Enzyme inhibitors coadministration with drugs

Ketoconazole is a potent inhibitor of the cytochrome P450 3A4 enzyme system. Coadministration of ketoconazole with other drugs metabolized by the same enzyme system may result in increased plasma concentrations of the drugs that could increase or prolong both therapeutic and adverse effects. Unless otherwise specified, dosage adjustment may be necessary. 

The pharmacological inhibition of the serotonin eliminating enzyme MAO is used in the therapy of depression and hypertension. Tranylcypromine is an irreversible unselective MAO inhibitor which displays numerous interactions with amine-containing food and monoamine-related drugs, resulting in evenmally fatal hypertensive crisis, cranial hemorrhage, arrhythmias and seizure can occur. The coadministration with speciflc serotonin reuptake inhibitors (SSRI) can result in similar effects and is therefore contraindicated. Moclobemide, on the other hand, is a reversible inhibitor of MAOa, one of the two enzyme subtyppes (MAOa, MAOb) which is void of most interactions see with tranylcypromine. 

Drug Interactions Xanthine oxidase, a key enzyme in the catabolism of azathioprine metabolites, is blocked by aUopurinol. If azathioprine and allopurinol are used concurrently, the azathioprine dose must be decreased to 25-33% of the usual dose it is best not to use these two drugs together. Adverse effects resulting from coadministration of azathioprine with other myelosuppres-sive agents or angiotensin-converting enzyme inhibitors include leukopenia, thrombocytopenia, and anemia as a result of myelosuppression. 

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