Beta Blockers: Classifications & Effects

β-Blocker Classifications

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

Pharmacological Effects of Beta Blockers

• Cardiovascular effects include blocking β1 receptors, leading to decreased cardiac properties, reduced heart rate (bradycardia), and lowered cardiac output (COP).
• Blood pressure is lowered through reduced cardiac output, renin release from the kidney (β1), norepinephrine (NA) release, and central sympathetic outflow.
• Beta blockers block vascular α1 receptors and increase the synthesis of PGE2 and PGI2, which cause vasodilation.
• Respiratory effects include the potential to produce bronchospasm, even with selective β1 blockers at high doses, making them contraindicated in asthmatic patients.
• Ocular effects include lowering intraocular pressure (IOP) by decreasing aqueous humor secretion; Timolol is effective topically.
• Central nervous system effects include antianxiety effects, nightmares, and sexual dysfunction through central and peripheral mechanisms.
• Metabolic effects include increasing the hypoglycemic effect of insulin, increasing plasma potassium (hyperkalemia) in patients with renal failure, and increasing plasma triglycerides while decreasing HDL.
• Skeletal muscle effects include decreasing essential tremors through β2 receptor blockade in skeletal muscles.
• Pindolol acts as a partial agonist that does not cause excessive bradycardia.
• Esmolol is ultrashort-acting (half-life = 10 minutes) due to plasma esterase hydrolysis, and is given intravenously to control arrhythmia during surgery and emergencies.
• Labetalol blocks both β and α1 receptors, acting as a mixed blocker.

Therapeutic Uses of Beta Blockers

• Used in treating hypertension
• Used in ischemic heart disease by decreasing myocardial work and oxygen demand, redistributing blood to ischemic regions, and providing a cytoprotective effect in cases of classic angina and acute myocardial infarction.
• Treats cardiac arrhythmias (tachyarrhythmias), especially in thyrotoxic patients, by reducing A-V conduction, automaticity, and excitability (Propranolol stabilizes action).
  • Intravenous Esmolol is used for acute arrhythmia during surgery.
• Can improve hypertrophic obstructive cardiomyopathy.
  • Hypertrophic obstructive cardiomyopathy is characterized by congenital thickening of the ventricular wall and septum, leading to impaired aortic outflow, especially during exercise.
  • Beta blockers inhibit the heart's activity, reducing heart rate, contractility, and outflow resistance.
• Small doses of β-blockers are used in mild to moderate cases of chronic heart failure (HF) to reduce tachycardia & sympathetic overactivity.
  • Beta blockers inhibit renin release that causes cardiac remodeling.
  • Bisoprolol, Metoprolol, and Carvedilol are effective for chronic heart failure; Carvedilol has vasodilatory and antioxidant properties.
• Propranolol is used to treat hyperthyroidism by reducing tachycardia, anxiety, and tremors caused by sympathetic overactivity, and may also prevent peripheral conversion of T4 into T3.
• Propranolol is used to treat esophageal varices due to liver cirrhosis by reducing portal and hepatic blood flow and decreasing COP in the splanchnic vascular bed.
• Topical Timolol treats glaucoma (open-angle).
• It treats Pheochromocytoma when combined with alpha-blockers.
• Propranolol is used for migraine prophylaxis and treats anxiety.

Adverse Effects of Beta Blockers

• Common side effects are tiredness and fatigue due to decreased COP and blockade of β2-mediated vasodilation in skeletal muscles with non-selective agents.
• Can cause bradycardia and decreased myocardial contractility, resulting in negative inotropic and chronotropic effects.
• Can result in bronchospasm in susceptible individuals due to the block of β2 receptors in the bronchi.
• Can cause the aggravation of peripheral ischemia, mainly with non-selective agents.
• Central nervous system effects include nightmares and depression.
• Sudden withdrawal of beta-blockers can increase the risk of angina and arrhythmias.
  • Gradual withdrawal is recommended especially after prolonged use, due to adrenoceptor "supersensitivity."

Contraindications

• Absolute contraindications for β-blockers 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 is also an absolute contraindication.
• Relative contraindications include peripheral vascular diseases (PVD), diabetes mellitus, use in athletes (especially in strenuous sports, as beta-blockers interfere with strenuous physical activities), and hypotension.