ∆9-THC. Moreover, some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and/or intensify ∆9-THC-induced effects, whereas others suggest that it may inhibit ∆9-THC-induced effects. Finally, preliminary clinical trials suggest that high-dose oral CBD (150–600 mg/d) may exert a therapeutic effect for social anxiety disorder, insomnia and epilepsy, but also that it may cause mental sedation. Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed. PMID:24281562
A rapid recovery program: early home and pain free.
Lombardi, Adolph V; Berend, Keith R; Adams, Joanne B
2010-09-07
Enhancement of our perioperative pain management protocols has resulted in accelerated rehabilitation. At our facility, the majority of patients undergoing total and partial knee arthroplasty are treated with a single-shot spinal anesthetic consisting of a combination of bupivacaine and duramorph. The bupivacaine affords the immediate perioperative anesthetic while the duramorph results in sustained analgesia for a period of 12 to 24 hours. We use intra-articular injections delivered directly into the soft tissue of the knee. Our current intra-articular injection is 60 mL of 0.5% ropivacaine with 0.5 mg of epinephrine. In patients with a normal renal function, 30 mg of ketorolac is added. The injection is administered throughout all of the soft tissues in and around the knee. Prophylactic antiemetics are administered in the form of dexamethasone, ondansetron, and a scopolamine patch. The use of this perioperative anesthesia provides effective pain relief with no motor blockade. Patients are able to participate in physiotherapy within several hours of the operative procedure, performing active range of motion and ambulating with assistive devices. Patients with no significant cardiovascular history are given celecoxib preoperatively, which is continued for approximately 2 weeks postoperatively. Additionally, all patients are treated with oxycodone, either preoperatively or within 2 hours of arrival to the floor postoperatively. Patients younger than 70 years are given 20 mg of oxycodone while those older than 70 years are given 10 mg of oxycodone. The oxycodone is continued for the first 24 hours of the hospital stay. Patients are then managed with oxycodone and hydrocodone. Length of stay has decreased and currently averages <2 days. Copyright 2010, SLACK Incorporated.
Joo, Jin; Park, Yong Gyu; Baek, Jungwon; Moon, Young Eun
2015-07-08
Low-dose haloperidol is known to be effective for the prevention of postoperative nausea and vomiting (PONV). However, precise dose-response studies have not been completed, especially in patients at high risk for PONV who require combination therapy. This study sought to identify which dose of haloperidol 1mg or 2mg could be combined with dexamethasone without adverse effects in high-risk patients undergoing gynecological laparoscopic surgery. Female adults (n = 150) with three established PONV risk factors based on Apfel's score were randomized into one of three study groups. At the end of anesthesia, groups H0, H1, and H2 were given intravenous (IV) saline, haloperidol 1 mg, and haloperidol 2 mg, respectively. All patients were given dexamethasone 5 mg during the induction of anesthesia. The overall early (0-2 h) and late (2-24 h) incidences of nausea, vomiting, rescue anti-emetic administration, pain, and adverse effects (cardiac arrhythmias and extrapyramidal effects) were assessed postoperatively. The sedation score was recorded in the postanesthesia care unit (PACU). The total incidence of PONV over 24 h was significantly lower in groups H1 (29 %) and H2 (24 %) than in group H0 (54 %; P = 0.003), but there was no significant difference between groups H1 and H2. In the PACU, group H2 had a higher sedation score than groups H1 and H0 (P < 0.001). For high-risk PONV patients undergoing gynecological laparoscopic surgery, when used with dexamethasone, 1-mg haloperidol was equally effective as 2 mg in terms of preventing PONV with the less sedative effect. ClinicalTrials.gov ( NCT01639599 ).
Prüll, Kathrin; Weninger, Ernst; Mansmann, Ulrich; Küchenhoff, Helmut; Jovanovic, Alexander; Pollwein, Bernhard; Chappell, Daniel; Zwissler, Bernhard; von Dossow, Vera
2016-01-01
Background Postoperative nausea and vomiting (PONV) is one of the most common and distressing complications after general anesthesia and surgery, with young non-smoking females receiving postoperative opioids being high-risk patients. This register-based study aims to evaluate the effect of low-dose haloperidol (0.5 mg intravenously) directly after induction of general anesthesia to reduce the incidence of PONV in the postoperative anesthesiological care unit (PACU). Methods Multivariable regression models were used to investigate the association between low-dose haloperidol and the occurrence of PONV using a patient registry containing 2,617 surgical procedures carried out at an university hospital. Results Haloperidol 0.5 mg is associated with a reduced risk of PONV in the total collective (adjusted odds ratio = 0.75, 95% confidence interval: [0.56, 0.99], p = 0.05). The results indicate that there is a reduced risk in male patients (adjusted odds ratio = 0.45, 95% confidence interval: [0.28, 0.73], p = 0.001) if a dose of 0.5 mg haloperidol was administered while there seems to be no effect in females (adjusted odds ratio = 1.02, 95% confidence interval: [0.71, 1.46], p = 0.93). Currently known risk factors for PONV such as female gender, duration of anesthesia and the use of opioids were confirmed in our analysis. Conclusion This study suggests that low-dose haloperidol has an antiemetic effect in male patients but has no effect in female patients. A confirmation of the gender-specific effects we have observed in this register-based cohort study might have major implications on clinical daily routine. PMID:26751066
Intestinal Leiomyositis: A Cause of Chronic Intestinal Pseudo-Obstruction in 6 Dogs.
Zacuto, A C; Pesavento, P A; Hill, S; McAlister, A; Rosenthal, K; Cherbinsky, O; Marks, S L
2016-01-01
Intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the gastrointestinal tract and is a cause of chronic intestinal pseudo-obstruction in humans and animals. To characterize the clinical presentation, histopathologic features, and outcome of dogs with intestinal leiomyositis in an effort to optimize treatment and prognosis. Six client-owned dogs. Retrospective case series. Medical records were reviewed to describe signalment, clinicopathologic and imaging findings, histopathologic diagnoses, treatment, and outcome. All biopsy specimens were reviewed by a board-certified pathologist. Median age of dogs was 5.4 years (range, 15 months-9 years). Consistent clinical signs included vomiting (6/6), regurgitation (2/6), and small bowel diarrhea (3/6). Median duration of clinical signs before presentation was 13 days (range, 5-150 days). Diagnostic imaging showed marked gastric distension with dilated small intestines in 4/6 dogs. Full-thickness intestinal biopsies were obtained in all dogs by laparotomy. Histopathology of the stomach and intestines disclosed mononuclear inflammation, myofiber degeneration and necrosis, and fibrosis centered within the region of myofiber loss in the intestinal muscularis propria. All dogs received various combinations of immunomodulatory and prokinetic treatment, antimicrobial agents, antiemetics, and IV fluids, but none of the dogs showed a clinically relevant improvement with treatment. Median survival was 19 days after diagnosis (range, 3-270 days). Intestinal leiomyositis is a cause of intestinal pseudo-obstruction and must be diagnosed by full-thickness intestinal biopsy. This disease should be considered in dogs with acute and chronic vomiting, regurgitation, and small bowel diarrhea. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Claude, A K; Dedeaux, A; Chiavaccini, L; Hinz, S
2014-01-01
Vomiting is a common complication associated with the use of hydromorphine for pre-emptive analgesia in dogs. The ideal anti-emetic protocol for prevention of this complication has not been established. Maropitant administered concurrently or before hydromorphone would reduce the incidence of vomiting, signs of nausea, ptyalism, and increased panting compared to administration of acepromazine or a 0.9% saline control. Sixty mixed-breed female dogs scheduled for ovariohysterectomy. Randomized, blinded, placebo-controlled experimental study. Dogs were assigned to 4 experimental groups with 15 dogs per group. All groups received 0.2 mg/kg of hydromorphone IM. Group "Control" received 0.1 mL/kg saline SC 30-45 minutes before hydromorphone, group "Marop1" received 1 mg/kg maropitant SC 30-45 minutes before hydromorphone, group "Ace" received 0.02 mg/kg IM acepromazine 30-45 minutes before hydromorphone, and group "Marop2" received 1 mg/kg SC maropitant concurrently with hydromorphone. A trained and blinded observer documented adverse events from the time hydromorphone was administered until the time dogs were induced for surgery. Marop1 had significantly less vomiting (0%) compared to Control (87%; P < .01) and Ace (53%; P < .01). Marop2 had significantly less vomiting (27%) compared to Control (P < .01). Marop1 had significantly greater incidence of ptyalism (73%) compared to Ace (P < .01; 20%). Ace showed significantly less panting (33%) compared to Marop2 (93%; P < .01). In healthy dogs, maropitant citrate administered before hydromorphone significantly decreases the incidence of vomiting in dogs but does not improve signs of nausea, ptyalism, or increased panting. Copyright © 2014 by the American College of Veterinary Internal Medicine.
Midodrine as a Countermeasure to Orthostatic Hypotension Immediately After Space Shuttle Landing
NASA Technical Reports Server (NTRS)
Platts, Steven H.; Stenger, Michael B.; Ribeiro, L. Christine; Lee, Stuart M. C.
2010-01-01
Midodrine prevents post-space flight orthostatic intolerance when testing is conducted in a controlled laboratory setting within 2-4 hours after Space Shuttle landing. It is unknown if midodrine is as effective during re-entry and immediately following landing. METHODS: Cardiovascular responses to 10 minutes of 80 head-up tilt in five male astronauts were compared before and immediately after Space Shuttle missions. Preflight tests were conducted in the Johnson Space Center Cardiovascular Laboratory without midodrine. Post-flight testing was performed in the Crew Transport Vehicle on the Space Shuttle runway within 60 minutes of landing; midodrine was self-administered before re-entry. Survival analysis was performed (Gehan-Breslow test) to compare presyncope rates pre- to post-flight. Cardiovascular responses (last minute standing minus supine) to tilt before and after space flight were compared using paired t-tests. RESULTS: Midodrine did not prevent post-flight orthostatic hypotension in two of the five astronauts, but the rate of presyncope across the group did not increase (p=0.17) from pre- to post-flight. Also, although the change in heart rate from supine to the last minute of standing was not affected by space flight, systolic blood pressure decreased more (p=0.05) and diastolic blood pressure tended to decrease (p=0.08) after space flight. CONCLUSIONS: Accurate interpretation of the current results requires that similar data be collected in control subjects (without midodrine) on the CTV. However, drug interaction concerns with commonly used anti-emetics and potentiation of prolonged QTc intervals observed in long duration astronauts make the routine use of midodrine for immediate post-flight orthostatic hypotension unlikely. 2
TAO, YI; LI, WENKUI; LIANG, WENZHONG; VAN BREEMEN, RICHARD B.
2009-01-01
Dietary supplements containing preparations of ginger roots/rhizomes (Zingiber officinale Roscoe) are being used by consumers, and clinical trials using ginger dietary supplements have been carried out to evaluate their anti-inflammatory or anti-emetic properties with inconsistent results. Chemical standardization of these products is needed for quality control and to facilitate the design of clinical trials and the evaluation of data from these studies. To address this issue, methods based on liquid chromatography-tandem mass spectrometry (LC-MS-MS) were developed for the detection, characterization and quantitative analysis of gingerol-related compounds in botanical dietary supplements containing ginger roots/rhizomes. During negative ion electrospray with collision induced-dissociation, the cleavage of the C4-C5 bond with a neutral loss of 194 u and benzylic cleavage leading to the neutral loss of 136 u were found to be class characteristic fragmentation patterns of the pharmacologically active gingerols or shogaols, respectively. Based on these results, an assay using LC-MS-MS with neutral loss scanning (loss of 194 u or 136 u) was developed that is suitable for the fingerprinting of ginger dietary supplements based on the selective detection of gingerols, shogaols, paradols, and gingerdiones. In addition, a quantitative assay based on LC-MS-MS with selected reaction monitoring was developed for the quantitative analysis of 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, and 10-shogaol in ginger dietary supplements. After method validation, the quantities of these compounds in three commercially available ginger dietary supplements were determined. This assay showed excellent sensitivity, accuracy and precision and may be used to address the need for quality control and standardization of ginger dietary supplements. PMID:19817455