Carvedilol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy.
Carvedilol is a beta-adrenoceptor antagonist which also causes peripheral vasodilation primarily via alpha 1-adrenergic blockade. Carvedilol produces its antihypertensive effect partly by reducing total peripheral resistance by blocking alpha 1-adrenoceptors and by preventing beta-adrenoceptor-mediated compensatory mechanisms. This combined action avoids many of the unwanted effects associated with traditional beta-blocker or vasodilator therapy. In clinical trials published to date, most of which enrolled small numbers of patients, the antihypertensive efficacy of carvedilol administered once daily was similar to that of atenolol, labetalol, pindolol, propranolol, metoprolol, nitrendipine (in elderly patients), slow release nifedipine or captopril in patients with mild-to-moderate essential hypertension. Combined therapy with carvedilol 25 mg and hydrochlorothiazide 25 mg, nicardipine 60 mg or slow release nifedipine 20 mg has an additive antihypertensive effect. Carvedilol and atenolol at similar doses were equally effective at reducing blood pressure in patients who had previously not responded adequately to hydrochlorothiazide monotherapy. As a result of its multiple mechanisms of action, carvedilol is suited for the management of specific groups of hypertensive patients, such as those with renal impairment. In patients with non-insulin-dependent or insulin-dependent diabetes mellitus carvedilol does not appear to affect glucose tolerance or carbohydrate metabolism. Initial studies have demonstrated that carvedilol and slow release nifedipine have similar efficacy in patients with stable angina pectoris and there is evidence that carvedilol has a beneficial haemodynamic effect in patients with congestive heart failure (NYHA class II or III) secondary to ischaemic heart disease. A postmarketing surveillance study has shown that carvedilol is generally well tolerated with only 7% (164/2226) of patients (83% of the total number received 25mg daily for 12 weeks) withdrawing from treatment because of adverse events. Vertigo, headache, bronchospasm, fatigue and skin reactions were the most common events causing withdrawal. Thus, clinical experience to date suggests that carvedilol is likely to be a valuable addition to the options currently available for treating patients with mild-to-moderate essential hypertension, and may offer particular benefit in specific populations of hypertensive patients.
McTavish
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Adis International Limited, Auckland, New Zealand.
Campoli-Richards
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Sorkin
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D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000787:Angina Pectoris / Q000188:drug therapy; D000818:Animals; D002227:Carbazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D000077261:Carvedilol; D006333:Heart Failure / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D011412:Propanolamines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol