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BETA-BLOCKERS
Beta blockers (sometimes written as β-blockers) are a class of drugs used for various indications, but particularly for the
management of cardiac arrhythmias and cardioprotection after myocardial infarction.

Whilst once first-line treatment for hypertension, their role was downgraded in June 2006 in the UK to fourth-line as they
perform less well than other drugs, particularly in the elderly, and there is increasing evidence that the most frequently
used beta-blockers at usual doses carry a risk of provoking type 2 diabetes.

Beta blockers may also be referred to as beta-adrenergic blocking agents, beta-adrenergic antagonists, or beta
antagonists.

Pharmacology
Beta blockers block the action of endogenous catecholamines (epinephrine (adrenaline) and norepinephrine
(noradrenaline) in particular), on β-adrenergic receptors, part of the sympathetic nervous system which mediates the
"fight or flight" response.

There are three known types of beta receptor, designated β1, β2 and β3. β1-Adrenergic receptors are located mainly in
the heart. β2-Adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth
muscle, and skeletal muscle. β3-receptors are located in fat cells.

• β-Receptor antagonism

Stimulation of β1 receptors by epinephrine induces a positive chronotropic and inotropic effect on the heart and
increases cardiac conduction velocity and automaticity. Stimulation of β2 receptors induces smooth muscle relaxation
(resulting in vasodilation and bronchodilation amongst other actions), induces tremor in skeletal muscle, and increases
glycogenolysis in the liver and skeletal muscle. Stimulation of β3 receptors induces lipolysis.

Beta blockers inhibit these normal epinephrine-mediated sympathetic actions, but have minimal effect on resting
subjects. That is, they reduce the effect of excitement/physical exertion on heart rate and force of contraction, dilation of
blood vessels, opening of bronchi, reduce tremor, and breakdown of glycogen..

It is therefore somewhat unexpected that non-selective beta blockers have an antihypertensive effect, since they appear to
cause vasoconstriction. The antihypertensive mechanism appears to involve: reduction in cardiac output (due to negative
chronotropic and inotropic effects), reduction in renin release from the kidneys, and a central nervous system effect to
reduce sympathetic activity.

Antianginal effects result from negative chronotropic and inotropic effects, which decrease cardiac workload and oxygen
demand.

The antiarrhythmic effects of beta blockers arise from sympathetic nervous system blockade - resulting in depression of
sinus node function and atrioventricular node conduction, and prolonged atrial refractory periods. Sotalol, in particular,
has additional antiarrhythmic properties and prolongs action potential duration through potassium channel blockade.

• Intrinsic sympathomimetic activity

Some beta blockers (e.g. oxprenolol and pindolol) exhibit intrinsic sympathomimetic activity (ISA). These agents are
capable of exerting low level agonist activity at the β-adrenergic receptor while simultaneously acting as a receptor site
antagonist. These agents, therefore, may be useful in individuals exhibiting excessive bradycardia with sustained beta
blocker therapy.

Agents with ISA are not used post-myocardial infarction as they have not been demonstrated to be beneficial. They may
also be less effective than other beta blockers in the management of angina and tachyarrhythmia (Rossi, 2006).

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• α1-Receptor antagonism

Some beta blockers (e.g. labetalol and carvedilol) exhibit mixed antagonism of both β- and α1-adrenergic receptors,
which provides additional arteriolar vasodilating action.

Use
Indications for beta blockers include:

• Hypertension
• Angina
• Cardiac arrhythmia
• Congestive heart failure
• Myocardial infarction
• Glaucoma
• Migraine prophylaxis
• Symptomatic control (tachycardia, tremor) in anxiety and hyperthyroidism
• Essential tremor
• Phaeochromocytoma, in conjunction with α-blocker

Side effects
Common adverse drug reactions (ADRs) associated with the use of beta blockers include: nausea, diarrhoea,
bronchospasm, dyspnoea, cold extremities, exacerbation of Raynaud's syndrome, bradycardia, hypotension, heart
failure, heart block, fatigue, dizziness, abnormal vision, decreased concentration, hallucinations, insomnia, nightmares,
depression, sexual dysfunction, erectile dysfunction and/or alteration of glucose and lipid metabolism. Mixed α1/β-
antagonist therapy is also commonly associated with orthostatic hypotension. Carvedilol therapy is commonly
associated with oedema. (Rossi, 2006)

Central nervous system (CNS) adverse effects (hallucinations, insomnia, nightmares, depression) are more common in
agents with greater lipid solubility, which are able to cross the blood-brain barrier into the CNS. Similarly, CNS adverse
effects are less common in agents with greater aqueous solubility (listed below).

Adverse effects associated with β2-adrenergic receptor antagonist activity (bronchospasm, peripheral vasoconstriction,
alteration of glucose and lipid metabolism) are less common with β1-selective (often termed "cardioselective") agents,
however receptor selectivity diminishes at higher doses.