Beta adrenergic receptor antagonists or beta-blockers

CLASSIFICATION:

EFFECTS:

Beta-blockers have common effects and particular effects.

Common effects
  • The effects of beta-blockers are primarily cardiovascular.
  1. Slow heart rate by ↓slope of slow diastolic depolarization and constitute group II of antiarrhythmic drugs. 
  2. ↓ heart oxygen requirement, preventive treatment of angina pectoris.
  3. ↓ pathological arterial hypertension,
  4. ↓ cardiac output, 
  5. ↓ renin secretion, 
  6. ↓ sympathetic tone by a central effect
  • Beta-blockers ↓intraocular pressure by decreasing aqueous humor secretion.
Particular effects
  • Beta-mimetic activity or intrinsic sympathomimetic activity or ISA
  • High affinity for beta receptors but no or only a low capacity to activate these receptors. 
  • Prevent endogenous catecholamines from inducing beta effects and are thus true beta-blockers.
  • Beta-1 receptors blocker are known as cardioselective.
  • membrane-stabilizing effect which reduces transmembrane ion exchanges known as local anesthetic or antiarrhythmic effect, results from a decrease of the rate of depolarization by sodium entry.
  • Pindolol,Acebutolol ,Carvedilol, Betaxolol, Propranolol, Metoprolol, Labetalol
  • Propranolol inhibits the transport of iodine in the thyroid follicle.
  • Carvedilol would have, at least in vitro, antioxydant properties. 
  • Nebivolol has a NO-mimetic vasodilatator effect.
PHARMACOKINETICS:
One can distinguish liposoluble and water-soluble beta-blockers.
  • Liposoluble beta-blockers: propranolol and oxyprenolol :
  1. Quickly and completely absorbed by the digestive tract.
  2. Metabolized in the liver and can undergo an inactivation known as first metabolism. 
  3. Bound at 90% to plasma proteins.
  4. Great volume of distribution, i.e. they diffuse readily in tissues.
  5. Short duration of action(Esmolol)
  6. Short plasma half-life.
  • Water-soluble beta-blockers like atenolol, nadolol and sotalol have the following properties:
  1. Less absorbed by the digestive tract and in a more irregular way
  2. Little metabolized by the liver
  3. Do not cross blood brain barrier
  4. Not very bound to plasma proteins
  5. Eliminated primarily by the kidney in unchanged form
  6. Restricted volume of distribution
  7. Long plasma half-life(Atenolol)
  8. Nadolol has longest half life
  • Intermediate products such as pindolol and celiprolol
  • Labetalol has both alpha and & beta blocking action
USES:
  • Cardiovascular uses:
  1. Angina pectoris(unstable angina)
  2. Tachycardia of various origins including those of hyperthyroidism, in particular the of Grave's disease where one uses especially propranolol
  3. Arterial hypertension
  4. Myocardial infarction 
  5. Congestive heart failure
  • Three beta-blockers having shown efficacy in this therapeutic use are 
  • Bisoprolol, 
  • Metoprolol 
  • Carvedilol.
  • Other therapeutic uses:
  1. Prevention of primary and secondary digestive bleeding in portal hypertension by rupture of esophageal varices(propranolol is usually used)
  2. Migraine, tremor, transitory somatic symptoms of anxiety, alcohol addiction in which there appears a beta overstimulation( propranolol is usually prescribed)
  3. Glaucoma ( primary open angle glaucoma )by ophthalmic solutions, but they can diffuse into the general circulation and give adverse effects.
  4. Atherosclerosis
  5. Beta blockers mask all effects of hypoglycemia Sweating, Palpitations, Dizziness
  6. Asthma 
ADVERSE EFFECTS:
  • Aggravation of congestive heart failure(with calcium channel blockers)
  • Congestive heart failure is both an indication and a contraindication to the use of beta-blockers. 
  • Aggravation of bradyarrythmia; bradycardia, atrioventricular blocks. 
  • Coldness of the extremities
  • Aggravation of asthmatic disease
  • Worsened risk of anaphylactic shock
  • Metabolic disorders:
  1. O increase in triglycerides
  2. Increase in cholesterol and VLDL (very low density lipoproteins); hypoglycemia in diabetics
  3. Raised risk of developing type II diabetes after antihypertensive treatment 
  4. Various, rare disorders: immunological disorders, lupus, fibroses.
  • Rebound of symptoms: tachycardia, arterial hypertension, fainting, sweats, nervousness , especially risk of angina, myocardial infarction and sudden death.
  • Diffusion in the body after topical use of ophthalmic solutions elicit bradycardia, asthma, in the elderly.
  • Elimination in milk so contraindicated during lactation.
  • Beta-blockers cause hypotension, bradycardia, heart rhythm disorders and shock.
CONTRAINDICATIONS :
  • Decompensated CCF
  • Bradycardia , HR< 60/min
  • COPD , Asthma
  • Variant angina
  • Carbohydrate intolerance
  • Hyperlipidemia
  • Atherosclerosis
  • Sick sinus syndrome
  • Partial and complete heart block
  • Raynaud's disease 
  • Sotalol is contraindicated in renal failure
Exam Question
  • Beta blockers are contraindicated in Decompensated CCF, Asthma , Atherosclerosis
  • Beta blockers are antiarrhythmic agents TYPE II
  • Acebutol, Atenolol & Metoprolol are cardioselective beta blocker
  • Beta blockers are contraindicated in Asthma
  • Atenolol is longer acting than metoprolol 
  • Labetalol has both alpha and & beta blocking action
  • Nadolol has longest half life
  • Sotalol is contraindicated in renal failure
  • Beta blocker without local anaesthetic effect is Atenolol
  • Beta blockers are contraindicated in Sick sinus syndrome
  • Combination use of beta blockers and calcium channel blockers cause Heart block
  • Contraindication of topical beta blockers asthma
  • First line drug choice for management of hypertension in patients with angina Beta Blockers
  • Effect of beta blocker's on heart are Decrease in heart rate, Decreases cardiac output & Precipitates heart failure
  • First line drug for primary open angle glaucoma is Beta blockers
  • Shorest acting beta blocker Esmolol
  • Mechanism of action of timolol is Nonselective beta blocker
  • Beta blockers mask all effects of hypoglycemia Sweating, Palpitations, Dizziness
  • Lipid insoluble beta blockers Are long acting
  • Lipid insoluble beta blockers are Incompletely absorbed orally
  • Lipid insoluble beta blockers Do not cross blood brain barrier

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