propranolol hydrochloride
Inderal, Inderal LA

Available forms
Available by prescription only
Capsules (sustained-release): 60 mg, 80 mg, 120 mg, 160 mg
Injection: 1 mg/ml
Solution: 20 mg/5 ml, 40 mg/5 ml, 80 mg/ml (concentrated)
Tablets: 10 mg, 20 mg, 40 mg, 60 mg, 80 mg

Indications and dosages
 Hypertension. Adults: Initially, 80 mg P.O. daily in two to four divided doses or sustained-release form once daily. Increase at 3- to 7-day intervals to maximum daily dose of 640 mg. Usual maintenance dose is 160 to 480 mg daily.
Children: 1 mg/kg P.O. daily (maximum daily dose is 16 mg/kg).
 Management of angina pectoris. Adults: 10 to 20 mg t.i.d. or q.i.d., or one 80-mg sustained-release capsule daily. Dosage may be increased at 7- to 10-day intervals. Average optimum dose is 160 to 240 mg daily.
 Supraventricular, ventricular, and atrial arrhythmias; tachyarrhythmias caused by excessive catecholamine action during anesthesia, hyperthyroidism, and pheochromocytoma. Adults: 1 to 3 mg I.V. diluted in 50 ml D₅W or normal saline solution infused slowly, not to exceed 1 mg/minute. After 3 mg have been infused, another dose may be given in 2 minutes; subsequent doses no sooner than q 4 hours. Usual maintenance dose is 10 to 30 mg P.O. t.i.d. or q.i.d.
 Prevention of frequent, severe, uncontrollable, or disabling migraine or vascular headache. Adults: Initially, 80 mg daily in divided doses or one sustained-release capsule once daily. Usual maintenance dose is 160 to 240 mg daily, divided t.i.d. or q.i.d.
 To reduce mortality after MI. Adults: 180 to 240 mg P.O. daily in divided doses. Usually administered in three to four doses daily, beginning 5 to 21 days after infarct.
 Hypertrophic subaortic stenosis. Adults: 10 to 20 mg P.O. t.i.d. or q.i.d. before meals and h.s.
 Preoperative pheochromocytoma. Adults: 60 mg P.O. daily.
 Adjunctive treatment of anxiety ◇. Adults: 10 to 80 mg P.O. 1 hour before anxiety-provoking activity.
 Essential, familial, or senile movement tremors ◇. Adults: 40 mg P.O. b.i.d., as tolerated and needed.

Pharmacodynamics
Antihypertensive action: Exact mechanism unknown. May reduce blood pressure by blocking adrenergic receptors (thus decreasing cardiac output), by decreasing sympathetic outflow from the CNS, and by suppressing renin release.
Antianginal action: Decreases myocardial oxygen consumption by blocking catecholamine access to beta-adrenergic receptors, thus relieving angina.
Antiarrhythmic action: Decreases heart rate and prevents exercise-induced increases in heart rate. Also decreases myocardial contractility, cardiac output, and SA and AV nodal conduction velocity.
Migraine prophylactic action: Thought to result from inhibition of vasodilation.
MI prophylactic action: Exact mechanism unknown.

Pharmacokinetics
Absorption: Absorbed almost completely from GI tract; food enhances absorption.
Distribution: Distributed widely throughout body; more than 90% protein-bound.
Metabolism: Almost total hepatic metabolism; oral dosage form undergoes extensive first-pass metabolism.
Excretion: About 96% to 99% of given dose excreted in urine as metabolites; remainder excreted in feces as unchanged drug and metabolites. Biological half-life about 4 hours.

Contraindications and precautions
Contraindicated in patients with bronchial asthma, sinus bradycardia and heart block greater than first-degree, cardiogenic shock, and heart failure (unless failure is secondary to a tachyarrhythmia that can be treated with propranolol).
  Use cautiously in elderly patients; in patients with impaired renal or hepatic function, nonallergic bronchospastic diseases, diabetes mellitus, or thyrotoxicosis; and in those receiving other antihypertensives.

Interactions
Drug-drug. Aluminum hydroxide antacid: Decreases GI absorption. Separate administration times.
Antidiabetics, insulin: Alters dosage requirements in previously stable diabetic patients. Monitor serum glucose level.
Antihypertensives (especially catecholamine-depleting drugs such as reserpine): Potentiates antihypertensive effects. Monitor blood pressure.
Atropine, tricyclic antidepressants, other drugs with anticholinergic effects: May antagonize propranolol-induced bradycardia. Monitor patient closely.
Calcium channel blockers (especially I.V. verapamil): Depresses myocardial contractility or AV conduction. Rarely, concurrent I.V. use of a beta blocker and verapamil has resulted in serious adverse reactions, especially in patients with severe cardiomyopathy, heart failure, or recent MI. Use together cautiously.
Cimetidine: Decreased clearance of propranolol via inhibition of hepatic metabolism. Watch for enhanced beta-blocking effects.
Epinephrine: Causes severe vasoconstriction. Monitor blood pressure and observe patient carefully.
NSAIDs: May antagonize hypotensive effects. Monitor patient closely.
Phenytoin, rifampin: Accelerates clearance of propranolol. Adjust dosage as needed.
Sympathomimetics (such as isoproterenol, MAO inhibitors): Antagonizes beta-adrenergic stimulating effects. Monitor patient closely.
Tubocurarine and related compounds: High doses of propranolol may potentiate neuromuscular blocking effect. Monitor patient closely.
Drug-herb. Betel palm: Reduces temperature-elevating effects and enhances CNS effects. Discourage use together.
Drug-lifestyle. Alcohol use: Slows rate of absorption. Discourage alcohol use.

Adverse reactions
CNS: fatigue, lethargy, vivid dreams, hallucinations, mental depression, light-headedness, insomnia, fever.
CV: bradycardia, hypotension, heart failure, intermittent claudication, worsening of AV block.
GI: nausea, vomiting, diarrhea, abdominal cramping.
Hematologic: agranulocytosis.
Respiratory: bronchospasm.
Skin: rash.

Effects on lab test results
• May increase BUN, transaminase, alkaline phosphatase, and LDH levels.
• May decrease granulocyte count.

Overdose and treatment
Toxicity may cause severe hypotension, bradycardia, heart failure, and bronchospasm.
 After acute ingestion, induce emesis or empty stomach by gastric lavage; follow with activated charcoal to reduce absorption, and administer symptomatic and supportive care. Treat bradycardia with atropine (0.25 to 1 mg); if no response, administer isoproterenol cautiously. Treat cardiac failure with cardiac glycosides and diuretics and hypotension with glucagon or vasopressors; epinephrine is preferred. Treat bronchospasm with isoproterenol and aminophylline.

Special considerations
• Propranolol also has been used to treat aggression and rage, stage fright, recurrent GI bleeding in cirrhotic patients, and menopausal symptoms.
• Never administer propranolol as an adjunct in treatment of pheochromocytoma unless patient has been pretreated with alpha blockers.
• Monitor serum glucose level; drug may mask signs of hypoglycemia.
Breast-feeding patients
• Drug appears in breast milk. An alternative to breast-feeding is recommended during therapy.
Pediatric patients
• Safety and efficacy in children haven’t been established; use only if potential benefit outweighs risk.
Geriatric patients
• Elderly patients may need lower maintenance doses because of increased bioavailability or delayed metabolism; they also may experience enhanced adverse effects.

Patient education
• Warn patient not to stop drug abruptly.
• Instruct patient on proper use, dosage, and potential adverse effects of drug.
• Tell patient to call before taking OTC drugs that may interact with propranolol, such as nasal decongestants or cold preparations.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use