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Biomedical subjects

L F Prescott

Publications and source records attributed to L F Prescott.

At least 91 records · Page 5Linked to original sources
PubMed1983

Reactive metabolites as a cause of hepatotoxicity.

Many compounds, including established drugs, cause liver damage through biotransformation to reactive cytotoxic metabolites which bind covalently to hepatic macromolecules. The forms of expression of such injury include acute necrosis, chronic hepatitis, cirrhosis and neoplasia. Hepatotoxicity depends on the balance between metabolic activation and inactivation and reduced glutathione protects against the toxicity of some agents by trapping their reactive electrophilic metabolites. Toxicity is usually increased by induction and decreased by inhibition of hepatic microsomal enzymes.

Acetaminophen↗
PubMed1982

Diuresis or urinary alkalinisation for salicylate poisoning?

Forty-four adults with aspirin poisoning were treated with oral fluids only, standard forced alkaline diuresis, forced diuresis alone, or sodium bicarbonate (alkali) alone. Alkali alone was at least as effective and possibly more effective than forced alkaline diuresis in enhancing salicylate removal. Unlike the diuresis regimens it did not cause fluid retention or biochemical disturbances. The renal excretion of salicylate depends much more on urine pH than flow rate, and forced diuresis alone had little useful effect. In overdosage aspirin causes sodium and fluid retention and may impair renal function. Attempts to force a diuresis are potentially hazardous and the spurious fall in plasma salicylate concentration caused by haemodilution gives a false impression of efficacy. Further studies are required to determine the optimum treatment for salicylate poisoning.

Adolescent↗
PubMed1981

Treatment of severe acetaminophen poisoning with intravenous acetylcysteine.

Intravenous (IV) acetylcysteine, cysteamine, and methionine treatments were compared in patients with severe acetaminophen poisoning; a control group consisted of patients receiving supportive therapy only. Acetylcysteine proved the safest and most effective mode of treatment. Acetylcysteine was effective in preventing liver damage, hepatic failure, renal damage, and death when given eight to ten hours after poisoning. When treatment was delayed for ten to 24 hours, results were the same as in the supportive-therapy group. The alanine aminotransferase (ALT) activity remained normal in 76% of the patients treated within ten hours, as compared with 40% in both cysteamine- and methionine-treated groups and with 16% in the supportive-therapy group. The ingestion-treatment interval for complete protection with all three drugs was eight hours; beyond that time, the incidence of damage increased steadily. After 15 hours, all treatments were pointless. Based on my experience, IV administration is preferable, since nausea and vomiting may limit the effectiveness of oral therapy.

Acetaminophen↗
PubMed1981

Acetaminophen absorption and metabolism in celiac disease and Crohn's disease.

To investigate further the conflicting results in reports of drug absorption in patients with small intestinal mucosal disease, gastric emptying and the disposition of acetaminophen were assessed simultaneously in 41 subjects (13 controls, 12 patients with Crohn's disease, and 16 with celiac disease). Acetaminophen absorption as judged by plasma concentrations and gastric emptying were slower in patients with celiac disease and Crohn's disease. Total drug absorption as indicated by urinary recovery did not differ, but plasma acetaminophen half-life was shorter and glucuronide conjugation was enhanced in the patients with Crohn's disease. Contrary to expectation, the mean rate constant for acetaminophen absorption from the small intestine was not decreased in Crohn's disease and celiac disease. The abnormally slow acetaminophen absorption in the patients with Crohn's or celiac disease could be explained by slower gastric emptying of the drug solution.

Acetaminophen↗
PubMed1981

Effects of microsomal enzyme induction on paracetamol metabolism in man.

1 The metabolism of paracetamol after a single oral dose of 20 mg/kg was compared in fifteen patients with microsomal enzyme induction taking anticonvulsants or rifampicin and twelve healthy volunteers. 2 Induction was confirmed by measurement of the plasma antipyrine half-life (mean 6.4 h in the patients compared with 12.8 h in the volunteers). 3 The glucuronide conjugation of paracetamol was enhanced in the induced patients as shown by lower plasma paracetamol concentrations, a shorter paracetamol half-life, higher paracetamol glucuronide concentrations and an increased ratio of the area under the plasma concentration time curves of the glucuronide to the unchanged drug. There were no significant differences in sulphate conjugation. 4 There was a corresponding change in the pattern of urinary metabolite excretion. The induced patients excreted significantly less unchanged drug and sulphate conjugate and more glucuronide conjugate than the healthy volunteers. 5 The urinary excretion of the mercapturic acid and cysteine conjugated of paracetamol was the same in both groups. 6 Conversion of paracetamol to its potentially hepatotoxic metabolite does not seem to be increased in patients induced with anticonvulsants or rifampicin. There would seem to be no contraindication to the use of these drugs in combination.

Acetaminophen↗