CLINICAL RELEVANCE OF PHARMACOKINETIC DIFFERENCES BETWEEN BETA-BLOCKERS

Fundamental differences in the pharmacodynamic and pharmacokinetic pro files of beta-adrenergic blocking agents must be considered in optimiz ing their efficacy and determining the appropriate selection of these drugs in different patients. Beta blockers are contraindicated in pati ents with asthma and should be used cautiously in heart failure, Clini cally important distinctions are related to whether a beta blocker is beta(1)-selective or nonselective, Most adverse effects of beta-blocke r use are related to interference with beta(2)-mediated functions incl uding bronchodilation, vasodilation, and mobilization of free fatty ac ids, To achieve the potential benefits of beta(1) blockade (decreased heart rate, blood pressure, cardiac workload, and excitability), a low plasma concentration of a beta(1)-selective drug is required. Adverse effects of beta blockers can be further decreased by selecting a sust ained-release beta(1)-selective drug, Beta blockers are further differ entiated on the basis of lipophilicity or hydrophilicity, Lipophilic b eta blockers cross the blood-brain barrier, whereas hydrophilic agents do not enter the central nervous system, Some lipophilic agents (metr oprolol, timolol, and propanolol) have been shown to decrease mortalit y in coronary heart disease, particularly sudden death. (C) 1997 by Ex cerpta Medica, Inc.