Corresponding to differences in binding, tissue selectivity, and hemodynamics, the adverse effect profiles of the three types of calcium channel blockers also differ. Diltiazem is considered to be the best tolerated of the original calcium channel blockers.^15-17 With diltiazem, vasodilator-type side effects (headache, flushing, and hypotension) are less common than with nifedipine and the risk of AV conduction disturbances and heart block is lower than with verapamil.

The most frequently reported adverse effect of verapamil is constipation, which is probably due to this drug's high affinity for gastrointestinal smooth muscle.¹⁵ Hypotension, headaches, and peripheral edema have also been reported with verapamil, although to a lesser extent than with nifedipine. Verapamil's negative inotropic activity may cause or worsen heart failure in a small percentage of patients, and its dampening effect on AV node conduction may cause second- or third-degree heart block in some patients.¹⁶

As a group, the dihydropyridines are associated with the highest incidence of side effects among the calcium channel blockers, largely because of their powerful vasodilatory action.^18,19 Studies with nifedipine show these vasodilatory effects to be more common with short-acting preparations and less common with sustained-release preparations. Newer dihydropyridines, such as isradipine, felodipine, and amlodipine, also tend to be better tolerated than the conventional formulation of nifedipine.¹⁸ Any of the calcium channel blockers may also occasionally cause skin rash or gingival hyperplasia.

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