Beta Blockers

Warning: mkdir() [function.mkdir]: Permission denied in /home/webs/affiliatelib2/CacheManager.php on line 12

Warning: mkdir() [function.mkdir]: No such file or directory in /home/webs/affiliatelib2/CacheManager.php on line 12

Warning: fopen(/home/templatecore2cache//*cluesnet.com/35/35a49a2264da271423e2a144167004953e704bde.tc2cache) [function.fopen]: failed to open stream: No such file or directory in /home/webs/affiliatelib2/CacheManager.php on line 130

Warning: fwrite(): supplied argument is not a valid stream resource in /home/webs/affiliatelib2/CacheManager.php on line 131

Warning: fclose(): supplied argument is not a valid stream resource in /home/webs/affiliatelib2/CacheManager.php on line 132

of propranolol, the first clinically successful beta blockerBeta blockers (sometimes written as β-blockers) are a class of medication 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 United Kingdom to fourth-line as they do not perform as well as other drugs, particularly in the elderly, and there is increasing evidence that the most frequently used beta-blockers especially in combination with thiazide-type diuretics carry an unacceptable risk of provoking Diabetes mellitus type 2.

Sir James W. Black invented propranolol, the first beta adrenergic receptor antagonist that revolutionized the medical management of angina pectoris, considered to be one of the most important contributions to clinical medicine and pharmacology of the 20th century.

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 and in the kidneys. 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 β1 receptors on the kidney causes renin release. 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 nervous system 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 and opening of bronchi, and also reduce tremor and breakdown of glycogen.

It is therefore expected 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 nervous system 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 atrium (anatomy) refractory period (cardiac)s. Sotalol, in particular, has additional antiarrhythmic properties and prolongs action potential duration through potassium channel blockade.

Blockade of the sympathetic nervous system on renin release leads to reduced aldosterone via the renin angiotensin aldosterone system with a resultant decrease in blood pressure due to decreased sodium H20 retention.

Intrinsic sympathomimetic activity Some beta blockers (e.g. oxprenolol and pindolol) exhibit intrinsic sympathomimetic activity (ISA). These agents are capable of exerting low level receptor agonist activity at the β-adrenergic receptor while simultaneously acting as a receptor site receptor 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 pectoris and tachyarrhythmia.

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

Other effects Beta blockers decrease nocturnal melatonin release, perhaps partly accounting for sleep disturbance caused by some agents.Beta blockers protect against social anxiety: "Improvement of physical symptoms has been demonstrated with beta-blockers such as propranolol; however, these effects are limited to the social anxiety experienced in performance situations."

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 pectoris
Mitral valve prolapse
Cardiac arrhythmia
Congestive heart failure
Myocardial infarction
Glaucoma
Migraine prophylaxis
Symptomatic control (tachycardia, tremor) in anxiety and hyperthyroidism
Essential tremor
Phaeochromocytoma, in conjunction with alpha 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.Bisoprolol, carvedilol and sustained-release metoprolol are specifically indicated as adjuncts to standard ACE inhibitor and diuretic therapy in congestive heart failure.

The beta blockers are a benefit due to the reduction of the heart rate which will lower the myocardial energy expenditure. This is turns prolongs the diastolic filling and lengthens the coronary perfusion as a result. Beta blockers have also been a benefit to improving the ejection fraction of the heart despite an initial reduction in it.

Trials have shown that Beta blockers reduce the absolute risk of death by 4.5% over a 13 month period. As well as reducing the risk of mortality, the number of hospital visits and hospitalizations were also reduced in the trials.

Anxiety and performance enhancement Some people, particularly musicians, use beta blockers to avoid stage fright and tremor during public performance and Audition (performing arts)s. The physiological symptoms of the fight/flight response associated with performance anxiety and panic (pounding heart, cold/clammy hands, increased respiration, sweating, etc.) are significantly reduced, thus enabling anxious individuals to concentrate on the task at hand.

Currently, no beta blocker is approved for anxiolytic use by the U.S. Food and Drug Administration. Still, use of beta blockers to combat the physical symptoms of anxiety is not uncommon, particularly among performers, and there are studies which confirm their efficacy as anxiolytics.

Since they lower heart rate and reduce tremor, beta blockers have been used by some Olympic Games marksman to enhance performance, though beta blockers are banned by the International Olympic Committee (IOC). Although they have no recognisable benefit to most sports, it is acknowledged that they are beneficial to sports such as archery and shooting.

Adverse effects Adverse drug reactions (ADRs) associated with the use of beta blockers include: nausea, diarrhea, bronchospasm, dyspnea, cold extremities, exacerbation of Raynaud's syndrome, bradycardia, hypotension, heart failure, heart block, fatigue (medical), dizziness, abnormal vision, decreased concentration, hallucinations, insomnia, nightmares, clinical 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 edema.

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.

A 2007 study revealed that diuretics and beta-blockers used for hypertension increase a patient's risk of developing diabetes whilst ACE inhibitors and Angiotensin II receptor antagonists (Angiotensin Receptor Blockers) actually decrease the risk of diabetes. Clinical guidelines in Great Britain, but not in the United States, call for avoiding diuretics and beta-blockers as first-line treatment of hypertension due to the risk of diabetes.

Beta blockers must not be used in the treatment of cocaine, amphetamine, or other alpha adrenergic stimulant overdose. The blockade of only beta receptors increases hypertension, reduces coronary blood flow, left ventricular function, and cardiac output and tissue perfusion by means of leaving the alpha adrenergic system stimulation unopposed. http://www.emedicine.com/med/topic400.htm The appropriate antihypertensive drugs to administer during hypertensive crisis resulting from stimulant abuse are diuretics like furosemide and alpha blockers like phentolamine. http://www.emedicine.com/EMERG/topic23.htm

Examples of beta blockers

Non-selective agents

Alprenolol
Carteolol
Levobunolol
Mepindolol
Metipranolol
Nadolol
Oxprenolol
Penbutolol
Pindolol
Propranolol
Sotalol
Timolol

β1-Selective agents

Acebutolol
Atenolol
Betaxolol
Bisoprolol Bisoprolol MedlinePlus
Esmolol
Metoprolol
Nebivolol

Mixed α1/β-adrenergic antagonists

Carvedilol
Celiprolol
Labetalol

β2-Selective agents

Butaxamine (weak α-adrenergic agonist activity)

Side Effects / Health Consequences

Low Blood Pressure
Slow Heart Rate
Impaired Circulation
Loss of Sleep
Heart Failure
Asthma
Depression
Sexual Dysfunction
Nausea
Headaches
Dizziness
Muscle Cramps

Comparative information Pharmacological differences

Agents with intrinsic sympathomimetic action (ISA)

Acebutolol, carteolol, celiprolol, mepindolol, oxprenolol, pindolol

Agents with greater aqueous solubility

Atenolol, celiprolol, nadolol, sotalol

Agents with membrane stabilising activity

Acebutolol, betaxolol, pindolol, propranolol

Agents with antioxidant effect

Carvedilol
Nebivolol

Indication differences

Agents specifically indicated for cardiac arrhythmia

Esmolol, sotalol

Agents specifically indicated for congestive heart failure

Bisoprolol, carvedilol, metoprolol, nebivolol

Agents specifically indicated for glaucoma

Betaxolol, carteolol, levobunolol, metipranolol, timolol

Agents specifically indicated for myocardial infarction

Atenolol, metoprolol, propranolol

Agents specifically indicated for migraine prophylaxis

Timolol, propranolol

Propranolol is the only agent indicated for control of tremor, portal hypertension and esophageal variceal bleeding, and used in conjunction with α-blocker therapy in phaeochromocytoma.

References

Footnotes External links

Better Playing Through Chemistry by Blair Tindall, New York Times, October 17, 2004. (Discussing the use of beta-blockers among professional musicians.)
Musicians using beta blockers by Blair Tindall. Condensed version of above article.