Carvedilol: A novel cardiovascular drug with multiple actions

R. R. Ruffolo, D. A. Boyle, D. P. Brooks, G. Z. Feuerstein, R. P. Venuti, M. A. Lukas, George Poste

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Preclinical and clinical studies with carvedilol demonstrate clearly that the drug is both a β-adrenoceptor antagonist and a vasodilator. The vasodilating activity of carvedilol results primarily from α1-adrenoceptor blockade. Carvedilol is also a calcium channel antagonist and, although this activity does not contribute greatly to the overall antihypertensive effect of the drug, it may serve to maintain blood flow in specific regional vascular beds that would otherwise be compromised during antihypertensive therapy (i.e., cutaneous circulation). In both animals and humans, carvedilol lowers the mean arterial blood pressure primarily by decreasing peripheral vascular resistance, thereby confirming the vasodilating activity of the drug. Throughout the antihypertensive dose range, cardiac function remains stable and the cardiac output may even increase in patients with ischemic heart disease. Reflex tachycardia due to β-adrenoceptor blocking activity is not observed with carvedilol. Throughout the antihypertensive dose range, the heart rate either remains stable or is moderately reduced. Carvedilol is a renal sparing antihypertensive agent, inasmuch as renal blood flow, the glomerular filtration rate, and sodium excretion are maintained, both in animals and in humans. In view of the significant reduction in renal vascular resistance that is observed at antihypertensive doses, it is concluded that carvedilol does not compromise renal autoregulatory mechanisms, and this is in part responsible for the renal sparing effect of the drug. The unique combination of nonselective β-adrenoceptor blockade, α1-adrenoceptor blockade, and possibly calcium channel blockade works synergistically to reduce the infarct size in a variety of experimental models of acute myocardial infarction. The cardioprotective effect of carvedilol in animal models is greater than that observed with propranolol, indicating that the vasodilating activity of the drug, which further reduces cardiac work by decreasing afterload and myocardial wall tension, produces an additive effect to β-adrenoceptor blockade, thereby providing additional protection to ischemic myocardium. The cardioprotective effects of carvedilol may contribute to the potential use of the drug in the treatment of angina and CHF, and the salvage of myocardium by carvedilol during ischemia may provide additional clinical benefit for hypertensive patients treated with the drug.

Original languageEnglish (US)
Pages (from-to)127-157
Number of pages31
JournalCardiovascular Drug Reviews
Volume10
Issue number2
StatePublished - 1992
Externally publishedYes

Fingerprint

Cardiovascular Agents
Adrenergic Receptors
Antihypertensive Agents
Pharmaceutical Preparations
Vascular Resistance
Kidney
Myocardium
Arterial Pressure
carvedilol
Renal Circulation
Calcium Channel Blockers
Calcium Channels
Glomerular Filtration Rate
Vasodilator Agents
Tachycardia
Propranolol
Cardiac Output
Myocardial Ischemia
Blood Vessels
Reflex

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Ruffolo, R. R., Boyle, D. A., Brooks, D. P., Feuerstein, G. Z., Venuti, R. P., Lukas, M. A., & Poste, G. (1992). Carvedilol: A novel cardiovascular drug with multiple actions. Cardiovascular Drug Reviews, 10(2), 127-157.

Carvedilol : A novel cardiovascular drug with multiple actions. / Ruffolo, R. R.; Boyle, D. A.; Brooks, D. P.; Feuerstein, G. Z.; Venuti, R. P.; Lukas, M. A.; Poste, George.

In: Cardiovascular Drug Reviews, Vol. 10, No. 2, 1992, p. 127-157.

Research output: Contribution to journalArticle

Ruffolo, RR, Boyle, DA, Brooks, DP, Feuerstein, GZ, Venuti, RP, Lukas, MA & Poste, G 1992, 'Carvedilol: A novel cardiovascular drug with multiple actions', Cardiovascular Drug Reviews, vol. 10, no. 2, pp. 127-157.
Ruffolo RR, Boyle DA, Brooks DP, Feuerstein GZ, Venuti RP, Lukas MA et al. Carvedilol: A novel cardiovascular drug with multiple actions. Cardiovascular Drug Reviews. 1992;10(2):127-157.
Ruffolo, R. R. ; Boyle, D. A. ; Brooks, D. P. ; Feuerstein, G. Z. ; Venuti, R. P. ; Lukas, M. A. ; Poste, George. / Carvedilol : A novel cardiovascular drug with multiple actions. In: Cardiovascular Drug Reviews. 1992 ; Vol. 10, No. 2. pp. 127-157.
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