n CME : Your SA Journal of CPD - Drug interactions with the calcium-channel blockers : clinical pharmacology




Drug interactions are classified according to the underlying mechanisms: pharmacokinetic (affecting absorption, distribution, metabolism and excretion) and pharmacodynamic (shared drug effects, either beneficial or toxic). <BR>The elderly are particularly susceptible to drug interactions as they often are prescribed multiple drugs and have reduced hepatic and renal function. <BR>All CCBs are metabolised by the cytochrome P450 system (specifically the common drug-metabolising isoenzyme CYP3A), and their levels may be reduced or increased by co-administration with cytochrome P450 enzyme inducers or inhibitors respectively. <BR>In addition, verapamil and diltiazem (but not the other CCBs) are inhibitors of the CYP3A isoenzyme as well as the key drug transporter, p glycoprotein, resulting in increased levels of drugs that are substrates of either system. <BR>The most important pharmacodynamic interactions occur with drugs that share the negative inotropism and chronotropism of verapamil and diltiazem, notably the ß-blockers.


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