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Carvedilol
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| Systematic (IUPAC) name | |
| 1-(9H-carbazol-4-yloxy)- 3-[2-(2-methoxyphenoxy)ethylamino]propan-2-ol |
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| Identifiers | |
| CAS number | |
| ATC code | C07 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C24H26N2O4 |
| Mol. mass | 406.474 |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability | 25–35% |
| Protein binding | 98% |
| Metabolism | hepatic (CYP2D6, CYP2C9) |
| Half life | 7–10 hours |
| Excretion | renal 16%, faecal 60% |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status | |
| Routes | oral |
Carvedilol is a non-selective beta blocker indicated in the treatment of mild to moderate congestive heart failure (CHF). It is marketed under various trade names including Coreg (GSK), Dilatrend (Roche) and Eucardic (Roche), as a generic drug (as of September 5, 2007 in the U.S.).[1], and as a controlled-release formulation, marketed in the US as Coreg CR (GSK).
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Pharmacology
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 (Vanderhoff et al., 1998). 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.
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 (Packer et al., 2002).
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 in April 27, 2006 in a Dear Pharmacist letter. [1]
Approval of controlled-release formulation
On October 20, 2006, the FDA approved a controlled release formulation of carvedilol, to be marketed as Coreg CR.
References
- ^ Press Release, FDA Approves First Generic Versions of Coreg, U.S. Food and Drug Administration, Sep. 5, 2007
General references
- Packer M, Fowler MB, Roecker EB, et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002;106(17):2194-9. PMID 12390947
- Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001 May 31;344(22):1651-8. PMID 11386263. Carvedilol improves survival in severe heart failure, as well as in mild-to-moderate heart failure.
- Vanderhoff BT, Ruppel HM, Amsterdam PB. Carvedilol: The new role of beta blockers in congestive heart failure. Am Fam Physician 1998;58(7):1627-34. PMID 9824960
External links
- Coreg CR official website
- Physicians Desk Reference Info on Carvedilol
- Info on carvedilol through rxlist.com
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