A woman is taking oral contraceptives (OCs). Which of the following drugs is unlikely to reduce the effectiveness of the OCs
MICROSOMAL ENZYME INDUCTION Many drugs and carcinogens interact with DNA and increase the synthesis of microsomal enzyme protein, especially cytochrome P-450 and UGTs As a result rate of metabolism of inducing drug itself and/or other drugs is increased. Different inducers are relatively selective for ceain cytochrome P-450 isoenzyme families, e.g.: * Anticonvulsants (phenobarbitone, phenytoin, carbamazepine), rifampin, glucocoicoids induce CYP3A isoenzymes. * Phenobarbitone also induces CYP2B1 and rifampin also induces CYP2D6. * Isoniazid and chronic alcohol consumption induce CYP2E1. * Polycyclic hydrocarbons like 3-methylcholanthrene and benzopyrene found in cigarette smoke, charcoalbroiled meat, omeprazole and industrial pollutants induce CYP1A isoenzymes. * Other impoant enzyme inducers are: phenylbutazone, griseofulvin, DDT. Consequences of microsomal enzyme induction 1. Decreased intensity and/or duration of action of drugs that are inactivated by metabolism, e.g. failure of contraception with oral contraceptives. 2. Increased intensity of action of drugs that are activated by metabolism. Acute paracetamol toxi-city is due to one of its metabolites--toxicity occurs at lower doses in patients receiving enzyme inducers. 3. Tolerance--if the drug induces its own metabolism (autoinduction), e.g. carbamazepine, rifampin. 4. Some endogenous substrates (steroids, bili rubin) are also metabolized faster. 5. Precipitation of acute intermittent porphyria: enzyme induction increases porphyrin synthesisby derepressing d-aminolevulenic acid synthetase. 6. Intermittent use of an inducer may interfere with adjustment of dose of another drug prescribed on regular basis, e.g. oral anticoagulants, oral hypoglycaemics, antiepileptics, antihypeensives. Ref:- kd tripathi; pg num:-26,27
Ketoconazole
Phenytoin
Phenobarbital
Carbamazepine
General pharmacology