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Biomedical subjects

L F Prescott

Publications and source records attributed to L F Prescott.

204 records · Page 12Linked to original sources
PubMedDate not supplied

Mexiletine in the prophylaxis of ventricular arrhythmias during acute myocardial infarction.

In a double-blind study involving 165 patients we examined the role of mexiletine, a new antiarrhythmic drug, for the prophylaxis of ventricular arrhythmias after acute myocardial infarction. Mexiletine or placebo was given orally to patients on arrival in the coronary care unit, and continuous electrocardiographic tape recordings were used to document arrhythmias. Ventricular tachycardia and R-on-T ventricular ectopic beats were significantly reduced in the mexiletine patients, but too few episodes of ventricular fibrillation occurred for statistical comment. When arrhythmias did occur in the mexiletine group, it was usually early in the study, at which time plasma drug levels were low. Adverse effects were uncommon. Patients who were given therapy, but in whom acute myocardial infarction could not be confirmed, suffered no serious consequences of taking mexiletine. The results demonstrate the benefit and limitations of prophylactic oral antiarrhythmic therapy for patients with acute myocardial infarction.

Acute Disease↗
PubMedDate not supplied

Clinical pharmacokinetics of paracetamol.

In therapeutic doses paracetamol is a safe analgesic, but in overdosage it can cause severe hepatic necrosis. Following oral administration it is rapidly absorbed from the gastrointestinal tract, its systemic bioavailability being dose-dependent and ranging from 70 to 90%. Its rate of oral absorption is predominantly dependent on the rate of gastric emptying, being delayed by food, propantheline, pethidine and diamorphine and enhanced by metoclopramide. Paracetamol is also well absorbed from the rectum. It distributes rapidly and evenly throughout most tissues and fluids and has a volume of distribution of approximately 0.9L/kg. 10 to 20% of the drug is bound to red blood cells. Paracetamol is extensively metabolised (predominantly in the liver), the major metabolites being the sulphate and glucuronide conjugates. A minor fraction of drug is converted to a highly reactive alkylating metabolite which is inactivated with reduced glutathione and excreted in the urine as cysteine and mercapturic acid conjugates. Large doses of paracetamol (overdoses) cause acute hepatic necrosis as a result of depletion of glutathione and of binding of the excess reactive metabolite to vital cell constituents. This damage can be prevented by the early administration of sulfhydryl compounds such as methionine and N-acetylcysteine. In healthy subjects 85 to 95% of a therapeutic dose is excreted in the urine within 24 hours with about 4, 55, 30, 4 and 4% appearing as unchanged paracetamol and its glucuronide, sulphate, mercapturic acid and cysteine conjugates, respectively. The plasma half-life in such subjects ranges from 1.9 to 2.5 hours and the total body clearance from 4.5 to 5.5 ml/kg/min. Age has little effect on the plasma half-life, which is shortened in patients taking anticonvulsants. The plasma half-life is usually normal in patients with mild chronic liver disease, but its prolonged in those with decompensated liver disease.

Acetaminophen↗