Biomedical subjects
Publications and source records attributed to W S Nimmo.
The effect of ketamine analgesia on gastric emptying was assessed in five healthy volunteers. Gastric emptying, estimated indirectly by the absorption of orally administered paracetamol, was not significantly delayed following administration of i.m. ketamine when compared with placebo.
The pharmacokinetics and analgesic effects of i.m. and oral ketamine in a dose of 0.5 mg kg-1 were determined in six healthy volunteers. Analgesia was measured by the submaximal effort tourniquet test. Following both routes of administration, ketamine prolonged the period of pain-free ischaemic exercise. Pain thresholds were increased at 15 min and 30 min after i.m. injection and at 30 min after oral ketamine. The plasma ketamine concentration associated with analgesia was 150 ng ml-1 following the i.m. dose, but only 40 ng ml-1 after the oral dose. Oral administration was, however, associated with much greater concentrations of the metabolite norketamine, which may have contributed to the analgesic effect.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Temazepam 20 mg orally was compared with titrated doses of i.v. diazepam as sedation for elective upper gastro-intestinal endoscopy. The mean time from taking oral temazepam to endoscopy was 66 min, and from i.v. diazepam to endoscopy was 10 min. The endoscopists found that the sedation achieved was the same in both groups and allowed adequate examination of the upper alimentary tract. The oral presentation, avoiding the pain of injection and the possible shorter duration of action, made oral temazepam preferable to i.v. diazepam.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Eight healthy male volunteers ingested an aqueous solution containing acetaminophen (20 mg/kg) and a nonabsorbable isotopic marker. The concentrations of unconjugated acetaminophen in samples of blood plasma taken at frequent intervals were measured by gas-liquid chromatography. The data points followed a smooth curve in most cases and were fitted to the classical two-compartment pharmacokinetic model to obtain KA, the apparent first-order rate constant for absorption from the gastrointestinal tract. Gastric emptying was measured simultaneously from serial scintiscans of the subject's abdomen. The subjects were also studied after intramuscular injection of meperidine (150 mg) and pentazocine (60 mg) with and without naloxone (1.2 mg). The acetaminophen absorption curves and gastric emptying patterns were consistent with negligible absorption from the stomach. A new model is proposed in which the conventional single compartment used to represent the gastrointestinal tract is replaced by two compartments: one represents the stomach and the other the small intestine, from which absorption occurs rapidly. Pharmacokinetic analysis using this model showed good agreement in all cases, and provided an estimate of KA, the first-order rate constant for drug transfer from the intestinal lumen into the systemic circulation. The mean half-time for transfer was 6.8 +/- 0.9 min. As expected, KA was greater than KG (the first-order rate constant for gastric emptying), showing that gastric emptying was rate-limiting in the absorption of acetaminophen. The value of KA was greater than KA and the two were not related. The value of KA was not equal to KG in most studies because gastric emptying was not a single exponential process.
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.
Using the rate of absorption of paracetamol following oral administration of the drug, gastric emptying was measured in 21 patients following hysterectomy. Gastric emptying was inhibited markedly in patients receiving narcotic analgesia after operation, but only a moderate delay was observed in patients undergoing extradural analgesia.
Explore the source record for details and available documents.
The author describes how the rate of paracetamol absorption may be used as an indirect measure of gastric emptying rate in clinical situations such as during labour or post-partum, when direct measurement would be impracticable.
Drugs are usually given orally. They are not absorbed to any extent from the stomach but may be absorbed very rapidly from the small intestine. Thus factors influencing the rate of gastric emptying may alter the rate of absorption of most if not all orally administered drugs. Food, hormones, posture, peritoneal irritation, severe pain, gastric ulcer, diabetes and other metabolic diseases, as well as drugs such as alcohol, anticholinergics, narcotic analgesics, ganglion blocking drugs, antacids and metoclopramide all influence the rate of gastric emptying and they will, in turn, change the rate of absorption of another drug. In most instances, increasing the rate of gastric emptying and gastro-intestinal motility increases the rate of absorption of a drug but, for digoxin and riboflavin, increased gastrointestinal motility is associated with a decrease in the rate of absorption. Delayed drug absorption due to altered gastric emptying usually results in therapeutic failure, especially if the drug has a short biological half-life. At present it is not possible to predict accurately the magnitude and clinical relevance of all drug absorption interactions.
The rate of gastric emptying in women during labour was estimated indirectly from the kinetics of absorption of orally administered paracetamol (acetaminophen). Gastric emptying was normal in patients who had not received a narcotic analgesic but was markedly delayed in women given pethidine, diamorphine, or pentazocine. The inhibitory effect of diamorphine and pethidine on gastric emptying was not reversed by metoclopramide.
The effect of intramuscular pethidine or diamorphine on gastric emptying and the absorption of orally administered paracetamol was assessed in eight normal subjects. 2 Both drugs produced a significant and striking delay in gastric emptying and absorption of paracetamol. 3 It seems inevitable that pethidine and diamorphine will retard the absorption of other orally administered drugs.
Explore the source record for details and available documents.