Propranolol is used for the management of hypertension, angina, supraventricular and ventricular arrhythmias, acute myocardial infarction (MI), and essential tremor. Propranolol also is used for prophylaxis of migraine headache, management of hypertrophic subaortic stenosis, and as an adjunct in the management of pheochromocytoma. The drug also has been used in the management of thyrotoxicosis.
The choice of a β-adrenergic blocking agent (β-blocker) depends on numerous factors, including pharmacologic properties (e.g., relative β-selectivity, intrinsic sympathomimetic activity, membrane-stabilizing activity, lipophilicity), pharmacokinetics, intended use, and adverse effect profile, as well as the patient's coexisting disease states or conditions, response, and tolerance. While specific pharmacologic properties and other factors may appropriately influence the choice of a β-blocker in individual patients, evidence of clinically important differences among the agents in terms of overall efficacy and/or safety is limited. Patients who do not respond to or cannot tolerate one β-blocker may be successfully treated with a different agent.
In the management of hypertension or chronic stable angina pectoris in patients with chronic obstructive pulmonary disease (COPD) or type 1 diabetes mellitus, many clinicians prefer to use low dosages of a β1-selective adrenergic blocking agent (e.g., atenolol, metoprolol), rather than a nonselective agent (e.g., nadolol, pindolol, propranolol, timolol). However, selectivity of these agents is relative and dose dependent. Some clinicians also will recommend using a β1-selective agent or an agent with intrinsic sympathomimetic activity (e.g., pindolol), rather than a nonselective agent, for the management of hypertension or angina pectoris in patients with peripheral vascular disease, but there is no evidence that the choice of β-blocker substantially affects efficacy. Nonselective β-blockers are preferred for the management of hypertension or angina pectoris in patients with coexisting essential tremor or vascular (e.g., migraine) headache.
Propranolol is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Although β-blockers were previously considered a drug of choice for the initial management of hypertension, most current guidelines no longer recommend these drugs as first-line therapy because of the lack of established superiority over other recommended drug classes and at least one study demonstrating that they may be less effective than angiotensin II receptor antagonists in preventing cardiovascular death, MI, or stroke. However, β-blockers may still be considered in hypertensive patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes (angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics). (See and in )
In general, black hypertensive patients tend to respond better to monotherapy with thiazide diuretics or calcium-channel blocking agents than to monotherapy with β-blockers. Although β-blockers have lowered blood pressure in all races studied, monotherapy with these agents has produced a smaller reduction in blood pressure in black hypertensive patients; however, this population difference in response does not appear to occur during combined therapy with a β-blocker and a thiazide diuretic. (See and in .)
Propranolol's efficacy in the management of hypertension is similar to that of other β-blockers. Propranolol is not indicated for the treatment of hypertensive emergencies.
In contrast to many other antihypertensive agents, propranolol lowers blood pressure equally well in the upright or supine position. The drug appears to be safe and effective for the treatment of hypertension in patients with renal damage. Although it apparently is more effective in patients with normal or elevated plasma renin concentrations than in those with low plasma renin concentrations, propranolol does lower blood pressure in patients with low-renin hypertension.
For additional information on the role of β-blockers in the management of hypertension, see Uses in and in . For information on overall principles and expert recommendations for treatment of hypertension, see
Chronic Stable Angina
Propranolol is used for the management of chronic stable angina pectoris. β-Blockers are recommended as the anti-ischemic drugs of choice in most patients with chronic stable angina; despite differences in cardioselectivity, intrinsic sympathomimetic activity, and other clinical factors, all β-blockers appear to be equally effective for this indication. In a double-blind study in patients with stable angina, propranolol reduced the frequency of anginal attacks and increased exercise tolerance compared with placebo.
Combination therapy with a β-blocker and a nitrate appears to be more effective than either drug alone because β-blockers attenuate the increased sympathetic tone and reflex tachycardia associated with nitrate therapy while nitrate therapy (e.g., nitroglycerin) counteracts the potential increase in left-ventricular wall tension associated with a decrease in heart rate. Combined therapy with a β-blocker and a dihydropyridine calcium-channel blocker also may be useful because the tendency to develop tachycardia with the calcium-channel blocker is counteracted by the β-blocker. However, caution should be exercised in the concomitant use of β-blockers and the nondihydropyridine calcium-channel blockers verapamil or diltiazem because of the potential for excessive fatigue, bradycardia, or atrioventricular (AV) block.
(See Drug Interactions: Diuretics and Cardiovascular Drugs.)
β-Blockers, including propranolol, are used to slow ventricular rate in patients with supraventricular tachycardia (SVT). The American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) guideline for the management of adult patients with supraventricular tachycardia recommends the use of β-blockers in the treatment of various SVTs (e.g., atrial flutter, junctional tachycardia, focal atrial tachycardia, atrioventricular nodal reentrant tachycardia [AVNRT]); in general, an IV β-blocker is recommended for acute treatment, while an oral β-blocker is recommended for ongoing management of these arrhythmias. Vagal maneuvers and/or IV adenosine generally are considered first-line interventions for the acute treatment of SVT and should be attempted prior to other therapies when clinically indicated; if such measures are ineffective or not feasible, an IV β-blocker may be considered in hemodynamically stable patients. Although evidence of efficacy is limited, experts state that the overall safety of β-blockers warrants their use in patients with SVT. Patients should be closely monitored for hypotension and bradycardia during administration of these drugs.
IV β-blockers may be used for the acute treatment of patients with hemodynamically stable focal atrial tachycardia (i.e., regular SVT arising from a localized atrial site), and an oral β-blocker may be used for ongoing management. Multifocal atrial tachycardia, characterized by a rapid, irregular rhythm with at least 3 distinct P-wave morphologies, is commonly associated with an underlying condition (e.g., pulmonary, coronary, or valvular heart disease) and is generally not responsive to antiarrhythmic drug therapy.
Propranolol is used to slow ventricular rate in patients with atrial fibrillation or atrial flutter when ventricular rate cannot be controlled with standard measures. For acute treatment of atrial fibrillation or flutter, an IV β-blocker (e.g., esmolol, propranolol, metoprolol) may be used for ventricular rate control in patients without preexcitation; an oral β-blocker may be used for ongoing rate control in such patients. Choice of a specific β-blocker should be individualized based on the patient's clinical condition.
IV β-blockers may be used for the acute treatment of hemodynamically stable patients with paroxysmal supraventricular tachycardia (PSVT), including AVNRT, that is uncontrolled or unconverted by vagal maneuvers and adenosine; an oral β-blocker may be used for the ongoing management of such patients who are not candidates for, or prefer not to undergo, catheter ablation. Propranolol may be useful in the prophylactic management of refractory PSVT, especially when caused by catecholamines or cardiac glycosides or associated with Wolff-Parkinson-White syndrome.
β-Blockers are considered one of several drug therapy options for the treatment of junctional tachycardia (i.e., nonreentrant SVT originating from the AV junction), a rapid, occasionally irregular, narrow-complex tachycardia. While evidence is limited, there is some data indicating that β-blockers (specifically propranolol) are modestly effective in terminating and/or reducing the incidence of junctional tachycardia.
Although propranolol generally is less effective in the management of ventricular arrhythmias than supraventricular arrhythmias and is usually not the first drug of choice for ventricular arrhythmias, it may be considered when cardioversion or other drugs are not effective. Propranolol also may be used in the treatment of persistent premature ventricular complexes that impair the well-being of the patient and do not respond to conventional therapy.
β-Blockers may be useful in the management of certain forms of polymorphic ventricular tachycardia (e.g., associated with acute ischemia).
β-Blockers also have been used in patients with cardiac arrest precipitated by ventricular fibrillation or pulseless ventricular tachycardia. However, AHA states that routine administration of β-blockers after cardiac arrest is potentially harmful (e.g., may worsen hemodynamic instability, exacerbate heart failure, or cause bradyarrhythmias) and is therefore not recommended.
Tachyarrhythmias Associated with Cardiac Glycoside Intoxication
When AV block is not present, propranolol may be useful in the management of supraventricular or ventricular tachyarrhythmias associated with cardiac glycoside toxicity; however, because of the risk of adverse cardiovascular effects, the drug has a limited role in the management of these arrhythmias and other drugs are usually preferred. Propranolol can compromise conduction through the SA and AV nodes (possibly resulting in sinus bradycardia or asystole) and decrease myocardial automaticity; in addition, β-adrenergic blockade may result in deterioration of hemodynamic status in patients whose myocardial contractility depends on increased sympathetic nervous system activity. Oral propranolol may be useful in some patients for the management of cardiac glycoside-induced tachyarrhythmias that persist following discontinuance of the glycoside and correction of electrolyte abnormalities. IV propranolol should be used only if arrhythmias caused by cardiac glycoside intoxication are life-threatening and other therapy is ineffective. Use of digoxin immune Fab, if available, may be preferable and should be considered for the management of life-threatening cardiac glycoside-induced tachyarrhythmias that are unresponsive to conventional therapy.
Resistant Tachyarrhythmias Associated with Catecholamine Excess During Anesthesia
Propranolol may be used with extreme caution and constant ECG and central venous pressure monitoring in the management of resistant tachyarrhythmias associated with catecholamine excess during anesthesia; however, more effective and less hazardous therapy such as lessening the depth of anesthesia or improving ventilation is preferred.
(See Cautions: Precautions and Contraindications.)
Hypertrophic Subaortic Stenosis
Propranolol may be of benefit in the management of exertional or other stress-induced angina, vertigo, syncope, and palpitation in some patients with hypertrophic subaortic stenosis; however, clinical improvement may be only temporary.
An α-adrenergic blocking agent (e.g., phenoxybenzamine or phentolamine) alone is usually sufficient for management of the signs and symptoms of pheochromocytoma. Propranolol, however, may be used as an adjunct to α-adrenergic blocking agents to control symptoms resulting from excessive β-receptor stimulation in patients with inoperable or metastatic pheochromocytoma, or to control tachycardia prior to or during surgery in patients with pheochromocytoma. To prevent severe hypertension caused by unopposed α-adrenergic stimulation, treatment with an α-adrenergic blocking agent must always be instituted prior to the use of propranolol and continued during propranolol therapy in patients with pheochromocytoma.
Propranolol, which will not alter thyroid function tests, may be used orally as short-term (2-4 weeks) adjunctive therapy in the treatment of tachycardia and supraventricular arrhythmias in patients with thyrotoxicosis when these symptoms are distressful or hazardous, or when immediate therapy is necessary. Propranolol has been used IV and orally to treat symptomatic hypercalcemia secondary to thyrotoxicosis, but this use requires further study. Propranolol has also been used for the management of thyrotoxicosis in neonates. Safety of long-term administration of the drug in patients with thyrotoxicosis has not been established. The drug does not affect the underlying disease, which must be treated with an antithyroid agent.
Propranolol may be used for the prophylaxis of common migraine headache. When used prophylactically, the drug can prevent common migraine or reduce the number of attacks in some patients. The US Headache Consortium states that there is good evidence from multiple well-designed clinical trials that propranolol has medium to high efficacy for the prophylaxis of migraine headache. Propranolol is not recommended for the treatment of a migraine attack that has already started nor for the prevention or treatment of cluster headaches. For further information on management and classification of migraine headache, .
Propranolol is used to reduce the risk of cardiovascular mortality in patients who have survived the acute phase of MI and are clinically stable. In these patients, long-term (up to 39 months) administration of propranolol (begun within 5-21 days following MI) reduced overall mortality, cardiovascular mortality, arteriosclerotic heart disease (ASHD) mortality, and sudden death mortality within the ASHD category. Evidence of efficacy was obtained from a double-blind, placebo-controlled, multicenter study (Beta-Blocker Heart Attack Trial; BHAT). The effect of propranolol on reinfarction remains to be fully evaluated. For information on the use of β-blockers during the acute phase of MI, see Uses in .
The benefits of long-term β-blocker therapy for secondary prevention of MI have been well established in numerous clinical studies. Patients with MI complicated by heart failure, left ventricular dysfunction, or ventricular arrhythmias appear to derive the most benefit from long-term β-blocker therapy. Several large, randomized studies have demonstrated that prolonged oral therapy with a β-blocker can reduce the long-term rates of reinfarction and mortality (e.g., sudden or nonsudden cardiac death) following acute MI. It is estimated that such therapy could result in a relative reduction in mortality of about 25% annually for years 1-3 after infarction, with high-risk patients exhibiting the greatest potential benefit; the benefit of continued therapy may persist for at least several years beyond this period, although less substantially. Therefore, propranolol, like other β-blockers, can be used for secondary prevention following acute MI to reduce the risk of reinfarction and mortality. The American Heart Association/American College of Cardiology Foundation (AHA/ACCF) secondary prevention guideline recommends β-blocker therapy in all patients with left ventricular systolic dysfunction (ejection fraction of 40% or less) and prior MI; use of a β-blocker with proven mortality benefit (e.g., bisoprolol, carvedilol, or metoprolol succinate) is recommended. Although the benefits of long-term β-blockade in post-MI patients with normal left ventricular function are less well established, the guideline recommends continued β-blocker therapy for at least 3 years in such patients. Further studies are needed to establish the optimal duration of β-blocker therapy for secondary prevention of MI.
Propranolol is used for the management of essential (familial, hereditary) tremor. The tremor is a postural and action tremor manifested as involuntary, rhythmic, oscillatory movements, principally of the upper limbs and, less frequently, the head; other areas, including the voice, legs, jaw, eyelids, and mouth, also may be involved. Essential tremor occurs during active movement and when the limb is held in a fixed posture or position against gravity; the tremor usually is absent at rest, although, when it is of large amplitude, tremor occasionally may be evident at rest, particularly in geriatric patients.
Propranolol decreases the amplitude but not the frequency of essential tremor; complete suppression of the tremor rarely is achieved with treatment. Response to propranolol therapy is variable, but the drug appears to be most effective in the management of high-amplitude, low-frequency tremor. Clinical benefit often is most evident for tremor affecting the upper extremities, although benefit also has been observed for head and other tremors; voice tremor may be less responsive to therapy with the drug. Propranolol hydrochloride doses of 120-320 mg generally produce tremor amplitude reductions averaging about 4-50%; however, reductions averaging 25-75% have been reported. Therapy with the drug may improve functional ability (e.g., handwriting, eating, drinking, dressing) and provide some subjective improvement (e.g., reduced anxiety and embarrassment), but patients should be advised that complete relief rarely is achieved so that their expectations about potential therapeutic benefit are realistic. Although propranolol often is used for chronic suppressive therapy in essential tremor, single oral doses may be useful in some patients to prevent or minimize tremor that is considered bothersome during specific, planned activity or to manage an exacerbation of tremor during periods of stress (e.g., business meetings, examinations).
Propranolol has been used in the management of cyanotic spells of Fallot's tetralogy, acute exacerbations of schizophrenic disorder and anxiety states, recurrent GI bleeding in patients with cirrhosis, and many other conditions. In addition to essential tremor
(see Uses: Essential Tremor), propranolol also has been used in the management of other action tremors, including those associated with lithium therapy , anxiety, and thyrotoxicosis.