Which beta blocker?

Abstract

Nine beta adrenoceptor blocking drugs are currently marketed in Britain with one further compound possessing both alpha and beta adrenoceptor blocking activity. Several of these drugs are constituents of fixed dose combinations with diuretics; slow release formulations of several beta blockers are also marketed. The aim of this review is to discuss whether the differences between beta blockers are clinically important or merely represent marketing ploys used for advertising purposes by the pharmaceutical industry.A therapeutic agent is judged on two scores-efficacy and toxicity. Beta blockers pose problems because of their diverse clinical indications and the heterogeneity of their side effects.Assessment of risk versus benefit has to take account not only of the nature of the primary disease for which beta blockers are prescribed but also of any other disorders from which the patient may suffer. For example, a patient with angina may also have asthma, a patient with hypertension may have associated peripheral vascular disease, and a patient with a cardiac arrhythmia may also be on the verge of heart failure. Lipid solubilityRelative lipid solubility is one of the most important properties of beta blockers, and this can be measured by the extent to which the drug partitions between an organic solvent and water. Propranolol, oxprenolol, metoprolol, and timolol are the most lipid soluble beta blockers, and the least lipid soluble (and hence the most water soluble) are atenolol, nadolol, and sotalol, with acebutolol and pindolol occupying intermediary positions.1 The more lipophilic the beta blocker the more rapid and complete its absorption from the gastrointestinal tract is likely to be2-and the more likely it is to be extensively metabolised in the gut wall and liver (the so called "first pass effect")3 and to be eliminated rapidly. Variations between patients in rates of metabolism as a determinant of differences in response are thus more likely to occur with the relatively lipid soluble members of the group,4 as are drug interactions due to inhibition of hepatic drug metabolismfor example, with cimetidine.5 Lipophilic beta blockers will also gain access to the brain, and, with it, bring the likelihood of producing central nervous system side effects such as bad dreams. Muscle fatigue produced by beta blockers is an extremely common but complex adverse effect; there is no good evidence that it is related to their degree of lipid solubility.Water soluble beta blockers tend to be eliminated unchanged by the kidney and to have longer half lives in plasma, and will thus tend to accumulate in renal failure with the attendant risks of exaggerated effects. With respect to drug efficacy there is no evidence that high lipid solubility increases the ability ofthe beta blocker to control blood pressure, prevent angina, or stop cardiac arrhythmias. Currently the most convincing evidence for the secondary prevention of ischaemic heart disease has been shown with propranolol, timolol, and metoprolol,6 all of which are relati...

β-Blocker Underuse in Secondary Prevention of Myocardial Infarction

“…The proposed mechanisms to explain why β-blockers may worsen claudication are (1) a decrease in muscle blood flow during exercise distal to the stenosis due to decreased cardiac output secondary to β 1 -receptor blockade, 55 (2) an unopposed increase in α-adrenergic activity secondary to β 2 -receptor blockade, 56 and (3) a fall in systemic blood pressure proximal to the site of the stenosis. 55 These views are largely supported by several uncontrolled observations of intermittent claudication 57,58 and vasospastic phenomena 58–60 associated with β-blocker use.…”

The Use of β-Blockers in Heart Failure with Reduced Ejection Fraction

“…β-Blockers have been considered rather contraindicated in patients with peripheral artery disease and concomitant intermittent claudication. The decrease in cardiac output and the hypothesized blockade of β2-receptors (implicated in skeletal muscle vasodilation) are the main impacts of β-blockers invoked to support the cautious use of these drugs in patients with HFrEF and concomitant peripheral artery disease [ 70 , 71 ]. However, these pathophysiological assumptions are not supported by solid evidence but only by sporadic case reports and uncontrolled observations of worsening intermittent claudication and vasospastic phenomena associated with β-blocker use [ 72 , 73 ].…”

Stereoisomers and Drug Toxicity

“…For example, the hydrophilic {:l-adrenoceptor antagonist atenolol is better tolerated than the lipophilic propranolol (Breckenridge 1983). Some studies use open, nonspecific questions which give a relatively low incidence, while others conduct de-tailed interviews which have a higher detection rate.…”