Beta-adrenergic blockers

Beta-adrenergic blockers

Beta-adrenergic blockers, the most widely used adrenergic block-ers, prevent stimulation of the sympathetic nervous system by in-hibiting the action of catecholamines at beta-adrenergic receptors.

From not so selective…

Beta-adrenergic blockers can be selective or nonselective. Non-selective beta-adrenergic blockers affect:

·                 beta1 receptor sites (located mainly in the heart)

·                 beta2 receptor sites (located in the bronchi, blood vessels, and uterus).

Nonselective beta-adrenergic blockers include carteolol, carvedilol, labetalol, levobunolol, metipranolol, penbutolol, pin-dolol, sotalol, nadolol, propranolol, and timolol. (Carvedilol and labetalol also block alpha1 receptors.)

…to highly discriminating

Selective beta-adrenergic blockers primarily affect beta1-adrenergic sites. They include acebutolol, atenolol, betaxolol, bisoprolol, esmolol, and metoprolol.

The not so beta blockers

Some beta-adrenergic blockers, such as pindolol and acebutolol, have intrinsic sympathetic activity. This means that instead of at-taching to beta receptors and blocking them, these beta-adrenergic blockers attach to beta receptors and stimulate them. These drugs are sometimes classified as partial agonists.

Pharmacokinetics

Beta-adrenergic blockers are usually absorbed rapidly and well from the GI tract and are somewhat protein-bound. Food doesn’t inhibit—and may even enhance—their absorption. Some beta-adrenergic blockers are absorbed more completely than others.

Peak by I.V.

The onset of action of beta-adrenergic blockers is primarily dose-and drug-dependent. The time it takes to reach peak concentra-tion levels depends on the administration route. Beta-adrenergic blockers given I.V. reach peak levels much more rapidly than those taken by mouth.

Distribution

Beta-adrenergic blockers are distributed widely in body tissues, with the highest concentrations found in the:

·                 heart

·                 liver

·                 lungs

·                 saliva.

Metabolism and excretion

Except for nadolol and atenolol, beta-adrenergic blockers are me-tabolized in the liver. They’re excreted primarily in urine, either unchanged or as metabolites, but can also be excreted in feces, bile and, to some degree, breast milk.

Pharmacodynamics

Beta-adrenergic blockers have widespread effects in the body be-cause they produce their blocking action not only at adrenergic nerve endings but also in the adrenal medulla.

A matter of the heart

Effects on the heart include increased peripheral vascular resis-tance, decreased blood pressure, decreased force of the heart’s contractions, decreased oxygen consumption by the heart, slowed impulse conduction between the atria and ventricles, and de-creased cardiac output (the amount of blood the heart pumps each minute). (See How beta-adrenergic blockers work.)

Selective and nonselective effects

Some beta-adrenergic blocker effects depend on whether the drug is classified as selective or nonselective.

Selective beta-adrenergic blockers, which prefer to block beta1-receptor sites, reduce stimulation of the heart. They’re often referred to as cardioselective beta-adrenergic blockers.

Nonselective beta-adrenergic blockers, which block both beta1- and beta2-receptor sites, not only reduce stimulation of the heart but also cause the bronchioles of the lungs to constrict. For instance, nonselective beta-adrenergic blockers can cause bron-chospasm in patients with chronic obstructive lung disease. This adverse effect isn’t seen when cardioselective drugs are given at lower doses.

Pharmacotherapeutics

Beta-adrenergic blockers are used to treat many conditions and are under investigation for use in many more. As mentioned previ-ously, their clinical usefulness is based largely (but not exclusive-ly) on how they affect the heart. (SeeAre beta-adrenergic block-ers underused in elderly patients?)

Helping the heart

Beta-adrenergic blockers can be prescribed after a heart attack to prevent another heart attack or to treat:

·                 angina

·                 heart failure

·                 hypertension

·                 cardiomyopathy (a disease of the heart muscle)

·                 supraventricular arrhythmias (irregular heartbeats that origi-nate in the atria, SA node, or atrioventricular node).

Jack of all trades

Beta-adrenergic blockers are also used to treat:

·                 anxiety

·                 cardiovascular symptoms associated with thyrotoxicosis (over-production of thyroid hormones)

·                 essential tremor

·                 migraine headaches

·                 open-angle glaucoma

·                 pheochromocytoma (tumor of the adrenal gland).

Drug interactions

Many drugs can interact with beta-adrenergic blockers to cause potentially dangerous effects. Some of the most serious effects in-clude cardiac or respiratory depression, arrhythmias, severe bronchospasm, and severe hypotension that can lead to vascular collapse. Other interactions can also occur:

·                 Increased effects or toxicity can occur when cimetidine, digox-in, or calcium channel blockers (primarily verapamil) are taken with beta-adrenergic blockers.

·                 Decreased effects can occur when rifampin, antacids, calcium salts, barbiturates, or anti-inflammatories, such as indomethacin and salicylates, are taken with beta-adrenergic blockers.

·                 Lidocaine toxicity may occur when lidocaine is taken with beta-adrenergic blockers.

·                 The requirements for insulin and oral antidiabetic drugs can be altered when these drugs are taken with beta-adrenergic blockers.

·                 The ability of theophylline to produce bronchodilation is im-paired by nonselective beta-adrenergic blockers.

·                 Clonidine taken with a nonselective beta-adrenergic blocker can cause life-threatening hypertension during clonidine withdrawal.

·                 Sympathomimetics taken with nonselective beta-adrenergic blockers can cause hypertension and reflex bradycardia. (See Ad-verse reactions to beta-adrenergic blockers.)