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Alpha 1-blocking properties of carvedilol during acute and chronic administration
C Giannattasio1, B M Cattaneo, G Seravalle
1Medicina Interna, Centro di Fisiologia Clinica e Ipertensione, Università di Milano, Italy.
Insights
Carvedilol, a beta-blocker, demonstrates significant alpha 1-adrenergic blockade in hypertensive patients, contributing to its blood pressure-lowering effects. These vasodilating properties are maintained with prolonged use.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
Background:
- Carvedilol is recognized for its beta-adrenergic blocking activity and vasodilating properties.
- The vasodilating effect of carvedilol has been attributed to alpha 1-adrenergic blockade, but clinical evidence was lacking.
Purpose of the Study:
- To investigate and confirm the alpha 1-adrenergic blockade of carvedilol in a clinical setting.
- To compare the antihypertensive, beta-blocking, and alpha 1-adrenergic-blocking effects of carvedilol with prazosin.
Main Methods:
- A randomized, double-blind, crossover study involving eight patients with mild essential hypertension.
- Patients received either prazosin (2 mg) or carvedilol (25 mg) after a washout period.
- Intravenous infusions of phenylephrine and isoproterenol were administered before and after drug administration, and after 3 weeks of carvedilol treatment.
Main Results:
- Both carvedilol and prazosin lowered blood pressure similarly; carvedilol reduced heart rate, while prazosin did not.
- Carvedilol abolished the tachycardic response to isoproterenol and reduced the pressor response to phenylephrine.
- Prolonged carvedilol administration maintained its antihypertensive, beta-blocking, and alpha 1-adrenergic-blocking effects.
Conclusions:
- Carvedilol exhibits significant alpha 1-adrenergic blockade at clinically effective doses, contributing to its antihypertensive action.
- These alpha 1-blocking effects are sustained during prolonged administration.
- While effective, carvedilol's alpha 1-blocking effect is less pronounced than that of prazosin for comparable blood pressure reduction.
Abstract:
Carvedilol is a beta-adrenergic-blocking drug with vasodilating properties. This vasodilation has been ascribed to alpha 1-adrenergic blockade, but it has never been shown in the clinical setting. We addressed this issue by studying eight patients with mild essential hypertension who were given prazosin, 2 mg or carvedilol, 25 mg p.o. following a 2-week washout from previous treatment, according to a randomized double-blind, crossover experimental design. Before and 2 h after the administration of either prazosin or carvedilol, the patients were infused i.v. with increasing doses of phenylephrine (0.2-1.2 microgram/kg/min) and isoproterenol (0.01-0.05 microgram/kg/min). The patients were thereafter maintained on carvedilol 25 mg daily for 3 weeks, and the i.v. phenylephrine and isoproterenol infusions were repeated 2 h after the last tablet administration. The results showed that the single dose of carvedilol and prazosin lowered blood pressure (beat-to-beat finger pressure measurement) to a similar extent, but that heart rate was unaffected by prazosin and reduced by carvedilol. The tachycardic response to isoproterenol was abolished by carvedilol and unaffected by prazosin, whereas the pressor response to phenylephrine was reduced by carvedilol and virtually abolished by prazosin. The antihypertensive, beta-blocking and alpha 1-adrenergic-blocking effects of carvedilol were unchanged following prolonged administration of the drug. Thus, at a clinically effective dose, carvedilol not only has beta- but also sizeable alpha 1-blocking effects. These effects are preserved during prolonged administration of the drug. For a comparable antihypertensive action, however, the alpha 1-blocking effect is less pronounced than that of an alpha 1-blocker such as prazosin.