CLASSIFICATION:

EFFECTS:

• Beta-blockers have common effects and particular effects.

Common effects 

• The effects of beta-blockers are primarily cardiovascular.
  • Slow heart rate by ↓slope of slow diastolic depolarization and constitute group II of antiarrhythmic drugs. 
  • ↓ heart oxygen requirement,  preventive treatment of angina pectoris.
  • ↓ pathological arterial hypertension,
  • ↓ cardiac output, 
  • ↓ renin secretion, 
  • ↓ 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.
• True beta-blockers – Prevent endogenous catecholamines from inducing beta effects.

Beta-1 receptors blocker – Cardioselective/selective β₁/II generation beta blockers:

• Preferred in diabetes mellitus , bronchial asthma, peripheral vascular disease & hyperlipidemia.

Nebivolol – 

• NO-mimetic vasodilatator effect.
• Most cardioselective.

Beta blockers with membrane-stabilizing effect:

• Exhibits “Local anesthetic or antiarrhythmic effect” by reducing transmembrane ion exchanges. 
• Due to decreased depolarization rate by sodium entry.
• Should be avoided in Glaucoma – Risk of corneal anaesthesia.
• Pindolol, Acebutolol, Carvedilol, Betaxolol, Propranolol, Metoprolol & Labetalol.
  • Propranolol inhibits transport of iodine in thyroid follicle.
  • Carvedilol would have, at least in vitro, antioxydant properties. 

PHARMACOKINETICS:

Acts by being liposoluble & water-soluble drugs.

• Liposoluble beta-blockers (propranolol & oxyprenolol):
  • Quickly and completely absorbed by the digestive tract.
  • Metabolized in liver and can undergo an inactivation known as first metabolism. 
  • Bound at 90% to plasma proteins.
  • Great volume of distribution, i.e. they diffuse readily in tissues.
  • Short duration of action (Esmolol)
  • Short plasma half-life.

Water-soluble beta-blockers like atenolol, nadolol and sotalol:

• Less absorbed by digestive tract & more irregular way.
• Little metabolized by liver.
• Do not cross blood brain barrier.
• Not very bound to plasma proteins.
• Eliminated primarily by kidney in unchanged form – Hence, contraindicated in renal failure.
• Restricted volume of distribution.
• Long plasma half-life(Atenolol).
• Nadolol has longest half-life.
• Intermediate products such as pindolol & celiprolol.
• Labetalol has both alpha and & beta blocking action.
• Elimination in milk – Contraindicated during lactation.

USES:

Cardiovascular uses:

• Angina pectoris(unstable angina)

Tachycardia:

• Includes hyperthyroidic patients (Grave’s disease) taking propranolol.
  • Arterial hypertension
  • Myocardial infarction 

Congestive heart failure

• Three beta-blockers having shown efficacy in this therapeutic use are 
  • Bisoprolol, 
  • Metoprolol 
  • Carvedilol.

Other therapeutic uses:

• Prevention of primary and secondary digestive bleeding in portal hypertension by rupture of esophageal varices(propranolol is usually used)
• Migraine, tremor, transitory somatic symptoms of anxiety, alcohol addiction in which there appears a beta overstimulation (propranolol is usually prescribed).
• Glaucoma – Primary open angle glaucoma.
  • By ophthalmic solutions.
  • Diffuses into general circulation causing adverse effects.
• Atherosclerosis

ADVERSE EFFECTS:

• Aggravation of congestive heart failure (with calcium channel blockers).
• Non-selective (Ist generation beta blockers) mask all effects of hypoglycemia Sweating, Palpitations, Dizziness.
• Congestive heart failure is both an indication & contraindication to beta-blockers use.
  • Aggravation of bradyarrythmia; bradycardia, atrioventricular blocks. 
  • Beta-blockers like intrinsic sympathomimmetic activity like celiprolol, Oxprenolol, Pindolol, Pendutolol, Acebutolol, Alprenolol are useful.
  • Due to  partial agonistic activity apart from bloacking activity.

Masked hypoglycemic symptoms in diabetics:

• Tachycardia, sweating & tremors – Due to sympathetic stimulation acts as warning sings.
  • Beta-blockers mask these symptoms (Except sweating) – Mediated via cholingeric system.
  • Hence, patient directly fall into coma.
• Delayed recover from hypoglyβ₁cemia – Due to β₂ mediated hyperglycemia.
• Raised risk of developing type II diabetes after antihypertensive treatment.

Rebound of symptoms: 

• Tachycardia, arterial hypertension, fainting, sweats, nervousness , especially risk of angina, myocardial infarction and sudden death.
• Diffusion in body after topical use of ophthalmic solutions elicit bradycardia, asthma, in elderly.

Various, rare disorders: 

• Immunological disorders, lupus, fibroses.

CONTRAINDICATIONS :

• Decompensated CCF
• Bradycardia , HR< 60/min
• COPD
• Asthma
• Variant angina
• Carbohydrate intolerance
• Hyperlipidemia
• During lactation – Elimination in milk.
• Atherosclerosis
• Sick sinus syndrome
• Partial and complete heart block
• Raynaud’s disease – 
  • Due to vasoconstriction.
  • Worsens peripheral vascular disease.
• Sotalol is contraindicated in renal failure.

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