Beta-Blocker Classifications and Effects

Beta-Blocker Classifications

• Non-selective beta-blockers block both β1 and β2 receptors.
  • Examples of non-selective beta-blockers include Propranolol, Pindolol, and Timolol.
  • Propranolol has good CNS penetration and undergoes hepatic metabolism.
• Selective beta-blockers primarily block β1 receptors.
  • Atenolol, Bisoprolol, and Esmolol are examples of selective beta-blockers.
  • Atenolol has limited CNS penetration and is mainly excreted by the kidneys.
• Beta-blockers with vasodilator (VD) action include Carvedilol and Nebivolol.
  • Carvedilol is non-selective.
  • Nebivolol has the highest β1 selectivity.

Pharmacological Effects of Beta-Blockers

• Beta-blockers decrease all cardiac properties by blocking β1 receptors in the heart.
  • Results in lowering the heart rate and cardiac output, which leads to decreased blood pressure.
• Blood pressure reduction occurs through multiple mechanisms.
  • Decreased cardiac output.
  • Reduced renin release from the kidneys by blocking β1 receptors.
  • Decreased noradrenaline (NA) release and central sympathetic outflow.
  • Some beta-blockers can block vascular α1 receptors.
  • Some beta-blockers increase the synthesis of PGE2 and PGI2, which cause vasodilation.
• Can cause bronchospasm, even selective β1-blockers at high doses.
  • Contraindicated in individuals with asthma.
• Lower intraocular pressure (IOP) by reducing aqueous humor secretion; for example, Timolol.
  • Sufficient Timolol absorption after topical usage.
• Can have antianxiety effects, but may also cause nightmares and sexual dysfunction due to central and peripheral mechanisms.

Metabolic and Specific Properties of Beta-Blockers

• Can have metabolic effects.
  • Increased hypoglycemic effect of insulin due to decreased glycogenolysis in the liver via β2 receptor blockade.
  • Increase plasma potassium (hyperkalemia) in patients with renal failure.
  • Increase plasma triglycerides and lower HDL.
• Can reduce essential tremors by blocking β2 receptors in skeletal muscles.
• Pindolol is a partial agonist, which prevents excessive bradycardia.
• Esmolol has an ultrashort acting time (half-life = 10 minutes) due to rapid hydrolysis by plasma esterases.
  • It is administered via intravenous infusion to manage arrhythmia during surgery and emergencies.
• Labetalol blocks both β-receptors and α1-receptors.

Therapeutic Uses of Beta-Blockers

• Treatment for hypertension
• Ischemic heart disease, including classic angina and acute myocardial infarction.
  • Reduces myocardial work and oxygen demand.
  • Promotes blood redistribution to ischemic (subendocardial) regions.
  • Provides a cytoprotective effect.
• Cardiac arrhythmias (tachyarrhythmias), particularly in thyrotoxic patients.
  • Decreases A-V conduction, automaticity, and excitability (Propranolol acts as a stabilizer).
  • Intravenous Esmolol is utilized for rapid arrhythmia correction during surgical procedures.
• Hypertrophic obstructive cardiomyopathy, a congenital condition causing thickening of the ventricular wall and septum.
  • The inhibitory effect of β-blockers on the heart lessens outflow resistance by reducing heart rate and contractility.
• Mild to moderate cases of chronic heart failure (HF) may benefit from beta-blockers in small doses.
  • Beta-blockers reduce tachycardia and sympathetic over activity.
  • Reduces blood pressure and resultant ventricular strain related to heart failure.
  • Hinders renin release, slowing cardiac remodeling from RAAS.
  • Bisoprolol, Metoprolol, and Carvedilol are most effective.

Further Uses and Effects

• Help manage hyperthyroidism by alleviating tachycardia, anxiety, and tremors, which are caused by excessive sympathetic activity, by using Propranolol.
  • Propranolol also hinders the peripheral transformation of T4 to T3.
• Portal and hepatic blood flow can be reduced using Propranolol, reducing the risk in esophageal varices due to liver cirrhosis.
• Topical Timolol is used in the treatment of glaucoma to lessen the effects of open angle glaucoma.
• Combined with alpha-blockers to treat Pheochromocytoma.
• Can be used to treat migraine prophylaxis with Propranolol.
• Anxiety treatment can be done using Propranolol.

Adverse Effects and Contraindications

• Common adverse include, tiredness and fatigue.
  • Due to decreased cardiac output and β2-mediated vasodilation in skeletal muscles, caused by non-selective agents.
• Bradycardia and decreased myocardial contractility.
• Bronchospasm.
  • Due to the blockade of β2-receptors in the bronchi, in susceptible individuals.
• Reduced peripheral ischemia, mainly from non-selective agents.
• Potential CNS effects like nightmares and depression.
• Withdrawal should be gradual as abrupt cessation may exacerbate angina and arrhythmias.
• Absolute contraindications: bronchial asthma, any level of heart block, vasospastic (Prinzmetal’s) angina, acute heart failure, severe heart failure, or sudden withdrawal.
• Relative contraindications: peripheral vascular disease, diabetes mellitus, athletes (due to interference with strenuous activities), or hypotension.