Effects of droperidol in management of vestibular disorders.

PubMed

Johnson, W H; Fenton, R S; Evans, A

1976-07-01

The chemo-therapy of vestibular disease has involved a wide spectrum of pharmacological agents insofar as their mode of action is concerned. In our experience, however, droperidol is one pharmaceutical agent which is remarkably effective in depressing vestibular disturbance regardless of etiology. This medication (also called Inapsine) belongs to a relatively new class of compounds known as butyrophenones and its pharmacological action can best be described as a dopa blocking agent. The activity of droperidol on the nervous system first became evident when it was used in combination with the potent analgesic fentanyl citrate in order to produce an anesthetic condition that has been termed neuroleptanalgesia. This mixture (also called Innovar) is rapid in action and results in complete suppression of vestibular activity of both normal subjects and those with Ménière's disease as described by Dowdy, et al., in a preliminary report. These impressive results have prompted us to evaluate the effectiveness of this medication in the treatment of different disorders of the labyrinth. The patients chosen for evaluation were referred for vestibular examination at the Toronto General and St. Michael's Hospitals. Electronystagmography was used to record objectively the effects of the drugs being tested while subjective symptoms including side effects were also noted. These studies involved 20 patients receiving Innovar while 12 patients were tested with Inapsine. Innovar administered in a single dose (droperidol 5 mg, fentanyl 0.1 mg) to patients undergoing acute episodes of vestibular disease (vestibular neuronitis and Ménière's disease) was found effective in the following symptoms and/or signs: nausea, vertigo, nystagmus, the positive past-pointing test and the Romberg test. Innovar appeared to be effective in the amelioration of vomiting although the population was too small to demonstrate statistical significance in this regard. The drug mixture appeared to have no

Stability of butorphanol-tropisetron mixtures in 0.9% sodium chloride injection for patient-controlled analgesia use.

PubMed

Chen, Fu-Chao; Shi, Xiao-Ya; Li, Peng; Yang, Jin-Guo; Zhou, Ben-Hong

2015-02-01

Tropisetron is an adjuvant for butorphanol used in intravenous patient-controlled analgesia (PCA) and has been reported to provide superior pain control. It is efficacious in reducing the incidence of postoperative nausea and vomiting. However, this admixture is not available commercially and stability data applicable to hospital practice are limited. This study aimed to describe the drug compounding and evaluates the long-term (up to 14 days) stability of butorphanol and tropisetron in 0.9% sodium chloride injection for PCA use.In this study, commercial solutions of butorphanol tartrate and tropisetron hydrochloride were combined and further diluted with 0.9% sodium chloride injection to final concentrations of butorphanol tartrate 0.08 mg/mL and tropisetron hydrochloride 0.05 mg/mL. The polyolefin bags and glass bottles were stored at 4°C and 25°C for up to 14 days. The drug stabilities were determined by visual inspection, pH measurement, and high-pressure liquid chromatography assay of drug concentrations.The data obtained for admixtures prepared and stored at temperatures of 25°C and 4°C show the drugs have maintained at least 98% of the initial concentration. All solutions remained clear and colorless over the 14-day period, and the pH value did not change significantly.The results indicate that admixtures of butorphanol tartrate 0.08 mg/mL and tropisetron hydrochloride 0.05 mg/mL in 0.9% sodium chloride injection solution were stable for 14 days when stored in polyolefin bags or glass bottles at 4°C and 25°C and protected from light. The infusion is feasible for manufacturing in pharmacy aseptic units and can be stored for up to 14 days for routine use in PCA infusions.

Attenuation of oxidative and nitrosative stress in cortical area associates with antidepressant-like effects of tropisetron in male mice following social isolation stress.

PubMed

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.

Tropisetron sensitizes α7 containing nicotinic receptors to low levels of acetylcholine in vitro and improves memory-related task performance in young and aged animals.

PubMed

Callahan, Patrick M; Bertrand, Daniel; Bertrand, Sonia; Plagenhoef, Marc R; Terry, Alvin V

2017-05-01

Tropisetron, a 5-HT 3 receptor antagonist commonly prescribed for chemotherapy-induced nausea and vomiting also exhibits high affinity, partial agonist activity at α7 nicotinic acetylcholine receptors (α7 nAChRs). α7 nAChRs are considered viable therapeutic targets for neuropsychiatric disorders such as Alzheimer's disease (AD). Here we further explored the nAChR pharmacology of tropisetron to include the homomeric α7 nAChR and recently characterized heteromeric α7β2 nAChR (1:10 ratio) and we evaluated its cognitive effects in young and aged animals. Electrophysiological studies on human nAChRs expressed in Xenopus oocytes confirmed the partial agonist activity of tropisetron at α7 nAChRs (EC 50 ∼2.4 μM) with a similar effect at α7β2 nAChRs (EC 50 ∼1.5 μM). Moreover, currents evoked by irregular pulses of acetylcholine (40 μM) at α7 and α7β2 nAChRs were enhanced during sustained exposure to low concentrations of tropisetron (10 and 30 nM) indicative of a "priming" or co-agonist effect. Tropisetron (0.1-10 mg/kg) improved novel object recognition performance in young Sprague-Dawley rats and in aged Fischer rats. In aged male and female rhesus monkeys, tropisetron (0.03-1 mg/kg) produced a 17% increase from baseline levels in delayed match to sample long delay accuracy while combination of non-effective doses of donepezil (0.1 mg/kg) and tropisetron (0.03 and 0.1 mg/kg) produced a 24% change in accuracy. Collectively, these animal experiments indicate that tropisetron enhances cognition and has the ability to improve the effective dose range of currently prescribed AD therapy (donepezil). Moreover, these effects may be explained by tropisetron's ability to sensitize α7 containing nAChRs to low levels of acetylcholine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Compatibility of butorphanol and droperidol in 0.9% sodium chloride injection.

PubMed

Chen, Fu-Chao; Fang, Bao-Xia; Li, Peng; Yang, Jin-Guo; Zhou, Ben-Hong

2013-03-15

The compatibility and stability of butorphanol tartrate and droperidol in polyvinyl chloride (PVC) bags and glass bottles stored at 4°C and 25°C for up to 15 days were studied. Admixtures were assessed initially and for 15 days after preparation in PVC bags and glass bottles using 0.9% sodium chloride injection as a diluent and stored at 4°C and 25°C. The initial drug concentrations were 0.08 mg/mL for butorphanol tartrate and 0.05 mg/mL for droperidol. Samples were withdrawn from each container immediately after preparation and at predetermined intervals (2, 4, 8, 24, 48, 72, 120, 168, 240, and 360 hours after preparation). The solutions were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. Drug concentrations were determined using a validated high-pressure liquid chromatography method. After 15 days of storage, all formulations tested retained >98% of the initial concentrations of both drugs. The drug mixtures were clear in appearance, and no color change or precipitation was observed. Throughout this period, pH values remained stable. Admixtures of butorphanol tartrate 0.08 mg/mL and droperidol 0.05 mg/mL in 0.9% sodium chloride injection were stable for at least 360 hours when stored in PVC bags or glass bottles at 4°C and 25°C and protected from light.

Transdermal scopolamine: an alternative to ondansetron and droperidol for the prevention of postoperative and postdischarge emetic symptoms.

PubMed

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

Involvement of nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tropisetron and ondansetron in mice forced swimming test and tail suspension test.

PubMed

Haj-Mirzaian, Arya; Kordjazy, Nastaran; Amiri, Shayan; Haj-Mirzaian, Arvin; Amini-Khoei, Hossien; Ostadhadi, Sattar; Dehpour, AhmadReza

2016-06-05

Antidepressant-like effects of 5-hydroxytryptamine subtype 3 (5-HT3) antagonists including tropisetron and ondansetron have been previously demonstrated in the literature. It was reported that stimulation of 5-HT3 receptors activate the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, which is involved in regulation of behavioral and emotional functions. In our study, treating animals with tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01 and 0.1µg/kg) significantly decreased the immobility time in forced swimming test (FST) and tail-suspension test (TST). Co-administration of subeffective doses of tropisetron (1mg/kg) and ondansetron (0.001µg/kg) with subeffective dose of l-NAME (10mg/kg, nonselective NO synthase (NOS) inhibitor) and 7-nitroindazole (25mg/kg, neural NOS inhibitor) exerted antidepressant-like effect in FST and TST, while aminoguanidine (50mg/kg, inducible NOS inhibitor) did not enhance the antidepressant-like effect of 5-HT3 antagonists. Besides, l-arginine (750mg/kg, NO precursor) and sildenafil (5mg/kg, phosphodiesterase inhibitor) suppressed the anti-immobility effect of 5-HT3 antagonists. None of the treatments altered the locomotor behavior of mice in open-field test. Also, hippocampal (but not cortical) nitrite level was significantly lower in tropisetron and ondansetron-treated mice compared with saline-injected mice. Also, co-administration of 7-nitroindazole with tropisetron or ondansetron caused a significant decrease in hippocampal nitrite levels. In conclusion, we suggest that antidepressant-like effect of tropisetron and ondansetron are partially mediated by modulation of NO-cGMP pathway. Copyright © 2016. Published by Elsevier B.V.

Efficacy of prophylactic droperidol, ondansetron or both in the prevention of postoperative nausea and vomiting in major gynaecological surgery. A prospective, randomized, double-blind clinical trial.

PubMed

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.

Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling, characterization, and ex vivo skin permeation.

PubMed

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.

Comparison of medetomidine and fentanyl-droperidol in dogs: sedation, analgesia, arterial blood gases and lactate levels.

PubMed Central

Pettifer, G R; Dyson, D H

1993-01-01

Medetomidine and fentanyl-droperidol (Innovar-vet) were assessed over a three hour period in 80 healthy dogs. Following physical examination, electrocardiogram (ECG), arterial blood sample analysis, and dynamometer pressure threshold (analgesia score), the dogs were randomly assigned to one of four treatments: Miv--medetomidine (750 micrograms/M2) administered intravenously (IV), Mim--medetomidine (1000 micrograms/M2) administered intramuscularly (IM), Iiv--Innovar-vet IV (0.05 mL/kg) or Iim--Innovar-vet IM (0.1 mL/kg). All assessments were carried out by a single individual unaware of the treatment used. Objective assessments included temperature, heart and respiratory rates, analgesia score, arterial blood gases, acid-base and lactate levels. Subjective evaluation included degree of sedation, response to various clinical procedures, noise responsiveness, posture, and the incidence of side effects. Onset and duration of effect were also recorded. The ECG strips were assessed for arrhythmias. Data was analyzed using a 3-way analysis of variance for continuous variables and a Chi-square analysis of frequencies. A p value < or = 0.05 was considered significant. Medetomidine-treated animals had a decreased respiratory rate, longer duration of analgesic effect, increased incidence of bradycardia, vomiting and twitching, were less noise responsive and shivered less throughout the study. An increased incidence of second degree heart block with Miv (15 min), a delayed onset and recovery with Mim and increased lactate levels following Iiv (15 min) were observed. No differences were found in other measurements and good to excellent chemical restraint was produced with all treatments in 65% or more cases. Images Fig. 1. PMID:8490814

A comparison of three antiemetic combinations for the prevention of postoperative nausea and vomiting.

PubMed

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.

Efficacy of tropisetron in patients with advanced non-small-cell lung cancer receiving adjuvant chemotherapy with carboplatin and taxanes.

PubMed

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.

Inside the black box: current policies and concerns with the United States Food and Drug Administration's highest drug safety warning system.

PubMed

Halloran, Kylene; Barash, Paul G

2010-06-01

To evaluate the United States Food and Drug Administration use of the black-box warning system to promote drug safety and to examine the droperidol black-box warning as a case study. Scientific studies report that there is no basis to issue a black-box warning for perioperative administration of droperidol for postoperative nausea and vomiting on the basis of the potential of adverse cardiac events (prolongation of the QT interval and/or development of torsades de pointes). Rather than relying on well conducted clinical investigations, the Food and Drug Administration subjectively issued a black-box warning to droperidol, which effectively removed droperidol from clinical practice for the indication of postoperative nausea and vomiting. Newer data suggest that the incidence of prolongation of the QT interval and the occurrence of torsades de pointes is similar to more expensive alternative medications used to treat postoperative nausea and vomiting.

Serotonin receptor antagonists in prophylaxis of acute and delayed emesis induced by moderately emetogenic, single-day chemotherapy: a randomized study.

PubMed

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.

Postoperative nausea and vomiting in pediatric anesthesia.

PubMed

Höhne, Claudia

2014-06-01

Postoperative nausea and vomiting (PONV) has a high incidence in children and requires prophylactic and therapeutic strategies. PONV can be reduced by the avoidance of nitrous oxide, volatile anesthetics, and the reduction of postoperative opioids. The use of dexamethasone, 5-HT3 antagonists, or droperidol alone is potent, but combinations are even more effective to reduce PONV. Droperidol has a Food and Drug Administration warning. Hence, dexamethasone and 5-HT3 antagonists should be preferred as prophylactic drugs. It is further reasonable to adapt PONV prophylaxis to different risk levels. Prolonged surgery time, inpatients, types of surgery (e.g. strabismus and ear-nose-throat surgery), and patients with PONV in history should be treated as high risk, whereas short procedures and outpatients are to be treated as low risk. Concluding from the existing guidelines and data on the handling of PONV in children at least 3 years, the following recommendations are given: outpatients undergoing small procedures should receive a single prophylaxis, outpatients at high risk a double prophylaxis, inpatients with surgery time of more than 30 min and use of postoperative opioids should get double prophylaxis, and inpatients receiving a high-risk surgical procedure or with other risk factors a triple prophylaxis (two drugs and total intravenous anesthesia). Dimenhydrinate can be used as a second choice, whereas droperidol and metoclopramide can only be recommended as rescue therapy.

From Chemotherapy-Induced Emesis to Neuroprotection: Therapeutic Opportunities for 5-HT3 Receptor Antagonists.

PubMed

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.

The Effectiveness of the Human Patient Simulator in Teaching Anesthesia Pharmacology to First Year Nurse Anesthesia Students

DTIC Science & Technology

2002-12-01

month period. Simulator scenarios included overdose of inhalation anesthetic, oxygen source failure, cardiac arrest, malignant hypothermia, tension...may most effectively attenuate emergence delirium? a. Propofol b. Versed*** c. Fentanyl d. Droperidol 6. Barbituric acid is formed by the

Involvement of N-methyl-d-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test.

PubMed

Kordjazy, Nastaran; Haj-Mirzaian, Arya; Amiri, Shayan; Ostadhadi, Sattar; Amini-Khoei, Hossein; Dehpour, Ahmad Reza

2016-02-01

Recent evidence indicates that 5-hydroxytryptamine 3 (5-HT3) antagonists such as ondansetron and tropisetron exert positive behavioral effects in animal models of depression. Due to the ionotropic nature of 5-HT3 and N-methyl-d-aspartate (NMDA) receptors, plus their contribution to the pathophysiology of depression, we investigated the possible role of NMDA receptors in the antidepressant-like effect of 5-HT3 receptor antagonists in male mice. In order to evaluate the animals' behavior in response to different treatments, we performed open-field test (OFT), forced swimming test (FST), and tail-suspension test (TST), which are considered as valid tasks for measuring locomotor activity and depressive-like behaviors in mice. Our data revealed that intraperitoneal (i.p.) administration of tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01, and 0.1μg/kg) significantly decreased the immobility time in FST and TST. Also, co-administration of subeffective doses of tropisetron (1mg/kg, i.p.) or ondansetron (0.001μg/kg, i.p.) with subeffective doses of NMDA receptor antagonists, ketamine (1mg/kg, i.p.), MK-801 (0.05mg/kg, i.p.) and magnesium sulfate (10mg/kg, i.p.) resulted in a reduced immobility time both in FST and TST. The subeffective dose of NMDA (NMDA receptor agonist, 75mg/kg, i.p.) abolished the effects of 5-HT3 antagonists in FST and TST, further supporting the presumed interaction between 5-HT3 and NMDA receptors. These treatments did not affect the locomotor behavior of animals in OFT. Finally, the results of our study suggest that the positive effects of 5-HT3 antagonists on the coping behavior of mice in FST and TST are at least partly mediated through NMDA receptors participation. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of reference analgesics and psychoactive drugs on the noxious heat threshold of mice measured by an increasing-temperature water bath.

PubMed

Boros, Melinda; Benkó, Rita; Bölcskei, Kata; Szolcsányi, János; Barthó, Loránd; Pethő, Gábor

2013-12-01

The study aimed at validating an increasing-temperature water bath suitable for determining the noxious heat threshold for use in mice. The noxious heat threshold was determined by immersing the tail of the gently held awake mouse into a water container whose temperature was near-linearly increased at a rate of 24°C/min. until the animal withdrew its tail, that is, heating attained the noxious threshold. The effects of standard analgesic, neuroleptic and anxiolytic drugs were investigated in a parallel way on both the noxious heat threshold and the psychomotor activity assessed by the open field test. Morphine, diclofenac and metamizol (dipyrone) elevated the heat threshold of mice with minimum effective doses of 6, 30 and 1000 mg/kg i.p., respectively. These doses of morphine and diclofenac failed to induce any remarkable effect on psychomotor activity in the open field test while that of metamizol exerted a profound inhibition. The anxiolytic diazepam and the neuroleptic droperidol at doses evoking a mild and moderate, respectively, psychomotor inhibition failed to alter the heat threshold. Combination of a subliminal dose of morphine (regarding both antinociceptive and psychomotor inhibitory action) with diclofenac, metamizol, diazepam or droperidol at doses also subliminal regarding the thermal antinociceptive effect elevated the noxious heat threshold without major additional effects in the open field test. It is concluded that the increasing-temperature water bath is suitable for studying the thermal antinociceptive effects of morphine and diclofenac as well as the morphine-sparing action of diclofenac, metamizol, droperidol and diazepam. Behavioural testing is recommended when testing analgesics. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

Altered Gastrointestinal Function in the Neuroligin-3 Mouse Model of Autism

DTIC Science & Technology

2013-10-01

autism . Clearly, characterizing the dysfunction seen with the mixed 5 -HT3/ 5 -HT4 antagonist, tropisetron, when specific antagonists do not show such...gastrointestinal disorders. Current opinion in pharmacology 6, 547 (Dec, 2006). K. B. Neal, J. C. Bornstein, Mapping 5 - HT inputs to enteric neurons of...descending inhibition in guinea-pig ileum. PLoS ONE 10.1371/journal.pone.0040840 (2013) 3. ELLIS M, CHAMBERS JD, GWYNNE RM, BORNSTEIN JC Serotonin ( 5 - HT

The acute onset of nausea and vomiting following stereotactic radiosurgery: Correlation with total dose to area postrema

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexander, E. III; Siddon, R.L.; Loeffler, J.S.

1989-07-01

From 1986 to 1988, 44 patients have been treated for tumors or vascular lesions with stereotactic radiosurgery using a modified standard linear accelerator. In seven patients, nausea and vomiting occurred within 6 hours after the completion of radiosurgery. One of these patients with nausea and occasional vomiting pretreatment had exacerbation several hours after treatment, in spite of droperidol and prochlorperazine prophylaxis. Nausea and vomiting in the other six patients was self-limited and was completely resolved by 12 hours from onset. None of these six patients suffered from nausea and vomiting before treatment. This was directly correlated with the total dosemore » to the vomiting center in the floor of the fourth ventricle (area postrema). The median dose to the vomiting center in the seven patients was 618 cGy (range 275-1257). The final patient in the series received 1088 cGy to the area postrema after droperidol and dexamethasone prophylaxis without developing nausea or vomiting. In the remaining 36 patients who received from less than 5 to 184 cGy to area postrema, nausea and vomiting did not occur. We recommend that patients treated with large fractions of radiation by radiosurgery in this area be premedicated appropriately.« less

Airborne testing of three antimotion sickness preparations

NASA Technical Reports Server (NTRS)

Johnson, W. H.; Money, K. E.; Graybiel, A.

1976-01-01

Thirteen human volunteers were exposed to weekly flights in which standardized, steep turns were used to produce motion sickness. A combination of promethazine hydrochloride (25 mg) plus ephedrine sulphate (25 mg) was found to be equally as effective as the combination of 1-scopolamine hydrobromide (0.35 mg) plus d-amphetamine sulphate (5 mg). Droperidol (2.5 mg) was indistinguishable from the placebo. It was concluded that the treatment of choice for motion sickness is promethazine plus ephedrine.

A tribute to Dr. Paul A. J. Janssen: entrepreneur extraordinaire, innovative scientist, and significant contributor to anesthesiology.

PubMed

Stanley, Theodore H; Egan, Talmage D; Van Aken, Hugo

2008-02-01

Dr. Paul Janssen was the founder of Janssen Pharmaceutica and the developer of over 80 pharmaceutical compounds that proved useful in human, botanical, and veterinary medicine. He and his coworkers synthesized the fentanyl family of drugs, many other potent analgesics, droperidol, etomidate, and numerous other important medicines that were extremely useful in psychiatry, parasitology, gastroenterology, cardiology, virology, and immunology. Anesthesiology and medicine as a whole have benefited a great deal from his resourcefulness, creativity, and entrepreneurial spirit.

Stability of tramadol with three 5-HT3 receptor antagonists in polyolefin bags for patient-controlled delivery systems.

PubMed

Chen, Fu-Chao; Zhu, Jun; Li, Bin; Yuan, Fang-Jun; Wang, Lin-Hai

2016-01-01

Mixing 5-hydroxytryptamine-3 (5-HT3) receptor antagonists with patient-controlled analgesia (PCA) solutions of tramadol has been shown to decrease the incidence of nausea and vomiting associated with the use of tramadol PCA for postoperative pain. However, such mixtures are not commercially available, and the stability of the drug combinations has not been duly studied. The study aimed to evaluate the stability of tramadol with three 5-HT3 receptor antagonists in 0.9% sodium chloride injection for PCA administration. Test samples were prepared by adding 1,000 mg tramadol hydrochloride, 8 mg ondansetron hydrochloride, and 6 mg granisetron hydrochloride or 5 mg tropisetron hydrochloride to 100 mL of 0.9% sodium chloride injection in polyolefin bags. The samples were prepared in triplicates, stored at either 25°C or 4°C for 14 days, and assessed using the following compatibility parameters: precipitation, cloudiness, discoloration, and pH. Chemical stability was also determined using a validated high-pressure liquid chromatography method. All of the mixtures were clear and colorless throughout the initial observation period. No change in the concentration of tramadol hydrochloride occurred with any of the 5-HT3 receptor antagonists during the 14 days. Similarly, little or no loss of the 5-HT3 receptor antagonists occurred over the 14-day period. Our results suggest that mixtures of tramadol hydrochloride, ondansetron hydrochloride, granisetron hydrochloride, or tropisetron hydrochloride in 0.9% sodium chloride injection were physically and chemically stable for 14 days when stored in polyolefin bags at both 4°C and 25°C.

21 CFR 522.800 - Droperidol and fentanyl citrate injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... conjunction with atropine sulfate administered at the rate of 0.02 milligram per pound of body weight, or (b) Intravenously at the rate of 1 cubic centimeter per 25 to 60 pounds of body weight in conjunction with atropine... per 40 pounds of body weight in conjunction with atropine sulfate administered at the rate of 0.02...

Stability of tramadol with three 5-HT3 receptor antagonists in polyolefin bags for patient-controlled delivery systems

PubMed Central

Chen, Fu-chao; Zhu, Jun; Li, Bin; Yuan, Fang-jun; Wang, Lin-hai

2016-01-01

Background Mixing 5-hydroxytryptamine-3 (5-HT3) receptor antagonists with patient-controlled analgesia (PCA) solutions of tramadol has been shown to decrease the incidence of nausea and vomiting associated with the use of tramadol PCA for postoperative pain. However, such mixtures are not commercially available, and the stability of the drug combinations has not been duly studied. The study aimed to evaluate the stability of tramadol with three 5-HT3 receptor antagonists in 0.9% sodium chloride injection for PCA administration. Materials and methods Test samples were prepared by adding 1,000 mg tramadol hydrochloride, 8 mg ondansetron hydrochloride, and 6 mg granisetron hydrochloride or 5 mg tropisetron hydrochloride to 100 mL of 0.9% sodium chloride injection in polyolefin bags. The samples were prepared in triplicates, stored at either 25°C or 4°C for 14 days, and assessed using the following compatibility parameters: precipitation, cloudiness, discoloration, and pH. Chemical stability was also determined using a validated high-pressure liquid chromatography method. Results All of the mixtures were clear and colorless throughout the initial observation period. No change in the concentration of tramadol hydrochloride occurred with any of the 5-HT3 receptor antagonists during the 14 days. Similarly, little or no loss of the 5-HT3 receptor antagonists occurred over the 14-day period. Conclusion Our results suggest that mixtures of tramadol hydrochloride, ondansetron hydrochloride, granisetron hydrochloride, or tropisetron hydrochloride in 0.9% sodium chloride injection were physically and chemically stable for 14 days when stored in polyolefin bags at both 4°C and 25°C. PMID:27350741

Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine in patients undergoing abdominal hysterectomy during spinal anesthesia.

PubMed

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.

[Postoperative nausea and vomiting and opioid-induced nausea and vomiting: guidelines for prevention and treatment].

PubMed

Gómez-Arnau, J I; Aguilar, J L; Bovaira, P; Bustos, F; De Andrés, J; de la Pinta, J C; García-Fernández, J; López-Alvarez, S; López-Olaondo, L; Neira, F; Planas, A; Pueyo, J; Vila, P; Torres, L M

2010-10-01

Postoperative nausea and vomiting (PONV) causes patient discomfort, lowers patient satisfaction, and increases care requirements. Opioid-induced nausea and vomiting (OINV) may also occur if opioids are used to treat postoperative pain. These guidelines aim to provide recommendations for the prevention and treatment of both problems. A working group was established in accordance with the charter of the Sociedad Española de Anestesiología y Reanimación. The group undertook the critical appraisal of articles relevant to the management of PONV and OINV in adults and children early and late in the perioperative period. Discussions led to recommendations, summarized as follows: 1) Risk for PONV should be assessed in all patients undergoing surgery; 2 easy-to-use scales are useful for risk assessment: the Apfel scale for adults and the Eberhart scale for children. 2) Measures to reduce baseline risk should be used for adults at moderate or high risk and all children. 3) Pharmacologic prophylaxis with 1 drug is useful for patients at low risk (Apfel or Eberhart 1) who are to receive general anesthesia; patients with higher levels of risk should receive prophylaxis with 2 or more drugs and baseline risk should be reduced (multimodal approach). 4) Dexamethasone, droperidol, and ondansetron (or other setrons) have similar levels of efficacy; drug choice should be made based on individual patient factors. 5) The drug prescribed for treating PONV should preferably be different from the one used for prophylaxis; ondansetron is the most effective drug for treating PONV. 6) Risk for PONV should be assessed before discharge after outpatient surgery or on the ward for hospitalized patients; there is no evidence that late preventive strategies are effective. 7) The drug of choice for preventing OINV is droperidol.

Methylphenidate Actively Induces Emergence from General Anesthesia

PubMed Central

Solt, Ken; Cotten, Joseph F.; Cimenser, Aylin; Wong, Kin F.K.; Chemali, Jessica J.; Brown, Emery N.

2011-01-01

Background Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study we tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane anesthesia. Methods Using adult rats we tested the effect of methylphenidate IV on time to emergence from isoflurane anesthesia. We then performed experiments to test separately for methylphenidate-induced changes in arousal and changes in minute ventilation. A dose-response study was performed to test for methylphenidate–induced restoration of righting during continuous isoflurane anesthesia. Surface electroencephalogram recordings were performed to observe neurophysiological changes. Plethysmography recordings and arterial blood gas analysis were performed to assess methylphenidate-induced changes in respiratory function. Droperidol IV was administered to test for inhibition of methylphenidate's actions. Results Methylphenidate decreased median time to emergence from 280 to 91 s. The median difference in time to emergence without compared to with methylphenidate was 200 [155, 331] s (median, [95% confidence interval]). During continuous inhalation of isoflurane, methylphenidate induced return of righting in a dose-dependent manner, induced a shift in electroencephalogram power from delta to theta, and induced an increase in minute ventilation. Administration of droperidol (0.5 mg/kg IV) prior to methylphenidate (5 mg/kg IV) largely inhibited methylphenidate-induced emergence behavior, electroencephalogram changes, and changes in minute ventilation. Conclusions Methylphenidate actively induces emergence from isoflurane anesthesia by increasing arousal and respiratory drive, possibly through activation of dopaminergic and adrenergic arousal circuits. Our findings suggest that methylphenidate may be clinically

Prehospital chemical restraint of a noncommunicative autistic minor by law enforcement.

PubMed

Ho, Jeffrey D; Nystrom, Paul C; Calvo, Darryl V; Berris, Marc S; Norlin, Jeffrey F; Clinton, Joseph E

2012-01-01

When responders are dealing with an agitated patient in the field, safety for all involved may sometimes only be accomplished with physical or chemical restraints. While experiences using chemical restraint in the prehospital setting are found in the medical literature, the use of this by law enforcement as a first-response restraint has not previously been described. We report a case of successful law enforcement-administered sedation of a noncommunicative, autistic, and violent minor using intramuscular droperidol and diphenhydramine. Although this case has some unique characteristics that allowed chemical restraint to be given by the law enforcement agency, it calls attention to some specific prehospital issues that need to be addressed when dealing with autistic patients with extreme agitation.

The effect of caudal vs intravenous morphine on early extubation and postoperative analgesic requirements for stage 2 and 3 single-ventricle palliation: a double blind randomized trial.

PubMed

Stuth, Eckehard A E; Berens, Richard J; Staudt, Susan R; Robertson, Frederick A; Scott, John P; Stucke, Astrid G; Hoffman, George M; Troshynski, Todd J; Tweddell, James S T; Zuperku, Edward J

2011-04-01

High-dose single-shot caudal morphine has been postulated to facilitate early extubation and to lower initial analgesic requirements after staged single-ventricle (SV) palliation. With Institutional Review Board approval and written informed parental consent, 64 SV children aged 75-1667 days were randomized to pre-incisional caudal morphine-bupivacaine (100 μg·kg(-1) morphine (concentration 0.1%), mixed with 0.25% bupivacaine with 1 : 200,000 epinephrine, total 1 ml·kg(-1)) and postcardiopulmonary bypass (CPB) intravenous (IV) droperidol (75 μg·kg(-1)) ('active caudal group') or pre-incisional caudal saline (1 ml·kg(-1)) and post-CPB IV morphine (150 μg·kg(-1)) with droperidol (75 μg·kg(-1)) ('active IV group'). Assignment remained concealed from families and the care teams throughout the trial. Early extubation failure rates (primary or reintubation within 24 h), time to first postoperative rescue morphine analgesia, and 12-h postoperative morphine requirements were assessed for extubated patients. Thirty-one (12 stage 2) SV patients received caudal morphine and 32 (15 stage 2) received IV morphine. Extubation failure rates were 6/31 (19%) for caudal and 5/32 (16%) for IV morphine. For successfully extubated patients (n = 54), active caudal treatment significantly delayed the need for postoperative rescue morphine in stage 3 patients (P = 0.02) but not in stage 2 patients (P = 0.189) (Kaplan-Meier survival analysis with LogRank test). The reduction in 12-h postoperative morphine requirements with active caudal treatment did not reach significance (P = 0.085) but morphine requirements were significantly higher for stage 2 compared with stage 3 patients (P < 0.001) (two-way anova in n = 50 extubated patients). High-dose caudal morphine with bupivacaine delayed the need for rescue morphine analgesia in stage 3 patients. All stage 2 patients required early rescue morphine and had significantly higher postoperative 12-h morphine requirements than stage 3

Pharmacological characterization of the 5-HT receptor-mediated contraction in the mouse isolated ileum

PubMed Central

Tuladhar, B R; Womack, M D; Naylor, R J

2000-01-01

The pharmacological characterization of a 5-HT receptor-mediated contractile response in the mouse isolated ileum is described. In the presence of methysergide (1 μM), 5-hydroxytryptamine (5-HT, 0.3–100 μM) produced phasic concentration-dependent contractions of segments of the mouse isolated ileum with a pEC50 value of 5.47±0.09. The 5-HT3 receptor selective agonists m-chlorophenylbiguanide (0.3–100 μM, pEC50 5.81±0.04), 1-phenylbiguanide (3–100 μM, pEC50 5.05±0.06) and 2-methyl-5-HT (3–100 μM, pEC50 5.00±0.07) acted as full agonists to induce contractile responses. 5-methoxytryptamine (0.1–100 μM), RS 67506 (0.1–100 μM) and α-methyl-5-HT (0.1–100 μM) failed to mimic the 5-HT responses. The contractile response to 5-HT was not antagonized by either 5-HT2 receptor antagonists ritanserin (0.1 μM) or ketanserin (1 μM) nor the 5-HT4 receptor antagonist SB 204070 (0.1 μM). The 5-HT3 receptor selective antagonists granisetron (0.3–1 nM), tropisetron (1–10 nM), ondansetron (10 nM–1 μM) and MDL 72222 (10 nM–1 μM) caused rightward displacement of the concentration-response curves to 5-HT. The lower concentrations of the antagonists caused approximate parallel rightward shifts of the concentration-response curves to 5-HT with apparent pKB values for granisetron (9.70±0.39), tropisetron (9.18±0.20), ondansetron (8.84±0.24) and MDL 72222 (8.65±0.35). But higher concentrations of antagonists resulted in a progressive reduction in the maximum responses. The contractile response to 5-HT was abolished by tetrodotoxin (0.3 μM); atropine (0.1 and 1 μM) decreased the maximum response of the 5-HT concentration-response curve by approximately 65%. It is concluded that a neuronally located 5-HT3 receptor mediates a contractile response to 5-HT in the mouse ileum. The 5-HT3 receptor in the mouse ileum has a different pharmacological profile to that reported for the guinea-pig ileum. PMID:11139451

The effect of different anesthetics on neurovascular coupling

PubMed Central

Franceschini, Maria Angela; Radhakrishnan, Harsha; Thakur, Kiran; Wu, Weicheng; Ruvinskaya, Svetlana; Carp, Stefan; Boas, David A.

2010-01-01

To date, the majority of neurovascular coupling studies focused on the thalamic afferents' activity in layer IV and the corresponding large spiking activity as responsible for functional hyperemia. This paper highlights the role of the secondary and late cortico-cortical transmission in neurovascular coupling. Simultaneous scalp electroencephalography (EEG) and diffuse optical imaging (DOI) measurements were obtained during multiple conditions of event-related electrical forepaw stimulation in 33 male Sprague-Dawley rats divided into 6 groups depending on the maintaining anesthetic - alpha-chloralose, pentobarbital, ketamine-xylazine, fentanyl-droperidol, isoflurane, or propofol. The somatosensory evoked potentials (SEP) were decomposed into four components and the question of which best predicts the hemodynamic responses was investigated. Results of the linear regression analysis show that the hemodynamic response is best correlated with the secondary and late cortico-cortical transmissions and not with the initial thalamic input activity in layer IV. Baseline cerebral blood flow (CBF) interacts with neural activity and influences the evoked hemodynamic responses. Finally, neurovascular coupling appears to be the same across all anesthetics used. PMID:20350606

Anti-Hu antibodies activate enteric and sensory neurons

PubMed Central

Li, Qin; Michel, Klaus; Annahazi, Anita; Demir, Ihsan E.; Ceyhan, Güralp O.; Zeller, Florian; Komorowski, Lars; Stöcker, Winfried; Beyak, Michael J.; Grundy, David; Farrugia, Gianrico; De Giorgio, Roberto; Schemann, Michael

2016-01-01

IgG of type 1 anti-neuronal nuclear antibody (ANNA-1, anti-Hu) specificity is a serological marker of paraneoplastic neurological autoimmunity (including enteric/autonomic) usually related to small-cell lung carcinoma. We show here that IgG isolated from such sera and also affinity-purified anti-HuD label enteric neurons and cause an immediate spike discharge in enteric and visceral sensory neurons. Both labelling and activation of enteric neurons was prevented by preincubation with the HuD antigen. Activation of enteric neurons was inhibited by the nicotinic receptor antagonists hexamethonium and dihydro-β-erythroidine and reduced by the P2X antagonist pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid (PPADS) but not by the 5-HT3 antagonist tropisetron or the N-type Ca-channel blocker ω-Conotoxin GVIA. Ca++ imaging experiments confirmed activation of enteric neurons but not enteric glia. These findings demonstrate a direct excitatory action of ANNA-1, in particular anti-HuD, on visceral sensory and enteric neurons, which involves nicotinic and P2X receptors. The results provide evidence for a novel link between nerve activation and symptom generation in patients with antibody-mediated gut dysfunction. PMID:27905561

An update on pharmacotherapy for the treatment of fibromyalgia.

PubMed

Calandre, Elena P; Rico-Villademoros, Fernando; Slim, Mahmoud

2015-06-01

Fibromyalgia is a syndrome characterized by chronic generalized pain in addition to different symptoms such as fatigue, sleep disturbances, stiffness, cognitive impairment, and psychological distress. Multidisciplinary treatment combining pharmacological and nonpharmacological therapies is advised. Publications describing randomized controlled trials and long-term extension studies evaluating drug treatment for fibromyalgia were searched in PubMed and Scopus and included in this review. Different drugs are recommended for the treatment of fibromyalgia by different published guidelines, although only three of them have been approved for this indication by the US FDA, and none have been approved by the European Medicines Agency. According to the available evidence, pregabalin, duloxetine and milnacipran should be the drugs of choice for the treatment of this disease, followed by amitriptyline and cyclobenzaprine. Other drugs with at least one positive clinical trial include some selective serotonin reuptake inhibitors, moclobemide, pirlindole, gabapentin, tramadol, tropisetron, sodium oxybate and nabilone. None of the currently available drugs are fully effective against the whole spectrum of fibromyalgia symptoms, namely pain, fatigue, sleep disturbances and depression, among the most relevant symptoms. Combination therapy is an option that needs to be more thoroughly investigated in clinical trials.

Pharmacological profile of the receptors that mediate external carotid vasoconstriction by 5-HT in vagosympathectomized dogs.

PubMed Central

Villalón, C. M.; Ramírez-San Juan, E.; Castillo, C.; Castillo, E.; López-Muñoz, F. J.; Terrón, J. A.

1995-01-01

1. 5-Hydroxytryptamine (5-HT) can produce vasodilatation or vasoconstriction of the canine external carotid bed depending upon the degree of carotid sympathetic tone. Hence, external carotid vasodilatation to 5-HT in dogs with intact sympathetic tone is primarily mediated by prejunctional 5-HT1-like receptors similar to the 5-HT1D subtype, which inhibit the carotid sympathetic outflow. The present investigation is devoted to the pharmacological analysis of the receptors mediating external carotid vasoconstriction by 5-HT in vagosympathectomized dogs. 2. Intracarotid (i.c.) infusions for 1 min of 5-HT (0.3, 1, 3, 10, 30 and 100 micrograms) resulted in dose-dependent decreases in both external carotid blood flow and the corresponding conductance; both mean arterial blood pressure and heart rate remained unchanged during the infusions of 5-HT. These responses to 5-HT were resistant to blockade by antagonists at 5-HT2 (ritanserin) and 5-HT3/5-HT4 (tropisetron) receptors, but were partly blocked by the 5-HT1-like and 5-HT2 receptor antagonist, methiothepin (0.3 mg kg-1); higher doses of methiothepin (1 and 3 mg kg-1) caused little, if any, further blockade. These methiothepin (3 mg kg-1)-resistant responses to 5-HT were not significantly antagonized by MDL 72222 (0.3 mg kg-1) or tropisetron (3 mg kg-1). 3. The external carotid vasoconstrictor effects of 5-HT were mimicked by the selective 5-HT1-like receptor agonist, sumatriptan (3, 10, 30 and 100 micrograms during 1 min, i.c.), which produced dose-dependent decreases in external carotid blood flow and the corresponding conductance; these effects of sumatriptan were dose-dependently antagonized by methiothepin (0.3, 1 and 3 mg kg-1), but not by 5-HT1D-like receptor blocking doses of metergoline (0.1 mg kg-1). 4. The above vasoconstrictor effects of 5-HT remained unaltered after administration of phentolamine, propranolol, atropine, hexamethonium, brompheniramine, cimetidine and haloperidol, thus excluding the

[No inhibition of intestinal motility following ketamine-midazolam anesthesia. A comparison of anesthesia with enflurane and fentanyl/midazolam].

PubMed

Freye, E; Knüfermann, V

1994-02-01

Postoperative intestinal atonia is a complication which is likely to occur in patients predisposed for constipation and in patients after intra-abdominal operations. The postoperative delay of bowel movement, however, is often also related to the type of anaesthesia being used. In order to evaluate the magnitude of an anaesthetic-induced postoperative delay of bowel movement, two types of intravenous-based anaesthesia using fentanyl/midazolam (1 mg/25 mg; dosage 0.1 ml/kg/h), and ketamine/midazolam (250 mg/25 mg; dosage 0.1 ml/kg/h) respectively were compared with a volatile anaesthetic technique (enflurane; mean concentration 1.5 vol%). METHODS. In three groups of patients (each n = 15) undergoing elective surgery of the lower extremities, induction of anaesthesia was accomplished with methohexital (1-1.5 mg/kg) to facilitate intubation. For the maintenance of muscle relaxation vecuronium bromide was used. All patients were given droperidol to prevent postoperative emesis, and they were artificially ventilated with N2O/O2 (60:40) to normal end-expiratory CO2 concentrations. No anticholinergic agents were used at the end of operation since they are known to interfere with bowel motility. In order to determine gastro-intestinal motility, the H2 exhalation test was used. For this purpose 40 g lactulose in 100 ml of water was given to all patients via a gastral tube shortly before extubation. Lactulose is broken down by bacteria once it enters the colon, and H2 is released, taken up by the vascular system and exhaled. Postoperatively, patients were asked to exhale into a 20-ml syringe every 10 min. The content was analysed for hydrogen (ppm), using an electrochemical sensor (GMI exhaled hydrogen monitor). From the time of lactulose instillation to a threefold increase in end-expiratory hydrogen concentration (compared to the preoperative value), gastro-coecal transit time was computed. RESULTS. All three groups of patients were comparable in age, height and body

Pharmacological profile of dexketoprofen in orofacial pain.

PubMed

Miranda, Hugo F; Sierralta, Fernando; Aranda, Nicolás; Noriega, Viviana; Prieto, Juan Carlos

2016-12-01

Non-steroidal anti-inflammatory drugs (NSAIDs) may act through others mechanisms, in addition to inhibition of prostaglandin synthesis. These includes cholinergic, NO, serotonergic and opioids pathways. The aim of this work was to evaluate the effect of systemic action of (S)-+-ketoprofen (dexketoprofen, DEX) on pain behaviors using the orofacial formalin test in mice and the potential involvement of cholinergic, NO, serotonergic and opioids pathways. The pretreatment of the mice with 1mg/kg ip of atropine or opoid antagonists: 1mg/kg, ip of NTX or 1mg/kg ip of NTI or 1mg/kg of NOR-BNI ip, did not produce significant change in the ED 50 values of the antinociception to orofacial test induced by DEX. The pretreatment of the mice with 0.5mg/kg ip tropisetron, increased in a significant fashion the values of ED 50 of DEX. When the mice were treated with 5mg/kg ip of L-NAME or 25mg/kg ip of aminoguanidine or 50mg/kg ip of 7-nitroindazole reversed the antinociception of DEX. The findings of this study demonstrate activation of NO and 5-HTpathways play important roles in the systemic antinociceptive effect of DEX in a murine model of inflammatory pain. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Joint BAP NAPICU evidence-based consensus guidelines for the clinical management of acute disturbance: De-escalation and rapid tranquillisation.

PubMed

Patel, Maxine X; Sethi, Faisil N; Barnes, Thomas Re; Dix, Roland; Dratcu, Luiz; Fox, Bernard; Garriga, Marina; Haste, Julie C; Kahl, Kai G; Lingford-Hughes, Anne; McAllister-Williams, Hamish; O'Brien, Aileen; Parker, Caroline; Paterson, Brodie; Paton, Carol; Posporelis, Sotiris; Taylor, David M; Vieta, Eduard; Völlm, Birgit; Wilson-Jones, Charlotte; Woods, Laura

2018-06-01

The British Association for Psychopharmacology and the National Association of Psychiatric Intensive Care and Low Secure Units developed this joint evidence-based consensus guideline for the clinical management of acute disturbance. It includes recommendations for clinical practice and an algorithm to guide treatment by healthcare professionals with various options outlined according to their route of administration and category of evidence. Fundamental overarching principles are included and highlight the importance of treating the underlying disorder. There is a focus on three key interventions: de-escalation, pharmacological interventions pre-rapid tranquillisation and rapid tranquillisation (intramuscular and intravenous). Most of the evidence reviewed relates to emergency psychiatric care or acute psychiatric adult inpatient care, although we also sought evidence relevant to other common clinical settings including the general acute hospital and forensic psychiatry. We conclude that the variety of options available for the management of acute disturbance goes beyond the standard choices of lorazepam, haloperidol and promethazine and includes oral-inhaled loxapine, buccal midazolam, as well as a number of oral antipsychotics in addition to parenteral options of intramuscular aripiprazole, intramuscular droperidol and intramuscular olanzapine. Intravenous options, for settings where resuscitation equipment and trained staff are available to manage medical emergencies, are also included.

[Qualitative comparison of modified neurolept-, balanced and intravenous anesthesia. 2. Results of a clinical study, 1992].

PubMed

Harke, H; Schmidt, K; Gretenkort, P; Hommerich, P; Deutschmann, S; Eckes, C; Hense, W; Kleemann, A; Rehorn, W; Stöcker, H

1995-10-01

The safety and tolerance of neuroleptanaesthesia (NLA), balanced anaesthesia (BAL), and intravenous anaesthesia with propofol (IVA) were analysed for the first time in a prospective, randomised clinical trial. METHODS. In all, 1318 surgical patients received either NLA, BAL, or IVA. Patients who had regional anaesthesia, were aged under 18 years, or were non-cooperative or vitally threatened (ASA class i.v. to V) did not participate in the study. Premedication and anaesthetic course were set up at a standard of 30% oxygen and 70% nitrous oxide. Incidents, events, and complications due to anaesthesia were obtained (IEC key of the German Society of Anaesthesia and Critical Care Medicine, DGAI). Furthermore, postanaesthetic alertness based on specific recovery tests and the quality of anaesthesia from the patient's viewpoint, rated by patient questionnaires from the DGAI were evaluated. All parameters were calculated and checked for statistical significance using the chi-square test. RESULTS AND DISCUSSION. The groups were broadly comparable with respect to age (P = 0.91), ASA class (P = 0.42), preoperative blood pressure (P = 0.36), and length of anaesthesia (P = 0.82). The anaesthesia, which averaged 103 min, comprised the following regimens: (1) NLA: 7.1 mg droperidol and 0.008 mg/kg body weight fentanyl, (2) IVA: 493.4 mg propofol and 0.004 mg/kg body weight fentanyl, and (3) BAL: 2.6 mg droperidol and 0.004 mg/kg body weight fentanyl with 0.4 vol.% isoflurane. With respect to anaesthetic risk, the following reactions were observed: the use of NLA led to a high incidence of tachycardia (P = 0.001), arrhythmias (P = 0.05), and hypertensive reactions (P = 0.001), whereas in the IVA group only hypotension (P = 0.0001) occurred. However, after the use of BAL none of the aforementioned complications were detectable to any considerable degree. Similarly, patients who had cardiac disease showed greater IEC changes after the use of NLA than after BAL or IVA (P = 0

Study on the interactions of antiemetic drugs and 12-tungstophosphoric acid by absorption and resonance Rayleigh scattering spectra and their analytical applications

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.

Effect of preincision versus postincision infiltration with bupivacaine on postoperative pain.

PubMed

Victory, R A; Gajraj, N M; Van Elstraete, A; Pace, N A; Johnson, E R; White, P F

1995-05-01

To compare the efficacy of preincision wound infiltration with bupivacaine to wound infiltration at the end of the operation. A prospective, randomized, double-blind study. University medical center. 56 ASA status I and II women scheduled for abdominal hysterectomy were randomly assigned to one of three treatment groups. Group 1 (control) received no local anesthetic infiltration. Group 2 received subcutaneous infiltration with 40 ml of bupivacaine 0.5% (pH 6.9) 15 minutes prior to incision. Group 3 received wound infiltration with a similar solution at the end of surgery. Anesthesia was induced with thiopental 3.0 mg/kg i.v., droperidol 50 micrograms/kg i.v., and sufentanil 0.5 microgram/kg i.v. and maintained with nitrous oxide 67% in oxygen and sufentanil 0.1 microgram/kg IV boluses as required. Postoperative pain was treated with morphine via a patient-controlled analgesia delivery system for 24 hours, followed by oral hydrocodone for 3 days. The opioid consumption was recorded for 4 days postoperatively. Pain scores were measured at 4 to 8-hour intervals using 100 mm visual analog scales. There was no difference in either the opioid analgesic requirements or the pain scores between the three study groups. Wound infiltration, either preincision or postincision, had no clinically significant effect on the pain scores or analgesic requirements following abdominal hysterectomy.

Hydrogen Bonding: Between Strengthening the Crystal Packing and Improving Solubility of Three Haloperidol Derivatives.

PubMed

Saluja, Hardeep; Mehanna, Ahmed; Panicucci, Riccardo; Atef, Eman

2016-06-01

The purpose of this study is to confirm the impact of polar functional groups on inter and intra-molecular hydrogen bonding in haloperidol (HP) and droperidol (DP) and, hence, their effects on dissolution using a new approach. To confirm our theory, a new molecule: deshydroxy-haloperidol (DHP) was designed and its synthesis was requested from a contract laboratory. The molecule was then studied and compared to DP and HP. Unlike DHP, both the HP and DP molecules have hydrogen donor groups, therefore, DHP was used to confirm the relative effects of the hydrogen donor group on solubility and crystal packing. The solid dispersions of the three structurally related molecules: HP, DP, and DHP were prepared using PVPK30, and characterized using XRPD and IR. A comparative dissolution study was carried out in aqueous medium. The absence of a hydrogen bonding donor group in DHP resulted in an unexpected increase in its aqueous solubility and dissolution rate from solid dispersion, which is attributed to weaker crystal pack. The increased dissolution rate of HP and DP from solid dispersions is attributed to drug-polymer hydrogen bonding that interferes with the drug-drug intermolecular hydrogen bonding and provides thermodynamic stability of the dispersed drug molecules. The drug-drug intermolecular hydrogen bond is the driving force for precipitation and crystal packing.

A review of granisetron, 5-hydroxytryptamine3 receptor antagonists, and other antiemetics.

PubMed

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.

Interventions for preventing or treating alcohol hangover: systematic review of randomised controlled trials

PubMed Central

Pittler, Max H; Verster, Joris C; Ernst, Edzard

2005-01-01

Objective To assess the clinical evidence on the effectiveness of any medical intervention for preventing or treating alcohol hangover. Data sources Systematic searches on Medline, Embase, Amed, Cochrane Central, the National Research Register (UK), and ClincalTrials.gov (USA); hand searches of conference proceedings and bibliographies; contact with experts and manufacturers of commercial preparations. Language of publication was not restricted. Study selection and data extraction All randomised controlled trials of any medical intervention for preventing or treating alcohol hangover were included. Trials were considered if they were placebo controlled or controlled against a comparator intervention. Titles and abstracts of identified articles were read and hard copies were obtained. The selection of studies, data extraction, and validation were done independently by two reviewers. The Jadad score was used to evaluate methodological quality. Results Fifteen potentially relevant trials were identified. Seven publications failed to meet all inclusion criteria. Eight randomised controlled trials assessing eight different interventions were reviewed. The agents tested were propranolol, tropisetron, tolfenamic acid, fructose or glucose, and the dietary supplements Borago officinalis (borage), Cynara scolymus (artichoke), Opuntia ficus-indica (prickly pear), and a yeast based preparation. All studies were double blind. Significant intergroup differences for overall symptom scores and individual symptoms were reported only for tolfenamic acid, γ linolenic acid from B officinalis, and a yeast based preparation. Conclusion No compelling evidence exists to suggest that any conventional or complementary intervention is effective for preventing or treating alcohol hangover. The most effective way to avoid the symptoms of alcohol induced hangover is to practise abstinence or moderation. PMID:16373736

In vitro study on antioxidant potential of various drugs used in the perioperative period.

PubMed

Kang, M Y; Tsuchiya, M; Packer, L; Manabe, M

1998-01-01

Since surgical trauma not only intensifies the oxidative stress by generating reactive oxygen species (ROS), but also weakens the biological defense system against ROS attack, the antioxidant activity of drugs used during the perioperative period, which possibly normalizes the impaired redox state in the patient, is of fundamental importance and great clinical interest. We have applied the phycoerythrin fluorescence-based assay, in which 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-generated peroxyl radical attacks B-phycoerythrin (B-PE) to lead to a sensitive decrease in its fluorescence intensity linearly, to evaluate the antioxidant activity of major drugs in anesthetic practice. By the protective effect on B-PE fluorescence decay, the antioxidant activities of the drugs were classified into three groups: Group I drugs, which only slowed B-PE fluorescence decay (nicardipine, verapamil, diltiazem, ephedrine, aminophylline, vecuronium, lidocaine, mepivacaine, midazolam, thiamylal, droperidol, ketamine, hydroxyzine, butorphanol, prednisolone, hydrocortisone, betamethasone, dexamethasone, methylprednisolone, and furosemide); Group II drugs, which protected B-PE oxidation completely and stopped fluorescence decay in a certain duration (dopamine, epinephrine, norepinephrine, dobutamine, isoproterenol, and buprenorphine); and Group III drugs, which had no protective effect on B-PE oxidation (nitroglycerin, prostaglandin E1, neostigmine, pancuronium, suxamethonium, atropine, bupivacaine, pentazocine, and heparin). These results indicate that Group I and II drugs exert some antioxidant activity in vitro, as measured by their protection of fluorescence decay of B-PE. Careful consideration of these properties might, then, serve to facilitate more efficient drug application.

Evidence based knee injections for the management of arthritis

PubMed Central

Cheng, Olivia T.; Souzdalnitski, Dmitri; Vrooman, Bruce; Cheng, Jianguo

2012-01-01

Objective Arthritis of the knee affects 46 million Americans. We aimed to determine the level of evidence of intraarticular knee injections in the management of arthritic knee pain. Methods We systematically searched PUBMED/MEDLINE and the Cochrane databases for articles published on knee injections and evaluated their level of evidence and recommendations according to established criteria. Results The evidence supports the use of intraarticular corticosteroid injections for rheumatoid arthritis (1A+ level), osteoarthritis (1A+ level), and juvenile idiopathic arthritis (2C+ level). Pain relief and functional improvement are significant for months up to one year after the injection. Triamcinolone hexacetonide offers an advantage over triamcinolone acetonide and should be the intraarticular steroid of choice (2B+ level). Intraarticular injection of hyaluronate may provide longer pain relief than steroid injection in osteoarthritis (2B+ level). It can also be effective for rheumatoid arthritis knee pain (1A+ level). However, it is only recommended for patients with significant surgical risk factors and for patients with mild radiographic disease in whom conservative treatment has failed (2B± level). Botulinum toxin Type A injection is effective in reducing arthritic knee pain (2B+ level) and so is tropisetron (2B+ level) and tanezumab (2B+ level). The new agents, such as rAAV2-TNFR:Fc, SB-210396/CE 9.1, and various radioisotopes have provided various degrees of success, but their long-term safety and efficacy remains to be determined. Conclusions We conclude that strong evidence supports the use of intraarticular knee injection as a valuable intervention in the continuum of management of arthritis between conservative treatment and knee surgeries. PMID:22621287

Evidence for a central mechanism of action of S-(+)-ketoprofen.

PubMed

Díaz-Reval, María Irene; Ventura-Martínez, Rosa; Déciga-Campos, Myrna; Terrón, José A; Cabré, Francesc; López-Muñoz, Francisco Javier

2004-01-12

It has been observed that some non-steroidal anti-inflammatory drugs (NSAIDs) may act through several mechanisms, in addition to central inhibition of prostaglandin synthesis. These other mechanisms include the L-arginine-nitric oxide (L-arginine-NO) pathway, as well as endogenous opiate and serotonergic mechanisms. Some of these mechanisms can explain the efficacy of NSAIDs in chronic pain conditions such as rheumatoid arthritis. The present study was designed to elucidate the involvement of the above pathways/mechanisms in the antinociceptive effect of S-(+)-ketoprofen at supraspinal and spinal levels. S-(+)-ketoprofen induced dose-dependent antinociception in the pain-induced functional impairment model in the rat. The antinociceptive effect of S-(+)-ketoprofen was not altered by i.t. or intracerebroventricula (i.c.v.) pre-treatment with L-arginine (29.6 microg/site) and L-nitro-arginine-monomethylester (L-NAME) (21.1 microg/site) and neither was the effect of S-(+)-ketoprofen modified by the opiate antagonist, naloxone (1 mg/kg, s.c.). In marked contrast, both i.c.v. administration of the 5-hydroxytryptamine (5-HT)(1)/5-HT(2)/5-HT(7) receptor antagonist, methiothepin (1.5 microg/site), and i.t. administration of the 5-HT(3)/5-HT(4) receptor antagonist, tropisetron (0.9 microg/site), significantly inhibited the S-(+)-ketoprofen-induced antinociceptive effect. These data suggest that the antinociceptive response to S-(+)-ketoprofen involves serotoninergic mechanisms via both supraspinal 5-HT(1)/5-HT(2)/5-HT(7) receptors and 5-HT(3) receptors located at spinal level. A role of the L-arginine-NO and opiate systems in S-(+)-ketoprofen-induced antinociception in the pain-induced functional impairment model in the rat model seems unlikely.

Canadian Headache Society systematic review and recommendations on the treatment of migraine pain in emergency settings.

PubMed

Orr, Serena L; Aubé, Michel; Becker, Werner J; Davenport, W Jeptha; Dilli, Esma; Dodick, David; Giammarco, Rose; Gladstone, Jonathan; Leroux, Elizabeth; Pim, Heather; Dickinson, Garth; Christie, Suzanne N

2015-03-01

There is a considerable amount of practice variation in managing migraines in emergency settings, and evidence-based therapies are often not used first line. A peer-reviewed search of databases (MEDLINE, Embase, CENTRAL) was carried out to identify randomized and quasi-randomized controlled trials of interventions for acute pain relief in adults presenting with migraine to emergency settings. Where possible, data were pooled into meta-analyses. Two independent reviewers screened 831 titles and abstracts for eligibility. Three independent reviewers subsequently evaluated 120 full text articles for inclusion, of which 44 were included. Individual studies were then assigned a US Preventive Services Task Force quality rating. The GRADE scheme was used to assign a level of evidence and recommendation strength for each intervention. We strongly recommend the use of prochlorperazine based on a high level of evidence, lysine acetylsalicylic acid, metoclopramide and sumatriptan, based on a moderate level of evidence, and ketorolac, based on a low level of evidence. We weakly recommend the use of chlorpromazine based on a moderate level of evidence, and ergotamine, dihydroergotamine, lidocaine intranasal and meperidine, based on a low level of evidence. We found evidence to recommend strongly against the use of dexamethasone, based on a moderate level of evidence, and granisetron, haloperidol and trimethobenzamide based on a low level of evidence. Based on moderate-quality evidence, we recommend weakly against the use of acetaminophen and magnesium sulfate. Based on low-quality evidence, we recommend weakly against the use of diclofenac, droperidol, lidocaine intravenous, lysine clonixinate, morphine, propofol, sodium valproate and tramadol. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Risk factors for unstable blood glucose level: integrative review of the risk factors related to the nursing diagnosis.

PubMed

Teixeira, Andressa Magalhães; Tsukamoto, Rosangela; Lopes, Camila Takáo; Silva, Rita de Cassia Gengo E

2017-06-05

-se que alteração nos níveis de hemoglobina glicada, índice de massa corpórea>31 Kg/m2, história prévia de hipoglicemia, déficit cognitivo/demência, neuropatia autonômica cardiovascular, comorbidades e perda de peso correspondiam a fatores de risco descritos pela NANDA International . Outros fatores de risco identificados foram: idade avançada, raça negra, maior tempo de diagnóstico de diabetes, sonolência diurna, macroalbuminúria, polimorfismos genéticos, insulinoterapia, uso de antidiabéticos orais, uso de metoclopramida, atividade física inadequada e glicemia de jejum baixa. identificaram-se fatores de risco do diagnóstico risco de glicemia instável para pessoas com diabetes mellitus tipo 2, dos quais 42% correspondiam àqueles da NANDA International . Esses achados podem contribuir para a prática de enfermeiros clínicos na prevenção dos efeitos deletérios da variação glicêmica. identificar evidencias en la literatura acerca de posibles factores de riesgo del diagnóstico "riesgo de nivel de glucemia inestable" para personas con diabetes mellitus tipo 2 y compararlos con los factores de riesgo descritos por la NANDA International . revisión integradora orientada por la pregunta: ¿Cuáles son los factores de riesgo de nivel de glucemia inestable en personas con diabetes mellitus tipo 2? Se incluyeron estudios primarios cuyos resultados eran variaciones en los niveles glucémicos, publicados en inglés, portugués o español en el PubMed o CINAHL entre 2010 y 2015. se observó que una alteración en los niveles de: hemoglobina glucosilada, índice de masa corporal >31 Kg/m2, historia previa de hipoglucemia, déficit cognitivo/demencia, neuropatía autonómica cardiovascular, comorbilidades y pérdida de peso, correspondían a factores de riesgo descritos por la NANDA International . Otros factores de riesgo identificados fueron: edad avanzada, raza negra, mayor tiempo de diagnóstico de diabetes, somnolencia diurna, macroalbuminuria

Low doses of haloperidol combined with ondansetron are not effective for prophylaxis of postoperative nausea and vomiting in susceptible patients.

PubMed

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.

Potential intravenous drug interactions in intensive care.

PubMed

Moreira, Maiara Benevides; Mesquita, Maria Gefé da Rosa; Stipp, Marluci Andrade Conceição; Paes, Graciele Oroski

2017-07-20

To analyze potential intravenous drug interactions, and their level of severity associated with the administration of these drugs based on the prescriptions of an intensive care unit. Quantitative study, with aretrospective exploratory design, and descriptive statistical analysis of the ICU prescriptions of a teaching hospital from March to June 2014. The sample consisted of 319 prescriptions and subsamples of 50 prescriptions. The mean number of drugs per patient was 9.3 records, and a higher probability of drug interaction inherent to polypharmacy was evidenced. The study identified severe drug interactions, such as concomitant administration of Tramadol with selective serotonin reuptake inhibitor drugs (e.g., Metoclopramide and Fluconazole), increasing the risk of seizures due to their epileptogenic actions, as well as the simultaneous use of Ranitidine-Fentanyl®, which can lead to respiratory depression. A previous mapping of prescriptions enables the characterization of the drug therapy, contributing to prevent potential drug interactions and their clinical consequences. Analisar as potenciais interações medicamentosas intravenosas e seu grau de severidade associadas à administração desses medicamentos a partir das prescrições do Centro de Terapia Intensiva. Estudo quantitativo, tipologia retrospectiva exploratória, com análise estatística descritiva das prescrições medicamentosas do Centro de Terapia Intensiva de um Hospital Universitário, no período de março-junho/2014. A amostra foi composta de 319 prescrições e subamostras de 50 prescrições. Constatou-se que a média de medicamentos por paciente foi de 9,3 registros, e evidenciou-se maior probabilidade para ocorrência de interação medicamentosa inerente à polifarmácia. O estudo identificou interações medicamentosas graves, como a administração concomitante de Tramadol com medicamentos inibidores seletivos da recaptação da serotonina, (exemplo: Metoclopramida e Fluconazol

Actions of 5-hydroxytryptamine and 5-HT1A receptor ligands on rat dorso-lateral septal neurones in vitro.

PubMed

Van den Hooff, P; Galvan, M

1992-08-01

1. The actions of 5-hydroxytryptamine (5-HT) and some 5-HT1A receptor ligands on neurones in the rat dorso-lateral septal nucleus were recorded in vitro by intracellular recording techniques. 2. In the presence of tetrodotoxin (1 microM) to block any indirect effects, bath application of 5-HT (0.3-30 microM) hyperpolarized the neurones in a concentration-dependent manner and reduced membrane resistance. The hyperpolarization did not exhibit desensitization and was sometimes followed by a small depolarization. 3. The 5-HT1A receptor ligands, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) and buspirone but not the non-selective 5-HT1 receptor agonist, 1-m-trifluoromethylphenylpiperazine (TFMPP), also hyperpolarized the neurones. 4. 5-HT, 8-OH-DPAT and DP-5-CT appeared to act as full agonists whereas buspirone behaved as a partial agonist. The estimated EC50S were: DP-5-CT 15 nM, 8-OH-DPAT 110 nM, 5-HT 3 microM and buspirone 110 nM. 5. At a concentration of 3 microM, the putative 5-HT1A receptor antagonists, spiperone, methiothepin, NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine) and MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl-methylamino)ethyl]-8- azaspiro[4,5]decane-7,9-dione methyl sulphonate), produced a parallel rightward shift in the concentration-response curve to 5-HT with no significant reduction in the maximum response. The estimated pA2 values were: NAN-190 6.79, MDL 73005EF 6.59, spiperone 6.54 and methiothepin 6.17.6. The 5-HT2/5-HTlc receptor antagonist, ketanserin (3 microM) and the 5HT3 receptor antagonist, tropisetron (3 microM) did not antagonize the 5-HT-induced hyperpolarizations; however, ketanserin blocked the depolarization which sometimes followed the hyperpolarization.7. It is concluded that the 5-HT-induced membrane hyperpolarization of rat dorso-lateral septal neurones is mediated by 5-HTA receptors.

Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis.

PubMed

Tricco, Andrea C; Blondal, Erik; Veroniki, Areti Angeliki; Soobiah, Charlene; Vafaei, Afshin; Ivory, John; Strifler, Lisa; Cardoso, Roberta; Reynen, Emily; Nincic, Vera; Ashoor, Huda; Ho, Joanne; Ng, Carmen; Johnson, Christy; Lillie, Erin; Antony, Jesmin; Roberts, Derek J; Hemmelgarn, Brenda R; Straus, Sharon E

2016-12-23

Although serotonin (5-HT 3 ) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT 3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT 3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13-4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a

Survey of methadone-drug interactions among patients of methadone maintenance treatment program in Taiwan

PubMed Central

2012-01-01

Background Although methadone has been used for the maintenance treatment of opioid dependence for decades, it was not introduced in China or Taiwan until 2000s. Methadone-drug interactions (MDIs) have been shown to cause many adverse effects. However, such effects have not been scrutinized in the ethnic Chinese community. Methods The study was performed in two major hospitals in southern Taiwan. A total of 178 non-HIV patients aged ≥ 20 years who had participated in the Methadone Maintenance Treatment Program (MMTP) ≥ 1 month were recruited. An MDI is defined as concurrent use of drug(s) with methadone that may result in an increase or decrease of effectiveness and/or adverse effect of methadone. To determine the prevalence and clinical characteristics of MDIs, credible data sources, including the National Health Insurance (NHI) database, face-to-face interviews, medical records, and methadone computer databases, were linked for analysis. Socio-demographic and clinical factors associated with MDIs and co-medications were also examined. Results 128 (72%) MMTP patients took at least one medication. Clinically significant MDIs included withdrawal symptoms, which were found among MMTP patients co-administered with buprenorphine or tramadol; severe QTc prolongation effect, which might be associated with use of haloperidol or droperidol; and additive CNS and respiratory depression, which could result from use of methadone in combination with chlorpromazine or thioridazine. Past amphetamine use, co-infection with hepatitis C, and a longer retention in the MMTP were associated with increased odds of co-medication. Among patients with co-medication use, significant correlates of MDIs included the male gender and length of co-medication in the MMTP. Conclusions The results demonstrate clinical evidence of significant MDIs among MMTP patients. Clinicians should check the past medical history of MMTP clients carefully before prescribing medicines. Because combinations of

Characterization of prejunctional 5-HT receptors mediating inhibition of sympathetic vasopressor responses in the pithed rat.

PubMed Central

Villalón, C. M.; Contreras, J.; Ramírez-San Juan, E.; Castillo, C.; Perusquía, M.; Terrón, J. A.

1995-01-01

1. It has recently been shown that continuous infusions of 5-hydroxytryptamine (5-HT) are able to inhibit, in a dose-dependent manner, the pressor responses induced by preganglionic (T7-T9) sympathetic stimulation in pithed rats pretreated with desipramine (50 micrograms kg-1, i.v.). This inhibitory effect, besides being significantly more pronounced at lower frequencies of stimulation (0.03-I Hz) and devoid of tachyphylaxis, is reversible after interrupting the infusions of 5-HT (up to 5.6 micrograms kg-1 min-1). In the present study we have characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5-HT. 2. The inhibition induced by 5.6 micrograms kg-1 min-1 of 5-HT on sympathetically-induced pressor responses was not blocked after i.v. treatment with physiological saline (1 ml kg-1), ritanserin (0.1 mg kg-1), MDL 72222 (0.15 mg kg-1) or tropisetron (3 mg kg-1), which did not modify the sympathetically-induced pressor responses per se, but was significantly antagonized by the 5-HT1-like and 5-HT2 receptor antagonist, methysergide (0.3 mg kg-1), which also produced a slight attenuation of the pressor responses to 0.03 and 0.1 Hz per se. 3. Unexpectedly and contrasting with methysergide, the 5-HT1-like and 5-HT2 receptor antagonists, methiothepin (0.01, 0.03 and 0.1 mg kg-1) and metergoline (1 and 3 mg kg-1), apparently failed to block the above 5-HT-induced inhibition. Nevertheless, it is noteworthy that these antagonists also blocked the electrically-induced pressor responses per se, presumably by blockade of vascular alpha 1-adrenoceptors and, indeed, this property might have masked their potential antagonism at the inhibitory 5-HT1-like receptors. 4. Consistent with the above findings, 5-carboxamidotryptamine (5-CT, a potent 5-HT1-like receptor agonist), metergoline and methysergide mimicked the inhibitory action of 5-HT with the following rank order of agonist potency: 5CT > > 5-HT > metergoline > or = methysergide. 5

Interventions for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section

PubMed Central

Griffiths, James D; Gyte, Gillian ML; Paranjothy, Shantini; Brown, Heather C; Broughton, Hannah K; Thomas, Jane

2014-01-01

, 720 women). There were also reductions in postoperative nausea (average RR 0.40, 95% CI 0.25 to 0.64, four studies, 405 women) and vomiting (average RR 0.50, 95% CI 0.32 to 0.77, five studies, 565 women). We did not detect a significant reduction in intraoperative vomiting (average RR 0.56, 95% CI 0.31 to 1.00, seven studies, 668 women). Dopamine antagonists demonstrated a reduction in intraoperative nausea (average RR 0.38, 95% CI 0.25 to 0.57, nine studies, 636 women) and intraoperative vomiting (average 0.39, 95% CI 0.24 to 0.64, eight studies, 536 women), with similar reductions in postoperative nausea (average RR 0.60, 95% CI 0.40 to 0.91, five studies, 412 women) and vomiting (average RR 0.57, 95% CI 0.36 to 0.91, six studies, 472 women). These differences were observed with both metoclopramide and droperidol. Sedatives (most commonly propofol) demonstrated a reduction in intraoperative nausea (average RR 0.71, 95% CI 0.52 to 0.96, four studies, 285 women) and intraoperative vomiting (average RR 0.42, 95% CI 0.26 to 0.68, four studies, 285 women), also with a reduction in postoperative nausea (average RR 0.25, 95% CI 0.09 to 0.71, two studies 145 women) and vomiting (average RR 0.09, 95% CI 0.03 to 0.28, two studies, 145 women). Acupressure was found to be effective for intraoperative nausea (average RR 0.59, 95% CI 0.38 to 0.90, six studies, 649 women) but not postoperative nausea (average RR 0.83, 95% CI 0.68 to 1.00, three studies, 429 women). Acupressure was not effective at reducing vomiting either intraoperatively (average RR 0.74, 95% CI 0.46 to 1.18, six studies, 649 women) or postoperatively (average RR 0.69, 95% CI 0.45 to 1.06, three studies, 429 women). Other effective intervention classes included corticosteroids, antihistamines, and anticholinergics. There were insufficient data to demonstrate any class of intervention was superior to another. There were no significant differences observed in the comparison of combined versus single interventions