Pharmacogenetics of Beta-Blockers
β-Blockers are an important cardiovascular drug class, recommended as first-line treatment of numerous diseases such as heart failure, hypertension, and angina, as well as treatment after myocardial infarction. However, responses to a β-blocker are variable among patients. Results of numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to β-blockers. This review summarizes the pharmacogenetic data for β-blockers in patients with various diseases and discusses the potential implications of β-blocker pharmacogenetics in clinical practice.
Excessive activation of the adrenergic nervous system contributes to the pathophysiology or symptoms of many cardiovascular diseases. β-Blockers are competitive antagonists at the β-adrenergic receptors, thereby modulating activities in this pathway. β-Blockers are among the most widely prescribed of all drug classes, with more than 120 million prescriptions in the United States in 2004, and atenolol was the fourth most commonly prescribed of all drugs, with 42 million prescriptions in the same year. Currently, 17 β-blockers have been approved by the U.S. Food and Drug Administration ( Table 1 ). Although most of their pharmacologic effects are attributed to their ability to block β-adrenergic receptors, there are many differences among the agents. For example, some are rela-tively selective for the β1-adrenergic receptors, whereas others are nonselective. Further, some have ancillary properties in addition to their β-blocking effects, such as intrinsic sympathomimetic activity, α-adrenergic–receptor blockade, and direct vasodilating effects. There is also variability in the pharmacokinetic properties of the various β-blockers. However, all β-blockers antagonize the β1-adrenergic receptor, and this effect is believed to be responsible for most of the therapeutic benefit associated with β-blocker therapy.
β-Blockers are recommended as a first-line agent for various diseases, including heart failure, hypertension, and angina, as well as after myocardial infarction. However, β-blocker therapy often produces variable responses among patients. Genetic differences may contribute to this variability in responses to β-blockers. Pharmacogenetics is the study of genetic contributions to variable drug response, with the clinical potential to optimize therapy by identifying (predicting) the patients who will respond well (or poorly) to a given drug or those who are at high risk for adverse events from the drug.
In this review, the pharmacogenetics literature on β-blockers are summarized and the potential clinical implications of these data are discussed. Studies were identified in the MEDLINE database from 1966–July 2006 by combining the following Medical Subject Heading search terms: genetic polymorphism, single nucleotide polymorphism, pharmacogenetics, adrenergic b antagonists, as well as individual β-blocker names. We also reviewed the references of all identified articles.
Minor allele frequencies and the functional consequences of the major polymorphisms discussed in this review are summarized in Table 2 .
Abstract and Introduction
Abstract
β-Blockers are an important cardiovascular drug class, recommended as first-line treatment of numerous diseases such as heart failure, hypertension, and angina, as well as treatment after myocardial infarction. However, responses to a β-blocker are variable among patients. Results of numerous studies now suggest that genetic polymorphisms may contribute to variability in responses to β-blockers. This review summarizes the pharmacogenetic data for β-blockers in patients with various diseases and discusses the potential implications of β-blocker pharmacogenetics in clinical practice.
Introduction
Excessive activation of the adrenergic nervous system contributes to the pathophysiology or symptoms of many cardiovascular diseases. β-Blockers are competitive antagonists at the β-adrenergic receptors, thereby modulating activities in this pathway. β-Blockers are among the most widely prescribed of all drug classes, with more than 120 million prescriptions in the United States in 2004, and atenolol was the fourth most commonly prescribed of all drugs, with 42 million prescriptions in the same year. Currently, 17 β-blockers have been approved by the U.S. Food and Drug Administration ( Table 1 ). Although most of their pharmacologic effects are attributed to their ability to block β-adrenergic receptors, there are many differences among the agents. For example, some are rela-tively selective for the β1-adrenergic receptors, whereas others are nonselective. Further, some have ancillary properties in addition to their β-blocking effects, such as intrinsic sympathomimetic activity, α-adrenergic–receptor blockade, and direct vasodilating effects. There is also variability in the pharmacokinetic properties of the various β-blockers. However, all β-blockers antagonize the β1-adrenergic receptor, and this effect is believed to be responsible for most of the therapeutic benefit associated with β-blocker therapy.
β-Blockers are recommended as a first-line agent for various diseases, including heart failure, hypertension, and angina, as well as after myocardial infarction. However, β-blocker therapy often produces variable responses among patients. Genetic differences may contribute to this variability in responses to β-blockers. Pharmacogenetics is the study of genetic contributions to variable drug response, with the clinical potential to optimize therapy by identifying (predicting) the patients who will respond well (or poorly) to a given drug or those who are at high risk for adverse events from the drug.
In this review, the pharmacogenetics literature on β-blockers are summarized and the potential clinical implications of these data are discussed. Studies were identified in the MEDLINE database from 1966–July 2006 by combining the following Medical Subject Heading search terms: genetic polymorphism, single nucleotide polymorphism, pharmacogenetics, adrenergic b antagonists, as well as individual β-blocker names. We also reviewed the references of all identified articles.
Minor allele frequencies and the functional consequences of the major polymorphisms discussed in this review are summarized in Table 2 .