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Pharmacology: Pharmacodynamics: Carvedilol is a multiple action adrenergic receptor blocker with α1, β1 and β2 adrenergic receptor blockade properties. Carvedilol has been shown to have organ-protective effects. Carvedilol is a potent antioxidant and a scavenger of reactive oxygen radicals. Carvedilol is racemic, and both R(+) and S(-) enantiomers have the same α-adrenergic receptor blocking properties and antioxidant properties. Carvedilol has antiproliferative effects on human vascular smooth muscle cells. A decrease in oxidative stress has been shown in clinical studies by measuring various markers during chronic treatment of patients with carvedilol. Carvedilol's β-adrenergic receptor blocking properties are non-selective for β1 and β2 adrenoceptors and are associated with the S(-) enantiomer. Carvedilol has no intrinsic sympathomimetic activity and (like propranolol) it has membrane stabilizing properties. Carvedilol suppresses the renin-angiotensin-aldosterone system through β-blockade, which reduces the release of renin, thus making fluid retention rare.
Carvedilol reduces peripheral vascular resistance via selective blockade of α1-adrenoreceptors. Carvedilol attenuates the increase in blood pressure induced by phenylephrine, an α1-adrenoceptor agonist, but not that induced by angiotensin II. Carvedilol has no adverse effect on the lipid profile. A normal ratio of high-density lipoproteins to low density lipoproteins (HDL/LDL) is maintained.
Pharmacokinetics: Carvedilol is well absorbed from the gastrointestinal tract but is subject to considerable first-pass metabolism in the liver; the absolute bioavailability is about 25%. Peak plasma concentrations occur 1 to 2 hours after an oral dose. It has high lipid solubility. Carvedilol is more than 98% bound to plasma proteins. It is extensively metabolized in the liver, the metabolites being excreted mainly in the bile. The elimination half-life is about 6 to 10 hours. Carvedilol has been shown to accumulate in breast milk in animals.
