Mechanism of Action and Cardiac Effects
Propranolol directly affects myocardial electrophysiology by blocking $\beta_1$-adrenergic receptors. It suppresses sinoatrial node automaticity, thereby reducing heart rate. Additionally, the drug depresses conduction and automaticity in the atrioventricular (AV) node, as well as decreases the activity of Purkinje fibers and ventricular cardiomyocytes.
In clinical cardiology, these properties are used for:
- Treatment of supraventricular tachyarrhythmias: slowing AV conduction helps control ventricular rate (e.g., in tachyarrhythmic atrial fibrillation).
- Management of extrasystoles: suppressing ectopic foci of excitation in both the atria and ventricles.
- Secondary prevention after myocardial infarction: prescribed after the acute phase. It protects the heart from sympathetic nervous system hyperactivation, reduces the infarct size, and prevents fatal arrhythmias (ventricular fibrillation). Consequently, patient mortality is significantly reduced by 20–50%.
Non-Cardiac Indications
Due to the blockade of various types of adrenergic receptors, the drug is widely used outside of cardiology.
- Endocrine system: In thyrotoxicosis, propranolol performs a dual function. Symptomatically, it relieves tachycardia and palpitations. Pathogenetically, it inhibits the peripheral conversion of thyroxine ($T_4$) into the more active triiodothyronine ($T_3$).
- Neurology and psychiatry: The drug tones cerebral vessels, preventing painful pulsation, which is used for migraine prophylaxis. Blockade of skeletal muscle $\beta_2$-receptors helps successfully manage essential tremor. In addition, its inhibitory effect on the central nervous system helps alleviate panic attacks, fear, and anxiety.
Fun fact: Although beta-blockers lower intraocular pressure by reducing aqueous humor secretion, propranolol itself is not used for glaucoma. It exhibits a strong local anesthetic effect, creating an unacceptable risk of damaging the denervated cornea.
Side Effects and Safety Profile
The non-selectivity of the drug implies a high probability of adverse reactions across multiple organ systems.
- Cardiac risks ($\beta_1$-blockade): Excessive reduction in pumping function and decreased cardiac output (risk of heart failure), pronounced bradycardia, arterial hypotension, and suppressed AV conduction up to complete heart block.
- Respiratory and vascular effects ($\beta_2$-blockade): Increased bronchial tone creates a risk of bronchospasm (the drug is contraindicated in bronchial asthma). Increased vascular tone leads to cold extremities and a risk of tissue ischemia.
- Systemic effects: Lipid profile abnormalities (elevated triglycerides and VLDL alongside reduced anti-atherogenic HDL due to inhibition of endothelial lipoprotein lipase), stimulation of uterine contractions (risk of miscarriage), diarrhea, and risk of erectile dysfunction.
- CNS effects: Crossing the blood-brain barrier, the drug may provoke somnolence, lethargy, sleep disturbances, depressive states, and centrally mediated nausea.
Discontinuation and Use in Diabetes
Long-term use (more than 3 months) requires extreme caution upon completion. Due to up-regulation (compensatory receptor synthesis in response to blockade), abrupt withdrawal leads to catastrophic consequences. Endogenous catecholamines sharply increase renin secretion, vascular tone, and heart rate. In the first 7 days post-withdrawal, this can trigger worsening arterial hypertension, severe angina attacks, and myocardial infarction. To prevent this, the dose is tapered gradually over 2 weeks.
Special restrictions apply to patients with diabetes mellitus. Propranolol inhibits hepatic glycogenolysis, causing drug-induced hypoglycemia to last longer and run a more severe course. Most dangerous is the "masking" phenomenon. Receptor blockade conceals sympathoadrenal warning signals (tachycardia and tremor), leaving only sweating visible. This prevents early recognition of falling blood sugar levels, which is particularly critical in type 1 diabetes.