Enzyme Inducers and Inhibitors

(See Chapters 8and 9)
Most of this book concerns the effects of drugs on the body
(pharmacodynamics). Conversely, what the body does to the drug (known
as pharmacokinetics, including absorption, metabolism and excretion) is
slightly less relevant in a practical guide to prescribing, as these processes
are reasonably stable and thus a drug’s effect is usually predictable.
Problems arise, however, when other substances (in this case concomitantly
administered drugs) unintentionally alter these complex systems resulting
in increased or decreased drug levels and hence altered effects. Thus, from
an early stage it is important to recognize that when you prescribe
particular drugs (which are also enzyme inhibitors or enzyme inducers)
they may affect seemingly unrelated drugs (Table 1.1).
T ABLE  1.1 Most common enzyme inhibitors and inducers
Inducers Inhibitors
↑ Enzyme Activity→ ↓ Drug
Concentration ↓ Enzyme Activity→ ↑ Drug Concentration
AODEVICES:
PC BRAS: Phenytoin, Carbamazepine, Allopurinol, Omeprazole, Disulfiram, Erythro
Barbiturates, Rifampicin, Alcohol (chronic mycin, Valproate, Isoniazid, Ciprofloxacin, Et
excess), Sulphonylureas hanol (acute intoxication), Sulphonamides

Most drugs are metabolized to inactive metabolites by the cytochrome P450

enzyme system in the liver, preventing them exerting infinite effects. The
activity of these enzymes, however, may in turn be altered by the presence
of other particular drugs, known as enzyme inducers and inhibitors. An
enzyme inducer will increase P450 enzyme activity, hastening metabolism
of other drugs with the result that they exert a reduced effect (and thus a
patient will require more of some other drugs in the presence of an enzyme
inducer). Conversely, an enzyme inhibitor will decrease P450 enzyme
activity and, subsequently, there will be increased levels of other drugs
(which in the hands of a diligent physician require a reduced drug dose).
The classic example of this is the effect of newly introduced enzyme
inhibitors on patients taking warfarin. In particular, the addition of
erythromycin (an enzyme inhibitor) can sometimes and unpredictably
cause a dangerous rise in international normalized ratio (INR) if the
warfarin dose is not decreased; you should be aware of this in patients
presenting with excessive anticoagulation (see Chapter 3).