Adrenergic beta-antagonist
Adrenergic beta-receptor blockaders (beta-blockers) are "drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety".[1]
Beta-blockers vary within the class regarding their properties. Beta-blockers that have low intrinsic sympathomimetic activity (ISA), low membrane stabilizing activity, high beta 1-selectivity, and high lipophilicity may be more effective.[2]
Pharmacogenomics
Regarding the treatment of heart failure, there is conflicting evidence whether beta-blockers are as effective in African-American patients as in Anglo patients.[3] This may be due to a polymorphism in African-American patients of the G-protein-coupled receptor kinase (GRK5) (OMIM) that confers a natural "genetic beta-blockade".[4]
Variation adrenergic receptor genotype may also influence effectiveness.[5]
Beta-blockers such as metoprolol that are metabolized by cytochrome P-450 2D6 allele and may have more drug interactions[6] and inherited variations in metabolism.[7]
Classification
Generically available beta-blockers include:[8][9]
- Acebutolol
- Bisoprolol
- Nadolol
- Propranolol
- Timolol
Cardioselective / beta 1-selectivity
Generic beta-blockers with beta 1-selectivity:[8][10]
- Atenolol
- Bisoprolol
- Metoprolol
- Hepatically metabolized by cytochrome P-450 2D6 allele
- Lipophilic[11]
- Acebutolol
Non-generic:
- Betaxolol
Non-selective
Non-selective drugs include propranolol, timolol, nadolol, pindolol, penbutolol, and carteolol.
Intrinsic sympathomimetic activity
Generic beta-blockers with intrinsic sympathomimetic activity (less resting bradycardia and lipid changes):[8]
- Acebutolol
- Pindolol
Non-generic:
- Penbutolol
Beta-blockers with alpha blocking activity
Generic beta-blockers with alpha blocking activity (more orthostatic hypotension):[8]
- Carvedilol
- Labetalol
Clinical uses
The individual beta-blockers have been compared in the treatment of various diseases.[13]
Coronary heart disease
A meta-analysis has concluded that metoprolol may be the best beta-blocker for secondary prevention of myocardial infarction.[2]
Heart failure
Two cohort studies suggest that atenolol and carvedilol may be more effect than metoprolol for the treatment of heart failure.[14][15]
References
- ↑ Anonymous (2024), Adrenergic beta-antagonist (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ 2.0 2.1 Soriano JB, Hoes AW, Meems L, Grobbee DE (1997). "Increased survival with beta-blockers: importance of ancillary properties". Prog Cardiovasc Dis 39 (5): 445–56. PMID 9122425. [e]
- ↑ Shekelle PG, Rich MW, Morton SC, et al (2003). "Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials". J. Am. Coll. Cardiol. 41 (9): 1529–38. PMID 12742294. [e]
- ↑ Liggett, Stephen B et al. 2008. A GRK5 polymorphism that inhibits [beta]-adrenergic receptor signaling is protective in heart failure. Nat Med advanced online publication. http://dx.doi.org/10.1038/nm1750 (Accessed April 29, 2008).
- ↑ Zaugg M, Bestmann L, Wacker J, et al (July 2007). "Adrenergic receptor genotype but not perioperative bisoprolol therapy may determine cardiovascular outcome in at-risk patients undergoing surgery with spinal block: the Swiss Beta Blocker in Spinal Anesthesia (BBSA) study: a double-blinded, placebo-controlled, multicenter trial with 1-year follow-up". Anesthesiology 107 (1): 33–44. DOI:10.1097/01.anes.0000267530.62344.a4. PMID 17585213. Research Blogging.
- ↑ Onalan O, Cumurcu BE, Bekar L (May 2008). "Complete atrioventricular block associated with concomitant use of metoprolol and paroxetine". Mayo Clin. Proc. 83 (5): 595–9. PMID 18452693. [e]
- ↑ Nozawa T, Taguchi M, Tahara K, et al (November 2005). "Influence of CYP2D6 genotype on metoprolol plasma concentration and beta-adrenergic inhibition during long-term treatment: a comparison with bisoprolol". J. Cardiovasc. Pharmacol. 46 (5): 713–20. PMID 16220080. [e]
- ↑ 8.0 8.1 8.2 8.3 (June 2005) "Drugs for hypertension". Treat Guidel Med Lett 3 (34): 39–48. PMID 15912125. [e]
- ↑ (March 2008) "Nebivolol (Bystolic) for hypertension". Med Lett Drugs Ther 50 (1281): 17–9. PMID 18323772. [e]
- ↑ (January 2009) "Drugs for hypertension". Treat Guidel Med Lett 7 (77): 1–10. PMID 19107095. [e]
- ↑ 11.0 11.1 Tuininga YS, Crijns HJ, Brouwer J, et al (December 1995). "Evaluation of importance of central effects of atenolol and metoprolol measured by heart rate variability during mental performance tasks, physical exercise, and daily life in stable postinfarct patients". Circulation 92 (12): 3415–23. PMID 8521562. [e]
- ↑ Sarafidis P, Bogojevic Z, Basta E, Kirstner E, Bakris GL (February 2008). "Comparative efficacy of two different beta-blockers on 24-hour blood pressure control". J Clin Hypertens (Greenwich) 10 (2): 112–8. PMID 18259123. [e]
- ↑ Dean L (2007). “Comparing Beta Blockers”, PubMed Clinical Q&A. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information. “Based on http://www.ohsu.edu/drugeffectiveness/”
- ↑ Kramer JM, Curtis LH, Dupree CS, et al (December 2008). "Comparative effectiveness of beta-blockers in elderly patients with heart failure". Arch. Intern. Med. 168 (22): 2422–8; discussion 2428–32. DOI:10.1001/archinternmed.2008.511. PMID 19064824. Research Blogging.
- ↑ Go AS, Yang J, Gurwitz JH, Hsu J, Lane K, Platt R (December 2008). "Comparative effectiveness of different beta-adrenergic antagonists on mortality among adults with heart failure in clinical practice". Arch. Intern. Med. 168 (22): 2415–21. DOI:10.1001/archinternmed.2008.506. PMID 19064823. Research Blogging.