Carvedilol is a nonselective beta blocker/alpha-1 blocker used in the treatment of mild to severe congestive heart failure (CHF) and high blood pressure. It is marketed under various trade names including Carvil (Zydus Cadila), Coreg (GSK), Dilatrend , Kredex (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 Fritz Wiedemann at Boehringer Ingelheim. 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 slows the heart rhythm and reduces the force of the heart's pumping. This lowers blood pressure thus reducing the workload of the heart, which is particularly beneficial in heart failure patients.
- 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.
Carvedilol also acts as a functional inhibitor of acid sphingomyelinase.
Side effects
The most common side effects include dizziness, fatigue, low blood pressure, diarrhea, weakness, slowed heart rate, and weight gain.
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 severe CHF. Carvedilol (Carvil) is available at the following doses 3.125Â mg (smallest), followed by 6.25Â mg,12.5Â mg, and 25Â mg white tablets. Coreg CR is available at the following doses: 10Â mg(white/green capsules), 20Â mg(white/yellow capsules), 40Â mg(yellow/green capsules), and 80Â mg(white capsules).
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.
References
Further reading
- Chakraborty, Subhashis; Shukla, Dali; Mishra, Brahmeshwar; Singh, Sanjay (February 2010). "Clinical updates on carvedilol: a first choice β-blocker in the treatment of cardiovascular diseases". Expert Opinion on Drug Metabolism & Toxicology 6 (2): 237â€"250. doi:10.1517/17425250903540220. PMID 20073998.Â
External links
- Coreg CR official website
- Physicians Desk Reference Info on Carvedilol
- Info on carvedilol through rxlist.com