What is the mechanism of action and use of propranolol (beta-blocker)?

What Propranolol Does: Mechanism and Clinical Uses

Propranolol is a nonselective beta-adrenergic receptor blocker that competitively blocks both beta-1 and beta-2 receptors, reducing heart rate, myocardial contractility, and blood pressure while also blocking peripheral effects of adrenaline like tremor and tachycardia. 1

Core Mechanism of Action

• Propranolol blocks beta-adrenergic receptors throughout the body, preventing catecholamines (adrenaline and noradrenaline) from binding to these sites 1

• The drug decreases heart rate (negative chronotropic effect) and reduces the force of heart muscle contraction (negative inotropic effect) through beta-1 receptor blockade in the heart 2

• Propranolol causes vasoconstriction through beta-2 receptor blockade in blood vessels, which distinguishes it from cardioselective beta-blockers 2

• At higher doses, propranolol exerts a quinidine-like membrane-stabilizing effect on cardiac tissue, though the clinical significance of this for arrhythmia treatment remains uncertain 1

Cardiovascular Effects and Uses

Hypertension

• The antihypertensive effect occurs through multiple mechanisms: decreased cardiac output, inhibition of renin release from the kidneys, and reduced sympathetic outflow from the brain 1

• Beta-blockers are not first-line agents for hypertension unless the patient has coexisting ischemic heart disease or heart failure 3

Angina Pectoris

• Propranolol reduces myocardial oxygen demand by blocking catecholamine-induced increases in heart rate, blood pressure, and myocardial contractility 1

• The net effect during exercise is delayed onset of chest pain and increased work capacity 1

Arrhythmias

• Propranolol exerts antiarrhythmic effects primarily through beta-adrenergic blockade at therapeutic concentrations 1

Non-Cardiovascular Therapeutic Uses

Performance Anxiety and Tremor

• For situational performance anxiety (stage fright), propranolol 20-40 mg taken 1 hour before the event blocks peripheral manifestations of anxiety including rapid heart rate, tremors, and sweating 4

• Propranolol is first-line treatment for essential tremor, with effectiveness in up to 70% of patients 4

• The drug is particularly useful for reducing physiologic tremor during surgical procedures or public speaking 4

Migraine Prevention

• Propranolol is FDA-approved for migraine prophylaxis, though the exact mechanism remains unclear 5, 1

• Beta-adrenergic receptors have been demonstrated in brain blood vessels, which may explain the antimigraine effect 1

Thyroid Disorders

• Propranolol is the most widely studied beta-blocker for treating symptoms of thyrotoxicosis, hyperthyroidism, and Graves' disease 5

• Beyond controlling heart rate and tremor, propranolol inhibits peripheral conversion of T4 to the more active T3 hormone 5

Other Indications

• Propranolol reduces intraocular pressure by decreasing aqueous humor production, providing additional benefit in elderly patients with glaucoma who need the drug for cardiac indications 5

• The drug may reduce consolidation of emotional memory when given immediately after psychological trauma, showing efficacy for post-traumatic stress disorder prophylaxis 5

• Propranolol is commonly prescribed for panic disorder symptom relief, typically combined with cognitive behavioral therapy and/or SSRIs 5, 4

Critical Contraindications and Precautions

• Absolute contraindications include asthma, COPD, decompensated heart failure, cardiogenic shock, high-degree AV block without a pacemaker, and severe bradycardia 4, 3

• The nonselective nature (blocking both beta-1 and beta-2 receptors) explains why propranolol is contraindicated in bronchospastic disease—beta-2 blockade can cause bronchoconstriction 2

• Propranolol masks symptoms of hypoglycemia in diabetic patients, requiring caution in this population 4, 3

• Never abruptly discontinue propranolol after regular use—this can cause rebound hypertension, tachycardia, or angina 4, 3

• Common side effects include bradycardia, hypotension, fatigue, cold extremities, and sleep disturbances 4

Pharmacokinetic Considerations

• Propranolol is highly lipophilic and crosses the blood-brain barrier, explaining both its CNS effects (tremor reduction, anxiety relief) and side effects (sleep disturbances) 1

• The drug undergoes extensive first-pass hepatic metabolism, with only about 25% reaching systemic circulation 1

• Extended-release formulations provide more stable blood levels over 24 hours with once-daily dosing, though bioavailability is 30-50% lower than immediate-release formulations 1