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  • Title: Clinical pharmacology of carvedilol.
    Author: Tomlinson B, Prichard BN, Graham BR, Walden RJ.
    Journal: Clin Investig; 1992; 70 Suppl 1():S27-36. PubMed ID: 1350481.
    Abstract:
    Animal work has shown that carvedilol is a nonselective beta-blocking drug. It has a vasodilator action from alpha-receptor blockade, but there is evidence that it has further action to relax smooth muscle, possibly from calcium channel antagonism. Carvedilol is lipid soluble and 25% bioavailable, and it has a half-life of about 7 h. It lowers blood pressure at rest and reduces the tachycardia and the rise of blood pressure on exercise. It reduces the level of blood pressure reached during isometric exercise or the cold pressor test. Cardiac output at rest is maintained, and the haemodynamics in the compromised heart is improved. It has an important peripheral vasodilator action, peripheral flow being maintained to important organs, e.g. kidneys, despite the fall in blood pressure. Exercising renin and noradrenaline levels are increased, as are the latter at rest. Carvedilol is lipid neutral. Carvedilol shifts the dose-response curve to isoprenaline to the right, as well as to alpha-stimulants such as phenylephrine. Responses to angiotensin are little affected. The ratio of beta- to alpha-blockade has been found to be 7.6 for 50 mg and 12.5 for 100 mg of carvedilol. There is no evidence of a decline in alpha-blockade after 1 week of continuous administration.
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