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Biomedical subjects

J A Forrest

Publications and source records attributed to J A Forrest.

13 recordsLinked to original sources
PubMed1979

Paracetamol metabolism in chronic liver disease.

The plasma concentrations and urinary excretion of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates were measured in eight normal subjects, eight patients with mild liver disease and seven patients with severe liver disease following an oral dose of 1.5 g of paracetamol. The mean plasma paracetamol half-life was similar in normal subjects (2.43 h +/- 0.19) but was significantly prolonged in all patients with severe liver disease (4.25 h +/- 1.15:p = less than 0.001). Prolongation of the paracetamol half-life was related to reduced plasma albumin and increased prothrombin time. The mean ratios of plasma concentrations of unchanged paracetamol to paracetamol glucoronide and sulphate were significantly greater in patients with sever liver disease than the normal subjects. There were no significant differences in the overall 24-h urinary excretion of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates in the three groups. The glutathione conjugation of paracetamol did not seem to be impaired in patients with severe liver disease as evidence by the production of normal amounts of the cysteine and mercapturic acid conjugates. There is thus no evidence that they are at increased risk of hepatotoxicity when given a single therapeutic dose of paracetamol.

Acetaminophen↗
PubMed1979

Effect of long-term cimetidine on gastric acid secretion, serum gastrin, and gastric emptying.

Gastric acid secretion, gastric emptying, fasting serum gastrin and the serum gastrin response to a meal were measured in duodenal ulcer patients before, and at least five days after completing prolonged treatment with cimetidine (1 or 2 g/day for four or eight weeks followed by 600 mg twice daily for six months). Fasting serum gastrin and the gastrin response were also measured during treatment. Compared with pretreatment values, fasting serum gastrin concentrations were raised both during and five to 31 days after stopping treatment (P less than or equal to 0.02). The integrated gastrin response and the rate of gastric emptying of the solid component of the meal were increased during treatment (P less than 0.001 and P less than 0.002 respectively) but returned to pretreatment levels after stopping therapy. No significant changes were observed in the basal or maximal acid outputs or the rate of emptying of the liquid component of the meal. The results imply that the hypergastrinaemia associated with long-term cimetidine therapy does not result in increased gastric acid secretion.

Cimetidine↗
PubMed1979

Effects of lysine vasopressin and glypressin on the fibrinolytic system in cirrhosis.

In eight patients with cirrhosis of the liver and portal hypertension an intravenous infusion of lysine vasopressin induced a rapid increase in the plasma level of the fibrinolytic proenzyme plasminogen activator. In contrast, triglycyl lysine vasopressin (glypressin; GVP), in a dose known to lower portal venous pressure, produced no fibrinolytic response. This lack of fibrinolytic response represents an advantage of GVP over lysine vasopressin in addition to its longer in vivo half-life and lower cardiotoxicity. Clinical trials of GVP in the treatment of bleeding oesophageal varices are needed.

Aged↗
PubMed1978

Premedication for upper gastrointestinal endoscopy: a comparative study of flunitrazepam, diazepam and neuroleptanalgesia.

Flunitrazepam or diazepam with atropine and a combination of phenoperidine, droperidol and cyclizine (neuroleptanalgesia) were compared as premedication in three groups of 25 patients undergoing routine upper gastrointestinal endoscopy. Drug doses were titrated carefully against response and all three regimes were found to be similar in terms of safety, patient co-operation, relaxation and speed of recovery. Neuroleptanalgesia however produced a statistically significant rise in endtidal pCO2 and systolic blood pressure. The benzodiazepines, and in particular flunitrazepam, produced a significantly greater amnesia for the procedure, patients given these drugs being more willing to undergo repeat endoscopy.

Anti-Anxiety Agents↗
PubMed1978

Effect of cimetidine on serum gastrin and gastric emptying in man.

Paired studies of gastric emptying were performed in 10 healthy volunteers using a scintiscanning technique which provides information about the rate of emptying of both the liquid and solid components of a standard meal. Emptying rates of both components were not significantly different after oral administration of 400 mg cimetidine than after placebo. The increase in serum gastrin concentration produced by the meal was significantly greater after cimetidine than after placebo but there was no relationship between individual cimetidine-placebo differences in gastrin response and the corresponding cimetidine-placebo differences in rates of emptying. A positive correlation was demonstrated between the gastric emptying rate of the liquid component and the 1 h cimetidine absorption, indicating that normal individual variation in gastric emptying is probably responsible for much of the normal individual variation in the rate of cimetidine absorption.

Adult↗
PubMed1977

Antipyrine, paracetamol, and lignocaine elimination in chronic liver disease.

The plasma half lives of antipyrine, paracetamol, and lignocaine given by mouth were measured in 23 patients with stable chronic liver diseases of varying severity. Fifteen patients received all three drugs and 19 at least two. The half life of paracetamol was abnormally prolonged in nine out of 17 patients (mean 2-9 hours, normal 2-0 hours), of antipyrine in 10 out of 19 patients (mean 30-4 hours, normal 12-0 hours), and of lignocaine in 19 out of 21 patients (mean 6-6 hours, normal 1-4 hours). Prolongation of the half lives of all three drugs was significantly correlated with an increase of the vitamin-K1-corrected prothrombin time ratio and a reduction in serum albumin concentration. There was no correlation with serum bilirubin concentration or serum alanine aminotransferase activity. This suggests that impaired drug elimination was related to depressed hepatic protein synthesis. Considerable prolongation of the half life of one drug was invariably associated with delayed elimination of the others. The half life of lignocaine, however, was always the most prolonged and was a highly sensitive indicator of hepatic dysfunction. The pharmacokinetic characteristics of a drug as well as the severity of liver disease should be taken into account when considering drug dosage in patients with chronic liver disease.

Acetaminophen↗
PubMed1976

Effect of histamine H2-receptor blockade on gastric emptying and serum gastrin in man.

The effect of orally administered metiamide, a Histamine H2-receptor antagonist, on the rate of gastric emptying was assessed in 24 uncomplicated duodenal ulcer patients given a standard meal containing indium 113m D.T.P.A. chelate. Metiamide produced significant slowing of gastric emptying when compared with control studies performed on the same patients following oral administration of a placebo. In a further study the effect of metiamide on the serum gastrin response to a protein meal was assessed in seven healthy male volunteers. Paired experiments demonstrated that a significantly greater elevation of serum gastrin occurred after metiamide than after placebo. The delay in gastric emptying produced by metiamide may be mediated by an elevation of the serum gastrin concentration.

Adult↗
PubMed1976

Effect of the histamine H2-receptor antagonist, cimetidine, on gastric secretion and serum gastrin during insulin infusion in Man.

Cimetidine infusion (100 mg h-1) reduced the acid secretory response to insulin infusion (0.03 units Kg-1h-1) when compared to paired control tests in 6 healthy volunteers. There was no significant difference between cimetidine and control tests in terms of pepsin output or serum gastrin concentrations. Cimetidine also reduced the acid secretory response when administered after 90 minutes of insulin had established a secretory response in extended tests in 3 additional volunteers. Cimetidine may have therapeutic potential in the peptic ulcer diathesis.

Adult↗