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By O. L. Wade and Linda Beeley (Auth.)
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Additional resources for Adverse Reactions to Drugs
This is associated with an increase in microsomal enzyme protein and is called "enzyme induction". 7). Whether or not induction occurs depends not only on the nature of the drug but also on the dose used and the duration of treatment. 7 DRUGS WHICH PRODUCE SIGNIFICANT ENZYME INDUCTION IN MAN Barbiturates Glutethimide Phenazone (as in dichloralphenazone) Phenytoin Carbamazepine Alcohol (chronic, heavy drinking) Griseofulvin Rifampicin Phenylbutazone 51 daily dose of less than several hundred milligrams do not produce significant induction and this is probably the reason why many drugs which are enzyme inducers in animals have little effect in man.
Many drugs will displace each other from protein-binding in vitro but displacement will only be important in vivo if the following criteria are fulfilled: (1) The displaced drug is highly protein bound. If a drug is more than 90 per cent, bound to protein, displacement of only a small amount will have a significant effect on the free concentration whereas if more than 50 per cent, is already free, a small increase will have little effect. (2) The binding sites are easily saturated at normal therapeutic blood levels of the two drugs.
If the dose selected is too large toxicity may only become apparent after the patient has left hospital. One of the arguments for giving a loading dose is that toxicity will occur earlier and the correct maintenance dose can be established sooner. In patients with impaired renal function cumulative toxicity may occur with any drug eliminated mainly by renal excretion if normal doses are given. This ADVERSE REACTIONS TO DRUGS 26 is discussed later. Cumulative overdose may also occur if a drug is concentrated in particular tissues.
Adverse Reactions to Drugs by O. L. Wade and Linda Beeley (Auth.)