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Beta blocker Beta blockers (sometimes written as ß-blockers) are a class of drugs used for various indications, but particularly for the management of hypertension and cardiac arrhythmias. 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 ß-adrenergic receptors, part of the sympathetic nervous system which mediates the "fight or flight" response. There are three known types of beta receptor, designated ß1, ß2 and ß3. ß1-Adrenergic receptors are located mainly in the heart, kidney, and adipose tissue. ß2-Adrenergic receptors are located mainly in the heart, lung, GI tract, liver, pancreas, and skeletal muscle. The role and location of ß3-receptors is less well-defined. ß-Receptor antagonism Stimulation of ß1 receptors by epinephrine induces a positive chronotropic and inotropic effect on the heart and increases cardiac conduction velocity and automaticity. Stimulation of ß2 receptors induces smooth muscle relaxation (resulting in vasodilation and bronchodilation amongst other actions), induces tremor in skeletal muscle, increases glycogenolysis in the liver and skeletal muscle. 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 ß-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. a1-Receptor antagonism Some beta blockers (e.g. labetalol and carvedilol) exhibit mixed antagonism of both ß- and a1-adrenergic receptors, which provides additional arteriolar vasodilating action. Other effects Beta blockers decrease nocturnal melatonin release, perhaps partly accounting for sleep disturbance caused by some agents (Stoschitzky et al., 1999). Clinical use Large differences exist in the pharmacology of agents within the class, thus not all beta blockers are used for all indications listed below. 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 a-blocker Beta blockers have also been used in the following conditions:     * Hypertrophic obstructive cardiomyopathy     * Acute dissecting aortic aneurysm     * Marfan syndrome (chronic treatment with propranolol slows progression of aortic dilation and its complications)     * Prevention of variceal bleeding in portal hypertension     * Possible mitigation of hyperhidrosis Congestive heart failure Although beta blockers were once contraindicated in congestive heart failure, as they have the potential to worsen the condition, studies in the late 1990s showed their positive effects on morbidity and mortality in congestive heart failure (Hjalmarson, 2000; Leizorovicz, 2002; Packer, 2002). Bisoprolol, carvedilol and sustained-release metoprolol are specifically indicated as adjuncts to standard ACE inhibitor and diuretic therapy in congestive heart failure. Performance enhancement Since they lower heart rate and reduce tremor, beta blockers have been used by some Olympic marksmen to enhance performance, though beta blockers are banned by the International Olympic Committee (IOC). Some musicians use beta blockers to avoid stage fright and tremor during auditions and performances. Adverse 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, and/or alteration of glucose and lipid metabolism. Mixed a1/ß-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 ß2-adrenergic receptor antagonist activity (bronchospasm, peripheral vasoconstriction, alteration of glucose and lipid metabolism) are less common with ß1-selective (often termed "cardioselective") agents, however receptor selectivity diminishes at higher doses. Examples of beta blockers Dichloroisoprenaline, the first beta blocker. Enlarge Dichloroisoprenaline, the first beta blocker. Historical     * Dichloroisoprenaline     * Practolol     * Pronethaolol Non-selective agents     * Alprenolol     * Carteolol     * Levobunolol     * Mepindolol     * Metipranolol     * Nadolol     * Oxprenolol     * Penbutolol     * Pindolol     * Propranolol     * Sotalol     * Timolol ß1-Selective agents     * Acebutolol     * Atenolol     * Betaxolol     * Bisoprolol     * Esmolol     * Metoprolol     * Nebivolol Mixed a1/ß-adrenergic antagonists     * Carvedilol     * Celiprolol     * Labetalol ß2-Selective agents     * Butoxamine (weak a-adrenergic agonist activity) Comparative information Pharmacological differences     * Agents with intrinsic sympathomimetic action (ISA)           o Acebutolol, carteolol, celiprolol, mepindolol, oxprenolol, pindolol     * Agents with greater aqueous solubility           o Atenolol, celiprolol, nadolol, sotalol     * Agents with membrane stabilising activity           o Acebutolol, betaxolol, pindolol, propranolol     * Agents with antioxidant effect           o Carvedilol Indication differences     * Agents specifically indicated for cardiac arrhythmia           o Esmolol, sotalol     * Agents specifically indicated for congestive heart failure           o Bisoprolol, carvedilol, sustained-release metoprolol     * Agents specifically indicated for glaucoma           o Betaxolol, carteolol, levobunolol, metipranolol, timolol     * Agents specifically indicated for myocardial infarction           o Atenolol, metoprolol, propranolol     * Agents specifically indicated for migraine prophylaxis           o Metoprolol, propranolol Propranolol is the only agent indicated for control of tremor, portal hypertension and oesophageal variceal bleeding, and used in conjunction with a-blocker therapy in phaeochromocytoma (Rossi, 2006).