Fluradoline and aspirin for orthopedic postoperative pain.

Fluradoline (150 or 300 mg), a novel tricyclic with both antidepressant and analgesic properties in animals, was compared with aspirin, 650 mg, and placebo when given orally for postoperative orthopedic pain in a double-blind, single-dose, parallel-group study. Analgesic measurements were made by two trained nurse observers using standard verbal rating and visual analogue scales. Aspirin was statistically superior to placebo on all analgesic measures, demonstrating assay sensitivity. Fluradoline, 300 mg, was distinguished from placebo and fluradoline, 150 mg, but not from aspirin, 650 mg. Overall, fluradoline, 300 mg, was equivalent to aspirin, 650 mg. Fluradoline, 300 mg, produced a significant elevation in mood score. Neither aspirin, 650 mg, nor fluradoline caused untoward side effects, but fluradoline, 300 mg, increased blood pressure.

Ketorolac and acetaminophen for orthopedic postoperative pain.

In a double-blind, single-dose, parallel-group study, ketorolac (5, 10, or 20 mg) was compared with acetaminophen (500 or 1000 mg) when taken by mouth for postoperative orthopedic pain. Analgesic measurements were made by trained nurse observers who used standard verbal rating and visual analog scales. Acetaminophen, 1000 mg, was statistically superior to 500 mg acetaminophen, demonstrating assay sensitivity. Ketorolac, 20 mg, was distinguished from 500 mg acetaminophen, 5 mg ketorolac, and 10 mg ketorolac, but not from 1000 mg acetaminophen. The higher doses of ketorolac induced a longer lasting peak analgesic effect than did acetaminophen, but the magnitude of the peak pain relief was changed little by an increased ketorolac dose. Overall, 10 mg ketorolac appeared equivalent to 1000 mg acetaminophen. Acetaminophen, 500 mg, induced less sedation than the higher doses of ketorolac, but neither drug caused untoward side effects.

Modelling dementia: effects of scopolamine on memory and attention.

Scopolamine, a muscarinic cholinergic antagonist, is capable of inducing transient memory impairment in normal subjects. Against the background of the cholinergic hypothesis of Alzheimer's disease (AD) the present study was designed to investigate the effects of low oral doses of scopolamine on a range of cognitive functions known or hypothesized to be affected in AD. Twenty healthy volunteers (18-48 yr) performed a battery of automated cognitive tasks under each of five treatments: oral scopolamine 0.3 mg, 0.6 mg, 1.2 mg; oral methylscopolamine 0.6 mg; placebo. Alongside analogous tests of verbal and non-verbal memory, the battery enabled assessments of a range of attentional functions: alerting, sustained attention, selective attention, and covert orientation. A profile of effects was observed within and beyond the realm of memory. While some functions were unaffected by the drug (e.g. alerting) and others were impaired at the highest dose (e.g. verbal learning) still others were affected in a linear dose-dependent manner (sustained attention; visual contrast sensitivity). These observations are discussed in the context of the "scopolamine model" of AD.

Effects of lorazepam on memory, attention and sedation in man.

The effects of three doses of lorazepam (0.5, 1.0 and 2.0 mg PO) on various aspects of memory, attention and sedation are described. Lorazepam produced dose-related deficits in verbal secondary memory, choice reaction time and a novel vigilance task. It also produced a dose-dependent increase in subjective sedation, and an enhancement of visual contrast sensitivity. These results are compared with those reported earlier using the muscarinic antagonist scopolamine, and discussed in relation to models of Alzheimer's disease.

Scopolamine and benzodiazepine models of dementia: cross-reversals by Ro 15-1788 and physostigmine.

The muscarinic antagonist scopolamine and the benzodiazepine lorazepam both produce transient impairments in memory and attention in normal volunteers. These impairments can be reversed by appropriate agents such as the cholinesterase inhibitor physostigmine in the case of scopolamine or the benzodiazepine antagonist Ro 15-1788 in the case of lorazepam. In this paper we investigated the pharmacological specificity of these reversals by examining the interactions of scopolamine and Ro 15-1788 and of lorazepam and physostigmine. There was no evidence that the effects of scopolamine and lorazepam on cognitive function could be attenuated by Ro 15-1788 and physostigmine, respectively. The results are discussed in terms of pharmacological models of Alzheimer's disease.

Open learning. Support for the learner-led team.

Employing open learning in educational programmes relies for its success on a firm integral structure. Patsy Poppleton argues that clearly defined roles with adequate support for all participants is essential.

Mandatory sublingual buprenorphine for postoperative pain.

This study examined the analgesic effect, vital signs and side effects when 0.4 mg doses of buprenorphine were given pre-emptively for the treatment of postoperative pain after elective total hip replacement. Pain intensity, pain relief, retrospective peak pain intensity and pain relief, sedation, vital signs and side effects were measured 1 hour after surgery and then in the morning and evening of the first 2 postoperative days. There was a significant improvement in pain measured over the 3 days, with concomitant reduction in side effects and sedation. However, there was a significant increase in the number of patients with a pulse rate greater than 100 beats per minute. No particular benefit for postoperative pain relief was observed in patients receiving buprenorphine premedication in comparison with those who had received morphine or placebo.

Perineural injection of morphine fails to relieve postoperative pain in humans.

Ten patients scheduled for bilateral foot surgery were given general anesthesia plus ankle blocks. One side was blocked with 0.02% morphine and the other with 0.9% saline. A second group of 10 patients for bilateral foot surgery had one side blocked with 0.02% morphine and the other with 0.01% morphine. A within-patient blind comparison of postoperative analgesia between the two sides was performed by nurse observers, using categorical and visual analogue scales for both pain intensity and pain relief. Postoperative analgesia recorded by the nurse observer was not significantly different between morphine and saline. Similarly, there was no significant difference in postoperative analgesia between legs blocked with the higher or lower dose of morphine. Thus, perineural morphine does not relieve postoperative pain at doses equivalent to 2-4 mg in a 70-kg man.

A comparison of intramuscular and sublingual buprenorphine, intramuscular morphine and placebo as premedication.

Buprenorphine premedication by two routes, 0.4 mg sublingual and 0.3 mg intramuscular was compared double-blind, double-dummy with intramuscular morphine 10 mg and placebo in 74 patients undergoing elective total hip replacement. Anxiety, depressive mood, sedation, vital signs and side-effects were measured before surgery. All patients then received a standardised general anaesthetic using a muscle relaxant and ventilation. The effects of the premedication on the anaesthetic were assessed by a scoring system. Intra- and postoperative blood gases, plasma cortisol and glucose were measured and the 1 hour postoperative pain intensity, side-effects and sedation were assessed. No differences between the premedications were seen on any of the pre-, intra- or postoperative measurements, suggesting that even with adequate measurement sensitivity it is difficult to distinguish opiate from placebo premedication.