Beta blockers

Beta blockers are a group of drugs that inhibit the sympathetic activation of β-adrenergic receptors. Cardioselective blockers (e.g., atenolol, bisoprolol) primarily block β₁ receptors in the heart, causing decreased heart rate, cardiac contractility, cardiac workload, and AVN conduction. Nonselective beta blockers (e.g., pindolol, propranolol) inhibit all β receptors and may cause bronchoconstriction, peripheral vasoconstriction, and metabolic imbalances (e.g., hypoglycemia and hyperglycemia, hypertriglyceridemia) in addition to cardiac effects. Cardioselective beta blockers have a lower side-effect profile and are preferred in the management of coronary heart disease, compensated heart failure, acute coronary syndrome, and certain types of arrhythmias. Propranolol, a nonselective beta blocker, is the first-line drug in the management of essential tremor, portal hypertension, migraine prophylaxis, and thyroid storm. Beta blockers are contraindicated in patients with symptomatic bradycardia, AV block, decompensated heart failure, and asthma. Initiation and cessation of beta-blocker therapy should always be gradual to avoid side effects or symptoms of withdrawal (e.g., rebound tachycardia, hypertension, acute cardiac death).

See also “Beta blocker poisoning.”

With the exception of nebivolol, all cardioselective beta blockers begin with the letters A to M (B₁ = first half of the alphabet). Except for beta blockers with alpha-blocking action (labetalol, bucindolol, carvedilol), all noncardioselective beta blockers begin with the letters N to Z (B₂ = second half of the alphabet).

References^{[6][7][8][9][10]}

Beta blockers competitively bind to and block β-adrenergic receptors, thereby inhibiting sympathetic (adrenergic and/or noradrenergic) stimulation of β receptors. See “The sympathetic vs. parasympathetic nervous system” for details regarding the effects of β-adrenergic stimulation.

Effects of β-adrenergic blockade

Beta blockers competitively inhibit adrenergic substances (e.g., adrenaline, noradrenaline) at β receptors.
A rule to remember the main effector organs for β receptors: There is 1 heart (β₁ blockers act on the heart) and 2 lungs (β₂ blockers affect bronchial smooth muscles).

Intrinsic sympathomimetic activity (ISA) ^[6][8]

• Mechanism of action: partial agonist activity
  • Beta blockers with ISA bind to and stimulate the β-adrenergic receptor (agonistic effect) while competitively inhibiting the binding of epinephrine and norepinephrine to β-adrenergic receptors (antagonistic effect).
  • Produce partial sympathetic activity while inhibiting the normal and activated sympathetic activity
• Effects
  • Cause less bradycardia and less peripheral vasoconstriction because of their mild agonistic action
  • Have a favorable effect on lipid profile (esp. pindolol and acebutolol): preferred in patients with metabolic syndrome ^[10]
  • Not recommended in patients with congestive heart failure, ischemic heart disease, and tachyarrhythmias ^[13]
• Agents: pindolol, acebutolol, carteolol, alprenolol ^[14]

References:^[3]

See “Beta blocker poisoning” for features of overdose and their management.

Overview

Beta blockers should be introduced gradually with slow increases in dosage and slowly tapered off when no longer needed.

A number of beta blockers (e.g., metoprolol, carvedilol) are metabolized by CYP2D6. Genetic polymorphisms of CYP2D6 (e.g., ultra-rapid metabolization, poor metabolization) can influence adverse effects and tolerated doses. ^[24]

Beta-blocker withdrawal

Caused by the sudden termination of beta blockers

• Clinical features
  • Tachycardia, tachyarrhythmia
  • Hypertension
  • Acute coronary syndrome, sudden cardiac death ^[25]
• Prevention: Taper dose over 7–10 days before discontinuing. ^[26]

We list the most important adverse effects. The selection is not exhaustive.

Cardiovascular indications

• Hypertension : beta blockers lower BP by ↓ cardiac output and ↓ renin secretion ^[27][28]
• Coronary artery disease
  • Acute myocardial infarction ^[29]
    • Beta blockers should be initiated early in all patients (without contraindications) and continued long-term if tolerated. ^[30]
    • Beta blockers decrease the size of the infarct and also reduce early and delayed mortality rates in patients with acute MI.
  • Angina pectoris: first-line treatment for stable angina pectoris in addition to ACE inhibitors or ARBs ^[27][31]
• Heart failure: cardioselective beta blockers (preferred) in combination with ACE inhibitors/ARBs and spironolactone (slows progression of CHF) ^[3][27]
• Arrhythmias: atrial flutter, atrial fibrillation, PSVT, VT, and premature ventricular contractions (beta-blockers are class II antiarrhythmic agents; e.g., metoprolol, esmolol, propranolol) ^[32][33]

Specific indications for propranolol

• Essential tremor ^[34]
• Migraine prophylaxis ^[35]
• Portal hypertension
• Hyperthyroidism and thyroid storm
• Infantile hemangioma
• Akathisia

Miscellaneous

• Hypertensive crises; (e.g., malignant hypertension): IV labetalol (rapid onset of action)
• Glaucoma: topical beta blockers (timolol, betaxolol)
• Pregnancy-induced hypertension: Labetalol is the first-line drug.

We list the most important contraindications. The selection is not exhaustive.