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Biomedical subjects

I H Stevenson

Publications and source records attributed to I H Stevenson.

At least 55 records · Page 3Linked to original sources
PubMed1977

Determinants of anticoagulant control in patients receiving warfarin.

1 A hospital-based drug information system has been used to assess the time for which patients treated with warfarin were outside the range of Thrombotest values 5-10% and 5-15% and to examine possible contributory factors in situations where anticoagulation fell outside these ranges. 2 Anticoagulant control varied with the age of the patient and with concomitant drug therapy but not with patient sex or indication of anticoagulation. 3 Most patients were 'under-anticoagulated' at some stage but patients over 70 years spent significantly longer in the 5-10% range than those in the age range 30-59 years and Thrombotest values of less than 5% were found predominantly in the older group. 4 Patients given drugs known to interact with warfarin spent least time in the defined Thrombotest ranges. Those on drugs known to potentiate warfarin effect had significantly lower Thrombotest values than the other patients studied.

Adult↗
PubMed1977

Age as a determinant of sensitivity to warfarin.

1 Parallel human and rat studies were carried out to confirm the previous suggestion of an increased sensitivity to warfarin in old age. 2 The anticoagulant response to warfarin was found to be greater in the elderly groups despite, in the case of the patient study, the elderly subjects being given a smaller weight-related dose. 3 At the same plasma warfarin concentrations there was greater inhibition of vitamin K-dependent clotting factor synthesis in the elderly. There was no difference in the rate of clotting factor degradation in the two age groups. 4 There was no appreciable difference in warfarin pharmacokinetics (plasma half-life, apparent volume of distribution, plasma clearance, plasma protein binding or plasma warfarin alcohol levels) in the two age groups. 5 There appeared to be no major age-related differences in warfarin pharmacokinetics and the increased effect of warfarin in the elderly seemed to result from an increased intrinsic sensitivity to warfarin.

Adult↗
PubMed1976

Pharmacokinetics in the elderly.

The elderly are generally considered to be different from young people in terms of drug response and this applies particularly to quantitative differences. While altered drug handling is a major potential source of difference in responsiveness to drugs, the relative contribution of pharmacokinetics and pharmacodynamics to this difference is not clear. In the present review we have examined the available data on pharmacokinetics in the elderly. In the past, data pertaining to animal models have been extrapolated to man and in the absence of human experimentation these assumptions have tended to hold sway. This is best exemplified by studies on drug absorption. The absorption of actively transported substance may in fact be diminished in the elderly. However, most drugs are absorbed by passive diffusion and the recently available evidence in man indicates that there is no age-dependent change. While definitive data on the effect of old age on drug metabolising ability in animals is available, no direct assessments have been made in man. Many of the studies carried out using drug plasma half-life and clearance assessments are complicated by changes in distribution. This is best illustrated by a definitive study with diazepam, in which marked prolongation of plasma half-life was accompained by an increase in apparent volume of distribution in the elderly. This latter change influences plasma drug clearance and, possibly, drug concentration at its site of action. Thus, the implications for drug effect of such changes in volume of distribution remain to be clarified. In theory, the rate of elimination of antipyrine should provide a good index of drug metabolising ability. Both plasma half-life and clearance values suggest a decreased in metabolism in the elderly. No other drug has been studied as intensively and the evidence for a diminished metabolism of other drug in the elderly is less definite. Thus, while it is likely that the metabolism of some drugs is imparied in old age, it is not possible at this time to generalise with regard to the effect of age on drug metabolising ability in man. It is also difficult to generalise about age-related changes in plasma protein binding of drugs. With some drugs, binding to plasma protein does not appear to be altered and for two drugs-warfarin and phenytoin, the findings of different investigators conflict. Diminution of glomerular filtration rate, renal plasma flow and associated tubular function with age have been well documented. Drug clearance comparisons between old and young have been carried out for only three renally excreted drugs-digoxin, propicillin and sulphamethizole. With digoxine and sulphamethizole, the evidence is that renal excretion is diminished in the elderly. With propicillin, changes in volume of distribution predominate, resulting in higher plasma levels in the elderly but similar percent recovery in urine...

Aged↗
PubMed1976

Influence of diabetes mellitus on drug metabolism in man.

Drug metabolizing capacity was assessed in 29 normal subjects and in 28 diabetics on various treatment regimes using the rate of antipyrine elimination as reflux. Plasma half-life of antipyrine was markedly shorter (38%), and the plasma clearance of this drug greater (40%) in diabetics receiving insulin than in controls. There was also an indication of a small increase in rate of test drug elimination in diabetics taking chlorpropamide. Patients being controlled solely on diet or those on tolbutamide did not exhibit an altered rate of drug elimination. The rate of metabolism and inactivation of other drugs may be altered in diabetics taking insulin so that optimal doses of some comcomitantly administered drugs may be different in this group of patients.

Antipyrine↗
PubMed1975

The effect of fenfluramine on disposition and rate of antipyrine elimination.

The effect of fenfluramine, administered orally in a daily dose of 1 mg/kg for 40 days, on the disposition and rate of elimination of antipyrine was studied in 15 obese patients. Although the plasma half-life of antipyrine was unchanged, the apparent volume of distribution (1/kg) fell by 11.6% (p less than 0.001) and the plasma metabolic clearance rate (1/kg/h) of antipyrine was reduced by 14.1% (p less than 0.01). No correlation occurred between change in clearance, on the one hand, and change in patient weight or apparent volume of distribution of antipyrine, on the other. In vitro drug-metabolizing enzyme activity in the rat was measured using rate of aminopyrine and hexobarbital metabolism as indices. Fenfluramine inhibited the metabolism of both substrates. It is concluded that fenfluramine can diminish the rate of elimination of drugs which are extensively metabolized by reduction of microsomal enzyme activity. Also, drug clearance may be diminished by reduction of apparent volume of distribution.

Adolescent↗
PubMed1974

Abnormal drug metabolism after barbiturate and paracetamol overdose.

Drug-metabolizing capacity has been assessed by serial measurements of the plasma antipyrine half life in 11 patients with severe barbiturate intoxication and in 17 patients with acute hepatic necrosis due to paracetamol overdosage. Drug metabolism was strikingly enhanced after barbiturate over-dosage, and this effect was still present six weeks later. In contrast the antipyrine half life was greatly prolonged in patients with paracetamol-induced acute hepatic necrosis but returned to normal or near-normal values within seven to 21 days.

Acetaminophen↗
PubMed1974

A study of the factors affecting the sleeping time following intracerebroventricular administration of pentobarbitone sodium: effect of prior administration of centrally active drugs.

1 Injection of pentobarbitone sodium into a lateral cerebral ventricle of rats produced a loss of righting reflex. The duration of anaesthesia was dose-dependent.2 The optimum dose of pentobarbitone to allow study of the factors affecting the sleeping time was considered to be 650 mug injected in 25 mul water.3 In a study of the effect of age and sex on the sleeping time, the youngest rats used (88 g body weight) were found to be the most sensitive to barbiturate. Female rats were more sensitive than male animals.4 The duration of anaesthesia was not affected by induction or inhibition of hepatic drug-metabolizing enzyme activity.5 Prior administration (acute) of central nervous system depressant drugs shortened the latent period and prolonged the duration of sleep. Prior administration of stimulant drugs antagonized the effect of pentobarbitone.6 Animals withdrawn following chronic administration of a number of drugs, barbitone, barbitone/bemegride mixture, Mandrax (methaqualone: diphenhydramine; 10: 1), chlordiazepoxide, nitrazepam, chlorpromazine or ethanol, exhibited a significant tolerance to intracerebroventricularly administered pentobarbitone.7 Withdrawal of amphetamine, morphine, methyprylon or diazepam did not result in tolerance to intracerebroventricularly administered pentobarbitone.8 Chronic administration of all drugs except amphetamine and morphine induced a tolerance to intraperitoneally administered hexobarbitone (100 mg/kg).9 The usefulness of sleeping time determination following intracerebroventricular administration of pentobarbitone as an assessment of central nervous system excitability is discussed. It is concluded that this method gives a valid indication of the sensitivity of the central nervous system to barbiturate and of the level of excitability in general. The method is particularly applicable in situations where the activity of hepatic drug-metabolizing enzyme activity may be altered.

Aging↗