indication

For the prophylaxis of migraine.

pharmacology

Propranolol, the prototype of the beta-adrenergic receptor antagonists, is a competitive, nonselective beta-blocker similar to nadolol without intrinsic sympathomimetic activity. Propanolol is a racemic compound; the l-isomer is responsible for adrenergic blocking activity.

mechanism of action

Propranolol competes with sympathomimetic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart, inhibiting sympathetic stimulation. This results in a reduction in resting heart rate, cardiac output, systolic and diastolic blood pressure, and reflex orthostatic hypotension.

toxicity

Symptoms of overdose include bradycardia, cardiac failure, hypotension, and brochospasm. LD₅₀=565 mg/kg (orally in mice).

biotransformation

Hepatic

absorption

Propranolol is almost completely absorbed from the GI tract; however, plasma concentrations attained are quite variable among individuals.

half life

4 hours

route of elimination

Propranolol is extensively metabolized with most metabolites appearing in the urine.

drug interactions

Acetohexamide: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Aminophylline: Antagonism of action and increased effect of theophylline

Chlorpromazine: Increased effect of both drugs

Chlorpropamide: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Cimetidine: Cimetidine may increase the serum concentration of propranolol by decreasing its metabolism.

Citalopram: The SSRI, citalopram, may increase the bradycardic effect of the beta-blocker, propranolol.

Clonidine: Increased hypertension when clonidine stopped

Dihydroergotamine: Ischemia with risk of gangrene

Dihydroergotoxine: Ischemia with risk of gangrene

Diltiazem: Increased risk of bradycardia

Disopyramide: The beta-blocker, propranolol, may increase the toxicity of disopyramide.

Dyphylline: Antagonism of action and increased effect of theophylline

Epinephrine: Hypertension, then bradycardia

Ergonovine: Ischemia with risk of gangrene

Ergotamine: Ischemia with risk of gangrene

Escitalopram: The SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, propranolol.

Fenoterol: Antagonism

Fluoxetine: The SSRI, fluoxetine, may increase the bradycardic effect of the beta-blocker, propranolol.

Formoterol: Antagonism

Gliclazide: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Glipizide: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Glisoxepide: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Glyburide: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Glycodiazine: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Haloperidol: Increased effect of both drugs

Hydralazine: Increased effect of both drugs

Ibuprofen: Risk of inhibition of renal prostaglandins

Indomethacin: Risk of inhibition of renal prostaglandins

Insulin Glargine: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Isoproterenol: Antagonism

Lidocaine: The beta-blocker, propranolol, may increase the effect and toxicity of lidocaine.

Maprotiline: Propranolol increases the serum levels of cisapride

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Methyldopa: Possible hypertensive crisis

Methysergide: Ischemia with risk of gangrene

Orciprenaline: Antagonism

Oxtriphylline: Antagonism of action and increased effect of theophylline

Paroxetine: The SSRI, paroxetine, may increase the bradycardic effect of the beta-blocker, propranolol.

Phenobarbital: The barbiturate decreases the effect of the metabolized beta-blocker

Pipobroman: Antagonism

Pirbuterol: Antagonism

Piroxicam: Risk of inhibition of renal prostaglandins

Prazosin: Risk of hypotension at the beginning of therapy

Primidone: The barbiturate decreases the effect of metabolized beta-blocker

Procaterol: Antagonism

Propafenone: Propafenone may increase the effect of the beta-blocker, propranolol.

Repaglinide: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Rifampin: Rifampin may decrease the serum concentration of propranolol by increasing its metabolism.

Rizatriptan: Propranolol increases the effect and toxicity of rizatriptan

Salbutamol: Antagonism

Salmeterol: Antagonism

Sertraline: The SSRI, sertraline, may increase the bradycardic effect of the beta-blocker, propranolol.

Terazosin: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Terbinafine: Terbinafine may reduce the metabolism and clearance of Propranolol. Consider alternate therapy or monitor for therapeutic/adverse effects of Propranolol if Terbinafine is initiated, discontinued or dose changed.

Terbutaline: Antagonism

Theophylline: Antagonism of action and increased effect of theophylline

Thioridazine: Increased risk of cardiotoxicity and arrhythmias

Tolazamide: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Tolbutamide: The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.

Topotecan: The p-glycoprotein inhibitor, Propranolol, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.

Verapamil: Increased effect of both drugs