[Clinical pharmacology of calcium antagonists]

The most frequently used calcium antagonists verapamil, diltiazem and nifedipine have common pharmacokinetic properties. Renal excretion of the drugs is minimal because of their lipophilicity, and the drugs are mainly metabolized by the liver. The rate of elimination depends not only on hepatic function but also on hepatic blood flow. Following oral administration only a fraction of the dose reaches the systemic circulation because of extensive first-pass metabolism. Elderly patients, patients with liver disease and patients in cardiac failure accompanied by decreased hepatic blood flow may experience untoward side effects that usually can be predicted by the known pharmacologic properties of the drugs, such as excessive vasodilatation following nifedipine and bradycardia and av-block following verapamil. Clinically important interactions with other drugs may result from inhibition of the metabolism of certain drugs (carbamazepine, cyclosporine, quinidine) by verapamil and/or diltiazem, inhibition of renal excretion (digoxin) by verapamil and diltiazem, and synergistic effects of beta blockers and verapamil.