A single i.v. dose of ondansetron 8 mg prior to induction of anaesthesia reduces postoperative nausea and vomiting in gynaecological patients.

The effect of a single intravenous dose of ondansetron in preventing postoperative nausea and emesis (retching and vomiting) (PONV) was investigated in a randomized, double-blind, placebo-controlled, multicentre, international study. Women of ASA class I-III, requiring gynaecological laparotomy, vaginal hysterectomy, or major vaginal surgery were selected for study. Two hundred and thirty-five received placebo, 231 received 1 mg ondansetron, 228 received 8 mg ondansetron and 229 received 16 mg ondansetron, as an infusion over five minutes before the induction of anaesthesia. A standardized balanced anaesthetic technique was employed. This consisted of premedication with either diazepam or temazepam, thiopentone induction, maintenance with nitrous oxide in oxygen supplemented with enflurane or isoflurane, intraoperative analgesia with fentanyl, neuromuscular blockade with any choice of agent and reversal with neostigmine and atropine. Postoperative analgesia was achieved with morphine, and prochlorperazine or metoclopramide were given if a rescue antiemetic was required. A greater percentage of patients in the 8 mg and 16 mg ondansetron groups experienced no postoperative emesis (44% and 39% respectively) than in the placebo and 1 mg ondansetron groups (29% and 28% respectively) for the first 24 hr postoperative period (8 mg vs placebo and 1 mg: P < or = 0.001; 16 mg vs placebo: P < 0.05; 16 mg vs 1 mg: P < 0.05). Similarly, the percentage of patients who did not experience postoperative nausea were 20%, 26%, 31% and 28% for the placebo, 1 mg, 8 mg and 16 mg ondansetron treatment groups, respectively (8 mg and 16 mg vs placebo P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical development of ondansetron for use in the prevention and treatment of postoperative nausea and vomiting.

An international clinical trial programme has been established to assess the efficacy and safety of ondansetron in the prevention and treatment of postoperative nausea and vomiting. The programme included nine pilot studies and six key placebo-controlled studies. These studies have evaluated both oral and intravenous formulations of ondansetron in the prevention of postoperative nausea and vomiting, and intravenously administered ondansetron in the treatment of established symptoms. Most patients included in the trials were adult women, less than 50 years of age, receiving anaesthesia for gynaecological surgery. The primary efficacy analysis for emesis was based on the assessment of complete response (i.e. absence of emetic episodes or nausea in the first 24 h postoperatively). These trials clearly demonstrated the anti-emetic efficacy of ondansetron in the prevention and treatment of postoperative nausea and vomiting.

The effects of drugs, other foreign compounds, and cigarette smoke on the synthesis of protein by lung slices.

The incorporation of 14C-leucine into rabbit lung slices was monitored in the absence and presence of selected drugs and chemicals relevant to the perturbation of lung function and the development of lung disease. Known inhibitors of protein synthesis (cycloheximide and ricin) inhibited the incorporation of 14C-leucine. Marked inhibition was also recorded with the lung toxins paraquat and 4-ipomeanol. By contrast, orciprenaline, salbutamol, and terbutaline were without effect although some response was recorded with isoprenaline. The filtered gas phase of cigarette smoke and acrolein, one of its components, were inhibitory but protection was afforded by N-acetylcysteine. It is suggested that the inhibitory effects of cigarette smoke may be due to its acrolein content. It is further suggested that the use of lung slices and measurements of 14C-leucine incorporation provide valuable means for monitoring potential pulmonary toxins.

Moclobemide versus placebo in the treatment of depression: a multicentre study in Belgium.

Moclobemide was compared with placebo for antidepressant activity, tolerance and safety in 2 parallel groups of 23 and 24 depressed patients. At the end of treatment (4 weeks or longer), 9 patients on moclobemide (41%) showed an improvement greater than or equal to 50% on the Hamilton Rating Scale for Depression, compared with only 4 (17%) of those on placebo. The overall assessment of efficacy was significantly better for moclobemide (good or very good results in 50% of patients) than for placebo (80% poor results). Moclobemide was well or very well tolerated by 85% of patients and placebo by 100%. Moclobemide was thus shown to be clearly more effective than placebo and only slightly less well tolerated.

Moclobemide versus clomipramine in the treatment of depression: a single-centre study, Federal Republic of Germany.

Moclobemide was compared with clomipramine for safety and efficacy in 2 groups of 15 patients each with endogenous depression. The drugs were given under double-blind conditions in increasing doses; 1 patient in the moclobemide group dropped out because of lack of efficacy. Mean final improvement on the Hamilton Rating Scale for Depression was 51% in the moclobemide group and 54% in the clomipramine group. Efficacy and tolerance were rated good or very good by 47% (moclobemide) and 53% (clomipramine) (NS). The results indicate that moclobemide is as effective as clomipramine in treating endogenous depression.

Moclobemide versus clomipramine in the treatment of depression: a multicentre trial in Spain.

The efficacy, tolerability and safety of moclobemide were compared with those of clomipramine in a double-blind, randomized parallel group study over 4 weeks. Patients were suffering from various forms of depression: 33 received moclobemide and 31 clomipramine. The mean score on the Hamilton Rating Scale for Depression decreased gradually in both groups, with no significant differences between them; the final scores showed an improvement of 57% in the moclobemide group and 60% in the clomipramine group, compared with baseline. The investigators' assessment of efficacy at the end of treatment was good or very good for 60% of moclobemide patients and 50% of clomipramine patients, and tolerance was good or very good for 31 patients on moclobemide and 26 on clomipramine. The drugs thus showed comparable antidepressant efficacy, and both were mostly well tolerated, although adverse events were more prevalent in patients treated with clomipramine.

Moclobemide versus clomipramine in the treatment of depression: a double-blind multicentre study in Belgium.

Moclobemide and clomipramine were compared for efficacy, tolerance and safety in 63 mixed endogenous and nonendogenous depressed patients. Treatment was given for at least 4 weeks in a double-blind, randomized, parallel-group design. The mean Hamilton Rating Scale for Depression score decreased gradually during treatment with no differences between groups. Two patients on clomipramine and none on moclobemide were withdrawn for lack of efficacy, and poor tolerance caused 3 patients on moclobemide and 7 on clomipramine to stop treatment prematurely. Patients with endogenous depression responded better to clomipramine, whereas nonendogenous disorders did better on moclobemide. Adverse events were more frequent in the clomipramine group and more of these were severe or very severe than for moclobemide. Thus, although no significant difference in efficacy was seen, moclobemide appeared to be tolerated better than clomipramine. The numbers were small, however, and many patients received concomitant medication, and the results are therefore difficult to interpret.

Moclobemide versus amitriptyline in the treatment of depression: two small double-blind multicentre studies in Belgium.

Moclobemide was compared with amitriptyline for antidepressant efficacy, safety and tolerance. Two studies were conducted, both over at least 4 weeks; in the first, 8 patients were given moclobemide in doses ranging from 300 to 328 mg, and 9 patients amitriptyline in doses of 75 to 96 mg; in the second, the numbers were 13 on moclobemide and 14 on amitriptyline, and the mean doses were 294-408 mg and 95-129 mg respectively. Both studies showed the 2 treatments to be equally effective, and there were no significant differences at any point. Moclobemide appeared slightly more effective and slightly better tolerated than amitriptyline, but the numbers were too small for any valid conclusion.

Acrivastine in allergic rhinitis: a review of clinical experience.

Acrivastine is an antihistamine with reduced sedating potential. This comprehensive review of clinical experience with acrivastine in allergic rhinitis considers all currently available data both published and, as yet, unpublished. Unequivocal evidence of the efficacy of 8 mg acrivastine three times daily for the control of symptoms of seasonal allergic rhinitis has been provided by 11 placebo-controlled studies involving almost 1000 patients. Additional trials have generated further supportive data as well as evidence for the use of acrivastine in the treatment of perennial allergic rhinitis. In common with most antihistamines, acrivastine alone has limited effect on the symptom of blocked nose. In a further series of 11 studies, mainly conducted in the USA, the combination of 8 mg acrivastine plus 60 mg pseudoephedrine was found to control not only the histamine-mediated symptoms of allergic rhinitis but also blocked nose. There were few adverse events associated with the use of acrivastine and the small increase in incidence of drowsiness over that found with placebo was similar to that observed for terfenadine. The marked absence of other signs of significant depression of the central nervous system (or anticholinergic activity) suggests that acrivastine will be an important addition for the antihistaminic control of symptoms of allergic rhinitis.