Beta blocker

Beta blockers or beta-adrenergic blocking agents are a class of drugs used to treat a variety of cardiovascular conditions and some other diseases.

Operation
Beta blockers block the action of epinephrine and norepinephrine on the &beta;-adrenergic receptors in the body (primarily in the heart, peripheral blood vessels, bronchi, pancreas, and liver). The hormones and neurotransmitters stimulate the sympathetic nervous system by acting on these receptors.

There are three types of beta receptors: &beta;1-receptors located mainly in the heart, and &beta;2-receptors located all over the body, but mainly in the lungs, muscles and arterioles. &beta;3-receptors are less well characterised, but have a role in fat metabolism.

Activation of &beta;1-receptors by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Drugs that block these receptors therefore have the reverse effect: they lower the heart rate and blood pressure and hence are used in conditions when the heart itself is deprived of oxygen. They are routinely prescribed in patients with ischemic heart disease and hypertension. In addition, beta blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels.

Drugs that block &beta;2 receptors generally have a calming effect and are prescribed for anxiety, migraine, esophageal varices and alcohol withdrawal syndrome, among others.

Many beta blockers affect both type 1 and type 2 receptors; these are termed non-selective blockers. Propranolol and nadolol are examples. Selective beta blockers primarily affect &beta;1-receptors. Non-selective beta blockers should generally not be used in patients with asthma or any reactive airway disease. Doing so can precipitate bronchospasm by blocking the &beta;2 mediated relaxation of the bronchiole muscles.

Selective beta blockers generally only block the type 1 receptor. They gradually become less selective at higher doses. Examples of selective beta1 blockers in common use include atenolol and metoprolol.

Since they lower heart rate, beta blockers have been used by some Olympic marksmen to provide more aiming time between heart beats. Some musicians use beta blockers to avoid stage fright and tremor during auditions and performances. Beta blockers decrease nocturnal melatonin release.

Beta Blockers at a Glance
By receptor type:
 * Beta 1 selective (Cardio selective): Atenolol, Acebutolol, Betaxolol, Bisoprolol, Esmolol, Metoprolol, Nebivolol.
 * Preferable in pts. with Bronchospastic disease, Diabetes, Peripheral vascular ds. e.g. Raynaud’s phenomenon (bronchoconstriction, inhibition of glycogenolysis, vasoconstriction are due to b2 blockade)
 * Beta 2 selective—Butoxamine
 * Additional a1 antagonistic activity: Bucindolol, Carvedilol, Labetolol, Medroxolol
 * Potentially advantageous in pts. with hypertension, occlusive peripheral artery ds. (Promote vasodilatation)
 * Partial agonist (intrinsic sympathomimetic) activity: Acebutolol, Bopindolol, Carteolol, Celiprolol*, Labetolol, Oxiprenolol, Penbutolol, Pindolol (Beta 1 selective antagonist with b2-agonist activity; also has non-adrenergic receptor- mediated vasodilating property.)
 * Potentially advantageous in pts. with hypertension, occlusive peripheral artery ds. (Promote vasodilatation)
 * Less likely to cause Bradycardia, Bronchoconstriction, Lipid abnormalities.
 * Local anaesthetic action (Membrane stabilizing property/ Na+ channel blockade): Acebutolol, Propranolol, Propafenone; slight activity: Betaxolol, Labetolol, Metoprolol, Pindolol

By Lipid solubility:
 * High: Propranolol, Penbutolol
 * Readily cross BBB—central effects, large vol. of distribution
 * Low: Atenolol, Esmolol, Nadolol
 * Don’t cross BBB—no central effects

By Half-life:
 * Long: Betaxolol, Nadolol (14- 22 hrs.)
 * OD dosing.
 * Shortest: Esmolol (8- 10 mins.)
 * Hydrolyzed by esterases in erythrocytes)
 * Given as i.v. infusion in urgent settings.
 * Intermediate: between 3- 12 hrs.

By Oral bioavailability:
 * High: Betaxolol, Pindolol, Penbutolol, and Sotalol
 * Low: Carvedilol, Esmolol, Labetolol, Nadolol, Propranolol

Misc:
 * No effect on plasma rennin activity: Pindolol
 * Anti-oxidant activity: Carvedilol
 * Antiarrythmic action (independent of b blocking action): Sotalol

USES

 * Hypertension
 * Prophylaxis of Angina
 * Prophylaxis of MI—Metoprolol, Propranolol, Timolol
 * Mild- Moderate CHF (Contraindicated in compensated Ht. failure) – Bisoprolol, Bucindolol, Carvedilol, Metoprolol
 * Hypertrophic obstructive cardiomyopathy – esp. Propranolol
 * Pheochromocytoma (a blocker given before b blocker)
 * Ac. Dissecting aortic aneurysm
 * Marfan’s syndrome (Chr. Tt. with Propran. slows progression of aortic dilatation & its complications)
 * Hyperthyroidism
 * Prophylaxis of Migraine -- Metoprolol, Propranolol, Timolol
 * Somatic manifestations of anxiety (e.g. tremors)-- Propranolol
 * Glaucoma (↓ Aqueous production) –Betaxolol, Carteolol, Levobunolol, Metipranolol, Timolol
 * Prevention of vericial bleeding in portal hypertension -Propranolol, Nadolol