J Manag Care Pharm.
2005 May;11(4):317-21.
Cost-effectiveness analysis of ondansetron and prochlorperazine
for the prevention of postoperative nausea and vomiting.
Chang P, Okamoto M, Chen J, Frame D.
Western University of Health Sciences, Pomona, California 91766, USA.
changp@westernu.edu
OBJECTIVE: To compare the cost-effectiveness of 2 antiemetic agents,
ondansetron and prochlorperazine, for the prevention of postoperative
nausea and vomiting (PONV) in patients undergoing total hip replacement
or total knee replacement procedures. METHODS: The cost-effectiveness
analysis model was applied to data derived from a previous clinical study
conducted in 1995 and 1996. This study involved 78 adult patients (62.8%
female and 37.2% male) undergoing total hip replacement or total knee
replacement procedures. Patients were enrolled in a randomized, double-blind
manner to receive either ondansetron 4 mg intrvenously (n=37) or prochlorperazine
10 mg intramuscularly (n=41) immediately upon completion of surgery and
were monitored for occurrences of PONV during the subsequent 48 hours.
In our analysis, we measured the cost-effectiveness ratio (C/E ratio),
defined as the cost per successfully treated patient, for each antiemetic
agent using the clinical data obtained from the previous study. RESULTS:
The incidence of PONV and use of rescue antiemetics was significantly
greater in the ondansetron group compared with the prochlorperazine group.
The mean total costs of PONV management per patient in the prochlorperazine
and ondansetron groups were dollar 13.99 and dollar 51.98, respectively
(based on 2004 average wholesale prices [AWP]). The cost of successfully
treating one patient with prochlorperazine and ondansetron was dollar
31.87 and dollar 275.01, respectively. One-way sensitivity analysis was
performed adjusting the percent efficacy rate of each antiemetic and the
drug cost of ondansetron (up to a 50% reduction in AWP). Prochlorperazine
remained the dominant strategy across each scenario. CONCLUSION: The results
indicate that prochlorperazine is a more cost-effective antiemetic compared
with ondansetron for the prevention of PONV in a mixed gender, adult inpatient
population undergoing total joint arthroplasty.
Can J Anaesth. 2005 May;52(5):485-9.
Prevention of PONV by acustimulation with capsicum plaster is
comparable to ondansetron after middle ear surgery: [La prevention des
NVPO par acustimulation avec un emplatre de Capsicum est comparable a
celle de l'ondansetron apres une operation a l'oreille moyenne].
Misra MN, Pullani AJ, Mohamed ZU.
103, New PG Hostel, SRN Hospital, Allahabad, UP, India, PIN 211001.
ashokjayaraj@yahoo.com.
PURPOSE: To compare the efficacy of stimulation of P6 acupoint with capsicum
plaster in comparison with iv ondansetron for the prevention of postoperative
nausea and vomiting (PONV). METHODS: 120 patients of either sex, ASA I-II,
undergoing elective middle ear surgeries under general anesthesia were
included in this randomized, prospective, double-blinded and placebo-controlled
study. The anesthetic technique was standardized. Patients were divided
into three groups. Group I was the control group. Capsicum plaster (1
x 1cm) was affixed at the P6 acupoint on both forearms 30 min before induction
of anesthesia in patients of Group II. Patients of Groups I and III received
an inactive adhesive plaster at the same site. Ondansetron 4 mg iv was
given to patients of Group III at the end of surgery and the rest of the
patients received a placebo. The plasters were removed six hours after
transferring the patients to the postoperative unit. Criteria were fixed
for the administration of rescue antiemetics (ondansetron 4 mg iv). PONV
and the requirement for rescue antiemetics were recorded by a blinded
observer. RESULTS: The incidence of PONV and the requirement for rescue
antiemetics were significantly lower in both the acustimulation and ondansetron
groups at six hours. At 24 hr there was a reduction in the requirement
for rescue medication in the ondansetron group. CONCLUSION: Stimulation
of the P6 acupoint with capsicum plaster is an effective method for prevention
of PONV after middle ear surgery and its efficacy is comparable to ondansetron
for the first six hours after surgery.
J Clin Anesth. 2005 Feb;17(1):62-5. Related Articles, Links
The effectiveness of rescue antiemetics after failure of prophylaxis
with ondansetron or droperidol: a preliminary report.
Habib AS, Gan TJ.
Department of Anesthesiology, Duke University Medical Center, Durham,
NC 27710, USA.
STUDY OBJECTIVES: To compare the effectiveness of treating established postoperative nausea and vomiting (PONV) with an antiemetic acting at a different receptor with that of treating PONV with the antiemetic used for prophylaxis. DESIGN: Analysis of data collected in a previously published randomized, double-blind, placebo-controlled study. SETTING: Outpatient surgical procedures from 50 institutions in North America. PATIENTS: Patients (N = 2061) undergoing outpatient surgical procedures planned to last no more than 2 hours. INTERVENTIONS: Patients were randomized to receive ondansetron 4 mg, droperidol 1.25, droperidol 0.625 mg, or placebo. In the postoperative anesthesia care unit, patients who developed PONV received rescue antiemetics at the discretion of the attending anesthesiologist. The following antiemetics were used for rescue: ondansetron 4 mg, droperidol 0.625 to 1.25 mg, metoclopramide 10 mg, promethazine 6.25 to 25 mg, and dimenhydrinate 25 to 50 mg. MEASUREMENTS: The complete response rate (no nausea, no emesis, and no need for further rescue) after administration of the rescue antiemetic in patients with established PONV was calculated. The complete response rate after administration of each of the different rescue antiemetics was compared with that after administration of the same antiemetic used for PONV prophylaxis. MAIN RESULTS: In patients who failed prophylaxis with ondansetron 4 mg, the complete response rate was significantly higher (P = .02) after rescue with promethazine 6.25 to 25 mg (78%) than after rescue with ondansetron 4 mg (46%). In patients who failed prophylaxis with droperidol 0.625 and 1.25 mg, the complete response rate was significantly higher after rescue with promethazine 6.25 to 25 mg (77%; P = .02) and dimenhydrinate 25 to 50 mg (78%; P = .04) than after rescue with droperidol 0.625 to 1.25 mg (56%). CONCLUSION: In patients who failed prophylaxis with ondansetron or droperidol, promethazine was significantly more effective than the agent used for prophylaxis for the treatment of PONV. In patients who failed prophylaxis with droperidol, dimenhydrinate was also more effective than droperidol for the treatment of established PONV in the postoperative anesthesia care unit.
Pharmacol Res. 2005 Mar;51(3):255-9. Related Articles, Links
Ondansetron, a selective 5-HT3 antagonist, antagonizes methamphetamine-induced
anorexia in mice.
Ginawi OT, Al-Majed AA, Al-Suwailem AK.
Department of Pharmacology, College of Pharmacy, King Saud University,
P.O. Box 2457, Riyadh 11451, Saudi Arabia. otginawi@hotmail.com
Effects of some selective serotonergic (5-HT) antagonists on methamphetamine-induced anorexia were investigated in male mice. The least possible dose of methamphetamine alone that caused significant anorectic activity was 11 micromolkg(-1), i.p. (2 mgkg(-1)). Various doses of some selective serotonergic receptor antagonists were administered half an hour before the above mentioned dose of methamphetamine. Methiothepin potentiated, whereas NAN-190, methysergide, mianserin and ondansetron antagonized methamphetamine-induced anorectic activity. The least possible doses of these antagonists which modified methamphetamine-induced anorexia were as follows: methiothepin (1.1 micromolkg(-1), i.p.), NAN-190 (4.2 micromolkg(-1), i.p.), methysergide (2.1 micromolkg(-1), i.p.), mianserin (3.3 micromolkg(-1), i.p.) and ondansetron (0.003 micromolkg(-1), i.p.). The serotonergic antagonists at the above mentioned doses did not modify the food intake of animals not treated with methamphetamine, except for methiothepin, which produced a significant reduction, and mianserin, which produced a significant increase in food intake. The results of the present study indicated that the anorectic activity induced by methamphetamine is related to the interactions of methamphetamine with 5-HT receptor. Since a very small dose (0.003 micromolkg(-1)) of ondansetron (the 5-HT(3) antagonist), as compared with the other antagonists used in this study, antagonized the anorexia induced by methamphetamine, the 5-HT(3) receptor is likely to be the site for this interaction.
Eur J Pharmacol. 2004 Oct 25;503(1-3):99-102.
Ondansetron, given during the acute cocaine withdrawal, attenuates
oral cocaine self-administration.
Davidson C, Lazarus C, Lee TH, Ellinwood EH.
Department of Psychiatry, Box 3870, Duke University Medical Center, Durham,
NC 27710, USA. colda@duke.edu
We have previously shown that ondansetron, given 3.5 h after intravenous cocaine self-administration, can attenuate self-administration the following day. Here we tested ondansetron given either before or after a 14-h oral cocaine session in rats. Ondansetron (0.2 mg/kg sc) given 30 min before the cocaine session had no effect. However, when given 3.5 h after, ondansetron attenuated cocaine intake the following day while having no effect on water intake. Taken with our previous data in intravenous cocaine self-administration, we suggest that the acute cocaine withdrawal period may be an important treatment window and that ondansetron may be an effective cocaine abuse therapy.
Indian J Med Res. 2004 Sep;120(3):183-93.
Efficacy & tolerability of ondansetron compared to metoclopramide
in dose dependent cisplatin-induced delayed emesis.
Bhatia A, Tripathi KD, Sharma M.
Department of Pharmacology, Maulana Azad Medical College, New Delhi, India.
docbha@yahoo.com
BACKGROUND & OBJECTIVES: Delayed emesis with cisplatin is a significant problem, which is often poorly controlled with conventional antiemetics. There is a relative paucity of data on the control of delayed emesis and rather inconsistent results have been reported. The present study aimed to compare the efficacy and tolerability of ondansetron versus metoclopramide in dose related grades of cisplatin-induced delayed emesis. METHODS: A total of 80 chemotherapy naive patients with malignancy were randomized to receive cisplatin 60 mg/m2 intravenously (iv) either as a single dose on day 1 (high dose regimen) or split into three doses of 20 mg/m2 each on 3 days (low dose regimen) along with bleomycin +5- fluorouracil in 40 patients each. Patients were further randomized in each cisplatin regimen to receive either 20 mg metoclopramide (20 patients) or 8 mg ondansetron (20 patients) iv 30 min prior to cisplatin administration followed by the respective antiemetic orally 8 hourly for five days after the last cisplatin administration. Ten patients receiving high dose cisplatin in each group were also given dexamethasone 8 mg iv with the primary antiemetic. The assessment period started 24 h after last cisplatin infusion and ended at midnight on day 5. RESULTS: In low dose cisplatin regimen, complete suppression of delayed emesis occurred in 55 per cent patients receiving ondansetron and in 30 per cent patients receiving metoclopramide. Neither ondansetron nor metoclopramide could completely suppress delayed emesis in high dose cisplatin regimen. Protection from nausea in the delayed phase was seen in 85 per cent patients receiving ondansetron and in 70 per cent patients receiving metoclopramide in low dose regimen, while nausea protection rates were 70 vs 0 per cent respectively in the high dose regimen. Addition of dexamethasone to metoclopramide significantly augmented its antiemetic efficacy (P<0.02) and the combination of metoclopramide + dexamethasone was found to be as efficacious as ondansetron monotherapy. Twenty out of 80 patients reported 39 adverse events of mild intensity. No significant effects on QOL (quality of life) parameters were observed in any group over the 5-day period. INTERPRETATION & CONCLUSION: The results demonstrate that delayed emesis due to cisplatin is also dose related, and superior antiemetic efficacy of ondansetron compared to metoclopramide is maintained, though its superiority is less marked than against acute emesis. Metoclopramide and dexamethasone combination matched the antiemetic efficacy of ondansetron monotherapy.
Indian J Exp Biol. 2004 Sep;42(9):919-21.
Ondansetron amelioration of scopolamine induced cognitive deficits
in three-panel runway apparatus in rats.
Kumar N, Kela AK.
Department of Pharmacology, Lady Hardinge Medical College, New Delhi 110001,
India. nk999999@rediffmail.com
Effect of ondansetron (5-HT3-receptor antagonist) was studied on the working memory deficits induced by scopolamine, a muscarinic receptor antagonist in rats using a three-panel runway apparatus. Varying doses of scopolamine (0.1-0.56mg/kg, ip) were administered alone or in combination with ondansetron (0.01-1.0 mg/kg, ip) and memory errors and latency period of the session were recorded on a three-panel runway apparatus. Treatment with scopolamine (0.56 mg/kg) produced working memory deficits in rats. Treatment with ondansetron (1.0 mg/kg) significantly reduced the scopolamine-induced working memory deficits.
Expert Opin Pharmacother. 2004 Sep;5(9):1943-55.
An overview of the development of medications including novel
anticonvulsants for the treatment of alcohol dependence.
Johnson BA.
Department of Psychiatry, Division of Alcohol and Drug Addiction, The
University of Texas Health Science Center at San Antonio, 3939 Medical
Drive, Suite 100, San Antonio, TX 78229-3900, USA. bjohnson@uthscsa.edu
The development of treatments for alcohol dependence has been significantly complicated by the multiple actions of ethanol at the neurotransmitter level, heterogeneity among patients with alcohol dependence, the complexity of defining and measuring the phenomenon of craving, and the challenge of quantifying alcohol intake in patients. Increasingly, anticonvulsant medications are showing promise for the safe and effective amelioration of alcohol withdrawal symptoms. Furthermore, there is evidence that anticonvulsant medications are promising treatments for reducing drinking and preventing relapse among alcohol-dependent individuals. In recent years, many medications have been evaluated for the treatment of alcohol dependence, including those that interact with dopaminergic, serotonergic, opioid or glutamate and/or GABA systems. So far, naltrexone, acamprosate and, more recently, the anticonvulsant, topiramate, have shown some efficacy for the treatment of heterogeneous populations of individuals with alcohol dependence. Both ondansetron and sertraline appear to have some efficacy in treating different subgroups of alcoholic.
BJOG. 2004 Sep;111(9):940-3.
The safety of ondansetron for nausea and vomiting of pregnancy:
a prospective comparative study.
Einarson A, Maltepe C, Navioz Y, Kennedy D, Tan MP, Koren G.
The Motherisk Program, The Hospital for Sick Children, The University
of Toronto, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.
OBJECTIVE: Ondansetron (Zofran) is a drug used for the treatment of nausea and vomiting caused by cancer chemotherapy. Despite the fact that it is not indicated, women are being prescribed this drug for the treatment of nausea and vomiting of pregnancy (NVP). There is a paucity of information on fetal safety for this indication. The objective of this study is to determine whether this drug increases the baseline rate of major malformations. DESIGN: A prospective comparative observational study. SETTING: Teratogen Information Services (TIS). POPULATION: Pregnant women. METHODS: Our three groups included women who were exposed to ondansetron and women exposed to (1) other anti-emetics and (2) non-teratogen exposures. All of the women called either our NVP Helpline or TIS at The Motherisk Program in Toronto, Canada, or The Mothersafe Program in Sydney, Australia. MAIN OUTCOME MEASURE: Rates of major malformation. RESULTS: We have completed 176 pregnancy outcomes in each group. In the ondansetron cohort, there were 169 live births, 5 miscarriages, 2 therapeutic abortions, 6 (3.6%) major malformations and the mean birthweight was 3362 g [SD 525]. There were no statistical differences in any of the study endpoints between the ondansetron and the comparison groups. CONCLUSIONS: This drug does not appear (although the sample size is limited) to be associated with an increased risk for major malformations above baseline.
Alcohol Clin Exp Res. 2004 Aug;28(8):1161-71.
Effect of 5-HT3 receptor over-expression on the discriminative
stimulus effects of ethanol.
Shelton KL, Dukat M, Allan AM.
Department of Pharmacology and Toxicology, Virginia Commonwealth University
School of Medicine, Richmond, Virginia 23298-0613, USA. klshelto@hsc.vcu.edu
BACKGROUND: Drug discrimination studies using selective antagonists and agonists have suggested that 5-HT3 receptors may modulate ethanol's discriminative stimulus effects. However, conflicting data between laboratories leaves the issue of 5-HT3 receptor involvement in ethanol's discriminative stimulus effects in question. The present study utilized transgenic mice that over-express 5-HT3 receptors in conjunction with traditional pharmacological techniques to examine the contribution of 5-HT3 receptors to ethanol's discriminative stimulus. METHODS: Ten 5-HT3 over-expressing (5-HT3 OE) and 18 B6SJL wild-type (WT) mice were trained to discriminate 1.5 g/kg ethanol from saline in daily 15 min, milk reinforced operant sessions. After training, ethanol substitution and response-rate suppression dose response curves were determined for ethanol, midazolam, dizocilpine, cocaine, mCPP, MD-354, YC-30 and MDL-72222. Antagonism tests combining ethanol with MDL-72222 and ondansetron were also conducted. RESULTS: The 5-HT3 OE and WT mice learned the ethanol discrimination in a comparable number of training sessions. Similar patterns of substitution were generated in both groups of mice for most test drugs. 5-HT3 OE mice were more sensitive to the rate suppressing effects of dizocilpine and MDL-72222 than were WT mice. Neither of the 5-HT3 antagonist tested significantly attenuated ethanol's discriminative stimulus effects in either 5-HT3 OE or WT mice. CONCLUSIONS: The results of the present study are consistent with a minimal role of 5-HT3 receptors in transducing ethanol's discriminative stimulus effects. Over-expression of 5-HT3 receptors does not alter the relative efficacy of GABAA positive modulators or NMDA antagonists for producing ethanol-like discriminative stimulus effects. However, 5-HT3 receptor over-expression does appear to modulate the response-rate altering effects of the uncompetitive NMDA antagonist, dizocilpine, and the 5-HT3 antagonist, MDL-72222. Copyright 2004 Research Society on Alcoholism
Ann Pharmacother. 2004 Oct;38(10):1683-91. Epub 2004 Aug 17.
5-HT3 receptor antagonists for prevention of late acute-onset
emesis.
Constenla M.
Complejo Hospitalario de Pontevedra, C/Loureiro Crespo, 2, 36001 Pontevedra,
Spain. mconstenla@nexo.es
OBJECTIVE: To review the currently available literature on the efficacy of the 5-HT(3) receptor antagonists in the prevention of late acute-onset chemotherapy-induced nausea and vomiting (12-24 h after cytotoxic treatment). DATA SOURCES:Primary articles were identified by PubMed search (performed in March 2004) and through secondary sources. Search terms included granisetron, ondansetron, tropisetron, dolasetron, acute, chemotherapy, nausea, and vomiting (a further search was performed for palonosetron in March 2004). STUDY SELECTION AND DATA EXTRACTION: All studies that performed regular assessments (every 2-6 h) of antiemetic control over the first 24 hours with 5-HT(3) receptor antagonists were evaluated. DATA SYNTHESIS: Current guidelines recommend the use of 5-HT(3) receptor antagonists for the control of chemotherapy-induced nausea and vomiting but do not differentiate between the available agents. However, there is variability in the pharmacokinetic and pharmacodynamic profiles of these agents, and this has implications for dosing regimen, safety, efficacy, and potential drug-drug interactions. Cytotoxic agents vary in the time profile of their emetic effect; this must be considered when choosing an appropriate 5-HT(3) receptor antagonist. The optimal agent should be simple to administer and provide safe and effective antiemetic protection over the whole 24-hour period. CONCLUSIONS: The differences between the 5-HT(3) receptor antagonists have important consequences for their dosing and efficacy in the control of late acute-onset chemotherapy-induced nausea and vomiting.
Pain. 2004 Jul;110(1-2):259-68.
The 5-HT3 receptor facilitates at-level mechanical allodynia following
spinal cord injury.
Oatway MA, Chen Y, Weaver LC.
The Spinal Cord Injury Team, Biotherapeutics Research Group, Robarts Research
Institute, P.O. Box 5015, 100 Perth Drive, London, Ont., Canada N6A 5K8.
Spinal cord injury (SCI) results in the development of mechanical allodynia immediately rostral to the lesion site, within the dermatome border of normal sensation and sensory loss (at-level mechanical allodynia). We propose that an observed threefold increase in serotonergic fibre immunoreactivity within spinal segments corresponding to these allodynic dermatomes facilitates the maintenance of chronic neuropathic pain via activation of the 5-HT(3) receptor (5-HT(3)-R). Serotonin (5-HT), the non-selective 5-HT(1)/5-HT(2) receptor antagonist, methysergide, the 5-HT(3)-R agonist, m-chlorophenylbiguanide (m-CPBG) or the 5-HT(3)-R antagonist, ondansetron were intrathecally administered five weeks following SCI in rats. Ondansetron produced a robust, long-term reduction of at-level mechanical allodynia, while m-CPBG exacerbated allodynia. Exogenous 5-HT transiently reduced at-level mechanical allodynia. This effect was opposed by methysergide, which enhanced mechanical allodynia. Co-administration of 5-HT and ondansetron produced a short-lasting partial summation of effects, further decreasing mechanical allodynia while co-administration of methysergide attenuated the anti-allodynic effect of ondansetron. Depletion of spinal 5-HT via 5,7-dihydroxytryptamine (5,7-DHT) resulted in decreased at-level mechanical allodynia. The reduction of allodynia by ondansetron was lost following 5,7-DHT administration, suggesting that reduced allodynia following intrathecal ondansetron is via blockade of 5-HT-induced excitation of the 5-HT(3)-R. These results suggest that increased 5-HT fibre density immediately rostral to the SCI lesion site could have transient effects to reduce mechanical allodynia via actions at 5-HT(1) and/or 5-HT(2) receptors. However, the more long-lasting effects of this enhanced serotonergic input may facilitate chronic, at-level allodynia via the 5-HT(3)-R.
J Indian Med Assoc. 2004 Feb;102(2):73-4, 76, 78-9.
Ondansetron in prophylaxis of postoperative nausea and vomiting
in patients undergoing breast surgery: a placebo-controlled double blind
study.
Sinha PK, Ambesh SP.
Department of Anaesthesiology and Critical Care Medicine, Sanjay Gandhi
Postgraduate Institute of Medical Sciences, Lucknow 226014.
The present study was to evaluate the efficacy of ondansetron, 5-HT3 receptor antagonist, versus placebo in the prevention of postoperative nausea and vomiting (PONV) in a homogenous group of female patients undergoing breast reduction surgery under general anaesthesia. Approximately one hour before skin closure, 70 patients were randomly divided into two groups of 35 each. In a double blind manner each group of patients received either intravenous ondansetron (4mg) or a matching placebo. The overall incidences of PONV during first 24-hour were 60% and 20% in placebo and ondansetron group respectively (p<0.05). However, there was no significant difference after 24-hour postoperatively. In placebo group 42.9% of patients received rescue anti-emetic (metoclopramide) for the treatment of severe PONV (ie, 2 or more episodes of PONV), whereas, only 8.6% patients were administered such intervention in the ondansetron group (p<0.05). It is, therefore, concluded that prophylactic administration of intravenous ondansetron (4mg) one hour before skin closure is safe and effective in preventing PONV in female patients undergoing breast surgery and routine use of ondansetron in the patient population is recommended.
J Indian Med Assoc. 2003 Nov;101(11):638, 640, 642.
Comparison of ondansetron, dexamethasone, ondansetron plus dexamethasone
and placebo in the prevention of nausea and vomiting after laparoscopic
tubal ligation.
Biswas BN, Rudra A, Mandal SK.
Department of Anaesthesiology, Bankura Sammilani Medical College &
Hospital.
Laparoscopic tubal ligation is associated with an appreciably high rate of postoperative nausea and vomiting. This study was designed to compare the effectiveness of ondansetron, dexamethasone, ondansetron plus dexamethasone or placebo in the prevention of postoperative nausea and vomiting in patients after laparoscopic tubal ligation. In a prospective, randomised, double blind placebo controlled trial, 160 ASA I-II females received one of four regimens; ondansetron 4 mg, dexamethasone 8 mg, ondansetron 4 mg plus dexamethasone 8 mg or placebo (n=40 each) intravenously immediately before induction of anaesthesia. Patients were then observed for 24 hours postoperatively. The incidence of emetic episodes in the ondansetron with dexamethasone group was lower than in the placebo (p<0.001) and ondansetron (p=0.091) and dexamethasone (p=0.143) groups. A complete response (as no postoperative nausea and vomiting) was achieved in 60% of patients given ondansetron, 63% of the patients given dexamethasone, 78% of patients given ondansetron with dexamethasone and 37% of patients received placebo. The prophylactic use of ondansetron with dexamethasone is more effective in preventing postoperative nausea and vomiting.
CNS Drugs. 2004;18(8):485-504.
Pharmacotherapy of alcohol dependence: a review of the clinical
data.
Mann K.
Department of Addictive Behaviour and Addiction Medicine, Central Institute
of Mental Health, University of Heidelberg, Mannheim, Germany.
Over the last 20 years, the role of adjuvant pharmacotherapy in optimising outcome in rehabilitation programmes for alcohol-dependent patients has become increasingly evident. New avenues for rational drug treatment have arisen from better understanding of the neurobiological substrates of alcohol dependence, including adaptive changes in amino acid neurotransmitter systems, stimulation of dopamine and opioid peptide systems, and, possibly, changes in serotonergic activity. Disulfiram, naltrexone and acamprosate are currently the only treatments approved for the management of alcohol dependence. However, there is still no unequivocal evidence from randomised controlled clinical trials that disulfiram improves abstinence rates over the long term. Aversive therapy with disulfiram is not without risk for certain patients, and should be closely supervised. Both naltrexone and acamprosate improve outcome in rehabilitation of alcohol-dependent patients, but seem to act on different aspects of drinking pathology. Naltrexone is thought to decrease relapse to heavy drinking by attenuating the rewarding effects of alcohol. However, data from the naltrexone clinical trial programme are somewhat inconsistent, with several large studies being negative. Acamprosate is believed to maintain abstinence by blocking the negative craving that alcohol-dependent patients experience in the absence of alcohol. The clinical development programme has involved a large number of patients and studies, of which the vast majority have shown a beneficial effect of acamprosate on increasing abstinence rates. Both drugs are generally well tolerated; nausea is reported by around 10% of patients treated with naltrexone, while the most frequent adverse effect reported with acamprosate is diarrhoea. Another opioid receptor antagonist, nalmefene, has shown promising activity in pilot studies, and may have a similar profile to naltrexone. Data from studies of SSRIs in alcohol dependence are somewhat heterogeneous, but it appears that these drugs may indirectly improve outcome by treating underlying depression rather than affecting drinking behaviour per se. Similarly, the anxiolytic buspirone may act by ameliorating underlying psychiatric pathology. Dopaminergic neuroleptics, benzodiazepines and antimanic drugs have not yet demonstrated evidence of activity in large controlled clinical trials. Trials with drugs acting at serotonin receptors have yielded disappointing results, with the possible exception of ondansetron. Because the biological basis of alcohol dependence appears to be multifactorial, the future of management of alcoholism may be combination therapy, using drugs acting on different neuronal pathways, such as acamprosate and naltrexone. Pharmacotherapy should be used in association with appropriate psychosocial support and specific treatment provided for any underlying psychiatric comorbidities.
Exp Dermatol. 2004 May;13(5):298-304.
Antipruritic effects of two different 5-HT3 receptor antagonists
and an antihistamine in haemodialysis patients.
Weisshaar E, Dunker N, Rohl FW, Gollnick H.
Department of Dermatology and Venereology, Otto-von-Guericke-University,
Magdeburg, Germany. elke.weisshaar@med.uni-heidelberg.de
Pruritus is the most distressing symptom in haemodialysis (HD) patients. Its aetiology has not yet been delineated, and thus there are no good therapeutical options. Case reports and series attribute antipruritic potency to the serotonin receptor antagonists of the 5-HT3 type in renal pruritus. It was the aim of this study to investigate the antipruritic effect of two different 5-HT3 receptor antagonists and an antihistamine in 11 patients undergoing HD. Pruritus was induced by iontophoresis with serotonin and histamine and recorded before and after HD. These data were compared to those obtained after oral pretreatment with the 5-HT3 receptor antagonists tropisetron 5 mg and ondansetron 8 mg and the antihistamine cetirizine 10 mg. Ten healthy volunteers served as a control group. Vasocutaneous parameters (wheal and flare), skin temperature and alloknesis were also determined. Itching in HD patients and controls was not significantly diminished by oral pretreatment with the serotonin receptor antagonists. In controls, but not in HD patients, cetirizine significantly reduced itching, skin temperature and vasocutaneous parameters. Our data additionally demonstrate that there are no significant differences in vasocutaneous parameters, itching and alloknesis in HD patients before and after dialysis. We conclude that 5-HT3 receptor blockers such as tropisetron and ondansetron and the antihistamine cetirizine do not sufficiently reduce serotonin- and histamine-induced itching in haemodialyis patients.
Am J Health Syst Pharm. 2004 Apr 15;61(8):781-6.
Antiemetic effectiveness of ondansetron and granisetron in patients
with breast cancer treated with cyclophosphamide.
Dempsey CL, Coop AJ, Shillington A, Farley PA, Eberhardt DR,
O'Briant S.
EPI-Q, Inc., Oakbrook Terrace, IL 60181, USA.
PURPOSE: The antiemetic effectiveness of ondansetron 8 mg i.v, ondansetron
32 mg i.v, and granisetron 10 microg/kg or 1 mg i.v. as prophylaxis in
breast cancer patients regimens was studied. METHODS: Data from six U.S.
cancer centers were collected retrospectively for 224 patients who received
cyclophosphamide-containing therapy between January 1998 and June 2002.
Logistic-regression analysis was used to examine the likelihood of chemotherapy-induced
nausea and vomiting (CINV) both on an unadjusted basis and controlling
for concomitant radiation therapy and dexamethasone use. RESULTS: Seventy-six
patients (34%) received ondansetron 32 mg, 68 (30%) received ondansetron
8 mg, and 80 (36%) received granisetron (either 10 microg/kg or 1 mg).
Patients receiving ondansetron 8 mg were 2.5 times as likely to have CINV
on an adjusted basis as granisetron recipients (p < 0.01). There was
no increase in the risk of CINV with ondansetron 32 mg compared with granisetron.
Patients treated with ondansetron 8 mg required more rescue antiemetics
and more prophylactic antiemetics in subsequent chemotherapy cycles than
patients in the other groups. CONCLUSION: In a retrospective multicenter
study, granisetron 1 mg or 10 microg/kg and ondansetron 32 mg appeared
more effective than ondansetron 8 mg in preventing acute CINV related
to cyclophosphamide therapy.
