Beta Blockers: Classifications and Effects

Beta Blockers

• Beta-blockers are sympatholytic drugs.

Learning Outcomes

• Classifications of β-receptor blockers
• Pharmacological effects and uses of β blockers
• Adverse effects and contraindications of β blockers

Classification of Beta Blockers

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

Pharmacological Effects

• Cardiovascular (CVS) effects involve blocking β1 receptors, leading to decreased cardiac properties, heart rate (bradycardia), and cardiac output (COP).
• Beta-blockers lower blood pressure through decreased COP, decreased renin release from the kidney (β1), decreased noradrenaline (NA) release and central sympathetic outflow
• Some beta-blockers can block vascular α1 receptors
• Some can increase the synthesis of PGE2 and PGI2 (VD).
• Respiratory effects: Can produce bronchospasm, even selective β1 blockers at high doses.
  • Contraindicated in asthmatic patients.
• Eye: Decrease intraocular pressure (IOP) by decreasing aqueous humor secretion (Timolol).
  • Timolol can be absorbed after topical application.
• CNS: Can have antianxiety effects, cause night mares, and lead to sexual dysfunction via central and peripheral mechanisms.
• Metabolic effects: Can have a hypoglycemic effect on insulin, increase plasma K+ (hyperkalemia) in patients with renal failure, and increase plasma triglycerides while decreasing HDL.
• Skeletal muscle: Decrease essential tremors by blocking β2 receptors in skeletal muscles.

Specific Properties of Beta Blockers

• Pindolol is a partial agonist and does not cause excessive bradycardia.
• Esmolol is ultrashort acting (t 1/2 = 10 minutes) due to hydrolysis by plasma esterases.
  • Esmolol is given by intravenous infusion to control arrhythmia during surgery and emergency.
• Labetalol blocks both β-receptors and α1-receptors (mixed blocker).

Therapeutic Uses

• Used to treat hypertension.
• Ischemic heart disease (classic angina and acute myocardial infarction): Decrease myocardial work and O2 demand, redistribute blood to ischemic regions, and provide cytoprotective effects.
• Cardiac arrhythmias (tachyarrhythmias): Particularly in thyrotoxic patients, decreases A-V conduction, automaticity, and excitability (Propranolol).
  • I.V.I. Esmolol can be used for acute arrhythmia during surgery.
• Hypertrophic obstructive cardiomyopathy involves congenital thickening of the ventricular wall and septum, impairing blood flow through the aortic outlet during exercise.
  • Beta-blockers work to inhibit HR and contractility while decreasing outflow resistance to blood flow in the aorta.
• Small doses can treat mild to moderate cases of chronic heart failure (HF).
• Beneficial effects in heart failure: Reduce tachycardia and sympathetic overactivity, reduce BP and ventricular strain, and inhibit renin release.
  • Bisoprolol, Metoprolol, and Carvedilol are effective in chronic HF.
  • Carvedilol has VD and antioxidant properties.
• Hyperthyroidism: Propranolol helps reduce tachycardia, anxiety, and tremors due to sympathetic overactivity. Also prevents the peripheral conversion of T4 into T3.
• Esophageal varices due to liver cirrhosis: Propranolol reduces portal and hepatic blood flow, decreases COP and VC in the splanchnic vascular bed in an unopposed alpha-action.
• Glaucoma (open-angle): Topical timolol is used.
• Pheochromocytoma: Used in combination with alpha-blockers.
• Migraine prophylaxis: Propranolol is used.
• Anxiety: Propranolol is used.

Adverse Effects

• Common effects include tiredness and fatigue.
  • Due to decreased COP and the block of β2-mediated VD in skeletal muscles.
• Bradycardia and decreased myocardial contractility.
  • Negative inotropic and chronotropic effects.
• Bronchospasm in susceptible individuals such as asthmatics due to blocking β2-receptors in the bronchi.
• Aggravation of peripheral ischemia
  • Non-selective agents.
• CNS effects: Nightmares and depression.
• Sudden withdrawal of beta-blockers can increase the risk of angina and arrhythmias.
  • Gradual withdrawal is recommended, especially after prolonged use.

Contraindications

• Absolute contraindications: Bronchial asthma, any degree of heart block, vasospastic (Prinzmetal’s) angina, acute heart failure & severe chronic heart failure, and sudden withdrawal after long-term use.
• Relative contraindications: Peripheral vascular diseases (PVD), diabetes mellitus, athletes (strenuous sports), and hypotension.
• Beta-blockers interfere with strenuous physical activities.