Carvedilol

Carvedilol is a non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure (CHF). It is marketed under various trade names including Carvil (Zydus Cadila), Coreg (GSK), Dilatrend (Roche), Eucardic (Roche), and Carloc (Cipla) as a generic drug (as of September 5, 2007 in the U.S.)., and as a controlled-release formulation, marketed in the US as Coreg CR (GSK). Carvedilol was discovered by Robert R. Ruffolo, Jr. It has had a significant role in the treatment of Congestive heart failure.

Pharmacology
Carvedilol is both a beta blocker (β1, β2) and alpha blocker (α1):


 * Norepinephrine stimulates the nerves that control the muscles of the heart by binding to the β1- and β2-adrenergic receptors. Carvedilol blocks the binding to those receptors, which both slows the heart rhythm and reduces the force of the heart's pumping. This lowers blood pressure and reduces heart failure.


 * Norepinephrine also binds to the α1-adrenergic receptors on blood vessels, causing them to constrict and raise blood pressure. Carvedilol blocks this binding to the α1-adrenergic receptors too, which also lowers blood pressure.

Relative to other beta blockers, carvedilol has minimal inverse agonist activity. This suggests that carvedilol has a reduced negative chronotropic and inotropic effect compared to other beta blockers, which may decrease its potential to worsen symptoms of heart failure. However, to date this theoretical benefit has not been established in clinical trials, and the current version of the ACC/AHA guidelines on congestive heart failure management does not give preference to carvedilol over other beta-blockers.

Side effects
The most common side effects include dizziness, fatigue, hypotension, diarrhea, asthenia, bradycardia, and weight gain.

A case report of a patient with panic disorder associated sleep disturbances and nightmares with the improper usage of carvedilol.

Enantiomers
Carvedilol has enantiomers with distinct pharmacodynamics.

The term "racemic carvedilol" is sometimes used to explicitly denote that both enantiomers are applied.

Clinical use
Carvedilol is indicated in the management of congestive heart failure (CHF), as an adjunct to conventional treatments (ACE inhibitors and diuretics). The use of carvedilol has been shown to provide additional morbidity and mortality benefits in CHF. Carvedilol (Carvil) is available at the following doses 3.125 mg (smallest), followed by 6.25 mg, and 12.5 mg white tablets.

U.S. supply issues
On January 10, 2006 carvedilol supply became limited in the United States, due to changes in documentation procedures at a plant. This was lifted on April 27, 2006 in a Dear Pharmacist letter.

Approval of controlled-release formulation
On October 20, 2006, the FDA approved a controlled release formulation of carvedilol; it is marketed as Coreg CR.