Dihydropyridines from the first to the fourth generation: Better efficacy and safety

Dihydropyridines are among the most widely used drugs for the management of cardiovascular disease. Introduced in the 1960s, dihydropyridines have undergone several changes to optimise their efficacy and safety. Four generations of dihydropyridines are now available. The first-generation (nicardipine) agents have proven efficacy against hypertension. However, because of their short duration and rapid onset of vasodilator action, these drugs were more likely to be associated with adverse effects. The pharmaceutical industry responded to this problem by designing slow-release preparations of the short-acting drugs. These new preparations (second generation) allowed better control of the therapeutic effect and a reduction in some adverse effects. Pharmacodynamic innovation with regard to the dihydropyridines began with the third-generation agents (amlodipine, nitrendipine). These drugs exhibit more stable pharmacokinetics, are less cardioselective and, consequently, well tolerated in patients with heart failure. Highly lipophilic dihydropyridines are now available (lercanidipine, lacidipine). These fourth-generation agents provide a real degree of therapeutic comfort in terms of stable activity, a reduction in adverse effects and a broad therapeutic spectrum, especially in myocardial ischaemia and potentially in congestive heart failure.