SN2 SHORT NOTE 5M ★ High-yield

Define enzyme induction and inhibition. Compare them and describe their clinical consequences.

Pharmacology · 2nd Professional — Para-Clinical

Term	Definition
Enzyme induction	An increase in the synthesis or activity of drug-metabolising enzymes, usually microsomal CYP450, caused by a drug or other chemical
Enzyme inhibition	A decrease in the activity of drug-metabolising enzymes, usually by competition for the same enzyme

Feature	Induction	Inhibition
Mechanism	Increased enzyme protein synthesis (and reduced degradation)	Usually competitive binding to the same enzyme
Onset	Slow — several days to 2–3 weeks; requires transcription and translation	Rapid — hours to a few days
Offset after stopping	Slow — 1 to 3 weeks	Rapid
Plasma level of the affected drug	Falls	Rises
Usual clinical result	Loss of efficacy — therapeutic failure	Toxicity
With a prodrug	Reversed — more active drug is formed, so toxicity	Reversed — less active drug is formed, so failure

Inducers	Inhibitors
Rifampicin — the most powerful in common use	Azole antifungals — ketoconazole, itraconazole, fluconazole
Phenytoin, carbamazepine, phenobarbitone	Macrolides — erythromycin, clarithromycin (but not azithromycin)
Griseofulvin	Cimetidine (but not ranitidine)
Chronic alcohol	Ciprofloxacin, isoniazid, metronidazole
Tobacco smoke (polycyclic hydrocarbons; CYP1A2)	Sodium valproate, allopurinol, amiodarone, ritonavir
St John wort; rifabutin; nevirapine	Grapefruit juice; acute alcohol; omeprazole

CLINICAL PEARL

Alcohol induces and inhibits, depending on when you look.
acute intake inhibits metabolism by competing for the same enzymes — which is why a single binge with paracetamol or warfarin is dangerous.
chronic intake induces them, so a chronic alcoholic needs more of some drugs and is more vulnerable to paracetamol’s toxic metabolite. Same substance, opposite effects.

Rifampicin causes failure of oral contraceptives, warfarin, corticosteroids, oral hypoglycaemics, ciclosporin, digoxin and antiretrovirals. Alternative contraception must be advised — a matter of real importance in India, where tuberculosis treatment is so common
Enzyme inhibitors raise warfarin levels and cause bleeding — metronidazole, ciprofloxacin, azoles, amiodarone; the INR must be checked
Erythromycin or an azole with a statin raises statin levels and precipitates myopathy and rhabdomyolysis
Valproate inhibits lamotrigine metabolism, raising the risk of severe rash, so the lamotrigine dose is halved
Autoinduction — carbamazepine and rifampicin induce their own metabolism, so plasma levels fall after 2 to 3 weeks and the dose may need increasing
Phenobarbitone induction is used therapeutically in Crigler–Najjar type II and neonatal jaundice, to increase glucuronidation of bilirubin

Anticipate the interaction rather than react to it — when starting or stopping rifampicin, an azole or a macrolide, review every other drug the patient is taking
The danger comes at both ends — stopping an inducer causes levels to rise over the following weeks, and stopping an inhibitor causes them to fall; both need monitoring
Monitor INR, drug levels or clinical effect after any such change, rather than assuming the dose remains correct
Warn patients about grapefruit juice and St John wort, which they will not think of as drugs and will not report unless asked
Smokers need higher doses of theophylline and some antipsychotics; levels rise when they stop smoking, which is easily missed in a hospitalised patient

All questions in General Pharmacology: Pharmacokinetics