Betablocker

Beta-blockers, and beta -receptor blockers, β - blockers or beta -adrenoceptor antagonists, are a series of similarly acting drugs that block β - adrenergic receptors in the body and so the effect of " stress hormone " adrenaline and the neurotransmitter noradrenaline inhibit. The main effects of beta-blockers are the reduction of the resting heart rate and blood pressure, which is why they are used in the medical treatment of many diseases, especially hypertension and coronary heart disease.

Because of the well-documented efficacy in a favorable side effect profile and the large spread of diseases in which beta-blockers are used, they are among the most commonly prescribed drugs at all: 2006 in Germany 1.98 billion defined daily doses ( DDD ) Beta blocker prescribed. The best known and by far the most prescribed drug is metoprolol (for the year 2006: 780.9 million DDD).

In some sports the intake of β - blockers is not allowed; they are in disciplines that require high concentration and precise movements, as performance enhancing substances on the Prohibited List.

Active ingredients and chemical composition

Structurally, beta-blockers Phenol vicinal diols.

Crucial for the effectiveness of beta-blockers are the subtypes β1 and β2 of β - adrenergic receptor. The different drugs differ in their affinity for these receptors. The first beta blocker, propranolol, was developed in the 1960s. This affects approximately equally to both types of the receptor and is therefore referred to as non-selective beta-blockers. As a result, selective beta-blockers have been developed, mainly because the blockade of the β1 - adrenergic receptor is desired. A drug that blocks only the β1 - adrenoceptor is not available. Agents such as metoprolol or bisoprolol act in even more pronounced form but more on the β1 - subtype and are therefore referred to as selective beta-blockers.

In contrast to alpha-blockers Beta blockers have great structural similarity to β -agonists. Why do some of the beta-blocker, a slight excitatory ( agonistic ) effect on beta - receptors. This property is referred to as intrinsic sympathomimetic activity ( ISA) or partial agonist activity (PAA ) and is usually undesirable.

Some newer beta blockers have additional vasodilator ( vasodilating ) Features: Carvedilol causes a blockade of the α1 - adrenergic receptor, nebivolol, a nitric oxide release and celiprolol has an activating effect on β2 - adrenoceptor.

The significance of the enantiomeric purity of the active compounds synthetically produced is increasingly given attention, for the two enantiomers of a chiral drug almost always show a different pharmacology and pharmacokinetics. In an overview of the stereospecific effects of the enantiomers of many beta-blockers have been described. From ignorance of stereochemical relationships such differences were often ignored. Medicines contain drugs frequently as a racemate ( 1:1 mixture of enantiomers ), the fundamental reasons the use of better and have fewer side effects active enantiomer would be preferable. In the case of β - blocker whose pharmacological activity is usually almost entirely attributable to the (S)- enantiomer times more active than the distomer, ie (R)- enantiomer is 10 to 500. Timolol, levobunolol and penbutolol are marketed as enantiomerically pure (S ) -configured drugs, most other β - blockers are used as racemates.

Mechanism of Action

Beta blockers inhibit the activating effect of epinephrine and norepinephrine on the β - adrenergic receptors, causing the stimulative effect of the sympathetic nervous system on the target organs, especially the heart, is attenuated.

Two types of β -adrenoceptors play a role: About β1 -adrenoceptors, especially the cardiac output (heart force and frequency ) and direct blood pressure is stimulated. A stimulation of β2 - adrenergic receptors on the other hand acts on the smooth muscle of the bronchia, of the uterus, as well as the blood vessels. Blocking of these receptors on the smooth muscle twitch acts. This increases among other things, the tone of the bronchial muscles, which can cause them to spasm. Obstructive bronchial diseases such as bronchial asthma or COPD are therefore contraindications for therapy with β2 - effective beta-blockers.

The β1 - adrenoceptor is also found in the kidney, where it controls the secretion of pressor hormone renin. This is probably the main reason for the long-term efficacy of beta-blockers in lowering blood pressure.

Indications

Hypertension

In the drug treatment of arterial hypertension beta blockers are usually used in combination with other antihypertensive agents. The classification as a drug of first choice was provided by studies in question. According to the guidelines of hypertension treatment by 2008, they remain one of the drugs of first choice, because they have beneficial effects, particularly in patients with coronary artery disease and heart failure. The disadvantage is their impact, however, on the risk of weight gain, lipid and glucose metabolism. "Beta blockers should be avoided in patients with metabolic syndrome and its components as Bauchfettleibigkeit, high normal or elevated plasma glucose levels and impaired glucose tolerance. " (Quote Guideline )

The efficacy of beta-blockers to lower blood pressure is indeed undisputed exactly how this reduction is achieved but, is not fully understood. Probably it is a combination of effects. Thus, a reduction in blood pressure is achieved at the start of treatment by reduction of cardiac output. In the long run play probably the inhibition of sympathetic nerve activity and the reduction of renin release a role.

Coronary heart disease and heart attack

Beta blockers reduce the decrease in the cardiac output of the oxygen requirement of the heart. In addition, on the reduction of heart rate reached a better blood flow to the coronary arteries, as these are perfused only during diastole. Beta blockers are therefore the most important drugs in stable angina pectoris and are - used after a heart attack - with the same goal. For both indications, a life-prolonging effect of beta-blockers is well established.

Heart failure

Even with stable chronic heart failure studies show an improvement of prognosis by use of beta blockers from the stage NYHA II. Here is the reduction of Sympathikuseinflusses on the heart and the economization of cardiac work in the foreground, but the exact mechanism of action is not yet clear. Is important in the treatment of heart failure with beta-blockers, to make the treatment einschleichend, so to begin with low doses and to increase the dose slowly.

Cardiac arrhythmias

To treat tachycardic arrhythmia different classes of antiarrhythmic drugs are available. Beta blockers are therefore also referred to as "Class II antiarrhythmic drugs ." Unlike many other antiarrhythmic drugs, the life-prolonging effect of beta-blockers has been proven, so they are among the most important drugs used antiarrhythmic therapy. For the effectiveness of beta-blockers their arousal inhibitory effect on the heart plays a decisive role.

Further indications

Other indications for beta-blockers are or may be:

• Hyperthyroidism
• Tremor
• Glaucoma
• Migraine
• Pheochromocytoma
• Anxiety
• Portal hypertension
• Prevention of Ösophagusvarizenblutungen
• Hemangioma
• Dumping syndrome

Compliance

Important for the effectiveness of beta-blockers is - as with other regularly taken drugs - taking loyalty (Compliance): An analysis of the compliance of about 31,500 patients who had a heart attack survived at least 15 months and which among other beta-blockers were prescribed, was found that a bad intake loyalty lowers life expectancy. Compliance was judged to be good if the patients had at least 80 % of prescribed medication cashed, as moderate if they cashed 40-79 %. The mortality of the patients with " moderate " was increased as compared to those with " good " compliance by 1% (within one year) and 13% (two years).

Contraindications

Important relative and absolute contraindications that principle apply to all beta-blockers are:

• Bronchial asthma
• Chronic obstructive pulmonary disease (COPD)
• Pre-existing bradycardia with a heart rate below 50 bpm
• AV conduction disturbances
• Acute heart failure
• Co-administration of calcium channel blockers of the verapamil or diltiazem type (gain of cardiac depression )
• In the PAD are beta-blockers according to the current guidelines ( German Society for Angiology ) no longer contraindicated

Side effects

In general, beta-blockers are well tolerated even with prolonged use. The known side effects after discontinuation of the drug or dosage adjustment usually reversible. The main side effects, which in principle apply to all beta-blockers are:

• Bradycardia (too slow pulse )
• Heart failure
• Asthma attacks
• About conduction problems
• Delayed symptoms of hypoglycaemia
• Fatigue, depression, erectile dysfunction
• Amplification of peripheral circulatory disorders
• Triggering or worsening of symptoms of psoriasis