Carvedilol

Mechanism :

Carvedilol is a cardiovascular agent for the treatment of CHF that combines beta-adrenoceptor blockade and vasodilation in a single racemic mixture. Nonselective beta-adrenoceptor blocking activity is present in the S(-) enantiomer and alpha 1-adrenoceptor blocking activity is present at equal potency in both the R(+) and S(-) enantiomers. Carvedilol has no intrinsic sympathomimetic activity. Its action on beta-receptors is 10 times stronger than on alpha 1-receptors.

Indication :

• Congestive heart failure
• Left ventricular dysfunction following myocardial infarction
• Hypertension

Contraindications :

Contraindicated in patients with bronchial asthma or related bronchospastic conditions, second- or third-degree AV block, sick sinus syndrome or severe bradycardia (unless a permanent pacemaker is in place), or in patients with cardiogenic shock or who have decompensated heart failure requiring the use of intravenous inotropic therapy. Such patients should first be weaned from intravenous therapy before initiating carvedilol.

Use in patients with clinically manifest hepatic impairment is not recommended.

Contraindicated in patients with hypersensitivity to any component of the product.

Dosing :

Adverse Effect :

Cardiac failure, syncope, bradycardia, myocardial infarction, acute renal failure, AV block, worsening renal function, sleep disorder, aggravated depression, impaired concentration, abnormal thinking, emotional labiality, asthma, decreased libido in males, pruritus, rash, tinnitus, increased micturition frequency, dry mouth, increased sweating, diabetes mellitus.

Interaction :

Antihypertensive Agents: When administered concomitantly with other drugs that are antihypertensive in action or have hypotension as part of their adverse effect profile, carvedilol may have additive effects to excessively lower blood pressure.
Catecholamine-Depleting Agents: Patients taking both agents with b-blocking properties and a drug that can deplete catecholamines (e.g., reserpine and MAO inhibitors) should be observed closely for evidence of hypotension and/or marked bradycardia.
Antiarrhythmics and Calcium Channel Blockers: Isolated cases of conduction disturbance (rarely with hemodynamic compromise) have been observed when carvedilol is coadministered with antiarrhythmic agents or calcium channel blockers such as diltiazem and verapamil that can slow cardiac conduction.
Digoxin: Following concomitant administration of carvedilol and digoxin, peak concentration of digoxin increased by approximately 30% and steady-state trough concentrations of digoxin were increased by about 15%. Both digoxin and carvedilol slow AV conduction. Therefore, increased monitoring of digoxin levels is recommended when initiating, adjusting or discontinuing carvedilol.
Clonidine: Concomitant administration of clonidine with agents with beta-blocking properties may potentiate blood pressure and heart rate lowering effects. When concomitant treatment with agents with beta-blocking properties and clonidine is to be terminated, the beta-blocking agent should be discontinued first. Clonidine therapy can then be discontinued several days later by gradually decreasing the dosage.
Inducers and Inhibitors of Cytochrome P450: Since carvedilol undergoes substantial oxidative metabolism, care may be required in patients receiving inducers or inhibitors of cytochrome P450, as plasma concentrations may be altered.

Renal Dose :

Hepatic Dose :