Drug interactions
Drug metabolism can be enhanced or reduced in the presence of other drugs or environmental factors, such as alcohol, tobacco and food. This is a cause of some important drug interactions.
Enhancement of drug metabolism involves stimulation of microsomal enzyme activity by induction of enzyme synthesis. The inducing agent interacts with nuclear receptors in the cell to increase transcription of messenger RNA, which results in increased synthesis of enzyme. Examples of enzyme inducers are shown in Table 4.
Enzyme induction has three important outcomes:
Enzyme inhibition, often caused by the co-administration of other drugs as competing substrates, can lead to a reduction of drug metabolism. Examples of enzyme inhibitors are shown in Table 4.
Whereas enzyme induction occurs over a few days, and takes several days, if not weeks, to wear off, enzyme inhibition occurs immediately and ceases as soon as the inhibiting agent has been eliminated. Because enzyme inhibition occurs so much faster than enzyme induction, it causes the most dangerous drug interactions.
Table 4 Examples of drugs that induce or inhibit CYP enzymes. Note the potential for interactions to affect the metabolism of drugs that depend on a stable plasma concentration over a prolonged period for their efficacy and/or safety (e.g. warfarin, oestrogen-containing contraceptives). Note also the capacity for some drugs (e.g. carbamazepine, ethanol) to induce their own metabolism.
