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Biomedical subjects

I H Stevenson

Publications and source records attributed to I H Stevenson.

At least 73 records · Page 4Linked to original sources
PubMed1972

Changes in human drug metabolism after long-term exposure to hypnotics.

The influence of the newer, non-barbiturate hypnotics Mandrax (diphenhydramine-methaqualone) and nitrazepam on drug-metabolizing capacity was assessed and compared with the effect of amylobarbitone, a known inducer of drug-metabolizing enzymes. Plasma antipyrine and phenylbutazone half-lives and urinary output of 6beta-hydroxycortisol were used as indices. Volunteer subjects were exposed to therapeutic amounts of these agents and, in the case of Mandrax and barbiturates, further studies were carried out in dependent patients.Mandrax but not nitrazepam increased the rate of drug metabolism, presumably by enzyme induction. The degree of induction was comparable with that produced by hypnotic doses of amylobarbitone. The Mandrax-dependent and barbiturate-dependent patients were the fastest metabolizers studied. It is concluded that drug interactions resulting from interference with drug metabolism are as likely to occur with Mandrax as with barbiturates. On the other hand, it is unlikely that such drug interactions would occur with nitrazepam.

Adolescent↗
PubMed1972

Drug-metabolizing capacity in states of drug dependence and withdrawal.

1. Drug-metabolizing capacity was assessed in 8 barbiturate-dependent and in 3 Mandrax-dependent patients using, as indices, plasma antipyrine half-life and in some cases urinary output of 6beta-hydroxycortisol. For comparison, antipyrine half-life was also measured in volunteers before and after a period of taking hypnotic doses of these agents.2. Both indices indicated a very high drug-metabolizing capacity in the dependent subjects on admission, the antipyrine half-life value in the barbiturate patients being the shortest reported to date for any drug-exposed group. The urinary output of 6beta-hydroxycortisol was approximately three times that in a control population.3. This induction of drug-metabolizing capacity presumably contributed to the marked drug tolerance observed in the dependent patients.4. It appeared that drug-metabolizing capacity eventually returned to normal levels after withdrawal of the barbiturate.5. It is concluded that the abnormal drug-metabolizing capacity of dependent patients must be taken into account in assessing dose requirements for other drugs.

Adult↗
PubMed1972

Drug metabolism.

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Adult↗
PubMed1971

Effect of age and sex on human drug metabolism.

The capacity of inpatients in a geriatric hospital to metabolize drugs was measured. The mean plasma half-life values with antipyrine and with phenylbutazone were found to be 45% and 29% greater respectively in patients than in young controls. When women alone were considered the half-life of antipyrine was 78% longer in the elderly group. In a number of elderly individuals the rate of metabolism of these two drugs was found to be extremely slow. This decreased ability to metabolize drugs may contribute to the known high incidence of adverse drug reactions in the elderly.Within the control group a significant sex difference in the rate of antipyrine metabolism was found, the mean half-life being 30% longer in the males. It is clear from these results that the age and sex of subjects must be taken into account in studies of human drug metabolism.

Adolescent↗
PubMed1970

The sensitivity of the brain to barbiturate during chronic administration and withdrawal of barbitone sodium in the rat.

1. The sensitivity of the central nervous system to barbiturate was determined in rats during the chronic administration of barbitone sodium and after its withdrawal.2. The brain barbiturate concentration determined on awakening from a hypnotic dose administered intraperitoneally was found to increase throughout the period of barbitone administration.3. A similar gradual development of central nervous system tolerance was indicated by measuring the duration of anaesthesia following an intraventricular injection of pentobarbitone.4. The change in sensitivity of the brain which occurred during the period of barbitone administration was not demonstrable from the measurement of sleeping time following intraperitoneal injection of barbitone or pentobarbitone.5. After withdrawal, the sensitivity of the brain to barbiturate gradually returned to normal.6. It was concluded that the hypersensitivity to pentobarbitone, but not to barbitone, which develops after withdrawal of barbitone sodium is due to a decreased drug-metabolizing capacity.

Animals↗