Download e-book for kindle: Adverse Reactions to Drugs by O. L. Wade and Linda Beeley (Auth.)

By O. L. Wade and Linda Beeley (Auth.)

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4) Some interactions only occur in a small minority of patients at risk, for reasons which are unknown. Thus DRUG INTERACTIONS 58 ADVERSE REACTIONS TO DRUGS one patient on a monoamine oxidase inhibitor may eat cheese with impunity but another will have a fatal cerebral haemorrhage. Regardless of the frequency with which a particular interaction occurs, its clinical importance depends ultimately on the consequences. Interactions which alter the available concentration of a drug will matter most for drugs with a steep dose/response curve whose dose has to be adjusted within narrow limits to achieve the optimal therapeutic effect.

Drugs are absorbed mainly from the upper small intestine and the rate of gastric emptying would be expected to affect the rate of absorption. Food is known to delay the absorption of many drugs— probably by delaying gastric emptying—and drugs which affect gastric motility may influence the absorption of other drugs. Propantheline delays gastric emptying and has been shown to reduce the rate of absorption of paracetamol whereas metoclopramide which increases the rate 44 ADVERSE REACTIONS TO DRUGS of gastric emptying increases the rate of absorption of paracetamol (Nimmo, Heading, Tothill and Prescott, 1973).

Less commonly differences in the rate of metabolism of a drug have a bimodal distribution indicating control by a single gene. Isoniazid is inactivated by acetylation and the 34 ADVERSE REACTIONS TO DRUGS 24 22-j 20-1 8 18 3ΓΙ6-Ι |l4 I 10, mi I* 4-1 2H 0 X 3. 4 5 6 7 W ? P 8 9 r1 i 10 Π · ΙΖη Fig. 4. ) 6h. following oral administration of 9-7 mg. per kg. of body weight in 267 family members of 53 families (Clarke, Evans, Harris and McConnell, 1968). blood levels six hours after giving a standard dose to a group of individuals are bimodally distributed (Fig.

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