Propranolol is a competitive beta-adrenergic receptor antagonist, devoid of agonist activity, making it the prototype for comparison to the other beta-antagonists.[1] A British scientist, Sir James Black, first developed propranolol for the treatment of angina pectoris. Over the following years, propranolol started to gain recognition in the treatment of a variety of cardiovascular and noncardiovascular disease processes, making it a widely used pharmaceutical drug.[2] 

B-adrenoreceptor antagonists, including propranolol, have been advised to be used for the treatment of heart failure, atrial fibrillation, and coronary artery disease. Furthermore, they have demonstrated to improve mortality and morbidity in those with hypertension that is complicated with heart failure, angina, or any history of previous myocardial infarctions.[3] Propranolol can also be used to enhance the sympathetic response in angina and tachyarrhythmias, while also preventing acute ischemic attacks. It is also a critical drug used in the treatment of hyperthyroid induced thyrotoxicosis.[4]

Propranolol does not only have extensive use in cardiovascular disease, but it also has several implications in the treatment of noncardiovascular disease processes. It is used as a means of migraine prophylaxis, treatment of restless leg syndrome, essential tremors, and has even been of great success in the treatment of infantile hemangioma.[5] 

Off label use of propranolol includes the use in performance anxiety, which is a subset of a social phobia presenting with tachycardia, sweating, and flushing that occurs secondary to increased activation of the sympathetic nervous system.[6]

The extensive use of propranolol in the medical field highlights the vast importance of the discovery of the drug to society. 

Propranolol is a nonselective beta-adrenoreceptor antagonist, also classified as a class II antiarrhythmic. It exerts its response by competitively blocking beta-1 and beta-2 adrenergic stimulation in the heart, which is typically induced by epinephrine and norepinephrine.[7]

Beta-1 receptors are present on cardiac myocytes, including the sinoatrial and atrioventricular nodes. When there is an activation of these receptors, there is an increase in cyclic AMP, which leads to increased intracellular calcium. This process leads to increased contractility of muscle fibers. When there is a blockage of beta-adrenergic receptors, this results in an overall decreased workload of the heart, which leads to subsequent reduced oxygen demand and myocardial remodeling.[8]

Beta-2 receptor activation, on the other hand, leads to increased cyclic AMP that activates protein kinase A, leading to the relaxation of smooth muscle cells in a variety of organs and vessels. Therefore, when beta-2 receptors are blocked, this leads to a small amount of vasoconstriction. This effect can make the use of emergency epinephrine in asthmatics quite problematic, as it blocks the receptors that epinephrine would potentially bind to in the lungs.[9] Beta-blockers are highly protein-bound and are well distributed throughout the body with a Vd of about 4 to 6L/kg.[9]

Like most medications, beta-blockers are metabolized predominately in the liver( both the active and inactive compounds). Approximately a quarter of the ingested drug reaches systemic circulation due to the first-pass metabolism in the hepatic circulation.[10]

The active metabolite of propranolol is 4-hydroxypropranolol, which is formed through hydroxylation using the CYP2D6 enzyme.[11]

Furthermore, like most ingested medications, propranolol is predominantly cleared by the renal system, with a half-life of about 3 to 6 hours in patients with healthy renal systems.[10]

Propranolol administration can be either oral or intravenous. With intravenous administration, there should also be continuous electrocardiogram monitoring with a slow infusion. This route of administration primarily occurs in an inpatient setting.

The doses of propranolol vary, being primarily dependent on what condition the medication is treating.[12]

Common side effects of using propranolol include bradycardia, gastrointestinal issues, abdominal pain, nausea, erectile dysfunction, and wheezing/bronchospasms.[13] Propranolol use can also cause drowsiness, fatigue, and cold extremities. Some extreme side effects to be aware of include allergic reactions, insulin resistance, and hallucinations. Prescribers need to explain and discuss all of the side effects before giving patients a prescription for propranolol.[13]

Prescribers should exercise extreme caution when prescribing beta-blockers to patients with diabetes. The reason for this is because this class of medication can mask the symptoms of hypoglycemia, which includes flushing, tachycardia, sweating, and dizziness.[14]

Furthermore, since the main effect of propranolol is to decrease heart rate, it is contraindicated in those who have bradycardia (less than 60 beats per minute).

Propranolol is also contraindicated in those with any lung pathologies, such as COPD, asthma, or emphysema. The pathophysiology of this mechanism is solely due to the effects that beta-2 receptors have on lung function. Normally, activation of beta-2 receptors vasodilates the smooth muscle in the lungs. When using agents like propranolol in patients with underlying lung issues, the blockage of beta-2 causes vasoconstriction of smooth muscle, worsening respiratory function. In such patients, physicians should only prescribe selective beta-blockers, which only block beta-1 receptors and spare beta-2 receptors.[15]

During cocaine toxicity, prescribers should never use any beta-blocker with an unopposed alpha blockade, since this can lead to massive unopposed alpha-adrenergic activity and lead to an enormous spike in blood pressure which may even result in death.[16]

Since propranolol is metabolized by hepatic enzymes and excreted through the renal system, prescribers should proceed with caution when prescribing it to a patient with known hepatic or renal impairments. Furthermore, dosages may need to be adjusted to avoid toxicity resulting from the inability to metabolize or clear the medication from the body properly.