Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Aug 1992
Randomized Controlled Trial Comparative Study Clinical TrialA new method for rate of analgesic onset: two doses of intravenous morphine compared with placebo.
A new method of frequent early pain assessments for 1 hour only was used to determine time of onset of analgesia after intravenous administration of 10 mg morphine, 5 mg morphine, or placebo in a double-blind study; 79 patients were randomized if they required parenteral analgesia in the early postoperative period. Pain intensity was determined by a four-point categoric verbal rating scale and on a verbal ordinal scale from 0 to 100 (0 = no pain, 100 = worst pain imaginable) during the first hour after analgesic administration. The onset time of analgesia, assessed by 50% of patients achieving 25% reduction from their baseline pain assessment, was significantly faster for 10 mg morphine compared with 5 mg morphine (p = 0.02) and placebo (p less than 0.01). More familiar analgesic efficacy measures, including the sum of pain intensity differences and time to next analgesic dose, similarly showed the superiority of 10 mg morphine to placebo in the first hour, confirming sensitivity according to the conventional paradigm.
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Clin. Pharmacol. Ther. · Aug 1992
Comparative StudyDiffering effect of atropine on heart rate in Chinese and white subjects.
To determine if differences exist between Chinese and white subjects in their response to atropine and if the intrinsic heart rate and the autonomic contribution to the heart differ between the two races, eight white and eight Chinese males were studied. In all subjects the heart rate decreased after the first dose of atropine (0.003 mg/kg) with no difference in the bradycardia between the two races. ⋯ There was no difference in the intrinsic heart rate, in the relative vagal contribution, or in relative sympathetic contribution to the heart rate between the Chinese and white subjects. These data indicate that Chinese subjects are more sensitive to the effect of atropine, which is not related to the contribution of autonomic tone to the heart.
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Clin. Pharmacol. Ther. · Jul 1992
Comparative StudyEffect of carbetocin, a long-acting oxytocin analog on the postpartum uterus.
Carbetocin, a long-acting oxytocin analog, was administered by intravenous and intramuscular injection to 40 women 24 to 48 hours postpartum. Intravenous injection of 8 to 30 micrograms produced a tetanic uterine contraction within 2 minutes, lasting about 6 minutes, followed by rhythmic contractions for a further 60 +/- 18 minutes. Intramuscular injection of 10 to 70 micrograms also produced tetanic contraction in less than 2 minutes, lasting about 11 minutes, and followed by rhythmic contractions for an additional 119 +/- 69 minutes. ⋯ Carbetocin produced mild lower abdominal cramping in most patients and severe pain in three patients who received 50 or 100 micrograms intravenously or 70 micrograms intramuscularly. Approximately half of the patients also experienced flushing and warmth. Although carbetocin has not yet been studied immediately postpartum, its prolonged uterine activity suggests that carbetocin may offer advantages over oxytocin in management of the third stage of labor.
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Clin. Pharmacol. Ther. · Jul 1992
Randomized Controlled Trial Multicenter Study Clinical TrialOndansetron is effective in decreasing postoperative nausea and vomiting.
The efficacy of ondansetron, a selective 5-HT3 receptor antagonist, in preventing postoperative nausea and vomiting in surgical patients was studied. Fifty women were randomized in a double-blind manner to receive either two 8 mg doses of intravenous ondansetron or two doses of placebo vehicle: the first given just before general anesthesia induction and the second 8 hours later. During the first 24 postoperative hours, the number of emetic episodes was recorded and the subjects rated their nausea on a scale from 0 to 10. ⋯ The number of complete responders (no emetic episodes and no rescue therapy) was 1 of 24 (4%) and 15 of 26 (58%) in the placebo and ondansetron groups, respectively (p less than 0.001). Ondansetron is clearly more effective than placebo in the prophylaxis of postoperative nausea and vomiting. The adverse event profile for ondansetron was similar to that of placebo.
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Clin. Pharmacol. Ther. · Jul 1992
Case ReportsTreatment of opioid-induced constipation with oral naloxone: a pilot study.
Opioids cause constipation by binding to specific opioid receptors in the enteric and central nervous systems. First-pass glucuronidation limits systemic bioavailability of oral naloxone. This study was designed to determine if oral naloxone could reverse opioid-induced constipation without precipitating abstinence or recrudescence of pain in opioid-dependent individuals. ⋯ Peak plasma levels did not predict withdrawal. Oral naloxone ameliorates opioid-induced constipation in opioid-dependent persons. Titration of dose to a maximum of 12 mg at least 6 hours apart may be needed to avoid adverse reactions.