Beta-Blockers: Classification and Effects

Beta-Blockers: Classification

• Non-selective beta-blockers (block β1 and β2 receptors): Propranolol, Pindolol, and Timolol
  • Propranolol has good CNS penetration and undergoes hepatic metabolism
• Selective beta-blockers (block β1 receptors): Atenolol, Bisoprolol, and Esmolol
  • Atenolol has limited CNS penetration and is mainly excreted by the kidney
• Beta-blockers with vasodilatory (VD) action: Carvedilol and Nebivolol
  • Carvedilol is non-selective
  • Nebivolol has the highest β1 selectivity

Pharmacological Effects of Beta-Blockers

• Cardiovascular effects: Beta-blockers decrease all cardiac properties by blocking β1 receptors, leading to reduced heart rate (bradycardia) and cardiac output (COP)
• Lower blood pressure by reducing COP, renin release from the kidney (β1), NA release, and central sympathetic outflow
• Some beta-blockers can block vascular α1 receptors
• Some beta-blockers increase the synthesis of PGE2 and PGI2, resulting in vasodilation (VD)
• Respiratory effects: Beta-blockers can produce bronchospasm, even selective β1 blockers can do so at high doses, making them contraindicated in asthmatic patients
• Ocular effects: Beta-blockers like Timolol reduce intraocular pressure (IOP) by decreasing aqueous humor secretion
  • Sufficient Timolol can be absorbed after topical application
• Central nervous system (CNS) effects: Beta-blockers can have antianxiety effects, cause nightmares, and lead to sexual dysfunction via central and peripheral mechanisms
• Metabolic effects: Beta-blockers can cause a hypoglycemic effect by inhibiting glycogenolysis in the liver (β2), increase plasma potassium levels (hyperkalemia) in patients with renal failure, and increase plasma triglycerides while decreasing HDL
• Skeletal muscle effects: Beta-blockers can reduce essential tremors due to β2 blockade in skeletal muscles

Other Specific Beta-Blocker Properties

• Pindolol: A partial agonist that doesn't cause excessive bradycardia
• Esmolol: An ultrashort-acting beta-blocker (t 1/2 = 10 minutes) used intravenously to control arrhythmia during surgery and emergencies
  • It is rapidly hydrolyzed by plasma esterases
• Labetalol: Blocks both β-receptors and α1-receptors (mixed blocker)

Therapeutic Uses of Beta-Blockers

• Hypertension
• Ischemic heart disease, including classic angina and acute myocardial infarction
  • Beta-blockers decrease myocardial work and oxygen demand, redistribute blood to ischemic regions, and provide a cytoprotective effect
• Cardiac arrhythmias: Beta-blockers are used for tachyarrhythmias, especially in thyrotoxic patients
  • They decrease A-V conduction, automaticity, and excitability (Propranolol has a stabilizing action)
  • Intravenous Esmolol is used for acute arrhythmia during surgery
• Hypertrophic obstructive cardiomyopathy: Beta-blockers reduce heart rate and contractility, decreasing outflow resistance to blood flow in the aorta
• Chronic heart failure (HF): Small doses of beta-blockers are used in mild to moderate cases to reduce tachycardia and sympathetic overactivity, ventricular strain, and to inhibit renin release
  • Beta blockers such as Bisoprolol, Metoprolol and Carvedilol are effective and Carvedilol has VD and antioxidant properties
• Hyperthyroidism: Propranolol is used to reduce tachycardia, anxiety, and tremors caused by sympathetic overactivity
  • Propranolol also prevents peripheral conversion of T4 into T3
• Esophageal varices due to liver cirrhosis: Propranolol reduces portal and hepatic blood flow, leading to decreased COP and VC in the splanchnic vascular bed
• Glaucoma (open angle): Topical timolol is used
• Pheochromocytoma: Beta-blockers are used in combination with alpha-blockers
• Migraine prophylaxis: Propranolol is used
• Anxiety: Propranolol is used to treat anxiety

Adverse Effects of Beta-Blockers

• Tiredness and fatigue, are the most common
  • Occurs due to decreased COP and block of β2-mediated vasodilation in skeletal muscles (common with non-selective agents)
• Bradycardia and decreased myocardial contractility (negative inotropic and chronotropic effect)
• Bronchospasm in susceptible individuals due to blockade of β2 receptors in bronchi
• Aggravation of peripheral ischemia (mainly non-selective agents)
• CNS effects: Nightmares and depression
• Sudden withdrawal should be avoided, as it can increase the risk of angina and arrhythmias due to adrenoceptor "supersensitivity”; gradual withdrawal is recommended after prolonged use

Contraindications of Beta-Blockers

• Absolute contraindications include:
  • Bronchial asthma
  • Any degree of heart block
  • Vasospastic (Prinzmetal's) angina
  • Acute heart failure and severe chronic heart failure
  • Sudden withdrawal after long-term use
• Relative contraindications include:
  • Peripheral vascular diseases (PVD)
  • Diabetes mellitus
  • Athletes (strenuous sports), as beta-blockers interfere with strenuous physical activities
  • Hypotension