Treatment of disopyramide overdosage.
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Biomedical subjects
Publications and source records attributed to R K Medd.
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A slow (1.18 mumol.kg-1.mm-1) intravenous infusion of disopyramide (mol.wt 339) was given to 8 adult Beagle dogs. An initial phase of slow decline in cardiac output and broadening of the QRS complex on the ECG, with systolic blood pressure maintained above 13.5 kPa (100 mmHg), was followed by a phase of rapid circulatory failure without a correspondingly dramatic change in ECG appearances. Underventilation and cardiac arrhythmias were observed only in the agonal phase after several minutes of circulatory arrest. They were not therefore the primary cause of death, which was due to failure of myocardial contractility. Three positively inotropic drugs (isoprenaline, dopamine, and glucagon) are shown to be capable of restoring the failing circulation, provided they are given before the phase of complete circulatory standstill. In this respect isoprenaline appears superior to dopamine and glucagon.
An increased incidence of gallstones has been reported following truncal vagotomy and gastric drainage but never conclusively proven. In the Rhesus monkey, bile composition and flow is similar to man. A model of biliary drainage was established which permits continuous monitoring of bile kinetics. Following truncal vagotomy and pyloroplasty, a significant fall in the bile acid concentration was observed, accompanied by a rise in cholesterol concentration. This resulted in an overall rise in cholesterol saturation. Similar changes in hepatic bile composition were, however, also seen following pyloroplasty alone, and suggests that the vagotomy itself may not be the important factor in producing bile changes.
When 0.5 mgs of physostigmine salicylate was injected intravenously into adult beagle dogs which had been severely poisoned with amitriptyline, a transient improvement in cardiac output, systolic blood pressure, intraventricular conduction and in the maximum rate of rise of arterial blood pressure (arterial dP/dT max.) was observed. These effects were maximal at 15-20 minutes after injection and had largely disappeared 30 to 35 minutes after the injection.
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Dogs were given large doses of barbiturates, glutethimide, ethanol, methaqualone, ethchlorvynol, meprobamate, chloral hydrate, paracetamol and aspirin. These were treated by haemoperfusion using a column packed with charcoal coated with an acrylic hydrogel. Clearances for most drugs were significantly higher than those reported for haemodialysis. Minimal clearances of common biochemical entities were observed and although leucocyte and platelet counts were diminished, no deleterious effects attributable to this were encountered. Careful histological examination of tissues derived from perfused dogs revealed no evidence of charcoal emboli.