Karvil 6.25/Karvil 12.5/Karvil 25 Mechanism of Action

Alpha and Beta Blocking Agent.
Pharmacology: Carvedilol is a potent antihypertensive agent with a dual mechanism of action. It possesses both β-adrenergic receptor blocking activity and alpha-adrenergic antagonistic activity. Carvedilol is non-selective beta adrenoreceptor antagonist at clinically relevant doses. Alpha-blocking activity of carvedilol is thought to be the predominant mechanism of validation. However, there is no reflex tachycardia because of associated-blockade. At higher concentration it also exerts calcium channel antagonist property. The calcium channel blocking activity of carvedilol is responsible for increasing the blood flow in some regional vascular beds.
Pharmacokinetics: Absorption and Distribution: Carvedilol is rapidly absorbed after a single oral dose with maximum plasma concentration (Cmax) achieved within 1 to 2 hours (tmax) in healthy volunteers and hypertensive patients.
After oral administration, Carvedilol undergoes extensive first-pass hepatic metabolism that results in a relatively low and variable absolute bioavailability of about 25%.
Carvedilol is available as a racemic mixture of its R (+)- and S (-)-enantiomers and stereoselective differences in pharmacokinetics have been reported. In healthy volunteers, mean AUC values for the S (-)-enantiomer were lower than those for the R (+)-enantiomer after intravenous and oral administration of racemic Carvedilol. The difference was greatest after oral administration with the enantiomeric ratio (R: S) ranging from 1.6 to 4.4 (median 2.7). The mean maximum plasma concentration of R (+)-Carvedilol was 2.6-fold greater than that of S (-)-Carvedilol and absolute oral bioavailability was 31% for the R (+)-enantiomer and 15% for the S (-)-enantiomer in healthy volunteers indicating marked stereoselectivity in first-pass hepatic metabolism.
Carvedilol is a highly lipophilic compound that is extensively distributed into extravascular tissues following absorption. The volume of distribution is about 1.5 to 2 L/kg in healthy volunteers. Carvedilol is highly bound to plasma proteins (>95%). Binding appears to be lower for the S (-)-enantiomer than for the R enantiomer and is unchanged in patients with hepatic disease.
Metabolism and Excretion: Carvedilol is rapidly and extensively metabolised by the liver with less than 2% of a dose recovered as unchanged drug in urine. Clearance is almost exclusively via hepatic metabolism with the major metabolites being the glucuronide conjugate, aliphatic side-chain oxidative products and aromatic ring hydroxylated conjugates; some of these appear to be pharmacologically active although the clinical relevance of this has not been established.
The average elimination half-life of carvedilol is approximately 6 hours. Plasma clearance is approximately 500-700 mL/min. The primary route of excretion is via feces. Elimination is mainly biliary. A minor part is eliminated via the kidneys in the form of various metabolites.