Propranolol competitively blocks response to beta1 – and beta2- adrenergic stimulation which results in decreases in heart rate , myocardial contractility , blood pressure , and myocardial oxygen demand . Propranolol possesses moderate membrane – stabilizing (quinidine – like ) activity . The precise mechanism of antihypertensive effect is not known. Possible mechanisms include reduced cardiac output , decreased sympathetic outflow to peripheral vasculature , and inhibition of renin release by the kidneys.

Propranolol is indicated in the treatment of classic angina pectoris , also referred to as "effort – associated angina" Propranolol is indicated in the treatment and prophylaxis of arrhythmias (such as atrial fibrillation and flutter , AV nodal re – entrant tachycardias , and catecholamine – induced arrhythmias) . Also , propranolol is indicated in the treatment of hypertension ; treatment of hypertrophic subaortic stenosis ; treatment and prophylaxis of myocardial infarction ; treatment adjunct of pheochromocytoma ; prophylaxis of vascular headache ; treatment of essential , familial ,and senile tremors ; treatment adjunct of anxiety ; treatment adjunct of thyrotoxicosis ; treatment of mitral valve prolapse and treatment of neuroleptic – induced akathisia . Other indications include the prophylaxis of upper GI bleeding in patients with portal hypertension.

Cardiovascular: Bradycardia ; CHF ; Reduced peripheral circulation ; Chest pain ; Hypotension ; Impaired myocardial contractility; Worsening of AV conduction disturbance ; Cardiogenic shock ; Raynaud’s syndrome; Mesenteric thrombosis (rare) ; Syncope.
CNS: Mental depression ; Lightheadedness; Amnesia ; Emotional lability ; Confusion ; Hallucinations ; Dizziness ; Insomnia ; Fatigue ; Vivid dreams; Lethargy ; Cold extremities ; Vertigo ; Cognitive dysfunction ; Psychosis ; Hypersomnolence.
Dermatologic: Alopecia; Contact dermatitis; Eczematous eruptions; Erythema multiforme; Exfoliative dermatitis; Hyperkeratosis ; Nail changes ; Pruritus ; Psoriasiform eruptions ; Rash ; Ulcerative lichenoid ; Urticaria ; Stevens – Johnson syndrome ; Toxic epidermal necrolysis.
Endocrine & metabolic: Hypoglycemia ; Hyperglycemia ; Hyperlipidemia ; Hyperkalemia. GI: Diarrhea; Nausea; Vomiting; Stomach discomfort; Constipation; Anorexia.
Genitourinary: Impotence ; Proteinuria (rare) ; Oliguria (rare) ; Interstitial nephritis (rare) ; Peyronie’s disease.
Hematologic: Agranulocytosis ; Thrombocytopenia ; Thrombocytopenic purpura.
Neuromuscular & skeletal: Weakness ; Carpal tunnel syndrome (rare); Paresthesia; Myotonus; Polyarthritis; Arthropathy.
Ocular: Hyperemia of the conjunctiva ; Decreased tear production ; Decreased visual acuity ; Mydriasis.
Respiratory: Wheezing ; Pharyngitis ; Bronchospasm ; Pulmonary edema ; Respiratory distress ; Laryngospasm.
Miscellaneous: Lupus – like syndrome (rare) ; Anaphylactic/ anaphylactoid allergic reaction.

Hypersensitivity to propranolol, beta– blockers, or any component of the formulation; Uncompensated CHF (unless the failure is due to tachyarrhythmias being treated with propranolol) ; Cardiogenic shock ; Bradycardia ( heart rate less than 45 beats per minute ); Heart block (2nd or 3rd degree) ; Pulmonary edema ; Severe hyperactive airway disease (asthma or COPD ) ; Raynaud’s disease.

Administer cautiously in compensated heart failure and monitor for a worsening of the condition . Beta – blocker therapy should not be withdrawn abruptly (particularly in patients with CAD) , but gradually tapered ( over 2 weeks ) to avoid acute tachycardia , hypertension , and /or ischemia. Use cautiously with concurrent use of beta – blockers and either verapamil or diltiazem ; bradycardia or heart block can occur. Use cautiously in diabetics because it can mask prominent hypoglycemic symptoms. Propranolol can mask signs of thyrotoxicosis; abrupt withdrawal may intensify symptoms. Use cautiously in hepatic dysfunction (dosage adjustment required). Propranolol is not indicated for hypertensive emergencies. Propranolol should be used cautiously in the patients with history of mental depression. Propranolol may potentiate myasthenia gravis. Psoriasis may be exacerbated with propranolol.

Use of allergen immunotherapy or allergenic extracts for skin testing in patients taking propranolol may increase the potential for serious systemic reaction or anaphylaxis. Concurrent administration of amiodarone with propranolol may result in additive depressant effects on conduction and negative inotropic effects.Concurrent use of oral antidiabetic agents and insulin with propranolol may impair glycemic control. Propranolol may impair recovery from hypoglycemia in diabetics and may mask certain symptoms of developing hypoglycemia. NSAIDs , especially indomethacin and salicylates may reduce the antihypertensive effects of propranolol. If significant systemic absorption of the ophthalmic beta – adrenergic blocking agent occurs , concurrent use with propranolol may result in an additive effect either on intraocular pressure or on systemic effects of propranolol . Blood pressure control may be impaired when clonidine or guanabenz is used concurrently with propranolol ; so that hypertensive crisis after or during withdrawal of either agent may occur . Potentiation of antihypertensive effect should be anticipated when other hypotension – producing medications are used concurrently . Symptomatic bradycardia has been reported during concurrent use of diltiazem or verapamil with propranolol . Concurrent use of nifedipine with propranolol may produce excessive hypotension and in rare cases may increase the possibility of CHF. Calcium channel blocking agents may decrease the hepatic metabolism of propranolol ; caution is warranted given the potential for additive cardiodepressant effects during concurrent use. Concurrent use of diazoxide with propranolol prevents the tachycardia produced by diazoxide but may also increase the hypotensive effects . Cimetidine may reduce the clearance of hepatically metabolized propranolol, resulting in elevations of its plasma concentrations .Concurrent use of estrogens may decrease the antihypertensive effect of propranolol. Concurrent use with propranolol may reduce lidocaine elimination and increase the risk of lidocaine toxicity. Significant hypertension may occur up to 14 days following discontinuation of the MAO inhibitor ; therefore concurrent use with propranolol is not recommended. Smoking cessation may increase therapeutic effects of propranolol by decreasing metabolism , thereby dosage adjustments may be necessary. Concurrent use of phenothiazines with propranolol results in an increased plasma concentration of each medication. Concurrent use of propranolol with IV phenytoin may produce additive cardiac depressant effects. Concurrent use of xanthines, especially aminophylline or theophylline with propranolol may result in mutual inhibitions of therapeutic effects. Concurrent use with alpha – blockers (prazosin , terazosin ) may increase risk of orthostatic hypotension. Absorption of propranolol may be decreased by aluminium hydroxide , cholestyramine and colestipol. Carbamazepine, phenobarbital and rifampin may decrease the levels/effects of propranolol. Ciprofloxacin, fluvoxamine, ketoconazole, norfloxacin, ofloxacin, chlorpromazine , fluoxetine , quinidine, quinine and paroxetine may increase the levels /effects of propranolol . Metabolism of diazepam may be inhibited by propranolol. Propranolol may blunt hyperglycemic action of glucagon. Hypotensive effects of propranolol may be potentiated by haloperidol. The bioavailability of propranolol and hydralazine may be enhanced with concurrent dosing. Propranolol may increase bioavailability of serotonin 5–HT1D receptor agonists . Propranolol may increase bioavailability of warfarin and PT may be increased .

Monitor heart rate and blood pressure.

Tablets should be taken on an empty stomach.

• Usual adult dose:
  Antianginal – Oral , 80 to 320 mg per day given in 2 or 4 divided doses.
  Antiarrhythmic – Oral , 10 to 30 mg 3 or 4 times a day.
  Antihypertensive – Oral , 40 mg 2 times a day , the dosage being increased gradually as needed and tolerated , usually 120 to 240 mg a day ; doses up to a total of 640 mg a day may be necessary.
  Hypertrophic cardiomyopathy therapy adjunct – Oral , 20 to 40 mg 3 or 4 times a day.
  Myocardial infarction – Oral , 180 to 240 mg a day in divided doses.
  Pheochromocytoma therapy adjunct – Oral , 20 mg 3 times a day to 40 mg 3 or 4 times a day for 3 days prior to surgery , concomitantly with alpha – adrenergic blocking medication (should never be started until alpha – adrenergic blockade is at least partially established ). Doses of 30 to 160 mg per day in divided doses have been used for management of inoperable tumor.
  Vascular headache prophylactic – Oral, 20 mg 4 times a day initially, the dosage being increased gradually as needed and tolerated up to a total of 240 mg a day if necessary.
  Antitremor agent – Oral, 40 mg 2 times a day, the dosage being adjusted as needed and tolerated, up to 120 mg a day ; occasionally , doses up to 320 mg a day may be needed.
  Antianxiety therapy adjunct – Oral, 10 to 80 mg 30 to 90 minutes prior to the anxiety – provoking activity.
  Thyrotoxicosis therapy adjunct – Oral , 10 to 40 mg 3 or 4 times a day.
• Usual pediatric dose:
  Antiarrhythmic and antihypertensive – Initial : Oral, 500 mcg (0.5 mg) to 1 mg per kg of body weight per day in 2 to 4 divided doses, the dosage being adjusted as necessary to treat hypertension and prevent supraventricular tachycardia.
  Maintenance : Oral , 2 to 4 mg per kg per day in two divided doses.

• USP DI, 2004
• Up To Date, Vol. 13.1 (2005)
• Martindale, The Complete Drug Reference, 33 rd edition 2002