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Sample records for promethazine

  1. Promethazine affects autonomic cardiovascular mechanisms minimally

    NASA Technical Reports Server (NTRS)

    Brown, T. E.; Eckberg, D. L.

    1997-01-01

    Promethazine hydrochloride, Phenergan, is a phenothiazine derivative with antihistaminic (H1), sedative, antiemetic, anticholinergic, and antimotion sickness properties. These properties have made promethazine a candidate for use in environments such as microgravity, which provoke emesis and motion sickness. Recently, we evaluated carotid baroreceptor-cardiac reflex responses during two Space Shuttle missions 18 to 20 hr after the 50 mg intramuscular administration of promethazine. Because the effects of promethazine on autonomic cardiovascular mechanisms in general and baroreflex function in particular were not known, we were unable to exclude a possible influence of promethazine on our results. Our purpose was to determine the ground-based effects of promethazine on autonomic cardiovascular control. Because of promethazine's antihistaminic and anticholinergic properties, we expected that a 50-mg intramuscular injection of promethazine would affect sympathetically and vagally mediated cardiovascular mechanisms. Eight healthy young subjects, five men and three women, were studied at rest in recumbency. All reported drowsiness as a result of the promethazine injection; most also reported nervous excitation, dry mouth, and fatigue. Three subjects had significant reactions: two reported excessive anxiety and one reported dizziness. Measurements were performed immediately prior to injection and 3.1 +/- 0.1 and 19.5 +/- 0.4 hr postinjection. We found no significant effect of promethazine on resting mean R-R interval, arterial pressure, R-R interval power spectra, carotid baroreflex function, and venous plasma catecholamine levels.

  2. Promethazine

    MedlinePlus

    ... it is usually taken every 4 to 6 hours as needed. Promethazine may also be taken at bedtime the night before surgery to relieve anxiety and produce quiet sleep. Follow the directions on your prescription label ...

  3. Promethazine overdose

    MedlinePlus

    Little M. Toxicology emergencies. In: Cameron P, Jelinek G, Kelly A-M, Brown A, Little M, eds. Textbook of Adult Emergency ... US National Library of Medicine; Specialized Information Services; ... Data Network. Promethazine. Updated January 4, 2011. toxnet. ...

  4. Promethazine Misuse among Methadone Maintenance Patients and Community-Based Injection Drug Users

    PubMed Central

    Shapiro, Brad J.; Lynch, Kara L.; Toochinda, Tab; Lutnick, Alexandra; Cheng, Helen Y.; Kral, Alex H.

    2013-01-01

    Objective Promethazine has been reported to be misused in conjunction with opioids in several settings. Promethazine misuse by itself or in conjunction with opioids may have serious adverse health effects. To date, no prevalence data for the nonmedical use of promethazine has been reported. This study examines the prevalence and correlates of promethazine use in two different populations in San Francisco, California, USA: methadone maintenance clinic patients and community-based injection drug users (IDUs). Methods We analyzed urine samples for the presence of promethazine and reviewed the clinical records for 334 methadone maintenance patients at the county methadone clinic. Separately, we used targeted sampling methods to recruit and survey 139 community-based opioid IDUs about their use of promethazine. We assessed prevalence and factors associated with promethazine use with bivariate and multivariate statistics. Results The prevalence of promethazine positive urine samples among the methadone maintenance patients was 26 percent. Only 15 percent of promethazine positive patients had an active prescription for promethazine. Among IDUs reporting injection of opiates in the community-based survey, 17 percent reported having used promethazine in the past month; 24 percent of the IDUs who reported being enrolled in methadone treatment reported using promethazine in the past month. Conclusions The finding that one quarter of methadone maintenance patients in a clinic or recruited in community settings have recently used promethazine provides compelling evidence of significant nonmedical use of promethazine in this patient population. Further research is needed to establish the extent and nature of nonmedical use of promethazine. PMID:23385449

  5. Promethazine improves antibiotic efficacy and disrupts biofilms of Burkholderia pseudomallei.

    PubMed

    Sidrim, José Júlio Costa; Vasconcelos, David Caldas; Riello, Giovanna Barbosa; Guedes, Glaucia Morgana de Melo; Serpa, Rosana; Bandeira, Tereza de Jesus Pinheiro Gomes; Monteiro, André Jalles; Cordeiro, Rossana de Aguiar; Castelo-Branco, Débora de Souza Collares Maia; Rocha, Marcos Fábio Gadelha; Brilhante, Raimunda Sâmia Nogueira

    2017-01-01

    Efflux pumps are important defense mechanisms against antimicrobial drugs and maintenance of Burkholderia pseudomallei biofilms. This study evaluated the effect of the efflux pump inhibitor promethazine on the structure and antimicrobial susceptibility of B. pseudomallei biofilms. Susceptibility of planktonic cells and biofilms to promethazine alone and combined with antimicrobials was assessed by the broth microdilution test and biofilm metabolic activity was determined with resazurin. The effect of promethazine on 48 h-grown biofilms was also evaluated through confocal and electronic microscopy. The minimum inhibitory concentration (MIC) of promethazine was 780 mg l -1 , while the minimum biofilm elimination concentration (MBEC) was 780-3,120 mg l -1 . Promethazine reduced the MIC values for erythromycin, trimethoprim/sulfamethoxazole, gentamicin and ciprofloxacin and reduced the MBEC values for all tested drugs (p<0.05). Microscopic analyses demonstrated that promethazine altered the biofilm structure of B. pseudomallei, even at subinhibitory concentrations, possibly facilitating antibiotic penetration. Promethazine improves antibiotics efficacy against B. pseudomallei biofilms, by disrupting biofilm structure.

  6. Treatment efficacy of intramuscular promethazine for Space Motion Sickness

    NASA Technical Reports Server (NTRS)

    Davis, Jeffrey R.; Jennings, Richard T.; Beck, Bradley G.; Bagian, James P.

    1993-01-01

    Intramuscular promethazine and its efficacy in the treatment of Space Motion Sickness (SMS) were evaluated using standardized questions administered during postflight debriefings to crewmembers immediately after their first Shuttle flight. The comparison showed that 25 percent of crewmembers treated with IM promethazine were 'sick' on flight day 2, compared to 50 percent of crewmembers who did not receive promethazine, 90 percent reported immediate symptom relief as well. Untreated crewmembers typically have slow symptom resolution over 72-96 h, and those treated with oral scopolamine/dextroamphetamine show delayed symptom development. This study suggests that intramuscular promethazine is an effective treatment for SMS and merits continued use and further controlled investigations.

  7. Haloperidol plus promethazine for psychosis-induced aggression.

    PubMed

    Huf, Gisele; Alexander, Jacob; Gandhi, Pinky; Allen, Michael H

    2016-11-25

    Health services often manage agitated or violent people, and such behaviour is particularly prevalent in emergency psychiatric services (10%). The drugs used in such situations should ensure that the person becomes calm swiftly and safely. To examine whether haloperidol plus promethazine is an effective treatment for psychosis-induced aggression. On 6 May 2015 we searched the Cochrane Schizophrenia Group's Register of Trials, which is compiled by systematic searches of major resources (including MEDLINE, EMBASE, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings. All randomised clinical trials with useable data focusing on haloperidol plus promethazine for psychosis-induced aggression. We independently extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. We found two new randomised controlled trials (RCTs) from the 2015 update searching. The review now includes six studies, randomising 1367 participants and presenting data relevant to six comparisons.When haloperidol plus promethazine was compared with haloperidol alone for psychosis-induced aggression for the outcome not tranquil or asleep at 30 minutes, the combination treatment was clearly more effective (n=316, 1 RCT, RR 0.65, 95% CI 0.49 to 0.87, high-quality evidence). There were 10 occurrences of acute dystonia in the haloperidol alone arm and none in the combination group. The trial was stopped early as haloperidol alone was considered to be too toxic.When haloperidol plus promethazine was compared with olanzapine, high-quality data showed both approaches to be tranquillising. It was

  8. Use of promethazine to hasten adaptation to provocative motion

    NASA Technical Reports Server (NTRS)

    Lackner, J. R.; Graybiel, A.

    1994-01-01

    In an earlier study, the authors found that severely motion sick individuals could be greatly relieved of their symptoms by intramuscular injections of promethazine (50 mg) or scopolamine (.5 mg). Comparable 50-mg injections of promethazine also have been found effective in alleviating symptoms of space motion sickness. The concern has risen, however, that such drugs may delay or retard the acquisition of adaptation to stressful environments. In the current study, we controlled arousal using a mental arithmetic task and precisely equated the exposure history (number of head movements during rotation) of a placebo, control group and an experimental group who had received promethazine. No differences in total adaptation or in rates of adaptation were present between the two groups. Another experimental group also received promethazine and was allowed to make as many head movements as they could, before reaching nausea, up to 800. This group showed a greater level of adaptation than the placebo group. These results suggest a strategy for dealing with space motion sickness that is described.

  9. Use of injectable promethazine to decrease symptom scores of Space Motion Sickness

    NASA Technical Reports Server (NTRS)

    Beck, B. G.; Nicogossian, A. E.

    1992-01-01

    Space motion sickness (SMS) has been a problem affecting approximately 74 percent of first time shuttle flyers. Promethazine injections have been used for 29 cases of SMS to decrease the severity of their illness. Although reported to be effective in reducing symptoms in 27 of the 29 cases, there has been no proof of its efficacy. Methods: Retrospective analysis of medical debriefs examining the symptom scores for nausea, vomiting, decreased appetite, and stomach awareness were performed. Each symptom is rated on a mild = 1, moderate = 2, severe = 3 system for each flight day. Crewmember scores for the first three flight days on an initial flight in which injectable promethazine had not been used were compared to scores in a later flight in which the promethazine was utilized. Scores were also compared in a similar group of crewmembers who did not use promethazine. Results: There was a decrease in median scores for all symptoms except nausea, however, it was significant (p = 0.14) only for the vomiting scores. This significant decrease was not seen in the control group. Conclusions: Injectable promethazine has been associated with a significant decrease in vomiting compared to earlier flights in which injectable promethazine was not used.

  10. Autogenic-feedback training exercise is superior to promethazine for control of motion sickness symptoms

    NASA Technical Reports Server (NTRS)

    Cowings, P. S.; Toscano, W. B.

    2000-01-01

    Motion sickness symptoms affect approximately 50% of the crew during space travel and are commonly treated with intramuscular injections of promethazine. The purpose of this paper is to compare the effectiveness of three treatments for motion sickness: intramuscular injections (i.m.) of promethazine, a physiological training method (autogenic-feedback training exercise [AFTE]), and a no-treatment control. An earlier study tested the effects of promethazine on cognitive and psychomotor performance and motion sickness tolerance in a rotating chair. For the present paper, motion sickness tolerance, symptom reports, and physiological responses of these subjects were compared to matched subjects selected from an existing database who received either AFTE or no treatment. Three groups of 11 men, between the ages of 33 and 40 years, were matched on the number of rotations tolerated during their initial rotating-chair motion sickness test. The motion sickness test procedures and the 7-day interval between tests were the same for all subjects. The drug group was tested under four treatment conditions: baseline (no injections), a 25 mg dose of promethazine, a 50 mg dose of promethazine, and a placebo of sterile saline. AFTE subjects were given four 30-minute AFTE sessions before their second, third, and fourth motion sickness tests (6 hours total). The no-treatment control subjects were only given the four rotating-chair tests. Motion sickness tolerance was significantly increased after 4 hours of AFTE when compared to either 25 mg (p < 0.00003) or 50 mg (p < 0.00001) of promethazine. The control and promethazine groups did not differ. AFTE subjects reported fewer or no symptoms at higher rotational velocities than subjects in the control or promethazine groups. The primary physiological effect of promethazine was an inhibition of skin conductance level. The AFTE group showed significantly less heart rate and skin conductance variability during motion sickness tests

  11. Autogenic-feedback training exercise is superior to promethazine for control of motion sickness symptoms.

    PubMed

    Cowings, P S; Toscano, W B

    2000-10-01

    Motion sickness symptoms affect approximately 50% of the crew during space travel and are commonly treated with intramuscular injections of promethazine. The purpose of this paper is to compare the effectiveness of three treatments for motion sickness: intramuscular injections (i.m.) of promethazine, a physiological training method (autogenic-feedback training exercise [AFTE]), and a no-treatment control. An earlier study tested the effects of promethazine on cognitive and psychomotor performance and motion sickness tolerance in a rotating chair. For the present paper, motion sickness tolerance, symptom reports, and physiological responses of these subjects were compared to matched subjects selected from an existing database who received either AFTE or no treatment. Three groups of 11 men, between the ages of 33 and 40 years, were matched on the number of rotations tolerated during their initial rotating-chair motion sickness test. The motion sickness test procedures and the 7-day interval between tests were the same for all subjects. The drug group was tested under four treatment conditions: baseline (no injections), a 25 mg dose of promethazine, a 50 mg dose of promethazine, and a placebo of sterile saline. AFTE subjects were given four 30-minute AFTE sessions before their second, third, and fourth motion sickness tests (6 hours total). The no-treatment control subjects were only given the four rotating-chair tests. Motion sickness tolerance was significantly increased after 4 hours of AFTE when compared to either 25 mg (p < 0.00003) or 50 mg (p < 0.00001) of promethazine. The control and promethazine groups did not differ. AFTE subjects reported fewer or no symptoms at higher rotational velocities than subjects in the control or promethazine groups. The primary physiological effect of promethazine was an inhibition of skin conductance level. The AFTE group showed significantly less heart rate and skin conductance variability during motion sickness tests

  12. The Effects of Promethazine on Human Performance, Mood States, and Motion Sickness Tolerance

    NASA Technical Reports Server (NTRS)

    Cowings, Patricia S.; Stout, Cynthia; Toscano, William B.; Reynoso, Samuel; DeRoshia, Charles

    1996-01-01

    Intramuscular (IM) injections of promethazine in 25 mg or 50 mg dosages are commonly used to treat space motion sickness in astronauts. The present study examined the effects of IM injections of promethazine on neuropsy-chological performance, mood states, and motion sickness tolerance in humans. Twelve men, mean age 36 plus or minus 3.1 participated in one training (no injections) and three treatment conditions: a 25 mg injection of promethazine, a 50 mg injection of promethazine, and a placebo injection of sterile saline. Each condition, spaced at 7 day intervals, required an 8-10 hr session in which subjects were given four repetitions of 12 performance tasks, and one rotating chair motion sickness test. On the training day subjects were trained on each task to establish stability and proficiency. On treatment days, the order in which the drug or placebo was assigned to subjects was counter-balanced and a double-blind technique was used. Statistically significant decrements in performance were observed on 10 of 12 tasks when subjects were given 25 mg or 50 mg of promethazine as compared to the placebo. Performance decrements were associated with mean blood alcohol dose equivalency levels of 0.085% for 25 mg and 0. 1 37% for 50 mg dosages. The mood scale results showed significant changes in individual subjective experiences with maximum deterioration in the arousal state and fatigue level. When compared to placebo significant increases in motion sickness tolerance were found for both dosages of promethazine. These data suggest that effective dosages of promethazine currently used to counteract motion sickness in astronauts may significantly impair task components of their operational performance.

  13. Endogenous histamine and promethazine-induced gastric ulcers in the guinea pig

    NASA Technical Reports Server (NTRS)

    Djahanguiri, B.; Hemmati, M.

    1978-01-01

    Experiments performed with an inhibitor of diaminoxydase, aminoguanidine and an inhibitor of histidine decarboxylase, NSD 1055, showed that the frequency of gastric ulcers induced by promethazine was increased with the first inhibitor and decreased with the second. It is suggested that ulcers induced by promethazine in guinea pigs might be due to histamino-liberator effect of the antihistaminio compound.

  14. Effects of Promethazine on Performance During Simulated Shuttle Landings

    NASA Technical Reports Server (NTRS)

    Harm, D. L.; Putcha, L.; Sekula, B. K.; Berens, K. L.

    1999-01-01

    Promethazine (PMZ) is the antimotion sickness drug of choice in the U.S. Space Shuttle program; however, virtually nothing is known about the bioavailability and performance effects of this drug in the microgravity environment. PMZ has detrimental side effects on human performance on Earth that could affect Shuttle operations. In a recent ground-based study we examined: 1) the effects of promethazine (PMZ) on Shuttle landing performance using the portable inflight landing operations trainer (PILOT), and 2) saliva and urine samples to determine the pharmacokinetics of PMZ. The PILOT performance data is presented here.

  15. Midodrine Exacerbates Promethazine-induced Akathisia

    NASA Technical Reports Server (NTRS)

    Platts, Steven H.; Shi, Shang-Jin; Meck, Janice V.

    2006-01-01

    The study of physiological changes during spaceflight, and the pursuit of remedies to counteract those changes, often requires unique research protocols that lead to unexpected findings; some with important clinical implications. In our research into the development of treatments to counteract the detrimental cardiovascular effects of spaceflight, we have discovered an important drug interaction between promethazine and midodrine.

  16. Selective inhibition of Bacillus subtilis sporulation by acridine orange and promethazine.

    PubMed

    Burke, W F; Spizizen, J

    1977-03-01

    Two structurally similar compounds were found to inhibit sporulation in Bacillus subtilis 168. A dye, acridine orange, and an antischizophrenic drug, promethazine, blocked spore formation at concentrations subinhibitory to vegetative growth, while allowing synthesis of serine protease, antibiotic, and certain catabolite-repressed enzymes. The sporulation process was sensitive to promethazine through T2, whereas acridine orange was inhibitory until T4. The drug-treated cells were able to support the replication of phages phie and phi29, although the lytic cycles were altered slightly. The selective inhibition of sporulation by these compounds may be related to the affinity of some sporulation-specific genes to intercalating compounds.

  17. Portable system of programmable syringe pump with potentiometer for determination of promethazine in pharmaceutical applications.

    PubMed

    Saleh, Tawfik A; Abulkibash, A M; Ibrahim, Atta E

    2012-04-01

    A simple and fast-automated method was developed and validated for the assay of promethazine hydrochloride in pharmaceutical formulations, based on the oxidation of promethazine by cerium in an acidic medium. A portable system, consisting of a programmable syringe pump connected to a potentiometer, was constructed. The developed change in potential during promethazine oxidation was monitored. The related optimum working conditions, such as supporting electrolyte concentration, cerium(IV) concentration and flow rate were optimized. The proposed method was successfully applied to pharmaceutical samples as well as synthetic ones. The obtained results were realized by the official British pharmacopoeia (BP) method and comparable results were obtained. The obtained t-value indicates no significant differences between the results of the proposed and BP methods, with the advantages of the proposed method being simple, sensitive and cost effective.

  18. Abuse and Intentional Misuse of Promethazine Reported to US Poison Centers: 2002 to 2012.

    PubMed

    Tsay, M Ellen; Procopio, Gabrielle; Anderson, Bruce D; Klein-Schwartz, Wendy

    2015-01-01

    Promethazine abuse has been reported. The objective was to investigate promethazine abuse/misuse in the United States. An 11-year retrospective review was conducted of promethazine abuse and intentional misuse cases without co-ingestants in persons 10 years and older reported to the National Poison Data System. Data were stratified by product (promethazine-alone [PA] or co-formulation [PC]) and evaluated for demographics, toxicity, management sites, and outcomes. There were 354 single product abuse or misuse exposures-95 PA and 259 PC. Over the 11-year timeframe, the annual exposure rate per 100,000 population doubled. Exposures were most prevalent among 10 to 19 years old and young adults (20s), accounting for 69.5% of PA and 57.5% of PC cases. Clinical effects due to PA included drowsiness (43.2%), tachycardia (7.4%), agitation (13.7%), confusion (13.7%), slurred speech (12.6%), hallucinations (7.4%), dizziness (7.4%), and hypertension (5.3%). Drowsiness (53.4%) and tachycardia (20.8%) were more frequent with PC. There were significant differences between PA and PC in management site (P = 0.0078). Management sites for PA and PC, respectively, were emergency department (37.9%, 55.6%), non-health care facility (33.7%, 14.7%), critical care unit (8.4%, 11.2%), non-critical care unit (7.4%, 7.3%), psychiatry (2.1%, 4.2%), and other/unknown (10.5%, 7.0%). Outcomes for PA and PC, respectively, were no effect (21.0%, 12.4%), minor (58.9%, 53.7%), moderate (17.9%, 32.0%), and major effects (2.1%, 1.9%). Promethazine-alone abuse/misuse most frequently resulted in minor outcomes, and less than 20% required medical admission. Abuse/misuse of PC resulted in a higher frequency of health care facility treatment and a trend toward more moderate outcomes. These differences are most likely attributed to the co-formulate.

  19. Portable system of programmable syringe pump with potentiometer for determination of promethazine in pharmaceutical applications

    PubMed Central

    Saleh, Tawfik A.; Abulkibash, A.M.; Ibrahim, Atta E.

    2011-01-01

    A simple and fast-automated method was developed and validated for the assay of promethazine hydrochloride in pharmaceutical formulations, based on the oxidation of promethazine by cerium in an acidic medium. A portable system, consisting of a programmable syringe pump connected to a potentiometer, was constructed. The developed change in potential during promethazine oxidation was monitored. The related optimum working conditions, such as supporting electrolyte concentration, cerium(IV) concentration and flow rate were optimized. The proposed method was successfully applied to pharmaceutical samples as well as synthetic ones. The obtained results were realized by the official British pharmacopoeia (BP) method and comparable results were obtained. The obtained t-value indicates no significant differences between the results of the proposed and BP methods, with the advantages of the proposed method being simple, sensitive and cost effective. PMID:23960787

  20. Double-blind comparison of granisetron, promethazine, or a combination of both for the prevention of postoperative nausea and vomiting in females undergoing outpatient laparoscopies.

    PubMed

    Gan, Tong J; Candiotti, Keith A; Klein, Stephen M; Rodriguez, Yiliam; Nielsen, Karen C; White, William D; Habib, Ashraf S

    2009-11-01

    Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) are common problems after surgery. Prophylactic combination antiemetic therapy is recommended for patients at high risk for developing PONV and PDNV. Granisetron, a serotonin antagonist, is an effective antiemetic that is devoid of sedative side effect. Although promethazine is effective, commonly used doses are associated with sedation. This study investigates the combination of low doses of granisetron and promethazine for the prevention of PONV. Women undergoing ambulatory gynecological laparoscopy were enrolled. A standard general anesthetic regimen was prescribed. Fifteen minutes before the expected end of surgery, the patients were randomly assigned to receive granisetron 0.1 mg iv, promethazine 6.25 mg iv, or a combination of the two drugs. Prophylaxis with oral promethazine 12.5 mg, granisetron 1 mg, or both was started in the respective groups 12 hr after the end of surgery and continued every 12 hr until postoperative day 3 (a total of five oral doses). The following outcomes were recorded: total response rate (defined as no vomiting, no more than mild nausea, and no use of rescue antiemetic); incidence of nausea, vomiting, and use of rescue antiemetics; severity of nausea; patient activity level; and patient satisfaction with PONV management. Patients in the combination group had a higher total response rate at 6, 24, 48, and 72 hr after surgery compared with those who received promethazine alone (at 24 hr, Combination 69.6%, Promethazine 36.2%, Granisetron 53.3%; P = 0.0079). The maximum nausea scores were also lower in the combination group at 6, 24, 48, and 72 hr (Combination 1.7 +/- 2.2, Promethazine 4.0 +/- 3.6, Granisetron 3.1 +/- 3.2 at 24 hr; P < 0.05). There was no difference in the sedation scores, incidence of drowsiness, patient activity level, and satisfaction with PONV management. Low-dose granisetron and promethazine combination was more effective in

  1. Pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories and oral syrup to healthy subjects.

    PubMed

    Strenkoski-Nix, L C; Ermer, J; DeCleene, S; Cevallos, W; Mayer, P R

    2000-08-15

    The pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories at three dosage strengths and oral syrup were studied. The study had an open-label, randomized, crossover design. At intervals of five to nine days, healthy volunteers were given two 12.5-mg promethazine rectal suppositories, one 25-mg suppository, one 50-mg suppository, or 50 mg (10 mL) of promethazine oral syrup. Blood samples were collected before each dose and at intervals from 0.5 to 48 hours afterward. Promethazine concentration was determined by high-performance liquid chromatography, and pharmacokinetic values were calculated with noncompartmental methods. Thirty-six subjects (18 men and 18 women) completed the study. Absorption was highly variable for all the formulations. On average, absorption was more rapid and the maximum plasma concentration (Cmax) higher for the syrup than for the suppositories. Cmax was significantly lower for the 50-mg suppository (mean, 9.04 ng/mL) than for the syrup (19.3 ng/mL). The time to Cmax (tmax) was significantly shorter for the syrup (mean, 4.4 hours) than for the suppositories (6.7-8.6 hours). There were no significant differences in dose-normalized Cmax among the three suppository treatments. Area under the concentration-versus-time curve (AUC) was comparable between the syrup and the 50-mg suppository and between the treatments with two 12.5-mg suppositories and the 25-mg suppository. Elimination profiles were similar among all treatments (mean half-life [t1/2], 16-19 hours). There were no significant differences in pharmacokinetics on the basis of sex or race. The mean relative bioavailability for the three suppository treatments ranged from 70% to 97%. Individual relative bioavailabilities ranged from 4% to 343%. The pharmacokinetics of promethazine administered in oral syrup and rectal suppositories were highly variable, but, in general, the suppositories produced a lower Cmax and later tmax than the syrup. All

  2. Pre-medication and renal pre-conditioning: a role for alprazolam, atropine, morphine and promethazine.

    PubMed

    Pazoki-Toroudi, Hamid Reza; Ajami, Marjan; Habibey, Rouhollah

    2010-04-01

    Four pre-medication drugs are used to relieve pain, allay anxiety, reduce secretion and enhance hypnosis, were evaluated for their effects on ischemia reperfusion (I/R) injury which is one of the major complications of vascular and transplantation surgery. Right kidney was removed from female rats (210-250 g) 3 weeks before surgical procedure. Different doses of morphine (0.5, 2 and 5 mg/kg), promethazine (1, 2 and 5 mg/kg), atropine (0.1, 0.3 and 0.5 mg/kg) and alprazolam (0.08, 0.32 and 0.64 mg/kg) were administered subcutaneously 30 min before left renal artery occlusion and 6 h reperfusion. Left kidneys were processed for histological evaluations. Creatinine and BUN were measured in serum samples. Morphine, promethazine, atropine and alprazolam at all evaluated doses significantly decreased serum creatinine and BUN levels and histopathological scores. The effects of promethazine (1 mg/kg) and all doses of alprazolam were more potent than other pre-medication drugs and doses. This study suggested a protective effect of these pre-medication drugs on I/R injury. Although obvious studies are required, these findings may lead to effective therapies against I/R injury.

  3. Quantitation of promethazine and metabolites in urine samples using on-line solid-phase extraction and column-switching

    NASA Technical Reports Server (NTRS)

    Song, Q.; Putcha, L.; Harm, D. L. (Principal Investigator)

    2001-01-01

    A chromatographic method for the quantitation of promethazine (PMZ) and its three metabolites in urine employing on-line solid-phase extraction and column-switching has been developed. The column-switching system described here uses an extraction column for the purification of PMZ and its metabolites from a urine matrix. The extraneous matrix interference was removed by flushing the extraction column with a gradient elution. The analytes of interest were then eluted onto an analytical column for further chromatographic separation using a mobile phase of greater solvent strength. This method is specific and sensitive with a range of 3.75-1400 ng/ml for PMZ and 2.5-1400 ng/ml for the metabolites promethazine sulfoxide, monodesmethyl promethazine sulfoxide and monodesmethyl promethazine. The lower limits of quantitation (LLOQ) were 3.75 ng/ml with less than 6.2% C.V. for PMZ and 2.50 ng/ml with less than 11.5% C.V. for metabolites based on a signal-to-noise ratio of 10:1 or greater. The accuracy and precision were within +/- 11.8% in bias and not greater than 5.5% C.V. in intra- and inter-assay precision for PMZ and metabolites. Method robustness was investigated using a Plackett-Burman experimental design. The applicability of the analytical method for pharmacokinetic studies in humans is illustrated.

  4. To compare the effect of dextromethorphan, promethazine and placebo on nocturnal cough in children aged 1-12 y with upper respiratory infections: a randomized controlled trial.

    PubMed

    Bhattacharya, Malobika; Joshi, Neha; Yadav, Sangita

    2013-11-01

    To evaluate whether promethazine and dextromethorphan reduce nocturnal cough and improve sleep quality in children aged 1-12 y with upper respiratory tract infection (URI). This randomised double-blinded placebo-controlled trial was conducted in Pediatric outpatient department of Lok Nayak Hospital, Delhi. After randomization into promethazine, dextromethorphan and placebo groups, parental assessment of 120 children with URI for nocturnal cough severity (child), post-tussive vomiting (child) and sleep quality (child and parent) on the night before enrolment and after 3 d of assigned medication was measured using an internally validated indigenously prepared ordinal scale. Entire cohort improved in all the study parameters after 3 d. However, no superior benefit was noted when individual parameters were compared in the promethazine and dextromethorphan groups with the placebo group. Adverse effects were more frequent in the dextromethorphan and promethazine groups although the difference was not statistically significant. Nocturnal cough in URI is self-resolving and dextromethorphan and promethazine prescribed for the same are not superior to placebo.

  5. Bioavailability of intranasal promethazine dosage forms in dogs

    NASA Technical Reports Server (NTRS)

    Ramanathan, R.; Geary, R. S.; Bourne, D. W.; Putcha, L.

    1998-01-01

    Intramuscular promethazine (PMZ) is used aboard the US Space Shuttle to ameliorate symptoms of space motion sickness. Bioavailability after an oral dose of PMZ during space flight is thought to be impaired because of gastrointestinal disturbances associated with weightlessness and space motion sickness. In an attempt to find an alternative dosage form for use in space, we evaluated two intranasal (i.n.) dosage forms of PMZ in dogs for absorption and bioavailability relative to that of an equivalent intramuscular dose. Promethazine (5 mg kg-1) was administered as two intranasal dosage forms and as an intramuscular (i.m.) dose to three dogs in a randomised cross-over design. Serial blood samples were taken and analysed for PMZ concentrations and the absorption and bioavailability of PMZ were calculated for the three dosage forms. PMZ absorption from the carboxymethyl cellulose microsphere i.n. dosage form was more rapid and complete than from the myverol cubic gel formulation or from an i.m. injection. Bioavailability of the microsphere formulation was also greater than that of the gel formulation (AUC 3009 vs 1727 ng h ml-1). The bioavailability of the two i.n. dosage forms (relative to that of the i.m. injection) were 94% (microsphere) and 54% (gel). The i.n. microsphere formulation of PMZ offers great promise as an effective non-invasive alternative for treating space motion sickness due to its rapid absorption and bioavailability equivalent to the i.m. dose.

  6. Promethazine as a Novel Prophylaxis and Treatment for Nerve Agent Poisoning

    DTIC Science & Technology

    2008-12-01

    mitochondrial dysfunction. Mitochondrial damage after seizure activity has been previously documented (Cock et al., 2002), and mitochondrial...McDonough et al., 1998), the lack of brain pathology in surviving animals is solely due to the secondary anticholinergic activity of promethazine...rats, Experientia, 41(11), 1457-1458. Department of Health, Expert group on the management of chemical casualties by terrorist activity , 2003: Use

  7. Salivary Pharmacodynamics and Bioavailability of Promethazine in Human Subjects

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi; Harm, Deborah L.; Nimmagudda, Ram; Berens, Kurt L.; Bourne, David W. A.

    1999-01-01

    The acute effects of exposure to microgravity include the development of space motion sickness which usually requires therapeutic intervention. The current drug of choice, promethazine (PMZ), has side effects which include nausea, drowsiness, dizziness, sedation and impaired psychomotor performance. In a ground-based study with commercial airline pilots and shuttle simulator trainers, we measured sleep and psychomotor performance variables, and physiological variables such as blood pressure and heart rate, as a function of circulating drug concentrations in the body. We evaluated a non-invasive sampling method (saliva) as a means of assessing pharmacodynamics following a single intramuscular (IM) dose of PMZ.

  8. Bioavailability and Pharmacodynamics of Promethazine in Human Subjects

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi; Flynn, Chris; Paloski, W. H. (Technical Monitor)

    2000-01-01

    Space Motion Sickness (SMS) is often treated in space with promethazine (PMZ). Anecdotal reports indicate that the common side effects of drowsiness and decrements in cognitive performance that are associated with PMZ administration (50 mg IM on the ground, are absent or less pronounced in space suggesting I that-the bioavailability and/or pharmacodynamic behavior of PMZ may be altered during space flight. There are limited flight opportunities available for clinical research in space, the NRA-99, therefore, solicits research required to improve, or answer specific questions about in-flight diagnosis, therapy, and post-flight rehabilitation. We propose here, to establish a noninvasive method for pharmacodynamic and therapeutic assessment of PMZ. The specific objectives of the proposed research are to, 1. Establish a saliva to plasma ratio of PMZ after administration, 2. Estimate the relative bioavailability of the three flight-specific dosage forms of PMZ, and 3. Establish the dose-response relationship of PMZ. We will estimate the bioavailability of intramuscular injection (IM), oral tablets and rectal suppositories in normal subjects during ambulatory and antiorthostatic; bed rest (ABR) conditions using novel stable isotope techniques. Drowsiness, cognitive performance and salivary flow rate will be measured as a function of circulating drug concentrations after administration of three IM doses of PMZ. We will compare and contrast the bioavailability of PMZ during normal and ABR conditions to examine whether or not ABR can simulate changes in drug, absorption and availability similar to those anticipated in a microgravity environment. Results of this study will validate methods for an approved study with this medication awaiting a flight opportunity for manifestation. These data will also provide the much needed information on the dynamics and therapeutic index. of this medication and their implications on crew fatigue and performance in space. Key words

  9. The effect of dexamethasone and promethazine in combination with buparvaquone in the management of East Coast fever.

    PubMed

    Gwamaka, M; Matovelo, J A; Mtambo, M M A; Mbassa, G K; Maselle, R M; Boniphace, S

    2004-06-01

    The effects of dexamethasone and promethazine on the amelioration of pulmonary oedema in East Coast fever were investigated. The clinical effects of these drugs were further investigated when used in conjunction with the antitheilerial drug, buparvaquone. In the first experiment, 15 crossbred (Friesian x Zebu) steers were divided into four groups. With the exception of the animals in group IV, that served as a control group all the others were infected with Theileria parva sporozoites. On the second day of the febrile reaction, the steers in groups I and II were treated with dexamethasone (0.1 mg/kg) and promethazine (1 mg/kg), respectively. Group III steers served as the infected untreated controls. On the fifth day of the febrile reaction the animals in groups I, II and III were infused intravenously with tattoo ink suspension and 1 h later sacrificed for post-mortem examination and tissue sampling. The clinical picture indicated that both drugs significantly mitigated dyspnoea and the post mortem examination revealed a significant reduction in morphological changes. Tattoo ink particle count reflected a significant (P< 0.01) reduction in vascular leakage in the treated animals, with promethazine being significantly (P < 0.05) more effective than dexamethasone in this respect. In the second experiment, 18 steers were infected with T. parva sporozoites, and then were randomly allotted into three groups each of which contained six animals. After the onset of ECF clinical signs, the animals in the first two groups were treated with buparvaquone in combination with either dexamethasone (group I) or promethazine (group II), and the third group was treated with buparvaquone alone. The results indicated that all the animals in groups I, II and III recovered well and no significant differences were observed in clinical disposition between the groups. Two months later, serum samples were collected from the refractory animals and demonstrated the presence of antibodies

  10. Endogenous opioids, mu-opiate receptors and chloroquine-induced pruritus: a double-blind comparison of naltrexone and promethazine in patients with malaria fever who have an established history of generalized chloroquine-induced itching.

    PubMed

    Ajayi, A A; Kolawole, B A; Udoh, S J

    2004-12-01

    Chloroquine induces a severe generalized pruritus, in predisposed Black African patients, during treatment of malaria fever, and also in some Caucasian patients treated for rheumatological diseases. We have previously shown that chloroquine may release endogenous opioids and/or interact with micro-opiate receptors in rats, and that both histamine and malaria parasite blood density, contribute to the itching severity in malaria fever in humans. The aim of our present study was to assess and compare the antipruritic efficacy of the micro-opiate receptor antagonist, naltrexone, and the antihistamine, promethazine, in chloroquine treated patients with malaria fever. A double-blind, randomized, parallel group comparison of the chloroquine-induced pruritus intensity and time profile in patients with parasitologically proven malaria fever, who were pretreated with a single dose of either naltrexone 50 mg or promethazine 25 mg orally (six patients each). All patients had an established history of severe pruritus following chloroquine treatment of malaria fever. A self-assessed itching severity score was undertaken at 0, 6, 12, 24, 48 and 72 h after initial chloroquine dosing, and the areas under the pruritus-intensity time curve AUCP0-72 h was determined in each patient and correlated to the malaria parasite density in blood. Both naltrexone and promethazine subjectively reduced itching severity compared with prior historical experience. One patient on naltrexone and two on promethazine never experienced any itching. There was no statistically significant treatment effect, but a significant time effect (P = 0.001, F = 4.77 d.f. 5) by two-way repeated measures ANOVA. The AUCP for naltrexone was 82 +/- 25 units/h, and 57 +/- 34 units/h for promethazine [95% confidence interval for the difference being -73 to 123]. However, the malaria parasite density in the naltrexone group (740 +/- 178 microl(-1)) tended to be higher than in the promethazine group 314 +/- 69 microl(-1) (P

  11. Pharmacodynamics of Promethazine in Human Subjects

    NASA Technical Reports Server (NTRS)

    Gatlin, K. T.; Boyd, J. L.; Wang, Z.; Das, H.; Putcha, L.

    2005-01-01

    Promethazine (PMZ) is the drug of choice for the treatment of symptoms associated with space motion sickness in astronauts. Side effects of PMZ include sedation, dizziness and cognitive performance impairment. In this study, we examined pharmacodynamics (PD) in human subjects and validated methods for evaluating cognitive performance effects of medications in space. METHODS: PMZ (12.5,25, and 50 mg) or placebo was administered by IM injection to human subjects in a randomized double-blind treatment design. Samples and data were collected for 72 h post dose. PD evaluation was performed using a battery of performance tests administered using WinSCAT (Windows based Space Cognitive Assessment Test) on a laptop computer, and ARES (ANAM Readiness Evaluation System) on a PDA, plasma concentrations of PMZ were measured using a LC-MS method. RESULTS: Results indicate a linear correlation between PMZ concentration and cognitive performance parameters (p<0.01). Test accuracy decreased and test completion time and response time increased significantly with increasing plasma PMZ concentration. CONCLUSIONS: These results suggest a concentration dependent decrement in cognitive performance associated with PMZ. WinSCAT and ARES are sensitive tools for the assessment PMZ PD and may be applicable for such evaluations with other neurocognitive drugs.

  12. Bioavailability of Promethazine during Spaceflight

    NASA Technical Reports Server (NTRS)

    Boyd, Jason L.; Wang, Zuwei; Putcha, Lakshmi

    2009-01-01

    Promethazine (PMZ) is the choice anti-motion sickness medication for treating space motion sickness (SMS) during flight. The side effects associated with PMZ include dizziness, drowsiness, sedation, and impaired psychomotor performance which could impact crew performance and mission operations. Early anecdotal reports from crewmembers indicate that these central nervous system side effects of PMZ are absent or greatly attenuated in microgravity, potentially due to changes in pharmacokinetics (PK) and pharmacodynamics in microgravity. These changes could also affect the therapeutic effectiveness of drugs in general and PMZ, in particular. In this investigation, we examined bioavailability and associated pharmacokinetics of PMZ in astronauts during and after space flight. Methods. Nine astronauts received, per their preference, PMZ (25 or 50 mg as intramuscular injection, oral tablet, or rectal suppository) on flight day one for the treatment of SMS and subsequently collected saliva samples and completed sleepiness scores for 72 h post dose. Thirty days after the astronauts returned to Earth, they repeated the protocol. Bioavailability and PK parameters were calculated and compared between flight and ground. Results. Maximum concentration (Cmax) was lower and time to reach Cmax (tmax) was longer in flight than on the ground. Area under the curve (AUC), a measure of bioavailability, was lower and biological half-life (t1/2) was longer in flight than on the ground. Conclusion. Results indicate that bioavailability of PMZ is reduced during spaceflight. Number of samples, sampling method, and sampling schedule significantly affected PK parameter estimates.

  13. Using Latent Sleepiness to Evaluate an Important Effect of Promethazine

    NASA Technical Reports Server (NTRS)

    Feiveson, Alan H.; Hayat, Matthew; Vksman, Zalman; Putcha, Laksmi

    2007-01-01

    Astronauts often use promethazine (PMZ) to counteract space motion sickness; however PMZ may cause drowsiness, which might impair cognitive function. In a NASA ground study, subjects received PMZ and their cognitive performance was then monitored over time. Subjects also reported sleepiness using the Karolinska Sleepiness Score (KSS), which ranges from 1 - 9. A problem arises when using KSS to establish an association between true sleepiness and performance because KSS scores tend to overly concentrate on the values 3 (fairly awake) and 7 (moderately tired). Therefore, we defined a latent sleepiness measure as a continuous random variable describing a subject s actual, but unobserved true state of sleepiness through time. The latent sleepiness and observed KSS are associated through a conditional probability model, which when coupled with demographic factors, predicts performance.

  14. Low-Dose Adrenaline, Promethazine, and Hydrocortisone in the Prevention of Acute Adverse Reactions to Antivenom following Snakebite: A Randomised, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    de Silva, H. Asita; Pathmeswaran, Arunasalam; Ranasinha, Channa D.; Jayamanne, Shaluka; Samarakoon, Senarath B.; Hittharage, Ariyasena; Kalupahana, Ranjith; Ratnatilaka, G. Asoka; Uluwatthage, Wimalasiri; Aronson, Jeffrey K.; Armitage, Jane M.; Lalloo, David G.; de Silva, H. Janaka

    2011-01-01

    Background Envenoming from snakebites is most effectively treated by antivenom. However, the antivenom available in South Asian countries commonly causes acute allergic reactions, anaphylactic reactions being particularly serious. We investigated whether adrenaline, promethazine, and hydrocortisone prevent such reactions in secondary referral hospitals in Sri Lanka by conducting a randomised, double-blind placebo-controlled trial. Methods and Findings In total, 1,007 patients were randomized, using a 2×2×2 factorial design, in a double-blind, placebo-controlled trial of adrenaline (0.25 ml of a 1∶1,000 solution subcutaneously), promethazine (25 mg intravenously), and hydrocortisone (200 mg intravenously), each alone and in all possible combinations. The interventions, or matching placebo, were given immediately before infusion of antivenom. Patients were monitored for mild, moderate, or severe adverse reactions for at least 96 h. The prespecified primary end point was the effect of the interventions on the incidence of severe reactions up to and including 48 h after antivenom administration. In total, 752 (75%) patients had acute reactions to antivenom: 9% mild, 48% moderate, and 43% severe; 89% of the reactions occurred within 1 h; and 40% of all patients were given rescue medication (adrenaline, promethazine, and hydrocortisone) during the first hour. Compared with placebo, adrenaline significantly reduced severe reactions to antivenom by 43% (95% CI 25–67) at 1 h and by 38% (95% CI 26–49) up to and including 48 h after antivenom administration; hydrocortisone and promethazine did not. Adding hydrocortisone negated the benefit of adrenaline. Conclusions Pretreatment with low-dose adrenaline was safe and reduced the risk of acute severe reactions to snake antivenom. This may be of particular importance in countries where adverse reactions to antivenom are common, although the need to improve the quality of available antivenom cannot be overemphasized

  15. Effect profile of paracetamol, Δ9-THC and promethazine using an evoked pain test battery in healthy subjects.

    PubMed

    van Amerongen, G; Siebenga, P; de Kam, M L; Hay, J L; Groeneveld, G J

    2018-04-10

    A battery of evoked pain tasks (PainCart) was developed to investigate the pharmacodynamic properties of novel analgesics in early-phase clinical research. As part of its clinical validation, compounds with different pharmacological mechanisms of actions are investigated. The aim was to investigate the analgesic effects of classic and nonclassic analgesics compared to a sedating negative control in a randomized placebo-controlled crossover study in 24 healthy volunteers using the PainCart. The PainCart consisted of pain tasks eliciting electrical, pressure, heat, cold and inflammatory pain. Subjective scales for cognitive functioning and psychotomimetic effects were included. Subjects were administered each of the following oral treatments: paracetamol (1000 mg), Δ9-THC (10 mg), promethazine (50 mg) or matching placebo. Pharmacodynamic measurements were performed at baseline and repeated up to 10 h postdose. Paracetamol did not show a significant reduction in pain sensation or subjective cognitive functioning compared to placebo. Promethazine induced a statistically significant reduction in PTT for cold pressor and pressure stimulation. Furthermore, reduced subjective alertness was observed. Δ9-THC showed a statistically significant decrease in PTT for electrical and pressure stimulation. Δ9-THC also demonstrated subjective effects, including changes in alertness and calmness, as well as feeling high and psychotomimetic effects. This study found a decreased pain tolerance due to Δ9-THC and promethazine, or lack thereof, using an evoked pain task battery. Pain thresholds following paracetamol administration remained unchanged, which may be due to insufficient statistical power. We showed that pain thresholds determined using this pain test battery are not driven by sedation. The multimodal battery of evoked pain tasks utilized in this study may play an important role in early-phase clinical drug development. This battery of pain tasks is not sensitive to the

  16. Chloral hydrate, chloral hydrate--promethazine and chloral hydrate -hydroxyzine efficacy in electroencephalography sedation.

    PubMed

    Fallah, Razieh; Alaei, Ali; Akhavan Karbasi, Sedighah; Shajari, Ahmad

    2014-06-01

    To compare efficacy and safety of chloral hydrate (CH), chloral hydrate and promethazine (CH + P) and chloral hydrate and hydroxyzine (CH + H) in electroencephalography (EEG) sedation. In a parallel single-blinded randomized clinical trial, ninety 1-7 y-old uncooperative kids who were referred to Pediatric Neurology Clinic of Shahid Sadoughi University, Yazd, Iran from April through August 2012, were randomly assigned to receive 40 mg/kg of chloral hydrate or 40 mg/kg of chloral hydrate and 1 mg/kg of promethazine or 40 mg/kg of chloral hydrate and 2 mg/kg of hydroxyzine. The primary endpoint was efficacy in sufficient sedation (obtaining four Ramsay sedation score) and successful completion of EEG. Secondary endpoint was clinical adverse events. Thirty nine girls (43.3 %) and 51 boys (56.7 %) with mean age of 3.34 ± 1.47 y were assessed. Sufficient sedation and completion of EEG were achieved in 70 % (N = 21) of chloral hydrate group, in 83.3 % (N = 25) of CH + H group and in 96.7 % (N = 29) of CH + P group (p = 0.02). Mild clinical adverse events including vomiting [16.7 % (N = 5) in CH, 6.7 % (N = 2) in CH + P, 6.7 % (N = 2) in CH + H], agitation in 3.3 % of CH + P (N = 1) group and mild transient hypotension in 3.3 % of CH + H (N = 1) group occurred. Safety of these three sedation regimens was not statistically significant different (p = 0.14). Combination of chloral hydrate-antihistamines can be used as the most effective and safe sedation regimen in drug induced sleep electroencephalography of kids.

  17. Comparison of Cognitive Performance Tests for Promethazine Pharmacodynamics in Human Subjects

    NASA Technical Reports Server (NTRS)

    Vaksman, Z.; Boyd, J. L.; Wang, Z.; Putcha, L.

    2005-01-01

    The objective of this study is to compare cognitive function tests, Automated Neurological Assessment Metrics (ANAM) based Readiness Evaluation System (ARES(Registered TradeMark)) on a Palm Pilot and Windows based Spaceflight Cognitive Assessment Tool (WinSCAT(Registered TradeMark)) on a personal computer (PC) to assess performance effects of promethazine (PMZ) after administration to human subjects. In a randomized placebo-controlled cross-over design, subjects received 12.5, 25, and 50 mg intramuscular (IM) PMZ or a placebo and completed 14 sessions with WinSCAT(Registered TradeMark) (v. 1.26) and ARES(Registered TradeMark) (v. 1.27) consecutively for 72 h post dose. Maximum plasma concentrations (4.25, 6.25 and 13.33 ng/ml) were linear with dose and were achieved by 0.75, 8, and 24 h after dosing for the three doses, respectively. No significant differences in cognitive function after PMZ dosing were detected using WinSCAT(Registered TradeMark), however, tests from ARES(Registered TradeMark) demonstrated concentration dependent decrements in reaction time associated with PMZ dose.

  18. Bioavailability and Pharmacodynamics of Promethazine in Human Subjects

    NASA Technical Reports Server (NTRS)

    Boyd, J. L.; Boster, B.; Wang, Z.; Shah, V.; Berens, K. L.; Sipes, W. E.; Anderson, K. E.; Putcha, L.

    2004-01-01

    The acute effects of exposure to microgravity include the development of space motion sickness, which usually requires therapeutic intervention. The current drug of choice, promethazine (PMZ), is available to astronauts in three different dosage forms during space flight; its side effects include nausea, dizziness, sedation and impaired psychomotor performance. This ground-based study is designed to validate flight-suitable methods for pharmacodynamic evaluation of PMZ and to estimate bioavailability and pharmacodynamics of PMZ. Experimental design consists of intramuscular administration of three doses of PMZ (12.5,25 and 50 mg) and placebo in a randomized double blind fashion to human subjects and collecting blood, urine and saliva samples for 72 h. Subjects also complete cognitive performance test batteries, WinSCAT (Windows based Space Cognitive Assessment Test) and ARES (ANAM Readiness Evaluation System). Preliminary results indicate a significant relationship (p=9.88e-05) between circulating PMZ levels and cognitive performance parameters. Time to accurately complete memory tasks increases significantly with concentrations; higher concentrations also increase response time and decrease accuracy of substitution and matching tasks. AUC and half-life estimates for PMZ ranged between 0.12 and 1.7 mg.h/L and 15 and 50 h, respectively. These preliminary results indicate that PMZ may exhibit dose-dependent pharmacokinetics in humans; also, WinSCAT and ARES are sensitive for pharmacodynamic assessment of PMZ, and may be applicable for assessing the pharmacodynamics of other neurocognitive drugs.

  19. Beliefs and Social Norms about Codeine and Promethazine Hydrochloride Cough Syrup (CPHCS) Onset and Perceived Addiction among Urban Houstonian Adolescents: An Addiction Trend in the City of Lean

    ERIC Educational Resources Information Center

    Peters, Ronald J., Jr.; Kelder, Steven H.; Markham, Christine M.; Yacoubian, George S., Jr.; Peters, LeCresha A.; Ellis, Artist

    2003-01-01

    In the current study, we used a qualitative approach to investigate relevant beliefs and norms associated with codeine and promethazine hydrochloride cough syrup (CPHCS) consumption, initiation, and perceived addiction among 48 alternative school students who identified themselves as current CPHCS users. In general, both boys and girls believed…

  20. Ondansetron and promethazine have differential effects on hypothermic responses to lithium chloride administration and to provocative motion in rats

    PubMed Central

    Guimaraes, Drielle D; Andrews, Paul L R; Rudd, John A; Braga, Valdir A; Nalivaiko, Eugene

    2015-01-01

    We recently reported that provocative motion (rotation in a home cage) causes hypothermic responses in rats, similar to the hypothermic responses associated with motion sickness in humans. Many stimuli inducing emesis in species with an emetic reflex also provoke hypothermia in the rat, therefore we hypothesized that a fall in body temperature may reflect a “nausea-like” state in these animals. As rats do not possess an emetic reflex, we employed a pharmacological approach to test this hypothesis. In humans, motion- and chemically-induced nausea have differential sensitivity to anti-emetics. We thus tested whether the hypothermia induced in rats by provocative motion (rotation at 0.7 Hz) and by the emetic LiCl (63 mg/kg i.p.) have a similar differential pharmacological sensitivity. Both provocations caused a comparable robust fall in core body temperature (−1.9 ± 0.3°C and −2.0 ± 0.2°C for chemical and motion provocations, respectively). LiCl−induced hypothermia was completely prevented by ondansetron (2mg/kg, i.p., a 5-HT3 receptor antagonist that reduces cancer chemotherapy-induced nausea and vomiting), but was insensitive to promethazine (10 mg/kg, i.p., a predominantly histamine-H1 and muscarinic receptor antagonist that is commonly used to treat motion sickness). Conversely, motion-induced hypothermia was unaffected by ondansetron but promethazine reduced the rate of temperature decline from 0.20 ± 0.02 to 0.11 ± 0.03°C/min (P < 0.05) with a trend to decrease the magnitude. We conclude that this differential pharmacological sensitivity of the hypothermic responses of vestibular vs. chemical etiology in rats mirrors the observations in other pre-clinical models and humans, and thus supports the idea that a “nausea-like” state in rodents is associated with disturbances in thermoregulation. PMID:27227074

  1. LC/MS Method for the Determination of Stable Isotope Labeled Promethazine in Human Plasma

    NASA Technical Reports Server (NTRS)

    Zuwei, Wang; Boyd, Jason; Berens, Kurt L.; Putcha, Lakshmi

    2004-01-01

    Promethazine (PMZ) is taken by astronauts orally (PO), intramuscularly (IM) or rectally (PR) for space motion sickness. LC/MS method was developed with off-line solid phase extraction to measure plasma concentrations of PMZ given as stable isotope-labeled (SIL) formulations by the three different routes of administration simultaneously. Samples (0.5ml) were loaded on to Waters Oasis HLB co-polymer cartridges and eluted with 1.0 mL methanol. HPLC separation of the eluted sample was performed using an Agilent Zorbax SB-CN column (50 x 2.1 mm) at a flow rate of 0.2 mL/min for 6 min. Acetonitrile/ ammonium acetate (30 mM) in water (3:2, v/v), pH 5.6 plus or minus 0.1, was used as the mobile phase for separation. Concentrations of PMZ, PMZ-d4 and PMZ-d7 and chlorpromazine (internal standard) were determined using a Micromass ZMD single quadrupole mass spectrometer with Electrospray Ionization (ESI). ESI mass spectra were acquired in positive ion mode with selected ion monitoring of [M+ H]dot plus. The method is rapid, reproducible and the assay specific parameters are listed in a table. A novel, sensitive and specific method for the measurement of PMZ and SIL PMZ in human plasma is reported.

  2. A Prospective, Randomized, Double-Blinded, Double-Dummy Pilot Study to Assess the Preemptive Effect of Triple Therapy with Aprepitant, Dexamethasone, and Promethazine versus Ondansetron, Dexamethasone and Promethazine on Reducing the Incidence of Postoperative Nausea and Vomiting Experienced by Patients Undergoing Craniotomy Under General Anesthesia.

    PubMed

    Bergese, Sergio Daniel; Puente, Erika G; Antor, Maria A; Viloria, Adolfo L; Yildiz, Vedat; Kumar, Nicolas Alexander; Uribe, Alberto A

    2016-01-01

    Postoperative nausea and vomiting (PONV) is among the most common distressing complications of surgery under anesthesia. Previous studies have demonstrated that patients who undergo craniotomy have incidences of nausea and vomiting as high as 50-70%. The main purpose of this pilot study is to assess the incidence of PONV by using two different prophylactic regimens in subjects undergoing a craniotomy. Thus, we designed this study to assess the efficacy and safety of triple therapy with the combination of dexamethasone, promethazine, and aprepitant versus ondansetron to reduce the incidence of PONV in patients undergoing craniotomy. This is a prospective, single center, two-armed, randomized, double-dummy, double-blind, pilot study. Subjects were randomly assigned to one of the two treatment groups. Subjects received 40 mg of aprepitant pill (or matching placebo pill) 30-60 min before induction of anesthesia and 4 mg of ondansetron IV (or 2 ml of placebo saline solution) at induction of anesthesia. In addition, all subjects received 25 mg of promethazine IV and 10 mg of dexamethasone IV at induction of anesthesia. Assessments of PONV commenced for the first 24 h after surgery and were subsequently assessed for up to 5 days. The overall incidence of PONV during the first 24 h after surgery was 31.0% (n = 15) in the aprepitant group and 36.2% (n = 17) for the ondansetron group. The median times to first emetic and significant nausea episodes were 7.6 (2.9, 48.7) and 14.3 (4.4, 30.7) hours, respectively, for the aprepitant group and 6.0 (2.2, 29.5) and 9.6 (0.7, 35.2) hours, respectively, for the ondansetron group. There were no statistically significant differences between these groups. No adverse events directly related to study medications were found. This pilot study showed similar effectiveness when comparing the two PONV prophylaxis regimens. Our data showed that both treatments could be effective regimens to prevent PONV in patients

  3. Effect of sampling schedule on pharmacokinetic parameter estimates of promethazine in astronauts

    NASA Astrophysics Data System (ADS)

    Boyd, Jason L.; Wang, Zuwei; Putcha, Lakshmi

    2005-08-01

    Six astronauts on the Shuttle Transport System (STS) participated in an investigation on the pharmacokinetics of promethazine (PMZ), a medication used for the treatment of space motion sickness (SMS) during flight. Each crewmember completed the protocol once during flight and repeated thirty days after returned to Earth. Saliva samples were collected at scheduled times for 72 h after PMZ administration; more frequent samples were collected on the ground than during flight owing to schedule constraints in flight. PMZ concentrations in saliva were determined by a liquid chromatographic/mass spectrometric (LC-MS) assay and pharmacokinetic parameters (PKPs) were calculated using actual flight and ground-based data sets and using time-matched sampling schedule on ground to that during flight. Volume of distribution (Vc) and clearance (Cls) decreased during flight compared to that from time-matched ground data set; however, ClS and Vc estimates were higher for all subjects when partial ground data sets were used for analysis. Area under the curve (AUC) normalized with administered dose was similar in flight and partial ground data; however AUC was significantly lower using time-matched sampling compared with the full data set on ground. Half life (t1/2) was longest during flight, shorter with matched-sampling schedule on ground and shortest when complete data set from ground was used. Maximum concentration (Cmax), time for Cmax (tmax), parameters of drug absorption, depicted a similar trend with lowest and longest respectively, during flight, lower with time- matched ground data and highest and shortest with full ground data.

  4. Promethazine and its use as a treatment for space motion sickness

    NASA Technical Reports Server (NTRS)

    Bagian, James P.; Beck, Bradley G.

    1993-01-01

    Until Mar. 1989, no effective treatment--either prophylactic or symptomatic--for space motion sickness (SMS) had been discovered. Since Mar. 1989, intramuscular (IM) promethazine (PMZ) has been used in the treatment of SMS with extremely favorably results reported by the crew. A retrospective study was undertaken to quantify the efficacy of IM PMZ since its institution and the incidence of its major anticipated side-effect drowsiness and sedation. The results from a standardized crew medical debriefing conducted immediately after landing and follow-up interviews with the crews were used in establishing the efficacy and incidence of side effects from treatment. Only crews from the first 44 Shuttle flights on their first mission were considered. For a total of 132 crewmembers, 96 exhibited symptoms of SMS; and, of these, 20 were treated with IM PMZ. Ninety percent of those receiving IM PMZ 25-50mg received nearly immediate (less than 2 hours) relief of symptoms and 75 percent required no further treatment through the first 2 days of spaceflight. Those not receiving this treatment did not have any near-term resolution of their symptoms, and 50 percent were still ill through the second day of flight. This represents a significant difference at the p = 0.46 level. In stark contrast to the 60 percent to 73 percent incidence of sedation or drowsiness reported in individuals treated with PMZ in terrestrial environment at the doses used here, less than 5 percent reported these symptoms during spaceflight. IM PMZ is an effective therapy for SMS and is associated with minimal incidence of sedation or drowsiness. This combination of efficacy that is absent of significant side effects represents a substantial improvement in the operational situation of crewmembers afflicted with SMS. Studies to understand the mechanisms underlying these observations will be undertaken in the future.

  5. Effect of Sampling Schedule on Pharmacokinetic Parameter Estimates of Promethazine in Astronauts

    NASA Technical Reports Server (NTRS)

    Boyd, Jason L.; Wang, Zuwei; Putcha, Lakshmi

    2005-01-01

    Six astronauts on the Shuttle Transport System (STS) participated in an investigation on the pharmacokinetics of promethazine (PMZ), a medication used for the treatment of space motion sickness (SMS) during flight. Each crewmember completed the protocol once during flight and repeated thirty days after returned to Earth. Saliva samples were collected at scheduled times for 72 h after PMZ administration; more frequent samples were collected on the ground than during flight owing to schedule constraints in flight. PMZ concentrations in saliva were determined by a liquid chromatographic/mass spectrometric (LC-MS) assay and pharmacokinetic parameters (PKPs) were calculated using actual flight and ground-based data sets and using time-matched sampling schedule on ground to that during flight. Volume of distribution (V(sub c)) and clearance (Cl(sub s),) decreased during flight compared to that from time-matched ground data set; however, Cl(sub s) and V(sub c) estimates were higher for all subjects when partial ground data sets were used for analysis. Area under the curve (AUC) normalized with administered dose was similar in flight and partial ground data; however AUC was significantly lower using time-matched sampling compared with the full data set on ground. Half life (t(sub 1/2)) was longest during flight, shorter with matched-sampling schedule on ground and shortest when complete data set from ground was used. Maximum concentration (C(sub max)), time for C(sub max), (t(sub max)), parameters of drug absorption, depicted a similar trend with lowest and longest respectively, during flight, lower with time-matched ground data and highest and shortest with full ground data.

  6. Interaction of promethazine and adiphenine to human hemoglobin: A comparative spectroscopic and computational analysis

    NASA Astrophysics Data System (ADS)

    Maurya, Neha; ud din Parray, Mehraj; Maurya, Jitendra Kumar; Kumar, Amit; Patel, Rajan

    2018-06-01

    The binding nature of amphiphilic drugs viz. promethazine hydrochloride (PMT) and adiphenine hydrochloride (ADP), with human hemoglobin (Hb) was unraveled by fluorescence, absorbance, time resolved fluorescence, fluorescence resonance energy transfer (FRET) and circular dichroism (CD) spectral techniques in combination with molecular docking and molecular dynamic simulation methods. The steady state fluorescence spectra indicated that both PMT and ADP quenches the fluorescence of Hb through static quenching mechanism which was further confirmed by time resolved fluorescence spectra. The UV-Vis spectroscopy suggested ground state complex formation. The activation energy (Ea) was observed more in the case of Hb-ADP than Hb-PMT interaction system. The FRET result indicates the high probability of energy transfer from β Trp37 residue of Hb to the PMT (r = 2.02 nm) and ADP (r = 2.33 nm). The thermodynamic data reveal that binding of PMT with Hb are exothermic in nature involving hydrogen bonding and van der Waal interaction whereas in the case of ADP hydrophobic forces play the major role and binding process is endothermic in nature. The CD results show that both PMT and ADP, induced secondary structural changes of Hb and unfold the protein by losing a large helical content while the effect is more pronounced with ADP. Additionally, we also utilized computational approaches for deep insight into the binding of these drugs with Hb and the results are well matched with our experimental results.

  7. Interaction of promethazine and adiphenine to human hemoglobin: A comparative spectroscopic and computational analysis.

    PubMed

    Maurya, Neha; Ud Din Parray, Mehraj; Maurya, Jitendra Kumar; Kumar, Amit; Patel, Rajan

    2018-06-15

    The binding nature of amphiphilic drugs viz. promethazine hydrochloride (PMT) and adiphenine hydrochloride (ADP), with human hemoglobin (Hb) was unraveled by fluorescence, absorbance, time resolved fluorescence, fluorescence resonance energy transfer (FRET) and circular dichroism (CD) spectral techniques in combination with molecular docking and molecular dynamic simulation methods. The steady state fluorescence spectra indicated that both PMT and ADP quenches the fluorescence of Hb through static quenching mechanism which was further confirmed by time resolved fluorescence spectra. The UV-Vis spectroscopy suggested ground state complex formation. The activation energy (E a ) was observed more in the case of Hb-ADP than Hb-PMT interaction system. The FRET result indicates the high probability of energy transfer from β Trp37 residue of Hb to the PMT (r=2.02nm) and ADP (r=2.33nm). The thermodynamic data reveal that binding of PMT with Hb are exothermic in nature involving hydrogen bonding and van der Waal interaction whereas in the case of ADP hydrophobic forces play the major role and binding process is endothermic in nature. The CD results show that both PMT and ADP, induced secondary structural changes of Hb and unfold the protein by losing a large helical content while the effect is more pronounced with ADP. Additionally, we also utilized computational approaches for deep insight into the binding of these drugs with Hb and the results are well matched with our experimental results. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Side effects of antimotion sickness drugs

    NASA Technical Reports Server (NTRS)

    Wood, C. D.; Manno, J. E.; Manno, B. R.; Redetzki, H. M.; Wood, M. D.; Vekovius, W. A.

    1984-01-01

    The effects on operational proficiency of the antimotion sickness drugs scopolamine, promethazine and d-amphetamine are tested using a computerized pursuit meter. Proficiency is not significantly affected by oral doses of 0.25 mg or 0.50 mg scopolamine but is descreased by oral or I.M. doses of 25 mg promethazine. The performance decrement associated with 25 mg oral promethazine is prevented when combined with 10 mg oral d-amphetamine. The combination of 25 mg I.M. promethazine, 25 mg oral promethazine and 10 mg d-amphetamine produces less performance decrement than oral or I.M. doses of promethazine alone, though more performance decrement than a placebo. I.M. promethazine is adsorbed slowly and consequently may provoke drowsiness.

  9. Bioavailability and Pharmacodynamics of Promethazine on Long Duration Missions to the International Space Station

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi; Boyd, Jason L.; Cintron, Nitza; Berens, Kurt L.

    2004-01-01

    Space motion sickness (SMS) is often treated in space with promethazine (PMZ). Common side effects of PMZ administration (50 mg intramuscular) on the ground are drowsiness and impaired cognitive performance. Anecdotal reports indicate that these effects are absent or less pronounced in space. This suggests that the availability of PMZ to the body (bioavailability) and/or the response of the body to PMZ (pharmacodynamics) may change during space flight. Opportunities for clinical research in space are limited. The study described here is our response to a NASA Research Announcement for proposals for flight-based research needed to improve, or answer specific questions about, diagnosis and therapy during space flight, and post-flight rehabilitation. We propose here to evaluate noninvasive methods for determining the bioavailability and pharmacodynamics of PMZ. The specific objectives of the proposed research are to 1) compare pharmacokinetic and pharmacodynamic parameters of PMZ, estimated from saliva and plasma levels after administration of PMZ, 2) estimate the relative bioavailability of the three dosage forms of PMZ that are often administered to control motion sickness symptoms in space, and 3) establish the dose-response relationship of PMZ. We will estimate the bioavailability of an intramuscular injection (IM), oral tablet, and rectal suppository of PMZ in noma1 subjects during ambulatory and antiorthostatic bed rest (ABR) conditions using novel stable isotope techniques. We will compare and contrast the bioavailability of PMZ during normal and microgravity conditions to examine changes in drug absorption and bioavailability during microgravit. Results of this study will validate methods for an approved in-flight investigation with this medication awaiting an opportunity for manifestation..

  10. Bioelectrochemical sensing of promethazine with bamboo-type multiwalled carbon nanotubes dispersed in calf-thymus double stranded DNA.

    PubMed

    Primo, Emiliano N; Oviedo, M Belén; Sánchez, Cristián G; Rubianes, María D; Rivas, Gustavo A

    2014-10-01

    We report the quantification of promethazine (PMZ) using glassy carbon electrodes (GCE) modified with bamboo-like multi-walled carbon nanotubes (bCNT) dispersed in double stranded calf-thymus DNA (dsDNA) (GCE/bCNT-dsDNA). Cyclic voltammetry measurements demonstrated that PMZ presents a thin film-confined redox behavior at GCE/bCNT-dsDNA, opposite to the irreversibly-adsorbed behavior obtained at GCE modified with bCNT dispersed in ethanol (GCE/bCNT). Differential pulse voltammetry-adsorptive stripping with medium exchange experiments performed with GCE/bCNT-dsDNA and GCE modified with bCNTs dispersed in single-stranded calf-thymus DNA (ssDNA) confirmed that the interaction between PMZ and bCNT-dsDNA is mainly hydrophobic. These differences are due to the intercalation of PMZ within the dsDNA that supports the bCNTs, as evidenced from the bathochromic displacement of UV-Vis absorption spectra of PMZ and quantum dynamics calculations at DFTB level. The efficient accumulation of PMZ at GCE/bCNT-dsDNA made possible its sensitive quantification at nanomolar levels (sensitivity: (3.50±0.05)×10(8) μA·cm(-2)·M(-1) and detection limit: 23 nM). The biosensor was successfully used for the determination of PMZ in a pharmaceutical product with excellent correlation. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Oral ketamine/midazolam is superior to intramuscular meperidine, promethazine, and chlorpromazine for pediatric cardiac catheterization.

    PubMed

    Auden, S M; Sobczyk, W L; Solinger, R E; Goldsmith, L J

    2000-02-01

    An IM combination of meperidine, promethazine, and chlorpromazine (DPT) has been given as sedation for pediatric procedures for more than 40 years. We compared this IM combination to oral (PO) ketamine/midazolam in children having cardiac catheterization. A total of 51 children, ages 9 mo to 10 yr, were enrolled and randomized in this double-blinded study. All children received an IM injection at time zero and PO fluid 15 minutes later. We observed acceptance of medication, onset of sedation and sleep, and sedative efficacy. The cardiorespiratory changes were evaluated. Sedation was supplemented with IV propofol as required. Recovery time, parental satisfaction, and patient amnesia were assessed. Ketamine/midazolam given PO was better tolerated (P < 0.0005), had more rapid onset (P < 0.001), and provided superior sedation (P < 0.005). Respiratory rate decreased after IM DPT only. Heart rate and shortening fraction were stable. Oxygen saturation and mean blood pressure decreased minimally in both groups. Supplemental propofol was more frequently required (P < or = 0.02) and in larger doses (P < 0.05) after IM DPT. Parental satisfaction ratings were higher (P < 0.005) and amnesia was more reliably obtained (P = 0.007) with PO ketamine/midazolam. Two patients needed airway support after the PO medication, as did two other patients when PO ketamine/midazolam was supplemented with IV propofol. Although PO ketamine/midazolam provided superior sedation and amnesia compared to IM DPT, this regimen may require the supervision of an anesthesiologist for safe use. Oral medication can be superior to IM injections for sedating children with congenital heart disease; however, the safety of all medications remains an issue.

  12. 76 FR 11790 - Drugs for Human Use; Drug Efficacy Study Implementation; Oral Prescription Drugs Offered for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-03

    ... (containing promethazine hydrochloride, ipecac fluidextract, potassium guaiacolsulfonate, citric acid, sodium... promethazine hydrochloride, ipecac fluidextract, potassium guaiacolsulfonate, citric acid, sodium citrate, and... promethazine hydrochloride, ipecac fluidextract, potassium guaiacolsulfonate, citric acid, sodium citrate...

  13. Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties.

    PubMed

    Facchini, Gustavo; Eberlin, Samara; Clerici, Stefano Piatto; Alves Pinheiro, Ana Lucia Tabarini; Costa, Adilson

    2017-12-01

    Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response. Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property. In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients. © 2017 Wiley Periodicals, Inc.

  14. Treatment of severe motion sickness with antimotion sickness drug injections

    NASA Technical Reports Server (NTRS)

    Graybiel, Ashton; Lackner, James R.

    1987-01-01

    This report concerns the use of intramuscular injections of scopolamine, promethazine, and dramamine to treat severely motion sick individuals participating in parabolic flight experiments. The findings indicate that a majority of individuals received benefit from 50-mg injections of promethazine or 0.5 mg-injections of scopolamine. By contrast, 50-mg injections of dramamine and 25-mg injections of promethazine were nonbeneficial. The use of antimotion drug injections for treating space motion sickness is discussed.

  15. The lesser of two adverse reactions.

    PubMed

    Chakraborti, Chayan; Egan, John

    2010-01-01

    Fundamental to complex systems are interconnected processes involved in providing high-quality patient care. A case study and a root cause analysis (RCA) illustrate a patient safety effort with unintended consequences. A 38-year-old woman presented to the hospital for odynophagia and vomiting. The patient developed Mobitz type 2, second-degree heart block temporally associated with the administration of intravenous ondansetron. RESPONSE TO THE EVENT: An Ishikawa, or fishbone, diagram conducted to enumerate potential contributing factors indicated that a key factor appeared to be an institutional restriction against using intravenous (i.v.) promethazine, which resulted in ondansetron being the only readily available i.v. anti-emetic on formulary. The anesthesia department requested that i.v. promethazine be removed from all operating and recovery room automated medication dispensing machines. The pharmacy department, given the realization that individual departments were taking independent action regarding promethazine, discussed the matter with the medical director, who issued a memo banning the use of i.v. promethazine. An institutional ban on i.v. anti-emetics such as promethazine may have resulted in an increase in the use of ondansetron and contributed to this adverse reaction. The reason to restrict promethazine is not well reported in the literature. In limiting the use of promethazine for patient safety concerns, the inadvertent increase in adverse reactions of the alternative medication, ondansetron, may have been overlooked. The resultant RCA underscores the need for careful cataloguing of adverse medication effects. Stakeholders should anticipate as many "downstream effects" of quality and patient safety improvements as possible. Comprehensive reporting of adverse medication effects will augment the emerging science of patient safety.

  16. The Effect of a Combination Treatment Using Palonosetron, Promethazine, and Dexamethasone on the Prophylaxis of Postoperative Nausea and Vomiting and QTc Interval Duration in Patients Undergoing Craniotomy under General Anesthesia: A Pilot Study.

    PubMed

    Bergese, Sergio D; Puente, Erika G; Antor, Maria A; Capo, Gerardo; Yildiz, Vedat O; Uribe, Alberto A

    2016-01-01

    Postoperative nausea and vomiting (PONV) is a displeasing experience that distresses surgical patients during the first 24 h after a surgical procedure. The incidence of postoperative nausea occurs in about 50%, the incidence of postoperative vomiting is about 30%, and in high-risk patients, the PONV rate could be as high as 80%. Therefore, the study design of this single arm, non-randomized, pilot study assessed the efficacy and safety profile of a triple therapy combination with palonosetron, dexamethasone, and promethazine to prevent PONV in patients undergoing craniotomies under general anesthesia. The research protocol was approved by the institutional review board and 40 subjects were provided written informed consent. At induction of anesthesia, a triple therapy of palonosetron 0.075 mg IV, dexamethasone 10 mg IV, and promethazine 25 mg IV was given as PONV prophylaxis. After surgery, subjects were transferred to the surgical intensive care unit or post anesthesia care unit as clinically indicated. Ondansetron 4 mg IV was administered as primary rescue medication to subjects with PONV symptoms. PONV was assessed and collected every 24 h for 5 days via direct interview and/or medical charts review. The overall incidence of PONV during the first 24 h after surgery was 30% (n = 12). The incidence of nausea and emesis 24 h after surgery was 30% (n = 12) and 7.5% (n = 3), respectively. The mean time to first emetic episode, first rescue, and first significant nausea was 31.3 (±33.6), 15.1 (±25.8), and 21.1 (±25.4) hours, respectively. The overall incidence of nausea and vomiting after 24-120 h period after surgery was 30% (n = 12). The percentage of subjects without emesis episodes over 24-120 h postoperatively was 70% (n = 28). No subjects presented a prolonged QTc interval ≥500 ms before and/or after surgery. Our data demonstrated that this triple therapy regimen may be an adequate alternative regimen for the

  17. Ionophore-Based Potentiometric Sensors for the Flow-Injection Determination of Promethazine Hydrochloride in Pharmaceutical Formulations and Human Urine

    PubMed Central

    Hassan, Ahmed Khudhair; Saad, Bahruddin; Ghani, Sulaiman Ab; Adnan, Rohana; Rahim, Afidah Abdul; Ahmad, Norariza; Mokhtar, Marina; Ameen, Suham Tawfiq; Al-Araji, Suad Mustafa

    2011-01-01

    Plasticised poly(vinyl chloride)-based membranes containing the ionophores (α-, β- and γ-cyclodextrins (CD), dibenzo-18-crown-6 (DB18C6) and dibenzo-30-crown-10 (DB30C10) were evaluated for their potentiometric response towards promethazine (PM) in a flow injection analysis (FIA) set-up. Good responses were obtained when β- and γ-CDs, and DB30C10 were used. The performance characteristics were further improved when tetrakis(4-chlorophenyl) borate (KTPB) was added to the membrane. The sensor based on β-CD, bis(2-ethylhexyl) adipate (BEHA) and KTPB exhibited the best performance among the eighteen sensor compositions that were tested. The response was linear from 1 × 10−5 to 1 × 10−2 M, slope was 61.3 mV decade−1, the pH independent region ranged from 4.5 to 7.0, a limit of detection of 5.3 × 10−6 M was possible and a lifetime of more than a month was observed when used in the FIA system. Other plasticisers such as dioctyl phenylphosphonate and tributyl phosphate do not show significant improvements in the quality of the sensors. The promising sensors were further tested for the effects of foreign ions (Li+, Na+, K+, Mg2+, Ca2+, Co2+, Cu2+, Cr3+, Fe3+, glucose, fructose). FIA conditions (e.g., effects of flow rate, injection volume, pH of the carrier stream) were also studied when the best sensor was used (based on β-CD). The sensor was applied to the determination of PM in four pharmaceutical preparations and human urine that were spiked with different levels of PM. Good agreement between the sensor and the manufacturer’s claimed values (for pharmaceutical preparations) was obtained, while mean recoveries of 98.6% were obtained for spiked urine samples. The molecular recognition features of the sensors as revealed by molecular modelling were rationalised by the nature of the interactions and complexation energies between the host and guest molecules. PMID:22346617

  18. On the nature of the chemical mediators involved in anaphylactic reactions in mice

    PubMed Central

    Halpern, B. N.; Neveu, T.; Spector, S.

    1963-01-01

    The effects of mepyramine, promethazine, chlorpromazine and lysergic acid diethylamide have been compared on the capillary permeability changes of the skin, produced by histamine, by 5-hydroxytryptamine and by passive cutaneous anaphylaxis in mice. Promethazine, mepyramine and chlorpromazine can inhibit, in decreasing order of activity, the effect of histamine, whilst lysergic acid diethylamide is inactive. Lysergic acid diethylamide and chlorpromazine are equally potent inhibitors of the action of 5-hydroxytryptamine on the peripheral vascular bed, whilst mepyramine is inactive. Promethazine has intermediate activity. Passive cutaneous anaphylaxis is strongly inhibited by chlorpromazine and by promethazine. Mepyramine and lysergic acid diethylamide, each injected alone, affect only weakly the anaphylactic reaction. However, passive cutaneous anaphylaxis is almost completely abolished by the simultaneous injection of the two last antagonists. It is suggested that the anaphylactic reaction in mice is the result of simultaneous release of both mediators, histamine and 5-hydroxytryptamine, each of them strengthening the effect of the other. PMID:13952224

  19. Comparison of treatment strategies for Space Motion Sickness

    NASA Technical Reports Server (NTRS)

    Davis, J. R.; Jennings, R. T.; Beck, B. G.

    1992-01-01

    Treatment strategies for Space Motion Sickness were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of Space Motion Sickness were graded as mild, moderate or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through Private Medical Conferences with the crew. A symptom matrix was analyzed for 19 crewmembers treated with an oral combination of scopolamine and dextroamphetamine (scopdex) and 15 crewmembers treated with promethazine delivered by intramuscular (IM) or suppository routes. Scopdex has been given preflight as prophaxis for Space Motion Sickness but analysis showed delayed symptom presentation in 9 crewmembers or failed to prevent symptoms in 7. Only three crewmembers who took scopdex had no symptoms inflight. Fourteen out of 15 crewmembers treated with IM promethazine and 6 of 8 treated with promethazine suppositories after symptom development had immediate (within 12 h) symptom relief and required no additional medication. There were no cases of delayed symptom presentation in the crewmembers treated with promethazine. This response is in contrast to untreated crewmembers who typically have slow symptom resolution over 72-96 h. We conclude that promethazine is an effective treatment of Space Motion Sickness symptoms inflight. NASA policy currently recommends treating crewmembers with Space Motion Sickness after symptom development, and no longer recommends prophylaxis with scopdex due to delayed symptom development and apparent variable absorption of oral medications during early flight days.

  20. Comparison of treatment strategies for Space Motion Sickness

    NASA Astrophysics Data System (ADS)

    Davis, J. R.; Jennings, R. T.; Beck, B. G.

    Treatment strategies for Space Motion Sickness (SMS) were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of SMS were graded as mild, moderate, or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through Private Medical Conferences with the crew. A symptom matrix was analyzed for 19 crewmembers treated with oral combination of scopolamine and dextroamphetamine (scopdex) and 15 crewmembers treated with promethazine delivered by intramuscular i.m. or suppository routes. Scopdex has been given preflight as prophylaxis for SMS, but analysis showed delayed symptom presentation in 9 crewmembers or failed to prevent symptoms in 7. Only 3 crewmembers who took scopdex had no symptoms inflight. Fourteen out of 15 crewmembers treated with i.m. promethazine and 6 of 8 treated with promethazine suppositories after symptom development had immediate (within 1-2h) symptom relief and required no additional medication. There were no cases of delayed symptom presentation in the crewmembers treated with promethazine. This response is in contrast to untreated crewmembers who typically have slow symptom resolution over 72-96h. We conclude that promethazine is an effective treatment of SMS symptoms inflight. NASA policy currently recommends treating crewmembers with SMS after symptom development, and no longer recommends prophylaxis with scopdex due to delayed symptom development and apparent variable absorption of oral medications during early flight days.

  1. 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.

  2. Space Motion Sickness - Analysis of Medical Debriefs Data for Incidence and Treatment

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi; Younker, D.; Daniels, V.

    2011-01-01

    Astronauts use medications for the treatment of a variety of illnesses during space travel. Data mining efforts to assess minor clinical conditions occurring during Shuttle flights STS-1 through STS-94 revealed that space motion sickness (SMS) was the most common ailment during early flight days, occurring in approx.40% of crewmembers, followed by digestive system disturbances (9%) and infectious diseases, which most commonly involved the respiratory or urinary tracts. A more recent analysis of postflight medical debriefs data to examine trends with respect to medication use by astronauts during spaceflights indicated that 37% of all prescriptions recorded was for pain followed by sleep (22%), SMS (18%), decongestion (14%), and all others (14%). Further analysis revealed that about 150 of 317 crewmembers experienced symptoms of SMS. Nearly all (132 of 150) crewmembers took medication for the treatment of symptoms with a total of 387 doses. Promethazine was taken most often (201 doses); in most cases this resulted in alleviation of symptoms with 130 crewmembers (65%) reporting feeling much or somewhat better. Although fewer total doses of the combination of promethazine and dextroamphetamine (Phen/Dex) were taken (45 doses), slightly more than half of these doses resulted in improvement. The combination of scopolamine and dextroamphetamine (Scop/Dex) was reported to be effective in only 37% of cases, with 36 of 97 total doses resulting in improvement. A higher percentage (24%) of Scop/Dex doses was reported to be ineffective compared with promethazine alone or as Phen/Dex (10% and 7%, respectively). Comparisons of the effectiveness of the different dosage forms of promethazine revealed that intramuscular injection was most effective in alleviating symptoms with 55% feeling much better, 16% feeling somewhat better, and only 7% feeling no effect or worse. Overall, it appears that promethazine alone was used more frequently during flight and was reported effective for

  3. Medications influencing central cholinergic pathways affect fixation stability, saccadic response time and associated eye movement dynamics during a temporally-cued visual reaction time task.

    PubMed

    Naicker, Preshanta; Anoopkumar-Dukie, Shailendra; Grant, Gary D; Modenese, Luca; Kavanagh, Justin J

    2017-02-01

    Anticholinergic medications largely exert their effects due to actions on the muscarinic receptor, which mediates the functions of acetylcholine in the peripheral and central nervous systems. In the central nervous system, acetylcholine plays an important role in the modulation of movement. This study investigated the effects of over-the-counter medications with varying degrees of central anticholinergic properties on fixation stability, saccadic response time and the dynamics associated with this eye movement during a temporally-cued visual reaction time task, in order to establish the significance of central cholinergic pathways in influencing eye movements during reaction time tasks. Twenty-two participants were recruited into the placebo-controlled, human double-blind, four-way crossover investigation. Eye tracking technology recorded eye movements while participants reacted to visual stimuli following temporally informative and uninformative cues. The task was performed pre-ingestion as well as 0.5 and 2 h post-ingestion of promethazine hydrochloride (strong centrally acting anticholinergic), hyoscine hydrobromide (moderate centrally acting anticholinergic), hyoscine butylbromide (anticholinergic devoid of central properties) and a placebo. Promethazine decreased fixation stability during the reaction time task. In addition, promethazine was the only drug to increase saccadic response time during temporally informative and uninformative cued trials, whereby effects on response time were more pronounced following temporally informative cues. Promethazine also decreased saccadic amplitude and increased saccadic duration during the temporally-cued reaction time task. Collectively, the results of the study highlight the significant role that central cholinergic pathways play in the control of eye movements during tasks that involve stimulus identification and motor responses following temporal cues.

  4. Advances in Pharmacotherapeutics of Space Motion Sickness

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi

    2006-01-01

    Space Motion Sickness (SMS) is common occurrence in the U.S. manned space flight program and nearly 2/3 of Shuttle crewmembers experience SMS. Several drugs have been prescribed for therapeutic management of SMS. Typically, orally-administered SMS medications (scopolamine, promethazine) have poor bioavailability and often have detrimental neurocognitive side effects at recommended doses. Intramuscularly administered promethazine (PMZ) is perceived to have optimal efficacy with minimal side effects in space. However, intramuscular injections are painful and the sedating neurocognitive side effects of promethazine, significant in controlled ground testing, may be masked in orbit because injections are usually given prior to crew sleep. Currently, EVAs cannot be performed by symptomatic crew or prior to flight day three due to the lack of a consistently efficacious drug, concern about neurocognitive side effects, and because an in-suit vomiting episode is potentially fatal. NASA has long sought a fast acting, consistently effective anti-motion sickness medication which has only minor neurocognitive side effects. Development of intranasal formulations of scopolamine and promethazine, the two commonly used SMS drugs at NASA for both space and reduced gravity environment medical operations, appears to be a logical alternative to current treatment modalities for SMS. The advantages are expected to be fast absorption, reliable and high bioavailability, and probably reduced neurocognitive side effects owing to dose reduction. Results from clinical trials with intranasal scopolamine gel formulation and pre-clinical testing of a prototype microcapsule intranasal gel dosage form of PMZ (INPMZ) will be discussed. These formulations are expected to offer a dependable and effective noninvasive treatment option for SMS.

  5. Effectiveness and duration of intramuscular antimotion sickness medications

    NASA Technical Reports Server (NTRS)

    Wood, C. D.; Stewart, J. J.; Wood, M. J.; Mims, M.

    1992-01-01

    Motion sickness inhibits gastric motility, making the oral route ineffective for medications. The intramuscular route is an effective alternative. The rotating chair was used to produce the M 111 level of motion sickness on the Graybiel Symptom Scale. The intramuscular medications given 30 minutes before rotation were compared with placebo (saline, 1 mL) for effectiveness and duration in increasing the number of tolerated head movements. Average placebo number of head movements was 294. Promethazine 25 mg increased head movements by 78% (P < .05), with a duration of 12 hours. Scopolamine 0.2 mg increased head movements by 91% (P < .05), with a duration of 4 hours. The effect of caffeine 250 mg and ephedrine 25 mg was not significant. When combined with scopolamine, ephedrine produced an 32% additive effect. Scopolamine 0.08 mg, 0.1 mg, and 0.2 mg and also promethazine 12.5 mg and 25 mg were significant (P < .05). Promethazine appears to be the drug of choice for intramuscular use because of a longer duration and a high level of effectiveness. Scopolamine was of high effectiveness, but had a duration of 4 hours. It was eight times as potent by the intramuscular as by the oral route.

  6. Nausea and vomiting in pregnancy: a review of the pathology and compounding opportunities.

    PubMed

    Zur, Eyal

    2013-01-01

    Nausea and vomiting in pregnancy can have serious adverse effects on the quality of a woman's life, affecting her occupational, social, and domestic functioning, and her general well-being; therefore, it is very important to treat this condition appropriately and effectively. Evidence-based algorithms support the use of oral pyridoxine alone or combined with doxylamine as first-line treatment. Promethazine or dimenhydrinate, known as a second-line treatment, should be added to the first-line treatment or should be added only to pyridoxine according to different algorithms. In most of the world, there is a lack of approved medicines using this combination approach known as the first-line treatment. Therefore, compounding pharmacists should supply the demand by compounding 10-mg pyridoxine hydrochloride and 10-mg doxylamine succinate slow-release capsules. Since transdermal promethazine does not exist world wide, and, since this medicine has significant added values compared to the oral/rectal dosage forms, compounding pharmacists should offer physicians transdermal promethazine as a second-line therapy in nausea and vomiting in pregnancy. This review summarizes the nausea and vomiting in pregnancy problems and discusses the compounding opportunities that exist in this common and wide-spread pathology in order to improve a woman's quality of life.

  7. Prolonged anticholinergic delirium following antihistamine overdose.

    PubMed

    Scott, James; Pache, David; Keane, Greg; Buckle, Helen; O'Brien, Natalie

    2007-06-01

    A case of anticholinergic delirium in a female adolescent is described, exploring the pharmacokinetic reasons for the prolonged time course and reviewing the management provided. A 14 year old female hospitalised for depression ingested large quantities of promethazine and cyproheptadine. A severe anticholinergic delirium ensued which resolved after six days, much longer than the expected duration. The likely cause of the prolonged delirium was the interaction of promethazine and fluvoxamine through the inhibition of the CYP2D6 enzyme. The patient's young age, the severity of the poisoning and the use of drugs with anticholinergic properties to manage the delirium may also have contributed. The delirium may have been reversed had a cholinesterase inhibitor been provided soon after the overdose.

  8. Therapeutic effectiveness of medications taken during spaceflight

    NASA Technical Reports Server (NTRS)

    Pool, Sam L.; Putcha, Lakshmi

    1992-01-01

    The therapeutic effectiveness of medications during spaceflight is considered in light of extensive anecdotal and experimental evidence. Attention is given to a range of medications for space motion sickness, sleeplessness, and physical discomfort. About 70 individual cases are reviewed in which crewmembers used such medications as: (1) scopolamine hydrobromide, dextroamphetamine sulfate, and promethazine hydrochloride for motion sickness; (2) metoclopramide hydrochloride and naloxone hydrochloride for bowel motility; and (3) aspirin and acetaminophen for headache and back pain. The effectiveness of orally ingested medications for space motion sickness is shown to be very low, while promethazine hydrochloride is effective when administered intramuscularly. The medications for pain are shown to be generally effective, and the use of sleep-inducing medications is limited by potentially detrimental performance effects.

  9. Effect of formulation pH on transdermal penetration of antiemetics formulated in poloxamer lecithin organogel.

    PubMed

    Woodall, Rachel; Arnold, John J; McKay, Doug; Asbill, C Scott

    2013-01-01

    The purpose of this study was to assess the impact of altering formulation pH on the transdermal penetration of several commonly used antiemetic, weakly basic drugs incorporated into poloxamer lecithin organogel vehicle. Poloxamer lecithin organogel formulations containing promethazine hydrochloride (25 mg/mL), metoclopramide hydrochloride (10 mg/mL), and ondansetron hydrochloride (8 mg/mL) were examined for both drug release and transdermal penetration across porcine skin in modified Franz diffusion cells for a period of 24 hours. For the transdermal studies, each antiemetic drug was formulated at a pH above and below their acid dissociation constant (pKa) in an attempt to assure that the drug would be primarily in their respective ionized or non-ionized states. In addition, drug content in skin was assessed at the end of the 24-hour experiment. Drug content analysis was determined via high-performance liquid chromatography. As a percent of total drug release from the poloxamer lecithin organogel vehicle, promethazine hydrochloride demonstrated the most transdermal drug penetration after 24 hours (30.2% +/- 20.2%), followed by ondansetron hydrochloride (2.7% +/- 1.1%) and metoclopramide hydrochloride (1.8% +/- 1.6%). Subsequently, the pH of the Pluronic F-127 gel was adjusted in order to ensure that each antiemetic drug would be primarily in its unionized state. The transdermal permeation of each antiemetic drug primarily in its unionized state increased over that observed with the drug primarily in its ionized state after 24 hours (promethazine: 1.6-fold increase; metoclopramide: 1.3-fold increase; ondansetron: 1.8-fold increase). A similar trend was noted in the amount of each drug found in the skin after 24 hours (promethazine: 1.2-fold increase; metoclopramide: 2.4-fold increase; ondansetron: 3.0-fold increase). These results suggest that proper optimization of drug ionization state may be a useful strategy for compounding pharmacists to increase the efficacy

  10. ON THE LOCAL EDEMA PROVOKED BY CYSTAMINE IN THE RAT

    SciTech Connect

    Franchimont, P.; van Cauwenberge, H.; Lecomte, J.

    1962-06-30

    >Injection of this radioprotective compound in the rat foot caused localized edema which could be prevented by pretreatment with promethazine and UML 491. This indicates that cystamine induces edema by liberating histamine and 5-hydroxytryptamine. (H.H.D.)

  11. Indomethacin-antihistamine combination for gastric ulceration control

    NASA Technical Reports Server (NTRS)

    Brown, P. A.; Danellis, J. V. (Inventor)

    1981-01-01

    An anti-inflammatory and analgesic composition containing indomethacin and an H sub 1 or an H sub 2 histamine receptor antagonist in an amount sufficient to reduce gastric distress caused by the indomethacin is described. Usable antagonists include pyrilamine, promethazine, metiamide and cimetidine.

  12. Update on the incidence and treatment of space motion sickness

    NASA Technical Reports Server (NTRS)

    Beck, Bradley G.

    1993-01-01

    Flight surgeons routinely monitor crew symptoms and treatment of space motion sickness (SMS), not only during flight, but also to obtain information postflight from each crewmember. Recent statistics indicate that the incidence of SMS has not changed since STS-26 in Sep. 1988. The percentages of mild, moderate, and severe cases has only changed slightly. However, the treatment of SMS has significantly changed since STS-26. Scopolamine/dexedrine is no longer used as a prophylaxis for SMS symptoms because of evidence of delay in symptoms. Intramuscular promethazine has been used in more than 30 individuals with a reported decrease in symptoms greater than 90 percent. A delay in symptoms has not been reported, and the duration of certain SMS symptoms has decreased due to use of intramuscular promethazine. Case studies will be discussed and several therapeutic options and doses will be demonstrated. Further treatment possibilities will be examined.

  13. Belly Dancer's Dyskinesia: A Glimpse of a Rare Phenomenon

    PubMed Central

    Kushwaha, Suman

    2017-01-01

    Belly dancer's dyskinesia (BDD) is an extremely rare manifestation consisting of involuntary and repetitive rhythmic movements of the abdominal wall. These movements cannot be voluntarily suppressed but may be influenced by respiratory maneuvers. Investigations such as spinal cord and abdominal imaging usually fail to reveal any local abnormalities to explain the movement disorder. A 23-year-old male presented with sudden onset of undulating movements of the abdominal wall for the last two months after he took domperidone. There was no associated pain or effect of respiration. The movements used to subside during sleep. His radiological and hematological evaluations were inconclusive. The movements, however, subsided after administration of promethazine and clonazepam. The cause of BDD varies, making diagnosis difficult. One of the causes being drug induced but it has never been reported earlier by domperidone. Also, our report provides a possible way to manage BDD by clonazepam and promethazine. PMID:29104832

  14. Various anti-motion sickness drugs and core body temperature changes.

    PubMed

    Cheung, Bob; Nakashima, Ann M; Hofer, Kevin D

    2011-04-01

    Blood flow changes and inactivity associated with motion sickness appear to exacerbate the rate of core temperature decrease during subsequent body cooling. We investigated the effects of various classes of anti-motion sickness drugs on core temperature changes. There were 12 healthy male and female subjects (20-35 yr old) who were given selected classes of anti-motion sickness drugs prior to vestibular Coriolis cross coupling induced by graded yaw rotation and periodic pitch-forward head movements in the sagittal plane. All subjects were then immersed in water at 18 degrees C for a maximum of 90 min or until their core temperature reached 35 degrees C. Double-blind randomized trials were administered, including a placebo, a non-immersion control with no drug, and six anti-motion sickness drugs: meclizine, dimenhydrinate, chlorpheniramine, promethazine + dexamphetamine, promethazine + caffeine, and scopolamine + dexamphetamine. A 7-d washout period was observed between trials. Core temperature and the severity of sickness were monitored throughout each trial. A repeated measures design was performed on the severity of sickness and core temperature changes prior to motion provocation, immediately after the motion sickness end point, and throughout the period of cold-water immersion. The most effective anti-motion sickness drugs, promethazine + dexamphetamine (with a sickness score/duration of 0.65 +/- 0.17) and scopolamine + dexamphetamine (with a sickness score/duration of 0.79 +/- 0.17), significantly attenuated the decrease in core temperature. The effect of this attenuation was lower in less effective drugs. Our results suggest that the two most effective anti-motion sickness drugs are also the most effective in attenuating the rate of core temperature decrease.

  15. Blockers for excitatory effects of achatin-I, a tetrapeptide having a D-phenylalanine residue, on a snail neurone.

    PubMed

    Santos, D E; Liu, G J; Takeuchi, H

    1995-01-16

    Some histamine H1 receptor antagonists suppressed the inward current (Iin) of an Achatina identifiable neurone type, PON (periodically oscillating neurone), caused by an Achatina endogenous tetrapeptide having a D-phenylalanine residue, achatin-I (Gly-D-Phe-Ala-Asp), under voltage clamp. Achatin-I was applied locally to the neurone by brief pneumatic pressure ejection and antagonists were administered by perfusion. The dose-response curves of the effective histamine H1 antagonists indicated their potency order to suppress the Iin as follows: chlorcyclizine, promethazine, triprolidine and homochlorcyclizine > trimeprazine and clemastine > diphenylpyraline. The potent drugs were mostly piperazine and phenothiazine types. The effects of chlorcyclizine, promethazine and triprolidine on the dose (the duration of the pressure ejection)-response curve of achatin-I indicated that these drugs affected the Iin caused by achatin-I in a non-competitive manner. The antagonists for the receptors of the small-molecule neurotransmitters other than histamine H1, such as histamine H2, acetylcholine, gamma-aminobutyric acid (GABA), L-glutamic acid, dopamine, alpha- and beta-adrenalin and 5-hydroxytryptamine, had no effect on the Iin caused by achatin-I.

  16. The relation of motion sickness to the spatial-temporal properties of velocity storage

    NASA Technical Reports Server (NTRS)

    Dai, Mingjia; Kunin, Mikhail; Raphan, Theodore; Cohen, Bernard; Young, L. R. (Principal Investigator)

    2003-01-01

    Tilting the head in roll to or from the upright while rotating at a constant velocity (roll while rotating, RWR) alters the position of the semicircular canals relative to the axis of rotation. This produces vertical and horizontal nystagmus, disorientation, vertigo, and nausea. With recurrent exposure, subjects habituate and can make more head movements before experiencing overpowering motion sickness. We questioned whether promethazine lessened the vertigo or delayed the habituation, whether habituation of the vertigo was related to the central vestibular time constant, i.e., to the time constant of velocity storage, and whether the severity of the motion sickness was related to deviation of the axis of eye velocity from gravity. Sixteen subjects received promethazine and placebo in a double-blind, crossover study in two consecutive 4-day test series 1 month apart, termed series I and II. Horizontal and vertical eye movements were recorded with video-oculography while subjects performed roll head movements of approx. 45 degrees over 2 s to and from the upright position while being rotated at 138 degrees /s around a vertical axis. Motion sickness was scaled from 1 (no sickness) to an endpoint of 20, at which time the subject was too sick to continue or was about to vomit. Habituation was determined by the number of head movements that subjects made before reaching the maximum motion sickness score of 20. Head movements increased steadily in each session with repeated testing, and there was no difference between the number of head movements made by the promethazine and placebo groups. Horizontal and vertical angular vestibulo-ocular reflex (aVOR) time constants declined in each test, with the declines being closely correlated to the increase in the number of head movements. The strength of vertiginous sensation was associated with the amount of deviation of the axis of eye velocity from gravity; the larger the deviation of the eye velocity axis from gravity, the

  17. [Not Available].

    PubMed

    Burgot, J L

    1978-06-01

    Acids conjugated to various phenothiazine derivatives are titrated directly with sodium hydroxide, by means of an automatic thermometric titrimeter. The titration curves have sharp breaks, suitable for analytical use, and these are discussed, in the case of promethazine hydrochloride, as functions of various parameters such as pK(a), the solubility of the product and the enthalpy of neutralization (determined in this work).

  18. Evaluation of Several Common Antimotion Sickness Medications and Recommendations Concerning Their Potential Usefulness During Special Operations

    DTIC Science & Technology

    2009-12-02

    include oral caffeine (200 mg) to counteract any sedation from the treatment medications. Motion sickness was elicited via 12 roll tilts per minute...susceptibility (MSSQ) via ANCOVA. Three treatment conditions (promethazine, oral scopolamine, transdermal scopolamine) were not planned for ANCOVA...requested improved treatments for motion sickness, because the currently recommended regimen of meclizine was not as effective as desired and was sometimes

  19. Relative efficacy of the proposed Space Shuttle antimotion sickness medications

    NASA Astrophysics Data System (ADS)

    Hordinsky, J. R.; Schwartz, E.; Beier, J.; Martin, J.; Aust, G.

    1982-07-01

    Space motion sickness has been estimated as affecting between 1/3 and 1/2 of all space flight participants. NASA has at the moment proposed a combination of promethazine and ephedrine ( P/E) and one of scopolamine and dextroamphetamine ( S/D), both given orally, as well as a transdermally applied scopolamine (TAS), as preventive and ameliorative measures. The reported double-blind study tests the early phase actions and efficacy of the transdermal scopolamine (Transderm ™-V of ALZA Corporation) and compares these in detail to the oral medications. Motion sickness resistance was tested by standardized head movements while accelerating at 0.2°/sec 2 to a maximum rotation of 240°/sec, with an intermediate plateau of 10 min at 180°/sec. To permit weighting motion sickness protection against other system influences, cardiovascular, psychological (subjective and objective), and visual parameter changes were documented for the three therapeutic modes. The relative impact of the various modalities on operational and experimental components of space missions is discussed. A comparison to intramuscularly administered promethazine (a backup therapeutic mode suggested for Space Shuttle use) is also included.

  20. Effects of Motion on Skill Acquisition in Future Simulators

    DTIC Science & Technology

    2006-05-01

    performed by Jacobs (1976) concentrated on transfer of training under different motion conditions. Researchers used participants with no prior flying... Autogenic feedback training exercise is superior to promethazine for the treatment of motion sickness. Journal of Clinical Pharmacology, 40, 1154 -1165...motion in simulation was examined. A particular focus was paid to research on the effects of motion cueing on transfer of training from both ground

  1. PillCam(TradeMark), a Noninvasive Endoscopic Device for the Measurement of Gastrointestinal Motility Changes

    NASA Technical Reports Server (NTRS)

    Vaksman, Zahman; Crady, Camille; Raju, G. S.; Putcha, Lakshmi

    2007-01-01

    Introduction: Bioavailability and effectiveness of drugs given by mouth are governed in part by gastrointestinal (GI) motility and function. Microgravity has been shown to decrease GI motility as indicated by a 3 fold increase in gastrointestinal transit time (GITT). The PillCam(TradeMark), an endoscopic camera embedded in a capsule, is a novel noninvasive and unobtrusive device that is used for the diagnosis of GI pathology. The purpose of this study is to evaluate the usefulness of PillCam(TradeMark) as an alternative to the Lactulose Breath Hydrogen Test (LBHT) for estimating GI motility. The sensitivity and applicability of this device for detection and estimation of the effect of promethazine, a deterrent, and caffeine, a prokinetic, on GI motility were also examined. Method: In this semi-randomized cross-over design study, six male and six female subjects were administered the following 4 treatments: PillCam(TradeMark) alone, PillCam(TradeMark)+Lactulose (10g), PillCam(TradeMark)+caffeine (200mg), and PillCam(TradeMark)+Promethazine (50mg). Results: GITT ranged between 1:24 and 7:52 hr:min. Lactulose did not alter GITT. A significant increase in GITT was noticed after administration of PMZ when compared to values from PillCam(TradeMark) treatment alone or PillCam(TradeMark)+Lactulose treatment. No difference in GITT after caffeine treatment was noticed. While there were no gender related differences in GITT after administration of PillCam(TradeMark) or with lactulose, a significant difference (p<.05) between genders was observed after promethazine administration with mean GITT higher in males (5:50 hr:min) than females (4:15 hr:min). Conclusion: The PillCam(TradeMark) capsule is applicable for the determination of GITT using time stamped GI images. It can be successfully used for the assessment of drug induced changes in GI motility and therefore, may be applicable for microgravity and analog environment studies on GI motility and function.

  2. Restricted sedation and absence of cognitive impairments after administration of intranasal scopolamine.

    PubMed

    Weerts, Aurélie P; Pattyn, Nathalie; Putcha, Lakshmi; Hoag, Stephen W; Van Ombergen, Angelique; Hallgren, Emma; Van de Heyning, Paul H; Wuyts, Floris L

    2015-12-01

    Space motion sickness in astronauts during spaceflight causes significant discomfort, which might impede their functionality. Pharmacological treatment has been mainly restricted to promethazine. Transdermal and oral scopolamine have also been used in space; however, their use was reduced due to unpredictable effectiveness and side effects. Recently, intranasal scopolamine administration has gained much interest, since this route ensures fast and reliable absorption with a decreased incidence of undesirable side effects. The aim of this study was to evaluate the effect of intranasal scopolamine on cognitive performance and to determine its side effects. This double-blind, placebo controlled, repeated measures study evaluated vigilant attention, short-term memory, implicit memory and working memory. Side effects were reported on a 22-item questionnaire and sleepiness was assessed by the Karolinska, Stanford and Epworth Sleepiness Scales. Scopolamine had no effect on cognitive function. Only the Karolinska score was significantly increased for scopolamine compared to placebo. Participants reported a dry mouth and dizziness after receiving scopolamine. Results show that intranasal scopolamine did not impair cognitive performance. Intranasal scopolamine might be a good alternative to promethazine for the alleviation of space motion sickness, since the agent has minimal sedative effects and does not hamper cognitive performance. © The Author(s) 2015.

  3. Low temperature regeneration of activated carbons using microwaves: revising conventional wisdom.

    PubMed

    Calışkan, E; Bermúdez, J M; Parra, J B; Menéndez, J A; Mahramanlıoğlu, M; Ania, C O

    2012-07-15

    The purpose of this work was to explore the application of microwaves for the low temperature regeneration of activated carbons saturated with a pharmaceutical compound (promethazine). Contrary to expectations, microwave-assisted regeneration did not lead to better results than those obtained under conventional electric heating. At low temperatures the regeneration was incomplete either under microwave and conventional heating, being this attributed to the insufficient input energy. At mild temperatures, a fall in the adsorption capacity upon cycling was obtained in both devices, although this was much more pronounced for the microwave. These results contrast with previous studies on the benefits of microwaves for the regeneration of carbon materials. The fall in the adsorption capacity after regeneration was due to the thermal cracking of the adsorbed molecules inside the carbon porous network, although this effect applies to both devices. When microwaves are used, along with the thermal heating of the carbon bed, a fraction of the microwave energy seemed to be directly used in the decomposition of promethazine through the excitation of the molecular bonds by microwaves (microwave-lysis). These results point out that the nature of the adsorbate and its ability to interact with microwave are key factors that control the application of microwaves for regeneration of exhausted activated carbons. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Anti-motion-sickness therapy. [amphetamine preparation effects in human acceleration tolerance

    NASA Technical Reports Server (NTRS)

    Wood, C. D.

    1973-01-01

    Neither alterations in environmental temperature nor moderate intake of alcohol was found to alter susceptibility to motion sickness in subjects exposed to rotation in the Pensacola slow rotation room. Scopolamine with d-amphetamine was found to be the most effective preparation for the prevention of motion sickness under the experimental conditions of the studies reported here. Promethazine in combination with d-amphetamine was in the same range of effectiveness. Drug actions suggest that acetylcholine and norepinephrine may be involved in motion sickness.

  5. Studies on the metabolism of five model drugs by fungi colonizing cadavers using LC-ESI-MS/MS and GC-MS analysis.

    PubMed

    Martínez-Ramírez, Jorge A; Voigt, Kerstin; Peters, Frank T

    2012-09-01

    It is well-known that cadavers may be colonized by microorganisms, but there is limited information if or to what extent these microbes are capable of metabolizing drugs or poisons, changing the concentrations and metabolic pattern of such compounds in postmortem samples. The aim of the present study was to develop a fungal biotransformation system as an in vitro model to investigate potential postmortem metabolism by fungi. Five model drugs (amitriptyline, metoprolol, mirtazapine, promethazine, and zolpidem) were each incubated with five model fungi known to colonize cadavers (Absidia repens, Aspergillus repens, Aspergillus terreus, Gliocladium viride, and Mortierella polycephala) and with Cunninghamella elegans (positive control). Incubations were performed in Sabouraud medium at 25 °C for 5 days. After centrifugation, a part of the supernatants was analyzed by liquid chromatography-tandem mass spectrometry with product ion scanning. Another part was analyzed by full scan gas chromatography-mass spectrometry after extraction and derivatization. All model drugs were metabolized by the control fungus resulting in two (metoprolol) to ten (amitriptyline) metabolites. Of the model fungi, only Abs. repens and M. polycephala metabolized the model drugs: amitriptyline was metabolized to six and five, metoprolol to two and two, mirtazapine to five and three, promethazine to six and nine, and zolpidem to three and four metabolites, respectively. The main metabolic reactions were demethylation, oxidation, and hydroxylation. The presented in vitro model is applicable to studying drug metabolism by fungi colonizing cadavers.

  6. Using the Estimating Supplies Program to Develop Materiel Solutions for the U.S. Air Force Aeromedical Evacuation In-Flight Kit (FFQDM)

    DTIC Science & Technology

    2008-07-07

    Ibuprofen 800-mg tablet. Because of several negative side effects, Chlorpromazine HCL INJ can be replaced with Haloperidol HCL INJ or Promethazine HCL...CART 10S EA 6505013548591 FLUMAZENIL INJ 0.1MG/ML 10ML VI 10S VI 6505002688530 HALOPERIDOL INJ 5MG/ML 1ML AMPUL 10S AM 6505001538480 HYDROGEN...DIAZEPAM TAB 5MG INDIVIDUALLY SEALED 100S TB 6505013548591 FLUMAZENIL INJ 0.1MG/ML 10ML VI 10S VI 6505002688530 HALOPERIDOL INJ 5MG/ML 1ML AMP 10S AM

  7. Space Environment Effects on Stability of Medications Flown on Space Shuttles and the International Space Station (ISS)

    NASA Technical Reports Server (NTRS)

    Daniels, Vernie; Du, Jianping; Crady, Camille; Satterfield, Rick; Putcha, Lakshmi

    2007-01-01

    The purpose is to assess physical and chemical degradation of select pharmaceutical formulations from the Shuttle and ISS medical kits. Eleven pharmaceuticals dispensed as different dosage forms were selected based on their physical / chemical characteristics and susceptibility to environmental factors such as, temperature, humidity and light sensitivity. When available, ground-controls of the study medications with matching brand and lot numbers were used for comparison. Samples retrieved from flight were stored along with their matching controls in a temperature and humidity controlled environmental chamber. Temperature, humidity, and radiation data from the Shuttle and ISS were retrieved from onboard HOBO U12 Temp/RH Data Loggers, and from passive dosimeters. Physical and chemical analyses of the pharmaceuticals were conducted using validated United States Pharmacopeia (USP) methods. Results indicated degradation of 6 of the 11 formulations returned from space flights. Four formulations, Amoxicillin / Clavulanate, promethazine, sulfamethoxazole / trimethoprim, and ciprofloxacin tablets depicted discoloration after flight. Chemical content analyses using High or Ultra Performance Liquid Chromatography (HPLC / UPLC) methods revealed that dosage forms of Amoxicillin / Clavulanate, promethazine, sulfamethoxazole / trimethoprim, lidocaine, ciprofloxacin and mupirocin contained less than 95% of manufacturer s labeled claim of active drug compound. Shuttle and ISS environments affect stability and shelf life of certain mediations flown on these missions. Data analysis is in progress to examine the effect of specific space flight environmental factors on pharmaceutical stability. The degradation profiles generated from ground studies in analog environments will be useful in establishing predictive shelf-life profiles for medications intended for use during long-term space exploration missions.

  8. Antinauseants in Pregnancy: Teratogens or Not?

    PubMed Central

    Biringer, Anne

    1984-01-01

    Nausea and/or vomiting affect 50% of all pregnant women. For most women, this is a self-limited problem which responds well to conservative management. However, there are some situations where the risk to the mother and fetus posed by the illness are greater than the possible risks of teratogenicity of antinauseant drugs. Antihistamines have had the widest testing, and to date, there has been no evidence linking doxylamine, dimenhydrinate or promethazine to congenital malformations. Since no available drugs have official approval for use in nausea and vomiting of pregnancy the physician is left alone to make this difficult decision. PMID:21279128

  9. Case vignettes of movement disorders.

    PubMed

    Yung, C Y

    1983-08-01

    This paper reports five movement disorders cases to serve as a basis for discussion of the problems encountered in the clinical management of these cases, and the pathophysiological mechanisms involved in these disorders as presented. Case 1 is a description of the subjective experience of a patient with acute orofacial dystonia from promethazine. Case 2 is the use of clonazepam is post-head injury tics. Case 3 is the complication from discontinuation of haloperidol and benztropine mesylate treatment. Case 4 is myoclonus in subacute sclerosing Panencephalitis, and Case 5 is rebound tremor from withdrawal of a beta-adrenergic blocker.

  10. Investigation of anti-motion sickness drugs in the squirrel monkey

    NASA Technical Reports Server (NTRS)

    Cheung, B. S.; Money, K. E.; Kohl, R. L.; Kinter, L. B.

    1992-01-01

    Early attempts to develop an animal model for anti-motion sickness drugs, using dogs and cats; were unsuccessful. Dogs did not show a beneficial effect of scopolamine (probably the best single anti-motion sickness drug for humans thus far) and the findings in cats were not definitive. The authors have developed an animal model using the squirrel monkey (Saimiri sciureus) of the Bolivian phenotype. Unrestrained monkeys in a small lucite cage were tested in an apparatus that induces motion sickness by combining vertical oscillation and horizontal rotation in a visually unrestricted laboratory environment. Signs of motion sickness were scored using a rating scale. Ten susceptible monkeys (weighing 800-1000 g) were given a total of five tests each, to establish the baseline susceptibility level. Based on the anticholinergic activity of scopolamine, the sensitivity of squirrel monkey to scopolamine was investigated, and the appropriate dose of scopolamine for this species was determined. Then various anti-motion sickness preparations were administered in subsequent tests: 100 ug scopolamine per monkey; 140 ug dexedrine; 50 ug scopolamine plus 70 ug dexedrine; 100 ug scopolamine plus 140 ug dexedrine; 3 mg promethazine; 3 mg promethazine plus 3 mg ephedrine. All these preparations were significantly effective in preventing motion sickness in the monkeys. Ephedrine, by itself, which is marginally effective in humans, was ineffective in the monkeys at the doses tried (0.3-6.0 mg). The squirrel monkey appears to be a good animal model for antimotion sickness drugs. Peripherally acting antihistamines such as astemizole and terfenadine were found to be ineffective, whereas flunarizine, and an arginine vasopressin V1 antagonist, showed significant activity in preventing motion sickness.

  11. The role of pharmacologically-active amines in resistance to Trichostrongylus colubriformis in the guinea-pig

    PubMed Central

    Rothwell, T. L. W.; Dineen, J. K.; Love, R. J.

    1971-01-01

    The role of histamine and 5-hydroxytryptamine in resistance to Trichostrongylus colubriformis in the guinea-pig has been investigated by studying the effect of amine antagonists (promethazine, mepyramine and methysergide), inhibitors of amine synthesis (α-hydrazino analogue of histidine and α-methyl dopa), depletion of tissue stores of the amines with reserpine and by attempts to elevate levels of the amines by oral administration of the amines and their immediate metabolic precursors (L-histidine, L-tryptophan and 5-hydroxy-DL-tryptophan). The results show that promethazine suppressed the development of resistance during a primary infection and inhibited expulsion of the parasite in actively and adoptively immunized animals. Mepyramine and the α-hydrazino analogue of histidine inhibited expulsion of the parasite in actively immunized guinea-pigs although methysergide and α-methyl dopa were not effective. Reserpine suppressed rejection of a challenge infection in actively and adoptively immunized animals, and oral administration of the histamine precursor (L-histidine) and 5-hydroxytryptamine increased the resistance which develops during a primary infection. These results show that histamine and 5-hydroxytryptamine play roles in the mechanism of resistance to T. colubriformis in the guinea-pig. It is suggested that the mechanism of resistance to the helminth is biphasic. The first phase is immunologically specific and probably involves interaction between antigens and sensitized lymphocytes, which acts as a trigger for myeloid (eosinophil and basophil) involvement and the release of pharmacologically active amines. The second phase, which is non-specific, appears to be the final effector mechanism, and involves the rejection of the parasites either directly or indirectly by the action of the amines. PMID:4399728

  12. Evaluation of a new antinauseant drug for the prevention of motion sickness

    NASA Technical Reports Server (NTRS)

    Graybiel, A.; Knepton, J.

    1977-01-01

    The new drug, AHR 5645B, together with other drugs was evaluated in tests, conducted with eight male subjects, concerning its ability to prevent motion sickness. It was found that AHR 5645B, used in doses of 20, 50, and 100 mg, was not efficacious in preventing experimental motion sickness. A combination of 50 mg meclizine and 25 mg ephedrine sulfate produced the best results. Favorable results were also obtained with a combination of 12.5 mg promethazine hydrochloride and 12.5 mg ephedrine sulfate. The findings in the reported experiment point to the difficulty of identifying a highly efficacious antimotion sickness drug for everyone.

  13. [Anti-cholinergic effect of Pluchea ovalis (pers.) Dc. (asteraceae) root extract on isolated Wistar rat tracheae].

    PubMed

    Agbonon, A; Aklikokou, K; Kwashie, E-G; Gbéassor, M

    2004-09-01

    Ethanolic extract of Pluchea ovalis roots inhibit acetylcholine-induced bronchoconstriction observed in asthma. To understand the mechanism of P. ovalis root extract on airway smooth muscle contraction, we investigated the anti-cholinergic effect of the ethanolic extract on isolated isolated tracheae of the Wistar rat. For this purpose, three experimental conditions of incubation were used: idomethacin, indomethacin+propranolol or indomethacin+propranolo+ promethazine. The extract was applied in all three conditions at 0.25 mg/ml for 10 minutes prior to cumulative doses of acetylcholine (10(-8) to 5.10(-4) g/ml). The extract reduced acetylcholine-induced contraction and could have an antagonistic effect on muscarinic receptors of the rat trachea.

  14. Scombroid poisoning. A report of seven cases involving the Western Australian salmon, Arripis truttaceus.

    PubMed

    Smart, D R

    To present the clinical findings of scombroid poisoning due to ingestion of the Western Australian salmon, Arripis truttaceus, occurring in two separate outbreaks involving seven patients. Both outbreaks occurred in March and the fish had been caught in South Australian waters. Onset of symptoms in all patients occurred within half an hour of ingestion of the affected fish. The clinical syndrome included erythema and urticaria of the skin, facial flushing and sweating, palpitations, hot flushes of the body, headache, nausea, vomiting and dizziness. The fish implicated in one outbreak was noted to have a peppery taste. The diagnosis of scombroid poisoning was confirmed by the presence of the clinical syndrome, and by demonstration of high histamine levels in the cooked fish. Two patients had minor symptoms which had resolved before seeking medical advice. Another two patients had mild symptoms which disappeared after two hours of observation and required no specific treatment. Three patients had evidence of major toxicity which was successfully treated with parenterally administered promethazine. One of the three patients with major toxicity required overnight admission and repeated doses of promethazine to eradicate her symptoms. No patient had symptoms for longer than 12 hours. Scombroid poisoning is caused by ingestion of fish which has accumulated scombrotoxin during spoilage. The toxin is heat stable and has been identified as histamine. The clinical presentation closely resembles an acute allergic reaction. This similarity in symptoms may result in the diagnosis of scombroid poisoning being missed by clinicians. Patients with the symptom complex may be incorrectly informed that they are allergic to the fish species. Diagnosis is clinical and can be confirmed by analysis of the histamine content of the fish. Treatment is with antihistamines, however major toxicity may require the same aggressive management as acute anaphylaxis.

  15. Management of extravasation injuries: a focused evaluation of noncytotoxic medications.

    PubMed

    Reynolds, Paul M; MacLaren, Robert; Mueller, Scott W; Fish, Douglas N; Kiser, Tyree H

    2014-06-01

    Extravasations are common manifestations of iatrogenic injury that occur in patients requiring intravenous delivery of known vesicants. These injuries can contribute substantially to patient morbidity, cost of therapy, and length of stay. Many different mechanisms are behind the tissue damage during extravasation injuries. In general, extravasations consist of four different subtypes of tissue injury: vasoconstriction, osmotic, pH related, and cytotoxic. Recognition of high-risk patients, appropriate cannulation technique, and monitoring of higher risk materials remain the standard of care for the prevention of extravasation injury. Prompt interdisciplinary action is often necessary for the treatment of extravasation injuries. Knowledge of the mechanism of extravasation-induced tissue injury, agents for reversal, and appropriate nonpharmacologic treatment methods is essential. The best therapeutic agent for treatment of vasopressor extravasation is intradermal phentolamine. Topical vasodilators and intradermal terbutaline may provide relief. Intradermal hyaluronidase has been effective for hyperosmotic extravasations, although its use largely depends on the risk of tissue injury and the severity of extravasation. Among the hyperosmotic agents, calcium extravasation is distinctive because it may present as an acute tissue injury or may possess delayed clinical manifestations. Extravasation of acidic or basic materials can produce significant tissue damage. Phenytoin is the prototypical basic drug that causes a clinical manifestation known as purple glove syndrome (PGS). This syndrome is largely managed through preventive and conservative treatment measures. Promethazine is acidic and can cause a devastating extravasation, particularly if administered inadvertently through the arteriolar route. Systemic heparin therapy remains the accepted treatment option for intraarteriolar administration of promethazine. Overall, the evidence for managing extravasations due to

  16. Antihistamine effect on synaptosomal uptake of serotonin, norepinephrine and dopamine

    NASA Technical Reports Server (NTRS)

    Brown, P. A.; Vernikos, J.

    1980-01-01

    A study on the effects of five H1 and H2 antihistamines on the synaptosomal uptake of serotonin (5HT), norepinephrine (NE), and dopamine (DA) is presented. Brain homogenates from female rats were incubated in Krebs-Ringer phosphate buffer solution in the presence of one of three radioactive neurotransmitters, and one of the five antihistamines. Low concentrations of pyrilamine competitively inhibited 5HT uptake, had little effect on NE uptake, and no effect on DA uptake. Promethazine, diphenhydramine, metiamide, and cimetidine had no effect on 5HT or DA uptake at the same concentration. Diphenhydramine had a small inhibitory effect on NE uptake. It is concluded that pyrilamine is a selective and potent competitive inhibitor of 5HT uptake at concentrations between .05 and .5 micromolars.

  17. Experiment M131. Human vestibular function

    NASA Technical Reports Server (NTRS)

    Graybiel, A.; Miller, E. F., II; Homick, J. L.

    1977-01-01

    The lower susceptibility to vestibular stimulation aloft, compared with that on ground under experimental conditions, is attributed to a precondition, namely, either there is no need to adapt, or, as exemplified by the Skylab 3 pilot, adaptation to weightlessness is achieved. Findings in some of the astronauts emphasize the distinction between two categories of vestibular side effects: immediate reflex phenomena (illusions, sensations of turning, etc.), and delayed epiphenomena that include the constellation of symptoms and syndromes comprising motion sickness. The drug combinations 1-scopolamine and d-amphetamine and promethazine hydrochloride and ephedrine sulfate are effective in prevention and treatment of motion sickness. It is concluded that prevention of motion sickness in any stressful motion environment involves selection, adaptation, and the use of drugs.

  18. Curine inhibits mast cell-dependent responses in mice.

    PubMed

    Ribeiro-Filho, Jaime; Leite, Fagner Carvalho; Costa, Hermann Ferreira; Calheiros, Andrea Surrage; Torres, Rafael Carvalho; de Azevedo, Carolina Trindade; Martins, Marco Aurélio; Dias, Celidarque da Silva; Bozza, Patrícia T; Piuvezam, Márcia Regina

    2014-09-11

    Curine is a bisbenzylisoquinoline alkaloid and the major constituent isolated from Chondrodendron platyphyllum, a plant that is used to treat inflammatory diseases in Brazilian folk medicine. This study investigates the effectiveness of curine on mast cell-dependent responses in mice. To induce mast cell-dependent responses, Swiss mice were subcutaneously sensitized with ovalbumin (OVA-12 μg/mouse) and Al(OH)3 in a 0.9% NaCl solution. Fifteen days later, the animals were challenged with OVA through different pathways. Alternatively, the animals were injected with compound 48/80 or histamine, and several parameters, including anaphylaxis, itching, edema and inflammatory mediator production, were analyzed. Promethazine, cromoglycate, and verapamil were used as control drugs, and all of the treatments were performed 1h before the challenges. Curine pre-treatment significantly inhibited the scratching behavior and the paw edema induced by either compound 48/80 or OVA, and this protective effect was comparable in magnitude with those associated with treatment with either cromoglycate or verapamil. In contrast, curine was a weak inhibitor of histamine-induced paw edema, which was completely inhibited by promethazine. Curine and verapamil significantly inhibited pleural protein extravasations and prostaglandin D2 (PGD2) and cysteinyl leukotrienes (CysLTs) production following allergen-induced pleurisy. Furthermore, like verapamil, curine inhibited the anaphylactic shock caused by either compound 48/80 or an allergen. In in vitro settings, these treatments also inhibited degranulation as well as PGD2 and CysLT production through IgE-dependent activation of the mast cell lineage RBL-2H3. Curine significantly inhibited immediate allergic reactions through mechanisms more related to mast cell stabilization and activation inhibition than interference with the pro-inflammatory effects of mast cell products. These findings are in line with the hypothesis that the alkaloid

  19. Analysis of pharmaceutical preparations containing antihistamine drugs by micellar liquid chromatography.

    PubMed

    Martínez-Algaba, C; Bermúdez-Saldaña, J M; Villanueva-Camañas, R M; Sagrado, S; Medina-Hernández, M J

    2006-02-13

    Rapid chromatographic procedures for analytical quality control of pharmaceutical preparations containing antihistamine drugs, alone or together with other kind of compounds are proposed. The method uses C18 stationary phases and micellar mobile phases of cetyltrimethylammonium bromide (CTAB) with either 1-propanol or 1-butanol as organic modifier. The proposed procedures allow the determination of the antihistamines: brompheniramine, chlorcyclizine, chlorpheniramine, diphenhydramine, doxylamine, flunarizine, hydroxyzine, promethazine, terfenadine, tripelennamine and triprolidine, in addition to caffeine, dextromethorphan, guaifenesin, paracetamol and pyridoxine in different pharmaceutical presentations (tablets, capsules, suppositories, syrups and ointments). The methods require minimum handling sample and are rapid (between 3 and 12 min at 1 mLmin(-1) flow rate) and reproducible (R.S.D. values<5%). Limits of detection are lower than 1 microgmL(-1) and the recoveries of the analytes in the pharmaceutical preparations are in the range 100+/-10%.

  20. Biochemical sensor tubing for point-of-care monitoring of intravenous drugs and metabolites.

    PubMed

    Choi, Charles J; Wu, Hsin-Yu; George, Sherine; Weyhenmeyer, Jonathan; Cunningham, Brian T

    2012-02-07

    In medical facilities, there is strong motivation to develop detection systems that can provide continuous analysis of fluids in medical tubing used to either deliver or remove fluids from a patient's body. Possible applications include systems that increase the safety of intravenous (IV) drug injection and point-of-care health monitoring. In this work, we incorporated a surface-enhanced Raman scattering (SERS) sensor comprised of an array of closely spaced metal nanodomes into flexible tubing commonly used for IV drug delivery and urinary catheters. The nanodome sensor was fabricated by a low-cost, large-area process that enables single use disposable operation. As exemplary demonstrations, the sensor was used to kinetically detect promethazine (pain medication) and urea (urinary metabolite) within their clinically relevant concentration ranges. Distinct SERS peaks for each analyte were used to demonstrate separate detection and co-detection of the analytes.

  1. BUPRENORPHINE ABUSE IN INDIA : AN UPDATE

    PubMed Central

    Sharma, Yogesh; Mattoo, S.K.

    1999-01-01

    This study reviews the available Indian literature on buprenorphine abuse. Buprenorphine was introduced in 1986; the abuse, first noticed in 1987, increased rapidly till 1994, and then decreased gradually. Initiated through other addicts and medical practitioners, the abuse was mostly as a cheap, easily and legally available substitute for opioids. The typical young adult male abuser used an intravenous cocktail with diazepam, pheneramine or promethazine for a better kick. The withdrawal syndrome was typical of the opioids and without an expected delayed onset. Complications of pseudoaneurysm and recurrent koro in repeated withdrawal were reported. Buprenorphine as a detoxifying agent for opioids reportedly gave better symptom control in the first week but high rates of dependence induction were reported. The Indian data tends to caution against the Western enthusiasm to use buprenorphine for detoxification or maintenance of opioid abusers. PMID:21455379

  2. Clinical characteristics of cough mixture abusers referred to three substance abuse clinics in Hong Kong: a retrospective study.

    PubMed

    Tang, A K; Tang, W K; Liang, H J; Chan, F; Mak, S C; Ungvari, G S

    2012-12-01

    OBJECTIVES. Cough mixture is the third most commonly abused substance in patients attending the Prince of Wales Hospital Substance Abuse Clinic. The content of the local cough mixture is not well researched. Paranoid psychosis manifesting as persecutory delusions and derogatory hallucination, as well as mood symptoms, is common in these patients. The natural history and outcome of such psychoses associated with cough mixture abuse are not well known. This study aimed to address these questions. METHODS. This was a retrospective study of cough mixture abuse in Hong Kong. Case records of cough mixture abusers currently receiving treatment at the 3 substance abuse clinics at the Prince of Wales Hospital, Alice Ho Miu Ling Nethersole Hospital, and the North District Hospital were retrieved for data collection. The patients' demographic data, duration and intake pattern of cough mixture, and use of any other drugs were documented. The presenting psychopathology, first urine toxicology results, diagnosis, treatment, number of hospitalizations, and course of the illness were also recorded. RESULTS. A total of 63 patients with the diagnosis of cough mixture abuse were identified in the database; 89% were male. The mean +/- SD age of the patients was 34.4 +/- 6.2 years; 67% were single and 83% were unemployed. The mean +/- SD age of onset of cough mixture abuse was 20 +/- 5 years. Psychiatric symptoms developed a mean +/- SD of 7.6 +/- 6.0 years after onset of abuse. According to the ICD-10 Mental and Behavioural Disorders criteria, the top psychiatric diagnoses were substance-induced psychotic disorder (67%), schizophrenia (19%), depressive disorder (11%), and dysthymia (10%). The most common ingredients in the urine sample at first presentation were promethazine (75%), pseudoephedrine (67%), codeine (60%), ephedrine (57%), zopiclone (17%), and hydrocodone (16%). Additionally, 16% of patients were in the priority follow-up group. The mean +/- SD follow-up period was 6

  3. Quantitative analysis of drugs in hair by UHPLC high resolution mass spectrometry.

    PubMed

    Kronstrand, Robert; Forsman, Malin; Roman, Markus

    2018-02-01

    Liquid chromatographic methods coupled to high resolution mass spectrometry are increasingly used to identify compounds in various matrices including hair but there are few recommendations regarding the parameters and their criteria to identify a compound. In this study we present a method for the identification and quantification of a range of drugs and discuss the parameters used to identify a compound with high resolution mass spectrometry. Drugs were extracted from hair by incubation in a buffer:solvent mixture at 37°C during 18h. Analysis was performed on a chromatographic system comprised of an Agilent 6550 QTOF coupled to a 1290 Infinity UHPLC system. High resolution accurate mass data were acquired in the All Ions mode and exported into Mass Hunter Quantitative software for quantitation and identification using qualifier fragment ions. Validation included selectivity, matrix effects, calibration range, within day and between day precision and accuracy. The analytes were 7-amino-flunitrazepam, 7-amino-clonazepam, 7-amino-nitrazepam, acetylmorphine, alimemazine, alprazolam, amphetamine, benzoylecgonine, buprenorphine, diazepam, ethylmorphine, fentanyl, hydroxyzine, ketobemidone, codeine, cocaine, MDMA, methadone, methamphetamine, morphine, oxycodone, promethazine, propiomazine, propoxyphene, tramadol, zaleplone, zolpidem, and zopiclone. As proof of concept, hair from 29 authentic post mortem cases were analysed. The calibration range was established between 0.05ng/mg to 5.0ng/mg for all analytes except fentanyl (0.02-2.0), buprenorphine (0.04-2.0), and ketobemidone (0.05-4.0) as well as for alimemazine, amphetamine, cocaine, methadone, and promethazine (0.10-5.0). For all analytes, the accuracy of the fortified pooled hair matrix was 84-108% at the low level and 89-106% at the high level. The within series precisions were between 1.4 and 6.7% and the between series precisions were between 1.4 and 10.1%. From the 29 autopsy cases, 121 positive findings were

  4. Evaluation of antimotion sickness drug side effects on performance

    NASA Technical Reports Server (NTRS)

    Wood, C. D.; Manno, J. E.; Manno, B. R.; Redetzki, H. M.; Wood, M. J.

    1985-01-01

    The effects of antimotion-sickness drugs on the performance in computerized-pursuit-meter tests of groups of ten 18-30-yr-old male and female subjects are investigated experimentally using double-blind placebo techniques. The results are presented in tables and graphs and discussed in detail. The proficiency scores are as good as or better than placebo values for subjects given d-amphetamine (DA) 5 or 10 mg, promethazine (P) 25 mg + scopolamine (S) 400 ng + DA 10 mg, S 1 mg + DA 10 mg, S 250-600 ng, marezine 50 mg, meclizine 50 mg, dimenhydrinate 50 mg, S 1 mg + DA 5 mg, or P 25 mg + DA 10 mg. Significantly lower scores are seen in subjects given S 800 ng or 1 mg, P 25 mg (oral or IM), P 25 mg + S 400 ng, and P 25 mg oral + P 25 mg IM + DA 10 mg.

  5. Serotonin syndrome caused by drug to drug interaction between escitalopram and dextromethorphan.

    PubMed

    Dy, Prudence; Arcega, Victor; Ghali, Wael; Wolfe, Winifred

    2017-08-07

    A 63-year-old woman with a history of long-standing depression, maintained on escitalopram, presented with altered mental status. Patient had recently been prescribed dextromethorphan-promethazine cough syrup 2 weeks prior for an upper respiratory tract infection. On admission, she was lethargic and obtunded and found to have inducible myoclonus on examination. The rest of her physical exam was unremarkable. Pertinent lab and imaging findings showed QTc prolongation on ECG, negative electroencephalogram and CT head findings, essentially normal blood tests and a negative toxicology screen. The patient was admitted to the step down unit for close observation; both escitalopram and the cough syrup were suspended and was supportively managed. Overnight the patient's mental status improved and the serial EcGs showed resolution of the prolonged QTc. Patient was discharged home without further complication. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Comparison of efficacy of ginger with various antimotion sickness drugs

    NASA Technical Reports Server (NTRS)

    Wood, C. D.; Manno, J. E.; Wood, M. J.; Manno, B. R.; Mims, M. E.

    1988-01-01

    Ginger and several other medications were compared with scopolamine and d-amphetamine for effectiveness in prevention of motion sickness. Methods: Double-blind techniques were used. The subjects were given the medications two hours before they were rotated in a chair making head movements until a symptom total short of vomiting was reached. Standardized N.A.S.A. techniques were used for speed of rotation and end-point of motion sickness. Results: The three doses of ginger were all at the placebo level of efficacy. Amitriptyline, ethopropazine and trihexyphenidyl increased the tolerated head movements but the increase was not statistically significant. Significant levels of protection were produced by dimenhydrinate, promethazine, scopolamine and d-amphetamine. Protection was further increased by combination of these latter drugs with d-amphetamine. Efficacy was greatest as the dose was increased. Conclusions: The medication of choice in this study was scopolamine 0.6 mg with d-amphetamine 10 mg. This combination provided good protection with acceptable side effects.

  7. Prevention of experimental motion sickness by scopolamine absorbed through the skin

    NASA Technical Reports Server (NTRS)

    Graybiel, A.; Knepton, J.; Shaw, J.

    1976-01-01

    A double-blind placebo-controlled study compared the efficacy of the antimotion sickness drug scopolamine when administered by oral or transdermal routes. A secondary purpose was to extend our bioassay involving fixed-dose combinations of the homergic drugs promethazine and ephedrine. After receiving 12 apparently identical drug-placebo treatments, eight normal male students were exposed in a slow rotation room to stressful accelerations generated by their execution of 40 head movements out of the plane of the room's rotation at 1 rpm and at 1-rpm increments until either symptoms were experienced (just short of frank motion sickness) or the 27-rpm ceiling on the test was reached. Efficacy of a drug was defined in terms of the placebo-range and categorized as beneficial, inconsequential, or detrimental. The only detrimental effect was with scopolamine given orally. It is concluded that the advantages of the transdermal scopolamine, which include minimal side effects and prolonged effectiveness, deserve full exploitation.

  8. Anaesthesia for Barotherapy

    SciTech Connect

    Cass, N. M.

    An evaluation was made of various anesthetic techniques and agents employed in the newly developed high-pressure oxygen radiotherapeutic method. Results are reported for 334 courses of anesthesia given to patients prior to treatment with megavoltage x rays under high oxygen pressure. Reasons for anesthesia during barotherapy are discussed. The optimal anesthetic technique combines heavy premedication with pentobarbitone. Promethazine (25 mg) is given orally 4 hr before treatment. Two hours before treatment papaveretum and scopolamine are given hypodermically. On arrival in the treatment suite, patients are given pentobarbitone (Nembutal) intravenously. Since light hypnosis with barbiturates increases reflex response to pain, pethidinemore » was given intravenously in doses of 50 to 150 mg. Four % cocaine in adrenaline (1: 100,000 solution) is then applied to the nostrils, and the trachea and larynx sprayed with 4% lignocaine. In 334 anesthetic courses there were no deaths and minimal complications. Epileptiform convulsions occurred during three compressions. (BRB)« less

  9. Assessment of Evidence Base from Medical Debriefs Data on Space Motion Sickness Incidence and Treatment

    NASA Technical Reports Server (NTRS)

    Younker, D.R.; Daniels, V.R.; Boyd, J.L.; Putcha, L.

    2008-01-01

    An objective of this data compilation and analysis project is to examine incidence and treatment efficacy of common patho-physiological disturbances during spaceflight. Analysis of medical debriefs data indicated that astronauts used medications to alleviate symptoms of four major ailments for which astronauts received treatment for sleep disturbances, space motion sickness (SMS), pain (headache, back pain) and sinus congestion. In the present data compilation and analysis project on SMS treatment during space missions, subject demographics (gender, age, first-time or repeat flyer), incidence and severity of SMS symptoms and subjective treatment efficacy from 317 crewmember debrief records were examined from STS-1 through STS-89. Preliminary analysis of data revealed that 50% of crew members reported SMS symptoms on at least one flight and 22% never experienced it. In addition, there were 387 medication dosing episodes reported, and promethazine was the most commonly used medication. Results of analysis of symptom check lists, medication use/efficacy and gender and flight record differences in incidence and treatment efficacy will be presented. Evidence gaps for treatment efficacy along with medication use trend analysis will be identified.

  10. Absolute rate constants of alkoxyl radical reactions in aqueous solution. [Tert-butyl hydroperoxide

    SciTech Connect

    Erben-Russ, M.; Michel, C.; Bors, W.

    1987-04-23

    The pulse radiolysis technique was used to generate the alkoxyl radical derived from tert-butyl hydroperoxide (/sup t/BuOOH) in aqueous solution. The reactions of this radical with 2,2'-azinobis(3-ethyl-6-benzothiazolinesulfonate) (ABTS) and promethazine were monitored by kinetic spectroscopy. The unimolecular decay rate constant of the tert-butoxyl radical (/sup t/BuO) was determined to be 1.4 x 10/sup 6/ s/sup -1/. On the basis of this value, the rate constants for /sup t/BuO attack on quercetin, crocin, crocetin, ascorbate, isoascorbate, trolox c, glutathione, thymidine, adenosine, guanosine, and unsaturated fatty acids were determined. In addition, the reaction of /sup t/BuO with the polyunsaturated fatty acids (PUFA)more » was observed by directly monitoring the formation of the fatty acid pentadienyl radicals. Interestingly, the attack of /sup t/BuO on PUFA was found to be faster by about one order of magnitude as compared to the same reaction in a nonpolar solvent.« less

  11. Space motion sickness

    NASA Technical Reports Server (NTRS)

    Homick, J. L.

    1979-01-01

    Research on the etiology, prediction, treatment and prevention of space motion sickness, designed to minimize the impact of this syndrome which was experienced frequently and with severity by individuals on the Skylab missions, on Space Shuttle crews is reviewed. Theories of the cause of space motion sickness currently under investigation by NASA include sensory conflict, which argues that motion sickness symptoms result from a mismatch between the total pattern of information from the spatial senses and that stored from previous experiences, and fluid shift, based upon the redistribution of bodily fluids that occurs upon continued exposure to weightlessness. Attempts are underway to correlate space motion sickness susceptibility to different provocative environments, vestibular and nonvestibular responses, and the rate of acquisition and length of retention of sensory adaptation. Space motion sickness countermeasures under investigation include various drug combinations, of which the equal combination of promethazine and ephedrine has been found to be as effective as the scopolomine and dexedrine combination, and vestibular adaptation and biofeedback training and autogenic therapy.

  12. Chloral hydrate as a sedating agent for neurodiagnostic procedures in children.

    PubMed

    Fong, Choong Yi; Tay, Chee Geap; Ong, Lai Choo; Lai, Nai Ming

    2017-11-03

    reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in single small studies.Children who received oral chloral hydrate had lower sedation failure when compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study, moderate-quality evidence). Children who received oral chloral hydrate had a higher risk of sedation failure after one dose compared to those who received intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study, low-quality evidence), but after two doses there was no evidence of a significant difference between the two groups (RR 3.00, 95% CI 0.33 to 27.46; 1 study, very low-quality evidence). Children who received oral chloral hydrate appeared to have more sedation failure when compared with music therapy, but the quality of evidence was very low for this outcome (RR 17.00, 95% CI 2.37 to 122.14; 1 study). Sedation failure rates were similar between oral chloral hydrate, oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam.Children who received oral chloral hydrate had a shorter time to achieve adequate sedation when compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study, moderate-quality evidence), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study, moderate-quality evidence), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study, moderate-quality evidence), and rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study, low-quality evidence) and intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study, moderate-quality evidence).No data were available to assess the proportion of children with successful completion of neurodiagnostic procedure without interruption by the child awakening. Most trials did not assess

  13. Non-Pharmacological Countermeasure to Decrease Landing Sickness and Improve Functional Performance

    NASA Technical Reports Server (NTRS)

    Rosenberg, M. J. F.; Kreutzberg, G. A.; Galvan-Garza, R. C.; Mulavara, A. P.; Reschke, M. F.

    2017-01-01

    Upon return from long-duration spaceflight, 100% of crewmembers experience motion sickness (MS) symptoms. The interactions between crewmembers' adaptation to a gravitational transition, the performance decrements resulting from MS and/or use of promethazine (PMZ), and the constraints imposed by mission task demands could significantly challenge and limit an astronaut's ability to perform functional tasks during gravitational transitions. Stochastic resonance (SR) is "noise benefit": adding noise to a system might increase the information (examples to the left and above). Stochastic vestibular stimulation (SVS), or low levels of noise applied to the vestibular system, improves balance and locomotor performance (Goel et al. 2015, Mulavara et al. 2011, 2015). In hemi-lesioned rat models, Samoudi et al. 2012 found that SVS increased GABA release on the lesioned, but not the intact side. Activation of the GABA pathway is important in modulating MS and promoting adaptability (Cohen 2008) and was seen to reverse MS symptoms in rats after unilateral labyrinthectomy (Magnusson et al. 2000). Thus, SVS could be used to promote GABA pathways to reduce MS and promote adaptability, eliminate the need for PMZ or other performance-inhibiting drugs.

  14. SciTech Connect

    Hirode, Mitsuhiro; Ono, Atsushi; Miyagishima, Toshikazu

    We have constructed a large-scale transcriptome database of rat liver treated with various drugs. In an effort to identify a biomarker for diagnosis of hepatic phospholipidosis, we extracted 78 probe sets of rat hepatic genes from data of 5 drugs, amiodarone, amitriptyline, clomipramine, imipramine, and ketoconazole, which actually induced this phenotype. Principal component analysis (PCA) using these probes clearly separated dose- and time-dependent clusters of treated groups from their controls. Moreover, 6 drugs (chloramphenicol, chlorpromazine, gentamicin, perhexiline, promethazine, and tamoxifen), which were reported to cause phospholipidosis but judged as negative by histopathological examination, were designated as positive by PCA usingmore » these probe sets. Eight drugs (carbon tetrachloride, coumarin, tetracycline, metformin, hydroxyzine, diltiazem, 2-bromoethylamine, and ethionamide), which showed phospholipidosis-like vacuolar formation in the histopathology, could be distinguished from the typical drugs causing phospholipidosis. Moreover, the possible induction of phospholipidosis was predictable by the expression of these genes 24 h after single administration in some of the drugs. We conclude that these identified 78 probe sets could be useful for diagnosis of phospholipidosis, and that toxicogenomics would be a promising approach for prediction of this type of toxicity.« less

  15. Pharmacologic behavior management of pediatric dental patients diagnosed with attention deficit disorder/attention deficit hyperactivity disorder.

    PubMed

    Kerins, Carolyn A; McWhorter, Alton G; Seale, N Sue

    2007-01-01

    The purpose of this study was to conduct a survey of Texas pediatric dentists to determine: (1) the percentage of patients they treat with attention deficit disorder (ADD)/attention deficit hyperactivity disorder (ADHD); (2) the behavior management techniques that are utilized to treat their patients who suffer from ADD/ADHD; and (3) the relative success rates of these techniques in their practices. A 17-question, single-answer, multiple choice survey was mailed to 343 Texas pediatric dentists. The mailing list was obtained from American Academy of Pediatric Dentistry and Texas Academy of Pediatric Dentistry member rosters. One mailing was sent, including a self-addressed stomped envelope, for returned responses. A 54% response rate (186 surveys) revealed that nitrous oxide was the most frequently used pharmacologic behavior management technique; however, demerol/promethazine/nitrous oxide was rated as effective most often for treating ADD/ADHD patients. Practitioners believe the incidence of attention deficit disorder/attention deficit hyperactivity disorder is increasing, and they are familiar with the medications used to treat the conditions. Texas pediatric dentists are using a variety of sedation techniques and are interested in developing guidelines for sedation of these patients.

  16. Comparative study of the complex forming ability and enantioselectivity of cyclodextrin polymers by CE and 1H NMR.

    PubMed

    Danel, Cécile; Azaroual, Nathalie; Chavaria, Cédric; Odou, Pascal; Martel, Bernard; Vaccher, Claude

    2013-02-15

    The interactions between nine drugs (baclofen, bupivacaine, chlorpheniramine, ketoconazole, paliperidone, promethazine, propranolol, risperidone and verapamil) and six cyclodextrins (α-CD, β-CD, γ-CD, HP-β-CD, HP-γ-CD and Me-β-CD) or six polymers of cyclodextrins (polyα-CD, polyβ-CD, polyγ-CD, polyHP-β-CD, polyHP-γ-CD and polyMe-β-CD) were studied by affinity capillary electrophoresis and/or (1)H NMR at pH 2.5. An exhaustive qualitative study was performed through the determination of the retardation factor. Then, four compounds and both β-CD and polyβ-CD were selected for the quantitative study of the interactions at pH 2.5 and 7.0. By comparing the results obtained with the β-CD and polyβ-CD, it appears that the apparent binding constants are up to five times higher with the polymer. The 2D-NMR results seem to indicate that the structure of the polymeric network favours the inclusion of the guest in the hydrophobic cavity of the CD units. Moreover, the poly-CDs have shown very high enantioselective abilities at both pH. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Sudden death associated with intravenous injection of toad extract.

    PubMed

    Kostakis, Chris; Byard, Roger W

    2009-07-01

    A 24-year-old male died suddenly following the intravenous injection of what was believed to be the ring-derivate amphetamine 'ecstasy' (MDMA). Toxicological analyses of the victim's blood and the injected material, however, failed to reveal MDMA, but showed instead low levels of bufotenine, a tryptamine derivative alkaloid found in the secretions of various toads. In addition, resibufogenin, cinobufagin and bufalin, bufadienolides that are also found in toad venom, were identified in the injected material. While these substances also occur in certain South American plants, the finding of paracetamol, promethazine and diclofenac would be in keeping with ingredients found in the traditional Chinese herbal product Chan Su that derives from the skin glands and secretions of toads and that is often adulterated with standard pharmaceutical drugs. This case demonstrates the problems that users and sellers may encounter from the unknown composition of street drugs and herbal medicines, and the danger that may be incurred from the injection of such materials. It also shows the difficulties that may be associated with attempting to identify low levels of organic toxins in postmortem specimens necessitating a targeted screening approach guided by information obtained at the death scene.

  18. Point-of-care detection and real-time monitoring of intravenously delivered drugs via tubing with an integrated SERS sensor

    NASA Astrophysics Data System (ADS)

    Wu, Hsin-Yu; Cunningham, Brian T.

    2014-04-01

    We demonstrate an approach for detection, identification, and kinetic monitoring of drugs flowing within tubing, through the use of a plasmonic nanodome array (PNA) surface. The PNA structures are fabricated using a low-cost nanoreplica molding process upon a flexible plastic substrate that is subsequently integrated with a flow cell that connects in series with ordinary intravenous (IV) drug delivery tubing. To investigate the potential clinical applications for point-of-care detection and real-time monitoring, we perform SERS detection of ten pharmaceutical compounds (hydrocodone, levorphanol, morphine, oxycodone, methadone, phenobarbital, dopamine, diltiazem, promethazine, and mitoxantrone). We demonstrate dose-dependent SERS signal magnitude, resulting in detection limits (ng ml-1) well below typical administered dosages (mg ml-1). Further, we show that the detected drugs are not permanently attached to the PNA surface, and thus our approach is capable of performing continuous monitoring of drug delivery as materials flow through IV tubing that is connected in series with the sensor. Finally, we demonstrate the potential co-detection of multiple drugs when they are mixed together, and show excellent reproducibility and stability of SERS measurements for periods extending at least five days. The capabilities reported here demonstrate the potential to use PNA SERS surfaces for enhancing the safety of IV drug delivery.We demonstrate an approach for detection, identification, and kinetic monitoring of drugs flowing within tubing, through the use of a plasmonic nanodome array (PNA) surface. The PNA structures are fabricated using a low-cost nanoreplica molding process upon a flexible plastic substrate that is subsequently integrated with a flow cell that connects in series with ordinary intravenous (IV) drug delivery tubing. To investigate the potential clinical applications for point-of-care detection and real-time monitoring, we perform SERS detection of ten

  19. Transport of phenylethylamine at intestinal epithelial (Caco-2) cells: mechanism and substrate specificity.

    PubMed

    Fischer, Wiebke; Neubert, Reinhard H H; Brandsch, Matthias

    2010-02-01

    This study was performed to characterize the intestinal transport of beta-phenylethylamine (PEA). Uptake of [(14)C]PEA into Caco-2 cells was Na(+)-independent but strongly stimulated by an outside directed H(+) gradient. At extracellular pH 7.5, the concentration-dependent uptake of PEA was saturable with kinetic parameters of 2.6mM (K(t)) and 96.2nmol/min per mg of protein (V(max)). Several biogenic amines such as harmaline and N-methylphenylethylamine as well as cationic drugs such as phenelzine, tranylcypromine, d,l-amphetamine, methadone, chlorphenamine, diphenhydramine and promethazine strongly inhibited the [(14)C]PEA uptake with K(i) values around 1mM. Tetraethylammonium, N-methyl-4-phenylpyridinium and choline had no effect. We also studied the bidirectional transepithelial transport of [(14)C]PEA at cell monolayers cultured on permeable filters. Net transepithelial flux of [(14)C]PEA from apical-to-basolateral side exceeded basolateral-to-apical flux 5-fold. We conclude that PEA is transported into Caco-2 cells by a highly active, saturable, H(+)-dependent (antiport) process. The transport characteristics do not correspond to those of the known carriers for organic cations of the SLC22, SLC44, SLC47 and other families. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  20. Point-of-care detection and real-time monitoring of intravenously delivered drugs via tubing with an integrated SERS sensor.

    PubMed

    Wu, Hsin-Yu; Cunningham, Brian T

    2014-05-21

    We demonstrate an approach for detection, identification, and kinetic monitoring of drugs flowing within tubing, through the use of a plasmonic nanodome array (PNA) surface. The PNA structures are fabricated using a low-cost nanoreplica molding process upon a flexible plastic substrate that is subsequently integrated with a flow cell that connects in series with ordinary intravenous (IV) drug delivery tubing. To investigate the potential clinical applications for point-of-care detection and real-time monitoring, we perform SERS detection of ten pharmaceutical compounds (hydrocodone, levorphanol, morphine, oxycodone, methadone, phenobarbital, dopamine, diltiazem, promethazine, and mitoxantrone). We demonstrate dose-dependent SERS signal magnitude, resulting in detection limits (ng ml(-1)) well below typical administered dosages (mg ml(-1)). Further, we show that the detected drugs are not permanently attached to the PNA surface, and thus our approach is capable of performing continuous monitoring of drug delivery as materials flow through IV tubing that is connected in series with the sensor. Finally, we demonstrate the potential co-detection of multiple drugs when they are mixed together, and show excellent reproducibility and stability of SERS measurements for periods extending at least five days. The capabilities reported here demonstrate the potential to use PNA SERS surfaces for enhancing the safety of IV drug delivery.

  1. Does meperidine analgesia affect the incidence of obstetric lacerations at vaginal delivery?

    PubMed

    Mizrachi, Yossi; Leytes, Sophia; Levy, Michal; Ginath, Shimon; Bar, Jacob; Ezri, Tiberiu; Kovo, Michal

    2018-03-01

    To study whether meperidine analgesia affects the incidence of obstetric lacerations at normal vaginal deliveries. A retrospective cohort study of all women with term vertex singleton pregnancies, who underwent normal vaginal deliveries, in a single tertiary hospital, between 2011 and 2015, was performed. The incidence of various obstetric lacerations was compared between deliveries with meperidine analgesia and deliveries with no analgesia. Deliveries with epidural analgesia and instrumental deliveries were excluded. An intravenous infusion of 75 mg of meperidine was administered together with 25 mg of promethazine. A multivariate logistic regression analysis was performed to assess the association between meperidine analgesia and obstetric lacerations, after controlling for confounders. Overall, 5227 (91.8%) deliveries with no analgesia and 466 (8.1%) deliveries with meperidine analgesia were included. Meperidine analgesia was associated with a decreased risk of first- and second-degree perineal lacerations (adjusted OR = 0.63, 95% CI = 0.49-0.81), and a decreased risk of any suturing (adjusted OR = 0.73, 95% CI = 0.59-0.91), after controlling for confounders. Meperidine analgesia did not affect the risk of severe perineal lacerations or episiotomies. Meperidine analgesia may have a protective effect against first- and second-degree perineal lacerations.

  2. Velocity gap mode of capillary electrophoresis developed for high-resolution chiral separations.

    PubMed

    Li, Xue; Li, Youxin; Zhao, Lumeng; Shen, Jianguo; Zhang, Yong; Bao, James J

    2014-10-01

    A new CE method based on velocity gap (VG) theory has been developed for high-resolution chiral separations. In VG, two consecutive electric fields are adopted to drive analytes passing through two capillaries, which are linked together through a joint. The joint is immersed inside another buffer vial which has conductivity communication with the buffer inside the capillary. By adjusting the field strengths onto the two capillaries, it is possible to observe different velocities of an analyte when it passes through those two capillaries and there would be a net velocity change (NVC) for the same analyte. Different analytes may have different NVC which may be specifically meaningful for enantioseparations because enantiomers are usually hard to resolve. By taking advantage of this NVC, it is possible to enhance the resolution of a chiral separation if a proper voltage program is applied. The feasibility of using NVC to enhance chiral separation was demonstrated in the separations of three pairs of enantiomers: terbutaline, chlorpheniramine, and promethazine. All separations started with partial separation in a conventional CE and were significantly improved under the same experimental conditions. The results indicated that VG has the potential to be used to improve the resolving power of CE in chiral separations. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Toxicity study in blood and tumor cells of laser produced medicines for application in fabrics.

    PubMed

    Morán, M Carmen; Tozar, Tatiana; Simon, Agota; Dinache, Andra; Smarandache, Adriana; Andrei, Ionut Relu; Boni, Mihai; Pascu, Mihail Lucian; Cirisano, Francesca; Ferrari, Michele

    2016-01-01

    Phenothiazine derivatives are non-antibiotics with antimicrobial, fungistatic and fungicidal effects. We exposed to a high energy UV laser beam phenothiazines solutions in water at 20mg/mL concentration to increase antibacterial activity of resulting mixtures. Compared to previous results obtained on bacteria, more research is needed about UV laser irradiated phenothiazines applications on cancer cell cultures to evidence possible anticancerous properties. Evaluation of the safety of the newly obtained photoproducts in view of use on humans is also needed. Due to expensive animal testing in toxicology and pressure from general public and governments to develop alternatives to in vivo testing, in vitro cell-based models are attractive for preliminary testing of new materials. Cytotoxicity screening reported here shows that laser irradiated (4h exposure time length) chlorpromazine and promazine are more efficient against some cell cultures. Interaction of laser irradiated phenothiazines with fabrics show that promethazine and chlorpromazine have improved wetting properties. Correlation of these two groups of properties shows that chlorpromazine appears to be more recommended for applications on tissues using fabrics as transport vectors. The reported results concern stability study of phenothiazines water solutions to know the time limits within which they are stable and may be used. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. A constitutively active G protein-coupled acetylcholine receptor regulates motility of larval Schistosoma mansoni.

    PubMed

    MacDonald, Kevin; Kimber, Michael J; Day, Tim A; Ribeiro, Paula

    2015-07-01

    The neuromuscular system of helminths controls a variety of essential biological processes and therefore represents a good source of novel drug targets. The neuroactive substance, acetylcholine controls movement of Schistosoma mansoni but the mode of action is poorly understood. Here, we present first evidence of a functional G protein-coupled acetylcholine receptor in S. mansoni, which we have named SmGAR. A bioinformatics analysis indicated that SmGAR belongs to a clade of invertebrate GAR-like receptors and is related to vertebrate muscarinic acetylcholine receptors. Functional expression studies in yeast showed that SmGAR is constitutively active but can be further activated by acetylcholine and, to a lesser extent, the cholinergic agonist, carbachol. Anti-cholinergic drugs, atropine and promethazine, were found to have inverse agonist activity towards SmGAR, causing a significant decrease in the receptor's basal activity. An RNAi phenotypic assay revealed that suppression of SmGAR activity in early-stage larval schistosomulae leads to a drastic reduction in larval motility. In sum, our results provide the first molecular evidence that cholinergic GAR-like receptors are present in schistosomes and are required for proper motor control in the larvae. The results further identify SmGAR as a possible candidate for antiparasitic drug targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Motion sickness is linked to nystagmus-related trigeminal brain stem input: a new hypothesis.

    PubMed

    Gupta, Vinod Kumar

    2005-01-01

    Motion sickness is a common and distressing but poorly understood syndrome associated with nausea/vomiting and autonomic nervous system accompaniments that develops in the air or space as well as on sea or land. A bidirectional aetiologic link prevails between migraine and motion-sickness. Motion sickness provokes jerk nystagmus induced by both optokinetic and vestibular stimulation. Fixation of gaze or closure of eyes generally prevents motion sickness while vestibular otolithic function is eliminated in microgravity of space, indicating a predominant pathogenetic role for visuo-sensory input. Scopolamine, dimenhydrinate, and promethazine reduce motion-related nystagmus. Contraction of extraocular muscles generates proprioceptive neural traffic and can provoke an ocular hypertensive response. It is proposed that repetitive contractions of the extraocular muscles during motion-related jerk nystagmus rapidly augment brain stem afferent input by increasing proprioceptive neural traffic through connections of the oculomotor nerves with the ophthalmic nerve in the lateral wall of the cavernous sinus as well as by raising the intraocular pressure thereby stimulating anterior segment ocular trigeminal nerve fibers. This verifiable hypothesis defines the pathophysiological basis of individual susceptibility to motion sickness, elucidates the preventive mechanism of gaze fixation or ocular closure, advances the aetiologic link between MS and migraine, rationalizes the mechanism of known preventive drugs, and explores new therapeutic possibilities.

  6. Anti-allergic properties of Mangifera indica L. extract (Vimang) and contribution of its glucosylxanthone mangiferin.

    PubMed

    Rivera, Dagmar García; Balmaseda, Ivones Hernández; León, Alina Alvarez; Hernández, Belkis Cancio; Montiel, Lucía Márquez; Garrido, Gabino Garrido; Cuzzocrea, Salvatore; Hernández, René Delgado

    2006-03-01

    Vimang is the brand name of formulations containing an extract of Mangifera indica L., ethnopharmacologically used in Cuba for the treatment of some immunopathological disorders, including bronchial asthma, atopic dermatitis and other allergic diseases. However, the effects of Vimang on allergic response have not been reported until now. In this study, the effects of Vimang and mangiferin, a C-glucosylxanthone isolated from the extract, on different parameters of allergic response are reported. Vimang and mangiferin showed a significant dose-dependent inhibition of IgE production in mice and anaphylaxis reaction in rats, histamine-induced vascular permeability and the histamine release induced by compound 48/80 from rat mast cells, and of lymphocyte proliferative response as evidence of the reduction of the amount of B and T lymphocytes able to contribute to allergic response. In these experiments, ketotifen, promethazine and disodium cromoglicate were used as reference drugs. Furthermore, we demonstrated that Vimang had an effect on an in-vivo model of inflammatory allergy mediated by mast cells. These results constitute the first report of the anti-allergic properties of Vimang on allergic models, as well as suggesting that this natural extract could be successfully used in the treatment of allergic disorders. Mangiferin, the major compound of Vimang, contributes to the anti-allergic effects of the extract.

  7. Investigation of the effect of tablet surface area/volume on drug release from hydroxypropylmethylcellulose controlled-release matrix tablets.

    PubMed

    Reynolds, Thomas D; Mitchell, Shawn A; Balwinski, Karen M

    2002-04-01

    The purpose of this study was to investigate the influence of tablet surface area/volume (SA/Vol) on drug release from controlled-release matrix tablets containing hydroxypropylmethylcellulose (HPMC). Soluble drugs (promethazine HCl, diphenhydramine HCl, and propranolol HCl) were utilized in this study to give predominantly diffusion-controlled release. Drug release from HPMC matrix tablets with similar values of SA/Vol was comparable within the same tablet shape (i.e., flat-faced round tablets) and among different shapes (i.e., oval, round concave, flat-faced beveled-edge, and flat-faced round tablets). Tablets having the same surface area but different SA/Vol values did not result in similar drug release; tablets with larger SA/Vol values hadfaster release profiles. Utility of SA/Vol to affect drug release was demonstrated by changing drug doses, and altering tablet shape to adjust SA/Vol. When SA/Vol was held constant, similar release profiles were obtained with f2 metric values greater than 70. Thus, surface area/volume is one of the key variables in controlling drug release from HPMC matrix tablets. Proper use of this variable has practical application by formulators who may need to duplicate drug release profiles from tablets of different sizes and different shapes.

  8. Characterizing the interaction between enantiomers of eight psychoactive drugs and highly sulfated-β-cyclodextrin by counter-current capillary electrophoresis.

    PubMed

    Asensi-Bernardi, Lucía; Escuder-Gilabert, Laura; Martín-Biosca, Yolanda; Sagrado, Salvador; Medina-Hernández, María José

    2014-01-01

    The estimation of apparent binding constants and limit mobilities of the complexes of the enantiomers that characterize the interaction of enantiomers with chiral selectors, in this case highly sulfated β-cyclodextrin, was approached using a simple and economic electrophoretic modality, the complete filling technique (CFT) in counter-current mode. The enantiomers of eight psychoactive drugs, four antihistamines (dimethindene, promethazine, orphenadrine and terfenadine) and four antidepressants (bupropion, fluoxetine, nomifensine and viloxazine) were separated for the first time for this cyclodextrin (CD). Estimations of thermodynamic and electrophoretic enantioselectivies were also performed. Results indicate that, in general, thermodynamic enantioselectivity is the main component explaining the high resolution found, but also one case suggests that electrophoretic enantioselectivity itself is enough to obtain a satisfactory resolution. CFT results advantageous compared with conventional capillary electrophoresis (CE) and partial filling technique (PFT) for the study of the interaction between drugs and chiral selectors. It combines the use of a simple fitting model (as in CE), when the enantiomers do not exit the chiral selector plug during the separation (i.e. mobility of electroosmotic flow larger than mobility of CD), and drastic reduction of the consumption (and cost; ~99.7%) of the CD reagent (as in PFT) compared with the conventional CE. Copyright © 2013 John Wiley & Sons, Ltd.

  9. Examination of the effectiveness of peppermint aromatherapy on nausea in women post C-section.

    PubMed

    Lane, Betty; Cannella, Kathi; Bowen, Cathy; Copelan, David; Nteff, Grace; Barnes, Katrina; Poudevigne, Melanie; Lawson, Jacqueline

    2012-06-01

    This study examined the effect of peppermint spirits on postoperative nausea in women following a scheduled C-section. A pretest-posttest research design with three groups was used. The peppermint group inhaled peppermint spirits, the placebo aromatherapy control group inhaled an inert placebo, green-colored sterile water, and the standard antiemetic therapy control group received standard antiemetics, usually intravenous ondansetron or promethazine suppositories. Women were randomly assigned to a group on admission to the hospital. If they became nauseated, nurses on the mother-baby unit assessed their nausea (baseline), administered the assigned intervention, and then reassessed participants' nausea 2 and 5 minutes after the initial intervention. Participants rated their nausea using a 6-point nausea scale. Thirty-five participants became nauseated post-operatively. Participants in all three intervention groups had similar levels of nausea at baseline. The nausea levels of participants in the peppermint spirits group were significantly lower than those of participants in the other two groups 2 and 5 minutes after the initial intervention. Peppermint spirits may be a useful adjunct in the treatment of postoperative nausea. This study should be replicated with more participants, using a variety of aromatherapies to treat nausea in participants with different preoperative diagnoses.

  10. 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.

  11. The role of drug efflux pumps in Malassezia pachydermatis and Malassezia furfur defence against azoles.

    PubMed

    Iatta, Roberta; Puttilli, Maria Rita; Immediato, Davide; Otranto, Domenico; Cafarchia, Claudia

    2017-03-01

    This study aims to evaluate the effect of efflux pump modulators (EPMs) on the minimal inhibitory concentration (MIC) of fluconazole (FLZ) and voriconazole (VOR) in Malassezia furfur and Malassezia pachydermatis. The in vitro efficacy of azoles, in combination with EPMs (ie haloperidol-HAL, promethazine-PTZ and cyclosporine A-CYS), against 21 M. furfur from bloodstream infection patients and 14 M. pachydermatis from the skin of dogs with dermatitis, was assessed using a broth microdilution chequerboard analysis. Data were analysed using the model-fractional inhibitory concentration index (FICI) method. The MIC of FLZ and VOR of Malassezia spp. decreased in the presence of sub-inhibitory concentrations of HAL and/or PTZ. The synergic effect was observed only in strains with FLZ MIC≥128 μg/mL for M. furfur, FLZ MIC≥64 μg/mL for M. pachydermatis and VOR MIC≥4 μg/mL in both Malassezia spp. These results suggest that the drug efflux pumps are involved as defence mechanisms to azole drugs in Malassezia yeast. The synergism might be related to an increased expression of efflux pump genes, eventually resulting in azole resistance phenomena. Finally, the above FLZ and VOR MIC values might be considered the cut-off to discriminate susceptible and resistant strains. © 2016 Blackwell Verlag GmbH.

  12. Indirect spectrophotometric determination of propranolol hydrochloride and piroxicam in pure and pharmaceutical formulations.

    PubMed

    Gowda, Babu G; Seetharamappa, Jaldappa; Melwanki, Mahaveer B

    2002-06-01

    Two simple and sensitive indirect spectrophotometric methods for the assay of propranolol hydrochloride (PPH) and piroxicam (PX) in pure and pharmaceutical formulations have been proposed. The methods are based on the oxidation of PPH by a known excess of standard N-bromosuccinimide (NBS) and PX by ceric ammonium sulfate (CAS) in an acidic medium followed by the reaction of excess oxidant with promethazine hydrochloride (PMH) and methdilazine hydrochloride (MDH) to yield red-colored products. The absorbance values decreased linearly with increasing concentration of the drugs. The systems obeyed Beer's law over the concentration ranges of 0.5 - 12.5 and 0.3 - 16.0 microg/ml for PPH, and 0.4 - 7.5 and 0.2 - 10 microg/ml for PX with PMH and MDH, respectively. Molar absorptivity values, as calculated from Beer's law data, were found to be 1.36 x 10(4) and 2.55 x 10(4) l mol(-1) cm(-1) for PPH, and 2.08 x 10(4) and 2.05 x 10(4) l mol(-1) cm(-1) for PX with PMH and MDH, respectively. The common excipients and additives did not interfere with their determinations. The proposed methods have been successfully applied to the determinations of PPH and PX in various dosage forms. The results obtained by the proposed methods compare favorably with those of official methods.

  13. Multiple Time-of-Flight/Time-of-Flight Events in a Single Laser Shot for Improved Matrix-Assisted Laser Desorption/Ionization Tandem Mass Spectrometry Quantification.

    PubMed

    Prentice, Boone M; Chumbley, Chad W; Hachey, Brian C; Norris, Jeremy L; Caprioli, Richard M

    2016-10-04

    Quantitative matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) approaches have historically suffered from poor accuracy and precision mainly due to the nonuniform distribution of matrix and analyte across the target surface, matrix interferences, and ionization suppression. Tandem mass spectrometry (MS/MS) can be used to ensure chemical specificity as well as improve signal-to-noise ratios by eliminating interferences from chemical noise, alleviating some concerns about dynamic range. However, conventional MALDI TOF/TOF modalities typically only scan for a single MS/MS event per laser shot, and multiplex assays require sequential analyses. We describe here new methodology that allows for multiple TOF/TOF fragmentation events to be performed in a single laser shot. This technology allows the reference of analyte intensity to that of the internal standard in each laser shot, even when the analyte and internal standard are quite disparate in m/z, thereby improving quantification while maintaining chemical specificity and duty cycle. In the quantitative analysis of the drug enalapril in pooled human plasma with ramipril as an internal standard, a greater than 4-fold improvement in relative standard deviation (<10%) was observed as well as improved coefficients of determination (R 2 ) and accuracy (>85% quality controls). Using this approach we have also performed simultaneous quantitative analysis of three drugs (promethazine, enalapril, and verapamil) using deuterated analogues of these drugs as internal standards.

  14. SciTech Connect

    Harris, L.W.; Talbot, B.G.; Lennox, W.J.

    A pretreatment for organophosphorus (OP) anticholinesterase (e. g. , soman) intoxication should prevent lethality and convulsions (CNV) at 2 LD50s and be behavioral-decrement-free when given alone. Behavioral-deficit-free pretreatment regimens (PRGs) for guinea pigs consisted of Physostigmine (0.15 mg/kg, im) and adjunct. Adjuncts MG/KG, IM tested were akineton 0.25, aprophen 8, trihexyphenidyl 2, atropine 16, azaprophen 51, BENACTYZINE 1.25, cogentin 4, dextromethorphan 7.5, ethopropazine 12, kemadrin 11, MEMANTINE 5, promethazine 5, scopolamine 0.081 AND CONTROL 2. PRGs were given 30 min before soman (60 ug/kg, sc; 2 LD50S) or other OP agents. Animals were then observed and graded for signs ofmore » intoxication, including CNV at 7 time points and at 24 hr. Physostigmine alone reduced the incidence of CNV and lethality induced by 2 LD50s of soman by 42 and 60%, respectively. All of the PRGs tested abolished lethality and 12 shortened recovery time to 2 hr or less. Also, PRGs including azaprophen or atropine prevented CNV. When selected PRGs were tested against intoxication by sarin, tabun or VX, the efficacy was generally superior to that for soman. The data show that several PRGs are effective against soman intoxication in guinea pigs. Pretreatment, physostigmine, anticholinesterases, soman (GD).« less

  15. Contribution of mast cells to the oedema induced by Bothrops moojeni snake venom and a pharmacological assessment of the inflammatory mediators involved.

    PubMed

    Galvão Nascimento, Neide; Sampaio, Marlos Cortez; Amaral Olivo, Renata; Teixeira, Catarina

    2010-01-01

    The ability of Bothrops moojeni venom (BmV) to induce oedema in mice, the involvement of principal inflammatory mediators and mast cells (MCs) were investigated. The intraplantar injection of BmV (0.3-6 microg/paw) caused a dose- and time-dependent oedema with a peak between 30 and 60 min after venom injection (0.3-1 microg/paw), disappearing within 24h. Either MCs granule inhibition or depletion by cromoglycate or C48/80, respectively, markedly reduced BmV-induced oedema. MCs depletion by imatinib also reduced oedema. Intraperitoneal BmV injection (2.5-10 microg/site) induced MCs degranulation and release of PGD(2). Treatment with promethazine, cimetidine or thioperamide, histamine H1, H2 and H3/H4 receptor antagonists, respectively, markedly reduced the initial phase of oedema. Combined treatment with these antagonists further reduced, but not abrogated oedema. Indomethacin or eterocoxib (cyclooxygenase inhibitors) reduced oedema until 180 min, whereas zileuton (lipoxygenase inhibitor) affected this event until 60 min. Dexamethazone caused a long lasting reduction of oedema. However, L-NAME and aminoguanidine (NO synthase inhibitors) significantly increased BmV-induced oedema. In conclusion, BmV induces oedema, mediated by MCs degranulation, histamine by H1, H2, H3/H4 receptors, prostaglandins and leukotrienes, and down-regulated by NO. Partial neutralization of oedema was observed even when polyspecific bothropic antivenom was injected immediately after venom. Copyright 2009 Elsevier Ltd. All rights reserved.

  16. In Vitro Disease Model of Microgravity Conditioning on Human Energy Metabolism

    NASA Technical Reports Server (NTRS)

    Snyder, Jessica; Culbertson, C.; Zhang, Ye; Emami, K.; Wu, H.; Sun, Wei

    2010-01-01

    NASA and its partners are committed to introducing appropriate new technology to enable learning and living safely beyond the Earth for extended periods of time in a sustainable and possibly indefinite manner. In the responsible acquisition of that goal, life sciences is tasked to tune and advance current medical technology to prepare for human health and wellness in the space environment. The space environment affects the condition and function of biological systems from organ level function to shape of individual organelles. The objective of this paper is to study the effect of microgravity on kinetics of drug metabolism. This fundamental characterization is meaningful to (1) scientific understanding of the response of biology to microgravity and (2) clinical dosing requirements and pharmacological thresholds during long term manned space exploration. Metabolism kinetics of the anti-nausea drug promethazine (PMZ) were determined by an in vitro ground model of 3-dimensional aggregates of human hepatocytes conditioned to weightlessness using a rotating wall bioreactor. The authors observed up-regulated PMZ conversion in model microgravity conditions and attribute this to effect to model microgravity conditioning acting on metabolic mechanisms of the cells. Further work is necessary to determine which particular cellular mechanisms are governing the experimental observations, but the authors conclude kinetics of drug metabolism are responsive to gravitational fields and further study of this sensitivity would improve dosing of pharmaceuticals to persons exposed to a microgravity environment.

  17. Immunoassay screening of lysergic acid diethylamide (LSD) and its confirmation by HPLC and fluorescence detection following LSD ImmunElute extraction.

    PubMed

    Grobosch, T; Lemm-Ahlers, U

    2002-04-01

    In all, 3872 urine specimens were screened for lysergic acid diethylamide (LSD) using the CEDIA DAU LSD assay. Forty-eight samples, mainly from psychiatric patients or drug abusers, were found to be LSD positive, but only 13 (27%) of these could be confirmed by high-performance liquid chromatography with fluorescence detection (HPLC-FLD) following immunoaffinity extraction (IAE). Additional analysis for LSD using the DPC Coat-a-Count RIA was performed to compare the two immunoassay screening methods. Complete agreement between the DPC RIA assay and HPLC-FLD results was observed at concentrations below a cutoff concentration of 500 pg/mL. Samples that were LSD positive in the CEDIA DAU assay but not confirmed by HPLC-FLD were also investigated for interfering compounds using REMEDI HS drug-profiling system. REMEDI HS analysis identified 15 compounds (parent drugs and metabolites) that are believed to cross-react in the CEDIA DAU LSD assay: ambroxol, prilocaine, pipamperone, diphenhydramine, metoclopramide, amitriptyline, doxepine, atracurium, bupivacaine, doxylamine, lidocaine, mepivacaine, promethazine, ranitidine, and tramadole. The IAE/HPLC-FLD combination is rapid, easy to perform and reliable. It can reduce costs when standard, rather than more advanced, HPLC equipment is used, especially for labs that perform analyses for LSD infrequently. The chromatographic analysis of LSD, nor-LSD, and iso-LSD is not influenced by any of the tested cross-reacting compounds even at a concentration of 100 ng/mL.

  18. Evidence of significant synergism between antibiotics and the antipsychotic, antimicrobial drug flupenthixol.

    PubMed

    Jeyaseeli, L; Dasgupta, A; Dastidar, S G; Molnar, J; Amaral, L

    2012-06-01

    Previously, the antipsychotic, non-antibiotic compound flupenthixol dihydrochloride (Fp) was shown to exhibit distinct in vitro antibacterial activity against Gram-positive and Gram-negative bacteria and to significantly protect Swiss albino mice challenged with a known mouse virulent salmonella. The present study was designed to ascertain whether this drug could efficiently augment the action of an antibiotic or a non-antibiotic when tested in combination. A total of 12 bacterial strains belonging to various genera were selected for this study and were sensitive to the antibiotics penicillin (Pc), ampicillin, chloramphenicol, tetracycline, streptomycin, gentamicin, erythromycin, ciprofloxacin, and to the non-antibiotics methdilazine, triflupromazine, promethazine, and Fp. Pronounced and statistically significant synergism (p < 0.01) was observed when Fp was combined with Pc following the disc diffusion assay system. With the help of the checkerboard method, the fractional inhibitory concentration (FIC) index of this pair was found to be 0.375, confirming synergism. This pair of Fp+ Pc was then subjected to in vivo experiments in mice challenged with Salmonella enterica serovar Typhimurium NCTC 74. Statistical analysis of the mouse protection test suggested that this combination was highly synergistic (p < 0.001, Chi-squared analysis). Fp also revealed augmentation of its antimicrobial property when combined with streptomycin, gentamicin, ciprofloxacin, and the non-antibiotic methdilazine. The results of this study may provide alternatives for the therapy of problematic infections such as those associated with Salmonella spp.

  19. Development of a simple one-pot extraction method for various drugs and metabolites of forensic interest in blood by modifying the QuEChERS method.

    PubMed

    Matsuta, Shuntaro; Nakanishi, Keiko; Miki, Akihiro; Zaitsu, Kei; Shima, Noriaki; Kamata, Tooru; Nishioka, Hiroshi; Katagi, Munehiro; Tatsuno, Michiaki; Tsuboi, Kento; Tsuchihashi, Hitoshi; Suzuki, Koichi

    2013-10-10

    A rapid and convenient extraction method has been developed for the determination of various drugs and metabolites of forensic interest in blood by modifying the dispersive solid-phase extraction method "QuEChERS". The following 13 analytes with various chemical properties were used for the method development and its validation: amphetamine, methamphetamine, zolpidem, the carboxylate-form major metabolite of zolpidem M-1, flunitrazepam, 7-aminoflunitrazepam, phenobarbital, triazolam, α-hydroxytriazolam, brotizolam, α-hydroxybrotizolam, chlorpromazine, and promethazine. The modification of the QuEChERS method includes the use of relatively large amounts of inorganic salts in order to coagulate blood, which allows easy isolation of the organic extract phase. A combination of 100 mg anhydrous magnesium sulfate as a dehydrating agent, 50mg sodium chloride as a salting-out agent, and 500 μL acetonitrile containing 0.2% acetic acid as the organic solvent provided the optimum conditions for processing a 100 μL whole blood sample. The recoveries of the analytes spiked into whole blood at 0.5 μg/mL ranged between 59% and 93%. Although the addition of the graphitized carbon Envi-carb for cleanup decreased the recoveries of zolpidem and its carboxylate-form metabolite M-1, it was very effective in avoiding interferences by cholesterol. The present method can provide a rapid, effective, user-friendly, and relatively hygienic method for the simultaneous extraction of a wide range of drugs and metabolites in whole blood specimens. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Shortage of psychotropic medications in community pharmacies in Saudi Arabia: Causes and solutions.

    PubMed

    Al-Ruthia, Yazed Sulaiman; Mansy, Wael; Barasin, Mohammad; Ghawaa, Yazeed Mohammad; AlSultan, Mohammed; Alsenaidy, Mohammad A; Alhawas, Solaiman; AlGhadeer, Sultan

    2017-07-01

    Background: Patients with mental disorders, such as depression and anxiety, who seek medical care in private psychiatric clinics in Riyadh, Saudi Arabia, have recently expressed concerns to doctors about difficulty in filling psychotropic medications, such as Amitriptyline and Aripiprazole, at retail community pharmacies. Objectives: The aim of this study was to investigate whether there is a shortage of some commonly prescribed psychotropic medications in retail community pharmacies in Saudi Arabia, and if so, to explore the possible reasons behind the shortage of these medications. Methods: The availability of 28 commonly prescribed psychotropic medications was checked in multiple retail community pharmacies in 4 different regions of Saudi Arabia. Further, potential reasons behind the shortage of some psychotropic medications in retail community pharmacies were also explored. Results: Amitriptyline, Amoxapine, Aripiprazole, Bupropion, Buspirone, Duloxetine, Haloperidol, Hydroxyzine, Lithium, Prochlorperazine, Procyclidine, Promethazine, Thioridazine, Trazodone, and Trifluoperazine were unavailable in over half of the 248 community pharmacies surveyed. Four possible reasons behind the shortage of these medications were reported by 31 pharmacists working in different retail community pharmacies' purchasing departments, with a majority (58.06%) reporting the primary reason for a shortage of these medications that they are slow-moving items with low profit margins. Conclusions: The findings of this study should expedite the reform process in both the Ministry of Health and the Saudi Food and Drug Authority (SFDA) to publish and enforce an essential list of medications for retail community pharmacies, which should include the most commonly prescribed psychotropic medications.

  1. Massive attack of honeybee on macaws (Ara ararauna and Ara chloropterus) in Brazil - A case report.

    PubMed

    Milbradt, Elisane Lenita; Silva, Tarcísio Macedo; Hataka, Alessandre; Teixeira, Carlos Roberto; Okamoto, Adriano Sakai; Andreatti Filho, Raphael Lucio

    2017-09-15

    Three adult birds of the species Ara chloropterus and five of the species Ara ararauna from a conservation breeding facility suffered a massive attack by honeybees. The A. chloropterus birds presented swollen puncture lesions with stingers (mainly in the facial regions without feathers), swelling of the eyelids and subcutaneous tissue, and respiratory distress, and they were treated with intramuscular injections of 1.67 mg/kg of promethazine and 10 mg/kg of hydrocortisone followed by removal of the stingers. Complete remission of the clinical signs occurred 48 hours after start of treatment. The five A. ararauna birds died before they arrived at the veterinary hospital, and the necropsies found stingers in the areas of the face without feathers and the subcutaneous tissue, which were associated with erythema, bruising, and swelling. Food content from the crop was found in the oral cavity and the tracheal lumen, and marked congestion was observed in the heart, liver, spleen, lungs, kidneys, brain, and cerebellum. Among the histopathological findings, significant swelling of the myocytes in the endocardium and vascular dilation with erythroid repletion were observed, and there were multifocal areas of centrilobular necrosis associated with severe congestion and hemorrhaging in the hepatic tissue. Severe acute tubular necrosis and hydropic-vacuolar degeneration were observed in the kidneys. The clinical signs and pathological findings suggest envenomation due to a massive bee attack, the first such report for Psittacidae. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Potamotrygon motoro stingray venom induces both neurogenic and inflammatory pain behavior in rodents.

    PubMed

    Kimura, L F; Santos-Neto, M; Barbaro, K C; Picolo, G

    2018-05-25

    Freshwater stingray accidents cause an immediate, intense, and unrelieved pain which is followed by edema, erythema and necrosis formation. Treatment for stingray envenomation is based on administration of analgesic, antipyretic and anti-inflammatory drugs. Concerning pain control, it is prescribed to immerse punctured limb on hot water to alleviate pain. There are no studies demonstrating specific targets on which stingray venom acts to promote pain. Therefore, the aim of this work was to investigate some mechanisms of Potamotrygon motoro venom (PmV) that contribute to nociception induction. Evaluating spontaneous pain behavior in mice injected i.pl. with PmV, it was seen that PmV induced both neurogenic and inflammatory pain. PmV also induced hyperalgesia in both mice and rats, evaluated through electronic von Frey and rat paw pressure test, respectively. Partial inhibition of hyperalgesia was observed in mice treated with cromolyn or promethazine, which indicated that mast cell and histamine via H1 receptor participate in the inflammatory pain. To search for some targets involved in PmVinduced hyperalgesia, the participation of TRPV1, calcium channels, neurokinins, CGRP, and norepinephrine, was evaluated in rats. It was seen that PmV-induced hyperalgesia occurs with the participation of neurokinins, mainly via NK1 receptor, CGRP, and calcium influx, through both P/Q and L-type voltage-dependent calcium channels, besides TRPV1 activation. The data presented herein indicate that PmV causes hyperalgesia in rodents which is dependent on the participation of several neuroinflammatory mediators. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Effects of various antipsychotic drugs upon the striatal concentrations of para-hydroxyphenylacetic acid and meta-hydroxyphenylacetic acid in the mouse.

    PubMed Central

    Juorio, A. V.; McQuade, P. S.

    1983-01-01

    The endogenous concentrations of p- and m-hydroxyphenylacetic acid in the mouse caudate nucleus were determined by a gas chromatographic or a gas chromatographic-mass spectrometric technique and the concentrations were about 30 and 11 ng g-1 respectively. The subcutaneous administration of (+)-butaclamol (1 mg kg-1), haloperidol (5 mg kg-1), molindone (100 mg kg-1), sulpiride (50 mg kg-1) or chlorpromazine (20 mg kg-1) increased the concentration of mouse striatal p- and m-hydroxyphenylacetic acid; the effects were observed at 2 h after drug administration. Lower doses of chlorpromazine (2 mg kg-1), haloperidol (0.2 mg kg-1) and molindone (2 mg kg-1) did not affect p- or m-hydroxyphenylacetic acid concentrations. The time course for the concentration changes produced by chlorpromazine (20 mg kg-1) revealed that the formation of the metabolites occurred within 30 min after its administration and that their efflux from the caudate nucleus took at least 4 h for p-hydroxyphenylacetic acid and more than 8 h for m-hydroxyphenylacetic acid. Promethazine and (-)-butaclamol which have chemical structures related to chlorpromazine or (+)-butaclamol respectively but which lack antipsychotic activity, produced no effect on striatal p- or m-hydroxyphenylacetic acid concentrations. The results suggest that antipsychotic drugs increase the utilization of mouse striatal p- and m-tyramine and that after use the amines are metabolized by monoamine oxidase to form p- or m-hydroxyphenylacetic acid. The synthesis of the acid metabolites occurs within 30 min after chlorpromazine administration and their efflux from the caudate nucleus takes from 4-8 h. PMID:6196070

  4. Micellar and analytical implications of a new potentiometric PVC sensor based on neutral ion-pair complexes of dodecylmethylimidazolium bromide-sodium dodecylsulfate.

    PubMed

    Sanan, Reshu; Mahajan, Rakesh Kumar

    2013-03-15

    With an aim to characterize the micellar aggregates of imidazolium based ionic liquids, a new potentiometric PVC sensor based on neutral ion-pair complexes of dodecylmethylimidazolium bromide-sodium dodecylsulfate (C12MeIm(+)DS(-)) has been developed. The electrode exhibited a linear response for the concentration range of 7.9×10(-5)-9.8×10(-3) M with a super-Nernstian slope of 92.94 mV/decade, a response time of 5 s and critical micellar concentration (cmc) of 10.09 mM for C12MeImBr. The performance of the electrode in investigating the cmc of C12MeImBr in the presence of two drugs [promazine hydrochloride (PMZ) and promethazine hydrochloride (PMT)] and three triblock copolymers (P123, L64 and F68) has been found to be satisfactory on comparison with conductivity measurements. Various micellar parameters have been evaluated for the binary mixtures of C12MeImBr with drugs and triblock copolymers using Clint's, Rubingh's, and Motomura's approach. Thus the electrode offers a simple, straightforward and relatively fast technique for the characterization of micellar aggregates of C12MeImBr, complementing existing conventional techniques. Further, the analytical importance of proposed C12MeIm(+)-ISE as end point indicator in potentiometric titrations and for direct determination of cationic surfactants [cetylpyridinium chloride (CPC), tetradecyltrimethylammonium bromide (TTAB), benzalkonium chloride (BC)] in some commercial products was judged by comparing statistically with classical two-phase titration methods. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Intranasal scopolamine affects the semicircular canals centrally and peripherally.

    PubMed

    Weerts, Aurélie P; Putcha, Lakshmi; Hoag, Stephen W; Hallgren, Emma; Van Ombergen, Angelique; Van de Heyning, Paul H; Wuyts, Floris L

    2015-08-01

    Space motion sickness (SMS), a condition caused by an intravestibular conflict, remains an important obstacle that astronauts encounter during the first days in space. Promethazine is currently the standard treatment of SMS, but scopolamine is used by some astronauts to prevent SMS. However, the oral and transdermal routes of administration of scopolamine are known to have substantial drawbacks. Intranasal administration of scopolamine ensures a fast absorption and rapid onset of therapeutic effect, which might prove to be suitable for use during spaceflights. The aim of this study was to evaluate the effects of intranasally administered scopolamine (0.4 mg) on the semicircular canals (SCCs) and the otoliths. This double-blind, placebo-controlled study was performed on 19 healthy male subjects. The function of the horizontal SCC and the vestibulo-ocular reflex, as well as the saccular function and utricular function, were evaluated. Scopolamine turned out to affect mainly the SCCs centrally and peripherally but also the utricles to a lesser extent. Centrally, the most probable site of action is the medial vestibular nucleus, where the highest density of muscarinic receptors has been demonstrated and afferent fibers from the SCCs and utricles synapse. Furthermore, our results suggest the presence of muscarinic receptors in the peripheral vestibular system on which scopolamine has a suppressive effect. Given the depressant actions on the SCCs, it is suggested that the pharmacodynamic effect of scopolamine may be attributed to the obliteration of intravestibular conflict that arises during (S)MS. Copyright © 2015 the American Physiological Society.

  6. Photo-patch and patch tests in patients with dermatitis over the photo-exposed areas: A study of 101 cases from a tertiary care centre in India.

    PubMed

    Sharma, Vinod Kumar; Bhari, Neetu; Wadhwani, Ashok Roopchand; Bhatia, Riti

    2018-02-01

    Many patients with dermatitis over photo-exposed body areas are positive to many contact allergens and have a pre-existing allergic contact dermatitis. This study included patients who presented to a tertiary centre in India with dermatitis on photo-exposed body areas suspected of chronic actinic dermatitis. Their detailed histories were recorded and cutaneous and systemic examinations were performed. Patch testing was done in all the patients and photo-patch testing was carried out in 86 patients. Altogether 101 patients were included (69 males, 32 females). The most common presentation was lichenified hyperpigmented plaques on the photo-exposed sites. Photosensitivity was recorded in 64 (63%) patients and summer exacerbation in 52 (52%). Exposure to the Parthenium hysterophorus weed was recorded in 70 (69%) patients, 27 (26.7%) had a history of hair dye application and 20 (20%) had a history of atopy. Photo-patch test was positive in 11 (12.8%) patients and patch testing was positive in 71 (70%). Parthenium hysterophorus was the most common allergen implicated and was positive in three (4%) photo-patch and 52 (52%) patch tests. Other positive photo-patch test allergens were perfume mix, balsam of Peru, thiuram mix, Compositae mix and promethazine hydrochloride. Other common patch test allergens were parthenolide, colophony, fragrance mix and p-phenylenediamine (PPD) base. In the Indian population parthenium and perfume mix are the most common photoallergens in patients with dermatitis over photo-exposed areas, while parthenium, colophony, fragrance mix and PPD are the common positive allergens. © 2016 The Australasian College of Dermatologists.

  7. Diabetic and Nondiabetic Gastroparesis.

    PubMed

    McCallum; Brown

    1998-12-01

    Nutritional support is essential in treating patients with gastroparesis. Initially, dietary changes should be instituted to reduce extra fat and bulk, and patients should be encouraged to eat frequent small meals with liquid supplementation. Enteral feeding should be introduced in the event of weight loss or persistent vomiting. Medical therapy is usually necessary early in treatment. Cisapride is the initial agent of choice and may be combined with an antiemetic agent, such as promethazine or chlorpromazine or, if side effects occur, ondansetron and granesitron. If cisapride is ineffective or contraindicated, metoclopramide is a reasonable option, though limited by side effects. Erythromycin is useful in the acute treatment of postoperative ileus and hospitalized gastroparetic patients, but its role is limited based on concerns about poor long-term effectiveness and antimicrobial resistance. Once domperidone becomes available in the United States, it will be useful for its promotility and antiemetic qualities. Combination therapy should be considered if monotherapy with cisapride or metoclopramide alone is ineffective. While not yet well studied, combination therapy has the potential to offer dramatic benefit for patients with refractory gastroparesis. Metoclopramide may be added to cisapride for patients with breakthrough symptoms or refractory chronic symptoms. Other combinations include metoclopramide with erythromycin, domperidone with cisapride, and domperidone with erythromycin. In the future, gastric pacing may become an effective option for patients not responding to medical therapy. Total gastrectomy should be performed only for end-stage gastroparesis when all other therapy has failed. Both procedures should be reserved for centers that specialize in severe gastric motility disorders.

  8. Associations of Adverse Clinical Course and Ingested Substances among Patients with Deliberate Drug Poisoning: A Cohort Study from an Intensive Care Unit in Japan.

    PubMed

    Ichikura, Kanako; Okumura, Yasuyuki; Takeuchi, Takashi

    2016-01-01

    Some patients with deliberate drug poisoning subsequently have an adverse clinical course. The present study aimed to examine whether the type of drugs ingested and psychiatric diagnoses were related to an adverse clinical course. We conducted a cohort study of patients with deliberate drug poisoning admitted to the intensive care unit of a university hospital located in Tokyo, Japan, between September 2006 and June 2013. Intensive care unit (ICU) stay of ≥4 days was used as a primary outcome measure, while the incidence of aspiration pneumonitis was used as a secondary outcome measure. Ingested substances and psychiatric diagnoses were used as explanatory variables. Of the 676 patients with deliberate drug poisoning, 88% had a history of psychiatric treatment and 82% had ingested psychotropic drugs. Chlorpromazine-promethazine-phenobarbital combination drug (Vegetamin®) ranked fifth among the most frequently ingested substances in cases of deliberate drug poisoning and had the highest incidence of prolonged ICU stay (20%) and aspiration pneumonitis (29%). The top three major classes consisted of benzodiazepines (79%), new-generation antidepressants (25%), and barbiturates/non-barbiturates (23%). Barbiturate overdose was independently associated with increased odds of both prolonged ICU stay (8% vs. 17%; odds ratio [OR], 2.97; 95% confidence interval [CI], 1.60-5.55) and aspiration pneumonitis (8% vs. 24%; OR, 3.83; 95% CI, 2.18-6.79) relative to those associated with overdose of only other sedative-hypnotics (i.e., benzodiazepines). These results suggest that judicious prescribing of barbiturates by psychiatrists could reduce the risk of an adverse clinical course when a patient attempts an overdose.

  9. A new goldfish model to evaluate pharmacokinetic and pharmacodynamic effects of drugs used for motion sickness in different gravity loads

    NASA Astrophysics Data System (ADS)

    Lathers, Claire M.; Mukai, Chiaki; Smith, Cedric M.; Schraeder, Paul L.

    2001-08-01

    This paper proposes a new goldfish model to predict pharmacodynamic/pharmacokinetic effects of drugs used to treat motion sickness administered in differing gravity loads. The assumption of these experiments is that the vestibular system is dominant in producing motion sickness and that the visual system is secondary or of small import in the production of motion sickness. Studies will evaluate the parameter of gravity and the contribution of vision to the role of the neurovestibular system in the initiation of motion sickness with and without pharmacologic agents. Promethazine will be studied first. A comparison of data obtained in different groups of goldfish will be done (normal vs. acutely and chronically bilaterally blinded vs. sham operated). Some fish will be bilaterally blinded 10 months prior to initiation of the experiment (designated the chronically bilaterally blinded group of goldfish) to evaluate the neuroplasticity of the nervous system and the associated return of neurovestibular function. Data will be obtained under differing gravity loads with and without a pharmacological agent for motion sickness. Experiments will differentiate pharmacological effects on vision vs. neurovestibular input to motion sickness. Comparison of data obtained in the normal fish and in acutely and chronically bilaterally blinded fish with those obtained in fish with intact and denervated otoliths will differentiate if the visual or neurovestibular system is dominant in response to altered gravity and/or drugs. Experiments will contribute to validation of the goldfish as a model for humans since plasticity of the central nervous system allows astronauts to adapt to the altered visual stimulus conditions of 0-g. Space motion sickness may occur until such an adaptation is achieved.

  10. Preliminary Evaluation of Commercial Off the Shelf (COTS) Packing Materials for Flight Medication Dispenser (FMD) Technology Development

    NASA Technical Reports Server (NTRS)

    Du, Brian; Daniels, Vernie; Crady, Camille; Putcha, Lakshmi

    2010-01-01

    With the advent of longer duration space missions, pharmaceutical use in space has increased. During the first 33 space shuttle missions, crew members took more than 500 individual doses of 31 different medications . Anecdotal reports from crew members described medications as generally "well tolerated" and "effective". However, reported use of increased medication doses and discrepancies in ground vs. flight efficacy may result from reduced potency or altered bioavailability due to changes in chemical and/or physical parameters of pharmaceutical stability. Based on preliminary results from a ground-based irradiation and an inflight study on pharmaceutical stability, three susceptible medications, Amoxicillin/Clavulanate and Sulfamethoxazole/trimethoprim antibiotics tablets and promethazine (PMZ), an antihistamine were selected for testing using two types of Oliver-Tolas bags, TPC-1475(Clear) and TPF-0599B (Foil) for radiation Shielding effectiveness. The material composition of the bags included aluminum coated Mylar sheathing coated with multifunctional nanocomposities based on polyethylene with dispersed boron-rich nanophases. Two bags of each medication were irradiated for different time intervals with 14.6 rad/min to achieve 0.1 Gy, 1 Gy and 10 Gy of cumulative radiation dose. Active pharmaceutical content (API) in each medication was determined and results analyzed. No significant difference in API content was observed between control and irradiated samples for both antibiotic tablets suggesting both types of bags may offer protection against gamma radiation; results with PMZ were inconclusive. These preliminary results suggest that Oliver-Tolas TPL-1475 and TPF-0599B materials may possess characteristics suitable for protection against ionizing radiation and can be considered for designing and further testing of FMD technology.

  11. Respiratory effects of cigarette smoke, dust, and histamine in newborn rabbits

    SciTech Connect

    Trippenbach, T.; Kelly, G.

    1988-02-01

    We studied the respiratory effects of cigarette smoke, 5% histamine aerosol, and dust in unanesthetized 1- to 7-day-old rabbits in a body plethysmograph. Cigarette smoke immediately provoked the animal's arousal and irregular breathing. Histamine and dust had no effect in some of the youngest animals. In others, 5-15 s from the onset of the exposure to either of the two stimuli, respiratory rate increased and the depth of breathing decreased. These changes were more pronounced with age. The fact that effects of dust and aerosol lessened with time of exposure showed adaptation to the stimuli. The age dependence of themore » reflex response was also observed after injection of 50 micrograms of histamine per kilogram into the external jugular vein in anesthetized (50 mg ketamine + 3 mg acepromazine per kg) and tracheostomized rabbits during the 1st wk of life. In 1-day-old animals, a short-lasting excitation was followed by apnea or a prolongation of expiratory phase. Peak amplitude of the diaphragmatic EMG (EMGdi) increased in all animals, but only in the youngest was the EMGdi increase paralleled by an increase in tidal volume. In vagotomized animals or animals pretreated with H1-blocker, histamine never affected timing parameters in animals greater than 1 day old. In the youngest animals, respiratory depression due to histamine was not abolished after vagotomy or promethazine. The results imply that inputs from the upper airways and the rapidly adapting pulmonary mechanoreceptors exert their effects on the pattern of breathing immediately after birth in rabbits. The importance of those inputs increases with maturation.« less

  12. Studies on drug metabolism by fungi colonizing decomposing human cadavers. Part II: biotransformation of five model drugs by fungi isolated from post-mortem material.

    PubMed

    Martínez-Ramírez, Jorge A; Walther, Grit; Peters, Frank T

    2015-04-01

    The present study investigated the in vitro metabolic capacity of 28 fungal strains isolated from post-mortem material towards five model drugs: amitriptyline, metoprolol, mirtazapine, promethazine, and zolpidem. Each fungal strain was incubated at 25 °C for up to 120 h with each of the five models drugs. Cunninghamella elegans was used as positive control. Aliquots of the incubation mixture were centrifuged and 50 μL of the supernatants were diluted and directly analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with product ion scanning. The remaining mixture was analyzed by full scan gas chromatography-mass spectrometry (GC-MS) after liquid-liquid extraction and acetylation. The metabolic activity was evaluated through the total number of detected metabolites (NDM) produced in each model and fungal strains and the percentage of parent drug remaining (%RPD) after up to five days of incubation. All the tested fungal strains were capable of forming mammalian phase I metabolites. Fungi from the normal fungal flora of the human body such as Candida sp., Geotrichum candidum, and Trichosporon asahii) formed up to seven metabolites at %RPD values greater than 52% but no new fungal metabolites (NFM). In contrast, some airborne fungal strains like Bjerkandera adusta, Chaetomium sp, Coriolopsis sp., Fusarium solani and Mucor plumbeus showed NDM values exceeding those of the positive control, complete metabolism of the parent drug in some models and formation of NFM. NFM (numbers in brackets) were detected in four of the five model drugs: amitriptyline (18), metoprolol (4), mirtazapine (8), and zolpidem (2). The latter NFM are potential candidates for marker substances indicating post-mortem fungal metabolism. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Editor's Highlight: Off-Target Effects of Neuroleptics and Antidepressants on Saccharomyces cerevisiae.

    PubMed

    Caldara, Marina; Graziano, Sara; Gullì, Mariolina; Cadonici, Stefania; Marmiroli, Nelson

    2017-04-01

    Over the past years, the use of antidepressants and neuroleptics has steadily increased. Although incredibly useful to treat disorders like depression, schizophrenia, epilepsy, or mental retardation, these drugs display many side effects. Toxicogenomic studies aim to limit this problem by trying to identify cellular targets and off-targets of medical compounds. The baker yeast Saccharomyces cerevisiae has been shown to be a key player in this approach, as it represents an incredible toolbox for the dissection of complex biological processes. Moreover, the evolutionary conservation of many pathways allows the translation of yeast data to the human system. In this paper, a better attention was paid to chlorpromazine, as it still is one of the most widely used drug in therapy. The results of a toxicogenomic screening performed on a yeast mutants collection treated with chlorpromazine were instrumental to identify a set of genes for further analyses. For this purpose, a multidisciplinary approach was used based on growth phenotypes identification, Gene Ontology search, and network analysis. Then, the impacts of three antidepressants (imipramine, doxepin, and nortriptyline) and three neuroleptics (promazine, chlorpromazine, and promethazine) on S. cerevisiae were compared through physiological analyses, microscopy characterization, and transcriptomic studies. Data highlight key differences between neuroleptics and antidepressants, but also between the individual molecules. By performing a network analysis on the human homologous genes, it emerged that genes and proteins involved in the Notch pathway are possible off-targets of these molecules, along with key regulatory proteins. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Are Medications Involved in Vision and Intracrancial Pressure Changes Seen in Spaceflight?

    NASA Technical Reports Server (NTRS)

    Faust, K. M.; Wotring, V. E.

    2014-01-01

    data were also sorted by age and sex from each report. RESULTS Steroid-containing oral contraceptives had the highest number of reports associated with vision (n=166) and pressure symptoms (n=54). Corticosteroid-containing medications were also high; prednisone, for example, had 137 reports of vision issues and 79 of pressure issues. Pain relievers were also a medication class with vision and pressure-related adverse events reported. Common over-the-counter medications such as acetaminophen, aspirin and ibuprofen each had multiple reports for both vision and pressure symptoms. Antimicrobial medications ciprofloxacin and diflucan were also associated with a number of vision and pressure-related AERS. Unexpectedly, pseudoephedrine and promethazine were mentioned in fewer than 20 reports each over the 3.5 years of data examined. The FDA AERS represents a wealth of data, but there are several limitations to its use. The data are entered by the public or medical professionals, but are not checked for accuracy or completeness and may even be entered multiple times. The causal relationship between a particular adverse event and a particular medication is not tested. The cases represent a broad spectrum of demographics, occupations, and health histories, and thus do not model the astronaut population well. There is no information on the frequency of use of a medication for comparison purposes; it is not possible to assign a rate for any particular adverse event. Nonetheless, there are compelling trends. Use of corticosteroid-containing medications, pain relievers (even over-the-counter), and oral contraceptives were associated with higher numbers of vision- or intracranial pressure-related adverse events. In general, there were more vision problems than pressure problems reported. Certain medications that were once suspected of playing a role in the crew VIIP syndrome, namely pseudoephedrine and promethazine, were found to have extremely low numbers of VIIP-like AERS in the

  15. Neurogenic mediators contribute to local edema induced by Micrurus lemniscatus venom

    PubMed Central

    2017-01-01

    Background/Aims Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV) to induce local edema. We also explored mechanisms underlying this effect, focusing on participation of neuropeptides and mast cells. Methodology/Principal findings Intraplantar injection of MLV (1–10 μg/paw) in rats caused dose- and time-dependent edema with a peak between 15 min and 1 h after injection. MLV also induced degranulation of peritoneal mast cells (MCs). MC depletion by compound 48/80 markedly reduced MLV-induced edema. Pre-treatment (30 min) of rats with either promethazine a histamine H1 receptor antagonist or methysergide, a nonselective 5-HT receptor antagonist, reduced MLV-induced edema. However, neither thioperamide, a histamine H3/H4 receptor antagonist, nor co-injection of MLV with HOE-140, a BK2 receptor antagonist, altered the response. Depletion of neuropeptides by capsaicin or treatment of animals with NK1- and NK2-receptor antagonists (SR 140333 and SR 48968, respectively) markedly reduced MLV-induced edema. Conclusions/Significance In conclusion, MLV induces paw edema in rats by mechanisms involving activation of mast cells and substance P-releasing sensory C-fibers. Tachykinins NKA and NKB, histamine, and serotonin are major mediators of the MLV-induced edematogenic response. Targeting mast cell- and sensory C-fiber-derived mediators should be considered as potential therapeutic approaches to interrupt development of local edema induced by Micrurus venoms. PMID:29161255

  16. A Review of the Ingredients Contained in Over the Counter (OTC) Cough Syrup Formulations in Kenya. Are They Harmful to Infants?

    PubMed Central

    Kigen, Gabriel

    2015-01-01

    Background Cough syrups are widely used in the developing world, but safety of their use in infants and children less than two years has not been well documented. Some syrups contain multiple combinations of such drugs as promethazine, diphenhydramine and ephedrine; which are individually now contraindicated in children less than two years. Despite this, the syrups are available as over the counter drugs and may be dispensed to mothers who are unaware of the potentially hazardous effects to their infants. A descriptive cross-sectional study was used to investigate suitability of cough syrups sold within Eldoret municipality for use in children less than two years of age based on their formulations and available literature. Methods Two semi-structured questionnaires were administered to pharmacy attendants and mothers attending sick child clinic at a referral hospital to establish whether cough syrups containing more than one active ingredient of compounds, now contraindicated in children are administered to infants, and awareness of potential serious adverse effects. Data from labeled contents of cough syrups from retail pharmacies was recorded and corroborated with information from literature to determine those deemed to contain the ingredients. The second questionnaire was administered to mothers with children less than two years to ascertain whether they had used the identified syrups. A total of 260 mothers and 55 pharmacy attendants were interviewed. Results There was widespread use of the syrups in children, including infants, with 192 (74%) of the respondents having used identified syrups and over 90% of these on children less than 2 years including those less than three months.146 (76%) mothers had administered the syrup at double the recommended dose. Conclusion The regulatory authorities should make concerted efforts to discourage use of cough syrups containing ingredients that pose adverse events to infants, including campaigns to educate pharmacy

  17. A Review of the Ingredients Contained in Over the Counter (OTC) Cough Syrup Formulations in Kenya. Are They Harmful to Infants?

    PubMed

    Kigen, Gabriel; Busakhala, Naftali; Ogaro, Francis; Chesire, Emily; Saat, Nathan; Too, Robert; Nyandiko, Winstone

    2015-01-01

    Cough syrups are widely used in the developing world, but safety of their use in infants and children less than two years has not been well documented. Some syrups contain multiple combinations of such drugs as promethazine, diphenhydramine and ephedrine; which are individually now contraindicated in children less than two years. Despite this, the syrups are available as over the counter drugs and may be dispensed to mothers who are unaware of the potentially hazardous effects to their infants. A descriptive cross-sectional study was used to investigate suitability of cough syrups sold within Eldoret municipality for use in children less than two years of age based on their formulations and available literature. Two semi-structured questionnaires were administered to pharmacy attendants and mothers attending sick child clinic at a referral hospital to establish whether cough syrups containing more than one active ingredient of compounds, now contraindicated in children are administered to infants, and awareness of potential serious adverse effects. Data from labeled contents of cough syrups from retail pharmacies was recorded and corroborated with information from literature to determine those deemed to contain the ingredients. The second questionnaire was administered to mothers with children less than two years to ascertain whether they had used the identified syrups. A total of 260 mothers and 55 pharmacy attendants were interviewed. There was widespread use of the syrups in children, including infants, with 192 (74%) of the respondents having used identified syrups and over 90% of these on children less than 2 years including those less than three months.146 (76%) mothers had administered the syrup at double the recommended dose. The regulatory authorities should make concerted efforts to discourage use of cough syrups containing ingredients that pose adverse events to infants, including campaigns to educate pharmacy workers and mothers.

  18. Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird's eye view.

    PubMed

    Sharma, A; Hamelin, B A

    2003-04-01

    The so-called "classic" histamine H(1) receptor antagonists are highly lipophilic compounds associated with significant biotransformation and tissue distribution. They are categorized according to their chemical structure into ethanolamines, alkylamines, ethylenediamines, piperazines, phenothiazines and piperidines, all of which have characteristic metabolic fates. The former four categories undergo primarily cytochrome P450-mediated oxidative N-desalkylations and deamination whereas the aromatic rings of the latter two undergo P450-mediated oxidative hydroxylation and/or epoxide formation. The common tertiary amino group is susceptible to oxidative metabolism by flavin containing monooxygenases forming N-oxides, and the alicyclic tertiary amines produce small amounts (up to 7%) of N-glucuronides in humans. Species, sex and racial differences in the metabolism and pharmacokinetics of antihistamines are known. Specific P450-isozymes implicated in the metabolism were identified in a few cases, such as CYP2D6 that contributes to the metabolism of promethazine, diphenhydramine and chlorpheniramine. Low circulating plasma concentrations of antihistamines are in part explained by significant first-pass effect and tissue distribution. Antihistaminic effects last up to 6 hours though some compounds exhibit a longer duration of action due to circulating active metabolites. Importantly, diphenhydramine inhibited CYP2D6 leading to a clinically significant drug-drug interaction with metoprolol. Other classic antihistamines were shown to be potent in vitro inhibitors of CYP2D6 and CYP3A4. The prescription-free access to most classic antihistamines can easily lead to their co-administration with other drugs metabolized by the same enzyme system thereby leading to drug accumulation and adverse effects. In depth knowledge of the metabolic pathways of classic antihistamines and the enzymes involved is crucial to prevent the high incidence of drug interactions in humans, which are

  19. Palliative sedation in Germany: factors and treatment practices associated with different sedation rate estimates in palliative and hospice care services.

    PubMed

    Stiel, Stephanie; Nurnus, Mareike; Ostgathe, Christoph; Klein, Carsten

    2018-03-13

    Clinical practice of Palliative Sedation (PS) varies between institutions worldwide and sometimes includes problematic practices. Little available research points at different definitions and frameworks which may contribute to uncertainty of healthcare professionals in the application of PS. This analysis investigates what demographic factors and characteristics of treatment practices differ between institutions with high versus low sedation rates estimates in Palliative and Hospice Care in Germany. Data sets from 221 organisations from a prior online survey were separated into two sub-groups divided by their estimated sedation rate A) lower/equal to 16% (n = 187; 90.8%) and B) higher than 16% (n = 19; 9.2%) for secondary analysis. Demographic factors and characteristics of PS treatment practices between the two groups were compared using T-Tests and Chi 2 / Fisher Exact Tests and considered significant (*) at two-sided p < .05. Organisations in group B report that they discuss PS for a higher proportion of patients (38.5%/10.2%, p < 0.000**), rate agitation more often as an indications for PS (78.9%/ 53.5%, p = 0.050*), and are more likely to use Lorazepam (63.2%/ 37.4%, p = 0.047*), Promethazin (26.3%/ 9.6%, p = 0.044*), and (Es-)Ketamin (31.6%/ 12.8%, p = 0.039*) than representatives in group A. Both groups differ significantly in their allocation of three case scenarios to different types of PS. Both definitions and patterns of clinical practice between palliative and hospice care representatives show divergence, which may be influenced one by another. A comprehensive framework considering conceptual, clinical, ethical, and legal aspects of different definitions of PS could help to better distinguish between different types and nuances of PS.

  20. Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum

    PubMed Central

    Fejzo, Marlena S.; Magtira, Aromalyn; Schoenberg, Frederic Paik; MacGibbon, Kimber; Mullin, Patrick; Romero, Roberto; Tabsh, Khalil

    2014-01-01

    Objective The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors. Study design This is a case-control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test. Results Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p < 0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p < 0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p < 0.0089). Poor outcomes were associated with early start of symptoms (p < 0.019), and treatment with methylprednisolone (p < 0.0217), promethazine (p < 0.0386), and other antihistamines [diphenhy- dramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p < 0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome. Conclusion Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy. PMID:23751910

  1. Extravasation of Noncytotoxic Drugs: A Review of the Literature.

    PubMed

    Le, Ann; Patel, Samit

    2014-07-01

    Extravasation is a potential complication associated with intravenous therapy administration. Inadvertent leakage of medications with vesicant properties can cause severe tissue necrosis, which can lead to devastating long-term consequences. Recognizing potential agents is an essential step in mitigating the risk of extravasation. A literature search was carried out using PubMed with the following key words: extravasation, soft tissue injury, phlebitis, and infiltration, from January 1961 through January 2014. The publications were screened manually and reviewed to identify reports for medications that included synonyms of the International Nonproprietary Name, while excluding antineoplastic agents, radiographic contrast material, investigational or nonmarketed drugs, and animal data, to yield 70 articles. Furthermore, reference citations from publications were also reviewed for relevance and yielded 4 articles. We discovered 232 cases of extravasation involving 37 agents (in order of frequency): phenytoin, parenteral nutrition, calcium gluconate, potassium chloride, calcium chloride, dopamine, dextrose solutions, epinephrine, sodium bicarbonate, nafcillin, propofol, norepinephrine, mannitol, arginine, promethazine, vancomycin, tetracycline, dobutamine, vasopressin, sodium thiopental, acyclovir, amphotericin, ampicillin, cloxacillin, gentamicin, metronidazole, oxacillin, penicillin, amiodarone, albumin, furosemide, lipids, lorazepam, immunoglobulin, morphine, and sodium valproate. Potential properties contributing to extravasation include the following: pH, osmolarity, diluent, vasoactive properties, and inactive ingredients. Antidotes and supportive care agents used in the management of these cases of extravasation include hyaluronidase, phentolamine, terbutaline, topical anesthetics (such as lidocaine and prilocaine cream), topical antimicrobials (such as silver sulfadiazine and chlorhexidine), topical debridement agents (collagenase ointment), topical steroids

  2. 43 Management of acute low back pain in the ED: a systematic review.

    PubMed

    Ashbrook, Jane; Rodgdakis, Nikos; Goodwin, Peter; Yeowell, Gill; Callaghan, Michael

    2017-12-01

    There is no consensus on the management of low back pain in the ED and evidence suggests that these patients are likely to receive unwarranted imaging and inappropriate opioid prescription.The purpose of this study is to review the available literature pertaining to the clinical management of acute low back pain in the ED. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) guidelines were observed during this review.Trials were included if the population studied were adults with acute low back pain in an emergency setting. All diagnostic tests and therapeutic interventions were evaluated.Methodological quality and risk of bias was appraised using the Downs and Black checklist. 19 articles were identified including 1896 patients that were sub-grouped according to management.In the pharmacological subgroup corticosteroids were effective in patients with radicular pain, NSAIDs were as effective as other medication with less adverse events, Phenyramidol was not superior to placebo, promethazine and morhpine combined was not more effective than morphine alone and ketamine was no more effective than morphine but had a worse adverse effect profile.In the emergency transport group TENS and active warming both showed effects in reducing pain, anxiety and heart rate.In the physical therapy management group less pain and greater satisfaction were reported.In the adjunct interventions group showed a trend towards pain reduction in the use of heat/ice packs and short term pain relief in acupuncture and auricular acupuncture. More high quality trials are needed to determine an evidence-based management protocol for the treatment of acute low back pain in the ED. © 2017, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Radiation Exposure Alters Expression of Metabolic Enzyme Genes In Mice

    NASA Technical Reports Server (NTRS)

    Wotring, Virginia E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2010-01-01

    Most pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Because of the importance of the liver in drug metabolism it is important to understand the effects of spaceflight on the enzymes of the liver. Exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. This study is an effort to examine the effects of adaptive mechanisms that may be triggered by early exposure to low radiation doses. Using procedures approved by the JSC Animal Care & Use Committee, C57 male mice were exposed to Cs-137 in groups: controls, low dose (50 mGy), high dose (6Gy) and a fourth group that received both radiation doses separated by 24 hours. Animals were anesthetized and sacrificed 4 hours after their last radiation exposure. Livers were removed immediately and flash-frozen in liquid nitrogen. Tissue was homogenized, RNA extracted and purified (Absolutely RNA, Agilent). Quality of RNA samples was evaluated (Agilent Bioanalyzer 2100). Complementary DNA was prepared from high-quality RNA samples, and used to run RT-qPCR screening arrays for DNA Repair and Drug Metabolism (SuperArray, SABiosciences/Qiagen; BioRad Cfx96 qPCR System). Of 91 drug metabolism genes examined, expression of 7 was altered by at least one treatment condition. Genes that had elevated expression include those that metabolize promethazine and steroids (4-8-fold), many that reduce oxidation products, and one that reduces heavy metal exposure (greater than 200-fold). Of the 91 DNA repair and general metabolism genes examined, expression of 14 was altered by at least one treatment condition. These gene expression changes are likely homeostatic and could lead to development of new radioprotective countermeasures.

  4. Single Dose of the CXCR4 Antagonist BL-8040 Induces Rapid Mobilization for the Collection of Human CD34+ Cells in Healthy Volunteers.

    PubMed

    Abraham, Michal; Pereg, Yaron; Bulvik, Baruch; Klein, Shiri; Mishalian, Inbal; Wald, Hana; Eizenberg, Orly; Beider, Katia; Nagler, Arnon; Golan, Rottem; Vainstein, Abi; Aharon, Arnon; Galun, Eithan; Caraco, Yoseph; Or, Reuven; Peled, Amnon

    2017-11-15

    Purpose: The potential of the high-affinity CXCR4 antagonist BL-8040 as a monotherapy-mobilizing agent and its derived graft composition and quality were evaluated in a phase I clinical study in healthy volunteers (NCT02073019). Experimental Design: The first part of the study was a randomized, double-blind, placebo-controlled dose escalation phase. The second part of the study was an open-label phase, in which 8 subjects received a single injection of BL-8040 (1 mg/kg) and approximately 4 hours later underwent a standard leukapheresis procedure. The engraftment potential of the purified mobilized CD34 + cells was further evaluated by transplanting the cells into NSG immunodeficient mice. Results: BL-8040 was found safe and well tolerated at all doses tested (0.5-1 mg/kg). The main treatment-related adverse events were mild to moderate. Transient injection site and systemic reactions were mitigated by methylprednisolone, paracetamol, and promethazine pretreatment. In the first part of the study, BL-8040 triggered rapid and substantial mobilization of WBCs and CD34 + cells in all tested doses. Four hours postdose, the count rose to a mean of 8, 37, 31, and 35 cells/μL (placebo, 0.5, 0.75, and 1 mg/kg, respectively). FACS analysis revealed substantial mobilization of immature dendritic, T, B, and NK cells. In the second part, the mean CD34 + cells/kg collected were 11.6 × 10 6 cells/kg. The graft composition was rich in immune cells. Conclusions: The current data demonstrate that BL-8040 is a safe and effective monotherapy strategy for the collection of large amounts of CD34 + cells and immune cells in a one-day procedure for allogeneic HSPC transplantation. Clin Cancer Res; 23(22); 6790-801. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. Relating calls to US poison centers for potential exposures to medications to Centers for Disease Control and Prevention reporting of influenza-like illness.

    PubMed

    Beauchamp, Gillian A; McKeown, Nathanael J; Rodriguez, Sergio; Spyker, Daniel A

    2016-03-01

    The Centers for Disease Control (CDC) monitors influenza like illness (ILI) and the National Poison Data System (NPDS) warehouses call data uploaded by US poison centers regarding reported exposures to medication. We examined the relationship between calls to poison centers regarding reported exposures to medications commonly used to treat ILI and weekly reports of ILI. The CDC reports ILI, by age group, for each of 10 Health and Human Services (HHS) regions. We examined NPDS summary data from calls reported to poison centers regarding reported exposures to acetaminophen, cough/cold medications, and promethazine, for the same weeks, age groups, and HHS regions for influenza seasons 2000-2013. ILI and NPDS exposures were examined using graphical plots, descriptive statistics, stepwise regression analysis, and Geographic Information Systems (GIS). About 5,101,841 influenza-like illness cases were reported to the CDC, and 2,122,940 calls regarding reported exposures to medications commonly used to treat ILI, were reported by poison centers to the NPDS over the 13 flu seasons. Analysis of stepwise models of the linear untransformed data involving 24 NPDS data groups and for 60 ILI measures, over the 13 influenza seasons, demonstrated that reported exposures to medications used to treat ILI correlated with reported cases of ILI with a median R(2 )=( )0.489 (min R(2 )=( )0.248, max R(2 )=( )0.717), with mean ± SD of R(2 )=( )0.494 ± 0.121. Median number of parameters used (degrees of freedom - 1) was 7. NPDS data regarding poison center calls for selected ILI medication exposures were highly correlated with CDC ILI data. Since NPDS data are available in real time, it provides complimentary ILI monitoring. This approach may provide public health value in predicting other illnesses which are not currently as thoroughly monitored.

  6. Combining evidence from multiple electronic health care databases: performances of one-stage and two-stage meta-analysis in matched case-control studies.

    PubMed

    La Gamba, Fabiola; Corrao, Giovanni; Romio, Silvana; Sturkenboom, Miriam; Trifirò, Gianluca; Schink, Tania; de Ridder, Maria

    2017-10-01

    Clustering of patients in databases is usually ignored in one-stage meta-analysis of multi-database studies using matched case-control data. The aim of this study was to compare bias and efficiency of such a one-stage meta-analysis with a two-stage meta-analysis. First, we compared the approaches by generating matched case-control data under 5 simulated scenarios, built by varying: (1) the exposure-outcome association; (2) its variability among databases; (3) the confounding strength of one covariate on this association; (4) its variability; and (5) the (heterogeneous) confounding strength of two covariates. Second, we made the same comparison using empirical data from the ARITMO project, a multiple database study investigating the risk of ventricular arrhythmia following the use of medications with arrhythmogenic potential. In our study, we specifically investigated the effect of current use of promethazine. Bias increased for one-stage meta-analysis with increasing (1) between-database variance of exposure effect and (2) heterogeneous confounding generated by two covariates. The efficiency of one-stage meta-analysis was slightly lower than that of two-stage meta-analysis for the majority of investigated scenarios. Based on ARITMO data, there were no evident differences between one-stage (OR = 1.50, CI = [1.08; 2.08]) and two-stage (OR = 1.55, CI = [1.12; 2.16]) approaches. When the effect of interest is heterogeneous, a one-stage meta-analysis ignoring clustering gives biased estimates. Two-stage meta-analysis generates estimates at least as accurate and precise as one-stage meta-analysis. However, in a study using small databases and rare exposures and/or outcomes, a correct one-stage meta-analysis becomes essential. Copyright © 2017 John Wiley & Sons, Ltd.

  7. A Countermeasure for Space Motion Sickness

    NASA Technical Reports Server (NTRS)

    Reschke, M. F.; Somers, J. T.; Leigh, R. J.; Jones, G. Melvill

    2006-01-01

    Overall, the results obtained in both the U.S. and the Russian space programs indicate that most space crews will experience some symptoms of motion sickness (MS) causing significant impact on the operational objectives that must be accomplished to assure mission success. At this time the primary countermeasure for MS requires the administration of Promethazine. Promethazine is not a benign drug, and is most frequently administered just prior to the sleep cycle to prevent its side effects from further compromising mission objectives. Clearly other countermeasures for SMS must be developed. Currently the primary focus is on two different technologies: (1) developing new and different pharmacological compounds with less significant side effects, (2) preflight training. The primary problem with all of these methods for controlling MS is time. New drugs that may be beneficial are years from testing and development, and preflight training requires a significant investment of crew time during an already intensive pre-launch schedule. Granted, motion sickness symptoms can be minimized with either of the two methods detailed above, however, it may be possible to develop a countermeasure that does not require either extensive adaptation time or exposure to motion sickness. Approximately 25 years ago Professor Geoffrey Melvill Jones presented his work on adaptation of the vestibuloocular reflex (VOR) using optically reversed vision (left-right prisms) during head rotations in the horizontal plane. It was of no surprise that most subjects experienced motion sickness while wearing the optically reversing prisms. However, a serendipitous finding emerged during this research showing that the same subjects did not experience motion sickness symptoms when wearing the reversing prisms under stroboscopic illumination. The mechanism, by which this side-effect was believed to have occurred, is not clearly understood. However, the fact that no motion sickness was ever noted, suggests

  8. Fenton process on single and mixture components of phenothiazine pharmaceuticals: Assessment of intermediaries, fate, and preliminary ecotoxicity.

    PubMed

    Wilde, Marcelo L; Schneider, Mandy; Kümmerer, Klaus

    2017-04-01

    Pharmaceuticals do not occur isolated in the environment but in multi-component mixtures and may exhibit antagonist, synergistic or additive behavior. Knowledge on this is still scarce. The situation is even more complicated if effluents or potable water is treated by oxidative processes or such transformations occur in the environment. Thus, determining the fate and effects of parent compounds, metabolites and transformation products (TPs) formed by transformation and degradation processes in the environment is needed. This study investigated the fate and preliminary ecotoxicity of the phenothiazine pharmaceuticals, Promazine (PRO), Promethazine (PRM), Chlorpromazine (CPR), and Thioridazine (THI) as single and as components of the resulting mixtures obtained from their treatment by Fenton process. The Fenton process was carried out at pH7 and by using 0.5-2mgL -1 of [Fe 2+ ] 0 and 1-12.5mgL -1 of [H 2 O 2 ] 0 at the fixed ratio [Fe 2+ ] 0 :[H 2 O 2 ] 0 of 1:10 (w:w). No complete mineralization was achieved. Constitutional isomers and some metabolite-like TPs formed were suggested based on their UHPLC-HRMS n data. A degradation pathway was proposed considering interconnected mechanisms such as sulfoxidation, hydroxylation, N-dealkylation, and dechlorination steps. Aerobic biodegradation tests (OECD 301 D and OECD 301 F) were applied to the parent compounds separately, to the mixture of parent compounds, and for the cocktail of TPs present after the treatment by Fenton process. The samples were not readily biodegradable. However, LC-MS analysis revealed that abiotic transformations, such hydrolysis, and autocatalytic transformations occurred. The initial ecotoxicity tested towards Vibrio fischeri as individual compounds featured a reduction in toxicity of PRM and CPR by the treatment process, whereas PRO showed an increase in acute luminescence inhibition and THI a stable luminescence inhibition. Concerning effects of the mixture components, reduction in toxicity by

  9. A study of the risk of mental retardation among children of pregnant women who have attempted suicide by means of a drug overdose.

    PubMed

    Petik, Dora; Czeizel, Barbara; Banhidy, Ferenc; Czeizel, Andrew E

    2012-01-01

    The aim of the study was to estimate the effect on the fetal development of high doses of prescription drugs taken as a suicide attempt during pregnancy. Pregnant women were identified among self-poisoned females in the toxicological inpatient clinic in Budapest between 1960 and 1993. Congenital abnormalities, intrauterine development based on birth weight and post-conceptional age, mental retardation, cognitive-behavioral status were compared in exposed children born to mothers who had attempted suicide by means of a drug overdose during pregnancy with their siblings, born either before or after the affected pregnancy, as sib controls. Of a total of 1 044 pregnant women, 74 used the combination of amobarbital, glutethimide and promethazine (Tardyl®, one of the most popular drugs for treatment of insomnia in Hungary) for suicide attempt. Of these 74 women, 27 delivered live-born babies. The mean dose of Tardyl® used for suicide attempts was 24 times the usually prescribed clinical dose. The rate of congenital abnormalities and intrauterine retardation was not higher in exposed children than in their sib controls. However, of the 27 exposed children, eight (29.6%) were mentally retarded (X²₁=79.7, p= Sig) while mental retardation did not occur among 46 sib controls. These exposed children were born to mothers who attempted suicide with Tardyl® between the 14th and 20th post-conceptional weeks. The components of Tardyl® used separately for a suicide attempt during pregnancy were not associated with a higher risk of mental retardation. Therefore the high doses of Tardyl® associated with the high risk for mental retardation may be due to the interaction of its three drug components. The findings of the study showed that the high doses of a drug containing three components may be associated with a significantly increased risk for mental retardation without any structural defects, whereas each of these three component drugs taken alone was not associated with

  10. Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation).

    PubMed

    Ostinelli, Edoardo G; Brooke-Powney, Melanie J; Li, Xue; Adams, Clive E

    2017-07-31

    2016 update search, giving a total of 41 included studies and 24 comparisons. Few studies were undertaken in circumstances that reflect real-world practice, and, with notable exceptions, most were small and carried considerable risk of bias. Due to the large number of comparisons, we can only present a summary of main results.Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n=220, RR 0.88, 95%CI 0.82 to 0.95, very low-quality evidence) and experienced dystonia (2 RCTs, n=207, RR 7.49, 95%CI 0.93 to 60.21, very low-quality evidence).Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n=473, RR 0.78, 95%CI 0.62 to 0.99, low-quality evidence). More people in the haloperidol group experienced dystonia (2 RCTs, n=477, RR 6.63, 95%CI 1.52 to 28.86, very low-quality evidence).Four trials (n=207) compared haloperidol with lorazepam with no significant differences with regard to number of participants asleep at one hour (1 RCT, n=60, RR 1.05, 95%CI 0.76 to 1.44, very low-quality of evidence) or those requiring additional injections (1 RCT, n=66, RR 1.14, 95%CI 0.91 to 1.43, very low-quality of evidence).Haloperidol's adverse effects were not offset by addition of lorazepam (e.g. dystonia 1 RCT, n=67, RR 8.25, 95%CI 0.46 to 147.45, very low-quality of evidence).Addition of promethazine was investigated in two trials (n=376). More people in the haloperidol group were not tranquil or asleep by 20 minutes (1 RCT, n=316, RR 1.60, 95%CI 1.18 to 2.16, moderate-quality evidence). Acute dystonia was too common in the haloperidol alone group for the trial to continue beyond the interim analysis (1 RCT, n=316, RR 19.48, 95%CI 1.14 to 331.92, low-quality evidence). Additional data from new studies does not alter previous conclusions of this review. If no other alternative exists, sole use of intramuscular haloperidol could be life-saving. Where additional drugs are

  11. Effects of the aqueous extract of Pittosporum mannii Hook. f. (Pittosporaceae) stem barks on spontaneous and spasmogen-induced contractile activity of isolated rat duodenum.

    PubMed

    Joseph, Njiaza; Tom Esther, Ngo Lemba; Télesphore Benoît, Nguelefack; Paul Désiré, Dzeufiet Djomeni; Oumarou Bibi-Farouck, Aboubakar; Théophile, Dimo; Pierre, Kamtchouing

    2015-08-22

    Pittosporum mannii Hook. f. (Pittosporaceae) is a plant widely used in traditional medicine in Cameroon for the treatment of many gastrointestinal disorders including diarrhea. To date, no pharmacological study on the antidiarrheal and the antispasmodic properties of this plant has been reported. The aim of the present study was to evaluate in vitro the relaxant activity of the aqueous extract of stem barks of P. mannii (PMAE) on rat duodenum. Different concentrations of PMAE were tested separately (10-80 µg/mL) or cumulatively (5-80 µg/mL) on spontaneous and spasmogen (carbachol, histamine and KCl)-induced contractions of isolated rat duodenum strips. At concentrations ranging from 10 to 80 µg/mL, PMAE significantly decreased the tonus and the amplitude of spontaneous contractions. However, at high concentration (80 µg/mL), the extract elicited a transient relaxation was followed by a slight increase of tonus, while the amplitude remained lower compared to the normal spontaneous activity. The relaxant effect of the extract was not significantly affected in the presence of atropine (0.713 µg/mL) and promethazine (0.5 µg/mL). In addition, PMAE (20, 40, and 80 µg/mL) partially but significantly inhibited in a concentration related manner the contractions induced by carbachol (10(-9)-10(-4)M) and histamine (10(-9)-10(-4)M) on rat duodenum. PMAE (10-80 µg/mL) also significantly induced a concentration-dependent relaxation on KCl (20mM, 50mM, 10(-3)-6.10(-3)M)-induced contraction of rat duodenum. These results show that the aqueous extract of P. mannii stem barks possesses antispasmodic and spasmolytic effects at lower concentrations; therefore, supporting the use of the stem barks of this plant in the folk medicine for the treatment of diarrhea. However, caution should be paid while using higher concentrations that instead might produce spasmogenic effect and might worsen the diarrheal condition. The relaxant effect of PMAE appears to be non-specific of

  12. Dissociation of intracellular lysosomal rupture from the cell death caused by silica

    PubMed Central

    Kane, AB; Stanton, RP; Raymond, EG; Dobson, ME; Knafelc, ME; Farber, JL

    1980-01-01

    The relationship between intracellular lysosomal rupture and cell death caused by silica was studied in P388d(1) macrophages. After 3 h of exposure to 150 μg silica in medium containing 1.8 mM Ca(2+), 60 percent of the cells were unable to exclude trypan blue. In the absence of extracellular Ca(2+), however, all of the cells remained viable. Phagocytosis of silica particles occurred to the same extent in the presence or absence of Ca(2+). The percentage of P388D(1) cells killed by silica depended on the dose and the concentration of Ca(2+) in the medium. Intracellular lyosomal rupture after exposure to silica was measured by acridine orange fluorescence or histochemical assay of horseradish peroxidase. With either assay, 60 percent of the cells exposed to 150 μg silica for 3 h in the presence of Ca(2+) showed intracellular lysosomal rupture, was not associated with measureable degradation of total DNA, RNA, protein, or phospholipids or accelerated turnover of exogenous horseradish peroxidase. Pretreatment with promethazine (20 μg/ml) protected 80 percent of P388D(1) macrophages against silica toxicity although lysosomal rupture occurred in 60-70 percent of the cells. Intracellular lysosomal rupture was prevented in 80 percent of the cells by pretreatment with indomethacin (5 x 10(-5)M), yet 40-50 percent of the cells died after 3 h of exposure to 150 μg silica in 1.8 mM extracellular Ca(2+). The calcium ionophore A23187 also caused intracellular lysosomal rupture in 90-98 percent of the cells treated for 1 h in either the presence or absence of extracellular Ca(2+). With the addition of 1.8 mM Ca(2+), 80 percent of the cells was killed after 3 h, whereas all of the cells remained viable in the absence of Ca(2+). These experiments suggest that intracellular lysosomal rupture is not causally related to the cell death cause by silica or A23187. Cell death is dependent on extracellular Ca(2+) and may be mediated by an influx of these ions across the plasma membrane

  13. Pharmacotherapeutic Aspects of Space Medicine

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi

    2004-01-01

    Medications are used for a wide variety of indications during space flight. For example, astronauts have taken drugs in flight to ameliorate or prevent symptoms of space motion sickness, headache, sleeplessness, backache, nasal congestion, and constipation. Russian cosmonauts reportedly take medications to prevent metabolic disturbances of the myocardium and intestinal flora, and to optimize their work capacity. Although the discomfort associated with some acute responses to microgravity (e.g., space motion sickness) is expected to diminish with length of time in flight, other responses that have delayed onset (e.g., maintaining nutritional status, bone and muscle strength, and perhaps immune response) may affect health and quality of life during longer missions. Therefore, as the duration of space flights increases, the need for treatment with medications is expected to increase accordingly. Medications carried on Space Shuttle missions have varied somewhat from flight to flight, depending on the individual needs of the crewmembers. Medications use during Shuttle flights seems to be more prevalent than during earlier programs, perhaps because drugs are provided in easy-to-use forms. In fact, nearly all medications taken to date have been ingested orally in tablet form. However, given that the oral route may not be ideal for those suffering motion-sickness symptoms, intramuscular and intranasal preparations are being tested. For example, intramuscular administration of promethazine hydrochloride (Phenergan(Registered TradeMark)) has been reported to be more effective in alleviating motion-sickness symptoms. The difficulties involved in conducting definitive studies of drug efficacy during U.S. space flights have been compounded by the absence of a systematic approach to determining which drugs were taken by whom and under what circumstances. The use of some drugs in space has been less efficacious than expected. The onset, intensity, and duration of the response

  14. If 'atypical' neuroleptics did not exist, it wouldn't be necessary to invent them: perverse incentives in drug development, research, marketing and clinical practice.

    PubMed

    Charlton, Bruce G

    2005-01-01

    Perverse incentives in drug development, research, marketing and clinical usage can be illustrated by considering the example of the so-called 'atypical' neuroleptics which have grown to become a standard - indeed expanding - part of psychiatric practice despite their probable inferiority to older sedative agents. There is now ample evidence to suggest that neuroleptics (aka. anti-psychotics and major tranquillizers) are dangerous drugs, and patients' exposure to them should be minimized wherever possible. This clinical imperative applies whether neuroleptics are of the traditional type or atypical variety, albeit for different reasons since the traditional agents are neurotoxic, while atypicals are mainly metabolic poisons. Usage of traditional neuroleptics seems indeed to be declining progressively, but the opposite seems to be happening for 'atypicals', and new indications for these drugs are being promoted. Yet the atypical neuroleptics are a category of pharmaceuticals which are close to being un-necessary since there are safer, cheaper and pleasanter substitutes, such as benzodiazepines and the sedative antihistamines (e.g. promethazine). If 'atypical' neuroleptics did not exist, it would not be necessary to invent them. Analysis of how such expensive, dangerous and inferior drugs as the 'atypicals' have nevertheless come to dominate clinical practice casts light on the perverse incentives which now motivate the pharmaceutical industry in an era of massive state regulation. The lack of positive incentives to deploy off-patent drugs is longstanding, but there is a new disincentive in the widespread but erroneous belief that only randomized controlled trials (RCTs) can provide valid 'evidence' of effectiveness. Consequently, those who control RCTs now control clinical practice. It sometimes makes commercial sense to develop and market new drugs that are inferior to existing agents, since new drugs are patent-protected and can be promoted on the back of a mass

  15. NASA Astronaut Urinary Conditions Associated with Spaceflight

    NASA Technical Reports Server (NTRS)

    Law, Jennifer; Cole, Richard; Young, Millennia H.; Mason, Sara

    2016-01-01

    INTRODUCTION: Spaceflight is associated with many factors which may promote kidney stone formation, urinary retention, and/or Urinary Tract Infection (UTI). According to ISS mission predictions supplied by NASA's Integrated Medical Model, kidney stone is the second and sepsis (urosepsis as primary driver) the third most likely reason for emergent medical evacuation from the International Space Station (ISS). METHODS: Inflight and postflight medical records of NASA astronauts were reviewed for urinary retention, UTI and kidney stones during Mercury, Gemini, Apollo, Mir, Shuttle, and ISS expeditions 1-38. RESULTS: NASA astronauts have had 7 cases of kidney stones in the 12 months after flight. Three of these cases occurred within 90 to 180 days after landing and one of the seven cases occurred in the first 90 days after flight. There have been a total of 16 cases (0.018 events per person-flights) of urinary retention during flight. The event rates per mission are nearly identical between Shuttle and ISS flights (0.019 vs 0.021 events per person-flights). In 12 of the 16 cases, astronauts had taken at least one space motion sickness medication. Upon further analysis, it was determined that the odds of developing urinary retention in spaceflight is 3 times higher among astronauts who took promethazine. The female to male odds ratio for inflight urinary retention is 11:14. An astronaut with urinary retention is 25 times more likely to have a UTI with a 17% infection rate per mission. There have been 9 reported UTIs during spaceflight. DISCUSSION: It is unclear if spaceflight carries an increased post-flight risk of kidney stones. Regarding urinary retention, the female to male odds ratio is higher during flight compared to the general population where older males comprise almost all cases due to prostatic hypertrophy. This female prevalence in spaceflight is even more concerning given the fact that there have been many more males in space than females. Terrestrial

  16. Journal of Gravitational Physiology, Volume 12, Number 1

    NASA Technical Reports Server (NTRS)

    Fuller, Charles A. (Editor); Cogoli, Augusto (Editor); Hargens, Alan R. (Editor); Smith, Arthur H. (Editor)

    2005-01-01

    The following topics were covered: System Specificity in Responsiveness to Intermittent -Gx Gravitation during Simulated Microgravity in Rats; A Brief Overview of Animal Hypergravity Studies; Neurovestibular Adaptation to Short Radius Centrifugation; Effect of Artificial Gravity with Exercise Load by Using Short-Arm Centrifuge with Bicycle Ergometer as a Countermeasure Against Disused Osteoporosis; Perception of Body Vertical in Microgravity during Parabolic Flight; Virtual Environment a Behavioral and Countermeasure Tool for Assisted Gesture in Weightlessness: Experiments during Parabolic Flight; Artificial Gravity: Physiological Perspectives for Long-Term Space Exploration; Comparison of the Effects of DL-threo-Beta-Benzyloxyaspartate on the Glutamate Release from Synaptosomes before and after Exposure of Rats to Artificial Gravity; Do Perception and Postrotatory Vestibulo-Ocular Reflex Share the Same Gravity Reference?; Vestibular Adaptation to Changing Gravity Levels and the Orientation of Listing's Plane; Compound Mechanism Hypothesis on +Gz - Induced Brain Injury and Dysfunction of Learning and Memory; Environmental Challenge Impairs Prefrontal Brain Functions; Effect of 6-Days of Support Withdrawal on Characteristics of Balance Function; Hypergravity-Induced Changes of Neuronal Activities in CA1 Region of Rat Hippocampus; Audiological Findings in Antiorthostatic Position Modelling Microgravitation; Investigating Human Cognitive Performance during Spaceflight; The Relevance of the Minimization of Torque Exchange with the Environment in Weightlessness is Confirmed by Asimulation Study; Characteristics of the Eyes Pursuit Function during Readaptation to Terrestrial Gravity after Prolonged Flights Aboard the International Space Station; Comparison of Cognitive Performance Tests for Promethazine Pharmacodynamics in Human Subjects; Structural Reappraisal of Dendritic Tree of Cerebellar Purkinje Cell for Novel Functional Modeling of Elementary Sensorimotor Adaptive

  17. Parenteral treatment of episodic tension-type headache: a systematic review.

    PubMed

    Weinman, Danielle; Nicastro, Olivia; Akala, Olabiyi; Friedman, Benjamin W

    2014-02-01

    continuous outcomes otherwise. Our search returned 640 results. One hundred eighty-seven abstracts were reviewed, and 8 studies involving 486 patients were included in our analysis. The most common reasons for exclusion of abstracts were no assessment of acute pain relief, use of nonparenteral medications only, and no differentiation of headache type. Risk of bias ranged from low to high. The following medications were more effective than placebo for acute pain (NNT, 95%CI): metamizole (4, 2-26), chlorpromazine (4, 2-26), and metoclopramide (2, 1-3). The combination of metoclopramide + diphenhydramine was superior to ketorolac (4, 2-8) The following medications were not more effective than placebo: mepivacaine, meperidine + promethazine, and sumatriptan. Various parenteral medications other than salicylates or nonsteroidals provide acute relief of tension-type headache. Comparative efficacy studies are needed. © 2014 American Headache Society.

  18. Computer calculated dose in paediatric prescribing.

    PubMed

    Kirk, Richard C; Li-Meng Goh, Denise; Packia, Jeya; Min Kam, Huey; Ong, Benjamin K C

    2005-01-01

    Medication errors are an important cause of hospital-based morbidity and mortality. However, only a few medication error studies have been conducted in children. These have mainly quantified errors in the inpatient setting; there is very little data available on paediatric outpatient and emergency department medication errors and none on discharge medication. This deficiency is of concern because medication errors are more common in children and it has been suggested that the risk of an adverse drug event as a consequence of a medication error is higher in children than in adults. The aims of this study were to assess the rate of medication errors in predominantly ambulatory paediatric patients and the effect of computer calculated doses on medication error rates of two commonly prescribed drugs. This was a prospective cohort study performed in a paediatric unit in a university teaching hospital between March 2003 and August 2003. The hospital's existing computer clinical decision support system was modified so that doctors could choose the traditional prescription method or the enhanced method of computer calculated dose when prescribing paracetamol (acetaminophen) or promethazine. All prescriptions issued to children (<16 years of age) at the outpatient clinic, emergency department and at discharge from the inpatient service were analysed. A medication error was defined as to have occurred if there was an underdose (below the agreed value), an overdose (above the agreed value), no frequency of administration specified, no dose given or excessive total daily dose. The medication error rates and the factors influencing medication error rates were determined using SPSS version 12. From March to August 2003, 4281 prescriptions were issued. Seven prescriptions (0.16%) were excluded, hence 4274 prescriptions were analysed. Most prescriptions were issued by paediatricians (including neonatologists and paediatric surgeons) and/or junior doctors. The error rate in the

  19. Neurovestibular Session Summary

    NASA Technical Reports Server (NTRS)

    Oman, Charles; Cohen, Malcolm

    1999-01-01

    Oman - The early mission operational problems caused by space motion sickness have been largely resolved in recent years. This has been achieved by appropriate timeline adjustments, voluntary head movement restriction, and judicious use of promethazine. Crew members now simply accept that some symptoms "come with the job," and usually last only a few days. But as more people have flown longer flights, we've seen cases of space sickness and inversion illusion that take several weeks to resolve. Visual reorientation illusions continue throughout long flights, and occasionally cause difficulties. EVA astronauts sometimes suddenly fear they will fall out of the payload bay or off of the RMS or Strella arms. Orientation and navigation in three dimensions in the MIR station reportedly does not come naturally, because modules have different visual verticals. It is clear that the neurovestibular problems of spaceflight have not disappeared. After return to Earth, many crew members are disoriented and ataxic in the first hour after return, and require assistance leaving the vehicle, Flight surgeons say that the longer the mission, the stronger the aftereffects, certain of which last for weeks. We do not yet know how to predict who will be afflicted. Looking ahead to 3-4 month long voyages to Mars, it seems obvious that if cruise is in O-G, the crew may encounter neurovestibular problems on arrival. Artificial G may be broadly effective as a countermeasure for many of the physiological changes of spaceflight, but from the neurovestibular perspective, it is a double-edged sword. We know that the Coriolis stimulus resulting from rotation is potentially disorienting and nauseogenic. But we don't yet know how much artificial G will be enough, nor how successfully people can adapt to a specific angular velocity and hypo G level. Development of countermeasures remains a big challenge for our neurovestibular community. Maintaining an interdisciplinary perspective is important

  20. The Cardiovascular Effects of Morphine THE PERIPHERAL CAPACITANCE AND RESISTANCE VESSELS IN HUMAN SUBJECTS

    PubMed Central

    Zelis, Robert; Mansour, Edward J.; Capone, Robert J.; Mason, Dean T.

    1974-01-01

    attenuate the forearm arteriolar constrictor response (before morphine, + 25.7±5.4; after morphine, + 13.7±5.3 mm Hg/ml/min/100 ml, P < 0.05). However, morphine did not block the post-Valsalva overshoot of blood pressure, nor did it block the increase in forearm vascular resistance produced by the application of ice to the forehead. Similarly, morphine did not block the arteriolar or venoconstrictor effects of intra-arterially administered norepinephrine. Morphine infused into the brachial artery in doses up to 200 μg/min produced no changes in ipsilateral forearm VV[30], forearm blood flow, or calculated forearm resistance. Intra-arterial promethazine, atropine, and propranolol did not block the forearm arteriolar dilator response to intravenous morphine; however, intra-arterial phentolamine abolished the response. These data suggest that in human subjects, morphine induces a peripheral venous and arteriolar dilation by a reflex reduction in sympathetic alpha adrenergic tone. Morphine does not appear to act as a peripheral alpha adrenergic blocking agent but seems to attenuate the sympathetic efferent discharge at a central nervous system level. Images PMID:4612057

  1. Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review and economic assessment.

    PubMed

    O'Donnell, Amy; McParlin, Catherine; Robson, Stephen C; Beyer, Fiona; Moloney, Eoin; Bryant, Andrew; Bradley, Jennifer; Muirhead, Colin; Nelson-Piercy, Catherine; Newbury-Birch, Dorothy; Norman, Justine; Simpson, Emma; Swallow, Brian; Yates, Laura; Vale, Luke

    2016-10-01

    -three studies (75 reports) met the inclusion criteria. For RCTs, 33 and 11 studies had a low and high risk of bias respectively. For the remainder ( n  = 20) it was unclear. The non-randomised studies ( n  = 9) were low quality. There were 33 separate comparators. The most common were acupressure versus placebo ( n  = 12); steroid versus usual treatment ( n  = 7); ginger versus placebo ( n  = 6); ginger versus vitamin B6 ( n  = 6); and vitamin B6 versus placebo ( n  = 4). There was evidence that ginger, antihistamines, metoclopramide (mild disease) and vitamin B6 (mild to severe disease) are better than placebo. Diclectin ® [Duchesnay Inc.; doxylamine succinate (10 mg) plus pyridoxine hydrochloride (10 mg) slow release tablet] is more effective than placebo and ondansetron is more effective at reducing nausea than pyridoxine plus doxylamine. Diclectin before symptoms of NVP begin for women at high risk of severe NVP recurrence reduces risk of moderate/severe NVP compared with taking Diclectin once symptoms begin. Promethazine is as, and ondansetron is more, effective than metoclopramide for severe NVP/HG. I.v. fluids help correct dehydration and improve symptoms. Dextrose saline may be more effective at reducing nausea than normal saline. Transdermal clonidine patches may be effective for severe HG. Enteral feeding is effective but extreme method treatment for very severe symptoms. Day case management for moderate/severe symptoms is feasible, acceptable and as effective as inpatient care. For all other interventions and comparisons, evidence is unclear. The economic analysis was limited by lack of effectiveness data, but comparison of costs between treatments highlights the implications of different choices. The main limitations were the quantity and quality of the data available. There was evidence of some improvement in symptoms for some treatments, but these data may not be transferable across disease severities. Methodologically sound and

  2. MS Non-Pharmacological Countermeasure to Decrease Landing Sickness and Improve Functional Performance While Disorientad

    NASA Technical Reports Server (NTRS)

    Rosenberg, M. J. F.; Kreutzberg, G. A.; Galvan-Garza, R. C.; Mulavara, A. P.; Reschke, M. F.

    2017-01-01

    Upon return from spaceflight, a majority of crewmembers experience motion sickness (MS) symptoms. The interactions between crewmembers' adaptation to a gravitational transition, the performance decrements resulting from MS and/or use of promethazine (PMZ), and the constraints imposed by mission task demands could significantly challenge and limit an astronaut's ability to perform functional tasks during gravitational transitions. No operational countermeasure currently exists to mitigate the risks associated with these sensorimotor disturbances. Stochastic resonance (SR) can be thought of simply as "noise benefit" or an increase in information transfer by a system when in the presence of a non-zero level of noise. We have shown that low levels of stochastic vestibular stimulation (SVS) improve balance and locomotor performance due to SR (Goel et al. 2015, Mulavara et al. 2011, 2015). Additionally, a study in a 6-hydroxydopamine (6-OHDA) hemi-lesioned rat model of Parkinson's disease demonstrated improvements in locomotor activity after low-level SVS delivery possibly due to an increase in nigral gamma-aminobutyric acid (GABA) release in a dopamine independent way (Samoudi et al. 2012). SVS specifically increased GABA release on the lesioned, but not the intact side. These results suggest that SVS can cause targeted alterations of GABA release to affect performance of functional tasks. Activation of the GABA pathway is important in modulating MS and promoting adaptability (Cohen 2008). Magnusson et al. (2000) supported this finding by showing that the administration of a GABAB agonist caused a reversal of the symptoms that is normally seen after unilateral labyrinthectomy. Thus, GABA could play a significant role in reducing MS and promoting adaptability. We have taken advantage of the SR mechanism as a modulator of neurotransmitters to develop a unique SVS countermeasure system to mitigate MS symptoms and improve functional performance after landing. Healthy

  3. Miscellaneous treatments for antipsychotic-induced tardive dyskinesia.

    PubMed

    Soares-Weiser, Karla; Rathbone, John; Ogawa, Yusuke; Shinohara, Kiyomi; Bergman, Hanna

    2018-03-19

    participants), and most (61%) were published more than 20 years ago. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment, generation of the sequence, and blinding.Nineteen of the 31 included studies reported on the primary outcome 'No clinically important improvement in TD symptoms'. Two studies found moderate-quality evidence of a benefit of the intervention compared with placebo: valbenazine (RR 0.63, 95% CI 0.46 to 0.86, 1 RCT, n = 92) and extract of Ginkgo biloba (RR 0.88, 95% CI 0.81 to 0.96, 1 RCT, n = 157), respectively. However, due to small sample sizes we cannot be certain of these effects.We consider the results for the remaining interventions to be inconclusive: Low- to very low-quality evidence of a benefit was found for buspirone (RR 0.53, 95% CI 0.33 to 0.84, 1 RCT, n = 42), dihydrogenated ergot alkaloids (RR 0.45, 95% CI 0.21 to 0.97, 1 RCT, n = 28), hypnosis or relaxation, (RR 0.45, 95% CI 0.21 to 0.94, 1 study, n = 15), pemoline (RR 0.48, 95% CI 0.29 to 0.77, 1 RCT, n = 46), promethazine (RR 0.24, 95% CI 0.11 to 0.55, 1 RCT, n = 34), insulin (RR 0.52, 95% CI 0.29 to 0.96, 1 RCT, n = 20), branched chain amino acids (RR 0.79, 95% CI 0.63 to 1.00, 1 RCT, n = 52), and isocarboxazid (RR 0.24, 95% CI 0.08 to 0.71, 1 RCT, n = 20). There was low- to very low-certainty evidence of no difference between intervention and placebo or no treatment for the following interventions: melatonin (RR 0.89, 95% CI 0.71 to 1.12, 2 RCTs, n = 32), lithium (RR 1.59, 95% CI 0.79 to 3.23, 1 RCT, n = 11), ritanserin (RR 1.00, 95% CI 0.70 to 1.43, 1 RCT, n = 10), selegiline (RR 1.37, 95% CI 0.96 to 1.94, 1 RCT, n = 33), oestrogen (RR 1.18, 95% CI 0.76 to 1.83, 1 RCT, n = 12), and gamma-linolenic acid (RR 1.00, 95% CI 0.69 to 1.45, 1 RCT, n = 16).None of the included studies reported on the other primary outcome, 'no clinically significant extrapyramidal adverse effects'. This review has found that the use of valbenazine or extract