Stereospecific pharmacokinetics and pharmacodynamics of beta-adrenergic blockers in humans

The beta-blockers comprise a group of drugs that are mostly used to treat c ardiovascular disorders such as hypertension, cardiac arrhythmia, or ischem ic heart disease. Each of these drugs possesses at least one chiral center, and an inherent high degree of enantioselectivity in binding to the beta - adrenergic receptor. For beta-blockers with a single chiral center, the (-) enantiomer possesses much greater affinity for binding to the beta -adrene rgic receptors than antipode. The enantiomers of some of these drugs posses s other effects, such as antagonism at alpha-adrenergic receptors or Class III antiarrhythmic activity. However, these effects generally display a low er level of stereoselectivity than the beta-blocking activity. Except for t imolol, all of these drugs used systemically are administered clinically as the racemate. As a class, the beta blockers are quite diverse from a pharm acokinetic perspective, as they display a high range of values in plasma pr otein binding, percent of drug eliminated by metabolism or unchanged in the urine, and in hepatic extraction ratio. With respect to plasma concentrati ons attained after oral or intravenous dosing, in most cases the enantiomer s of the beta-blockers show only a modest degree of stereoselectivity. Howe ver, the relative magnitude of the concentrations of the enantiomers in pla sma is not constant in all situations and varies from drug to drug. Further , various factors related to the drug (e.g., dosing rate or enantiomer-enan tiomer interaction) or the patient (e.g., racial background, cardiovascular function, or the patient metabolic phenotype) may affect the stereospecifi c pharmacokinetics and pharmacodynamics of beta-blockers. An understanding of the stereospecific pharmacokinetics and pharmacodynamics of beta-blocker s may help clinicians to interpret and predict differences among patients i n pharmacologic responses to these drugs.