British journal of clinical pharmacology
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Br J Clin Pharmacol · Oct 1982
Randomized Controlled Trial Clinical TrialCodeine added to paracetamol induced adverse effects but did not increase analgesia.
1 In a double-blind crossover study identical oral surgical procedures were performed on two separate occasions in 24 outpatients. 2 At one operation they were given tablets containing paracetamol + codeine phosphate (400 mg + 30 mg), and at the other plain paracetamol (400 mg). The day of operation 2 tablets were taken 3, 6 and 9 h after surgery, the following two days 1 tablet four times daily. 3 Several measurements/assessments were recorded for a paired comparison of the postoperative courses. 4 No increase In the analgesic effect could be demonstrated by addition of codeine to paracetamol. 5 On the day of operation 18 patients reported adverse effects like nausea, dizziness and drowsiness with paracetamol + codeine, while only 3 patients experienced side effects with paracetamol alone (P less than 0.001). 6 Measurements revealed almost identical swelling after the two operations. 7 Compared with results obtained in previous studies, the present findings indicate that paracetamol may exert anti-inflammatory activity and reduce postoperative swelling, even when given 3 h after surgery. 8 On the day of operation and the following two days 20 patients preferred the treatment with plain paracetamol, while only 4 favoured paracetamol + codeine (P less than 0.001).
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Br J Clin Pharmacol · Jun 1982
Clinical Trial Controlled Clinical TrialEffects of combined alpha- and beta-blockade by labetalol in patients with coronary artery disease.
1 The effect of labetalol 100 mg orally twice daily on exercise tolerance has been compared with placebo in 19 normotensive subjects with angiographic evidence of coronary artery disease. 2 Labetalol, at the same work load as during placebo exercise, significantly reduced systolic and diastolic blood pressures, as well as heart rate and rate-pressure product. 3 Similarly, ST segment depression was reduced by labetalol from 2.0 +/- 0.4 to 1.36 +/- 0.6 mm (P less than 0.001), thus enabling an increase in exercise tolerance from a control value of 83.7 +/- 18 to 95.3 +/- 19 W (P less than 0.005). 4 In seven other patients, also with coronary artery disease, the haemodynamic effects of a single 0.6 mg/kg intravenous dose of the drug was evaluated during exercise. 5 Compared with conditions during control exercise, labetalol induced a significant reduction in rate-pressure product from 17228 +/- 2375 to 13445 +/- 2404 mmHg/min (P less than 0.005) and in peripheral vascular resistance from 612.0 +/- 61.2 to 512.7 +/- 36.2 dyn cm-5 m-2 (P less than 0.0025). These events were not accompanied by any change in cardiac index and in dP/dT left ventricular end-diastolic pressure (LVEDP) ratio. 6 These data suggest that labetalol may induce reduction in myocardial oxygen consumption, thereby increasing exercise tolerance in patients with coronary artery disease, without impairment of left ventricular performance.
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1 Observed and possible roles for the use of labetalol in anaesthesia are reviewed. 2 When used together with halothane inhalation anaesthesia, satisfactory conditions are achieved for safe hypotensive anaesthesia: (a) Labetalol and halothane have additive hypotensive effects. (b) The usual dose of labetalol is 25 mg intravenously together with 1% halothane. (c) The duration of hypotension can be controlled in the presence of halothane; withdrawal leads to rapid recovery of pre-surgery blood pressure. (d) High doses of halothane (3%) with labetalol predispose to the myocardial depressant effects of halothane and undesirable reductions in myocardial performance. 3 As it is now seen to be important to reduce the blood pressure before anaesthesia and surgery in hypertensive patients, then labetalol is likely to be satisfactory either by the intravenous route for immediate reduction or for less urgent reduction of raised arterial pressure by the oral route. 4 It is known that anaesthesia (for example, laryngoscopy) and surgery provoke hypertensive responses which are particularly undesirable in the patient with pre-existent myocardial ischaemia. In such cases it is likely that previous treatment with labetalol will satisfactorily modify unwanted hypertensive and cardiovascular responses.
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Br J Clin Pharmacol · Mar 1982
Tachyphylaxis after repeated dosage of decamethonium in anaesthetized man.
1 The tetanic and single twitch responses to the adductor pollicis muscle were used to study the neuromuscular effects of repeated dosage of decamethonium in nine anaesthetized patients. 2 In two of three patients who received the same total dose of decamethonium in three separate series of injections, blockade of the tetanic response was less after the third administration. In the third patient tachyphylaxis was evident after the second series of injections. 3 In three other patients, tachyphylaxis occurred after the second series of injections when the total dose of decamethonium administered was at least twice that given on the first occasion. 4 In terms of tachyphylaxis the single twitch response followed a similar pattern to that of the tetanic response. 5 Once tachyphylaxis had developed, neuromuscular block of the tetanic response by decamethonium was antagonised by neostigmine (2.5 mg) and enhanced by 2% halothane. 6 In contrast, in three patients who were not exposed to more than one series of injections of decamethonium, and presumably therefore before tachyphylaxis had developed, neuromuscular block of the tetanic response was potentiated by neostigmine. Under these circumstances recovery was unaffected by halothane. 7 Thus, when tachyphylaxis occurs with decamethonium the characteristics of the block change to resemble those of the competitive neuromuscular blocking agents; these findings could be of importance in clinical anaesthesia.
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Br J Clin Pharmacol · Feb 1982
A study of pethidine kinetics and analgesia in women in labour following intravenous, intramuscular and epidural administration.
1 Epidural administration of opiates for analgesia has recently generated widespread interest and would theoretically be advantageous as a method for relief of pain in labour. 2 Plasma pethidine concentrations were measured after intravenous, intramuscular and epidural administration of pethidine to women in labour and after epidural administration to non-pregnant female surgical patients. 3 Kinetic parameters were derived from the plasma concentration data in each group of subjects and the relationship between plasma kinetics and analgesia in labour were examined. 4 Absorption of pethidine from the epidural space in pregnant women in rapid and excepting the lower initial values, the average plasma concentration and area under the plasma concentration v time curve did not differ significantly (P less than 0.01) from those obtained with intravenous dosage, but were significantly higher (P less than 0.01) during the first 2 h after dosage than the results after intramuscular administration. The analgesia provided by the epidural route of administration was greater than with intravenous or intramuscular administration. 5 It is postulated that the analgesic efficacy of epidural pethidine in women in labour is due to a combination of systemic and local effects and that the local effect is attributable to the local anaesthetic properties of pethidine rather than a selective anti-nociceptive action on the spinal cord.