02.03.2.1 Induction

When there is induction of an enzyme, there is an increased rate of metabolism of drugs by that enzyme, and this leads to a decreased plasma concentration of drug, so that it may become ineffective. Lowering the concentration of a therapeutic drug may lead to it becoming ineffective. For instance, hyperforin (a component of St John’s Wort), an over-the-counter medicine for depression, induces CYP3A4. Use of St John’s Wort can lead to the failure of oral contraceptives, which are metabolised by CYP3A4. To avoid adverse effects, low doses of oral contraceptives are used to prevent conception. When the metabolism of oral contraceptives is increased by St John’s Wort, the levels of the oral contraceptives may fall below those needed for contraception, resulting in pregnancy.

Cigarette smoke and charboiled meats induce CYP1A, which is involved in the metabolism of paracetamol. Thus, smokers will have lower plasma levels of paracetamol for the same dose as non-smokers. Lowering the levels of paracetamol will lower the pain relief.

An example of autoinduction is alcohol, where chronic alcohol consumption induces the enzyme CYP2E1, which is involved in its metabolism. This partly explains the tolerance to alcohol that develops with repeated administration, whereby the same dose of alcohol makes a alcohol-naïve person drunk, with little apparent effect on an alcoholic person, who has induced CYP2E1, and greater metabolism of alcohol.