Chapter: Modern Pharmacology with Clinical Applications: Pharmacological Management of Chronic Heart Failure


Propranolol (Inderal) is the prototype β-blocker . It decreases the effects of sympathetic stimulation by competitive binding to β-adrenoceptors.


Table 16.3 summarizes the cardiac electrophysiological effects of class II, III, and IV agents, and Table16.4 sum-marizes the actions of the β-receptor blocking agents that make up the class II drugs. 

Bear in mind the complete spectrum of cardiovascular effects of these agents when prescribing their use. For example, while patients with a normally functioning cardiovascular system may tolerate adrenergic blockade of the heart, patients with compensated heart failure, who depend on adrenergic tone to maintain an adequate cardiac output, may un-dergo acute congestive heart failure if prescribed any of the class II drugs. Table 16.5 summarizes the clinical use of the β-adrenoceptor blocking drugs in the treatment of cardiac arrhythmias.


Propranolol (Inderal) is the prototype β-blocker . It decreases the effects of sympathetic stimulation by competitive binding to β-adrenoceptors.


Electrophysiological Actions

Propranolol has two separate and distinct effects. The first is a consequence of the drug’s β-blocking properties and the subsequent removal of adrenergic influences on the heart. The second is associated with its direct myo-cardial effects (membrane stabilization). The latter ac-tion, especially at high clinically employed doses, may account for its effectiveness against arrhythmias in which enhanced β-receptor stimulation does not play a significant role in the genesis of the rhythm disturbance.

Sinoatrial Node

Propranolol slows the spontaneous firing rate of nodal cells by decreasing the slope of phase 4 depolar-ization.


Propranolol has local anesthetic properties and ex-erts actions similar to those of quinidine on the atrial membrane action potential. Membrane responsiveness and action potential amplitude are reduced, and ex-citability is decreased; conduction velocity is reduced. Because these concentrations are similar to those that produce β-blockade, it is impossible to determine whether the drug acts by specific receptor blockade or via a membrane-stabilizing effect.

A-V Node

The depressant effects of propranolol on the A-V node are more pronounced than are the direct depres-sant effects of quinidine. This is due to propranolol’s dual actions of β-blockade and direct myocardial de-pression. Propranolol administration results in a de-crease in A-V conduction velocity and an increase in the A-V nodal refractory period. Propranolol does not display the anticholinergic actions of quinidine and other antiarrhythmic agents.

His-Purkinje System and Ventricular Muscle

Propranolol decreases Purkinje fiber membrane re-sponsiveness and reduces action potential amplitude. His-Purkinje tissue excitability also is reduced. These changes result in a decrease in His-Purkinje conduction velocity. However, these electrophysiological alter-ations are observed at propranolol concentrations in excess of those normally used in therapy. The most striking electrophysiological property of propranolol at usual therapeutic concentrations is a depression of catecholamine-stimulated automaticity.

Electrocardiographic Changes

Propranolol prolongs the PR interval but does not change the QRS interval. It may shorten the QT interval.

Hemodynamic Effects

The blockade of cardiac β-adrenoceptors prevents or reduces the usual positive inotropic and chronotropic actions of catecholamine administration on cardiac sympathetic nerve stimulation. Blockade of β-receptors prolongs systolic ejection periods at rest and during ex-ercise. Both alterations tend to increase myocardial oxygen consumption. However, these alterations are offset by factors that tend to reduce oxygen consump-tion, such as decreased heart rate and decreased force of contraction. The decrease in oxygen demand pro-duced by a decrease in heart rate and a decrease in force of contraction is usually greater than the increase in oxygen demand that results from increased heart size and increased ejection time. The net result is that oxy-gen demand is decreased.


The pharmacokinetic characteristics of propranolol:

Oral bioavailability : 30–40%

Onset of action : 1–2 hours

Peak response : 1.0–1.5 hours

Duration of action : 6–24 hours

Plasma half-life : 3–5 hours

Primary route of metabolism : Hepatic

Primary route of excretion : Renal

Therapeutic serum concentration : 0.02–1  μg /mL

Clinical Uses

Propranolol is indicated in the management of a variety of cardiac rhythm abnormalities that are totally or par-tially due to enhanced adrenergic stimulation. In se-lected cases of sinus tachycardia caused by anxiety, pheochromocytoma, or thyrotoxicosis, β-blockade will reduce the spontaneous heart rate.

Propranolol alone or in conjunction with digitalis can help control the ventricular rate in patients with atrial flutter or atrial fibrillation. Patients with supraventricular extrasystoles and intermittent parox-ysms of atrial fibrillation may benefit from β-receptor blockade with propranolol.

The arrhythmias associated with halothane or cyclo-propane anesthesia have been attributed to the interac-tion of the anesthetic with catecholamines, and they have been suppressed by IV administration of 1 to 3 mg propranolol. An increase in circulating catecholamines also has been observed in patients with acute myo-cardial infarction and has been correlated with the de-velopment of arrhythmias.

Clinically, tachyarrhythmias associated with digitalis excess (including supraventricular and ventricular ex-trasystoles) and ventricular tachycardia have been sup-pressed by propranolol. Although propranolol is highly effective in the treatment of digitalis-induced arrhyth-mias, phenytoin and lidocaine are preferred.

Long-term treatment with β-adrenoceptor blocking agents is clearly associated with an increased rate of

survival in patients with ischemic heart disease who have recovered from an acute myocardial infarction. Propranolol is the drug of choice for treating patients with the congenital long QT syndrome.

Adverse Effects

The toxicity associated with propranolol is for the most part related to its primary pharmacological action, inhi-bition of the cardiac β-adrenoceptors. In addition, propranolol exerts direct cardiac depressant effects that become manifest when the drug is administered rapidly by the IV route. Glucagon immediately reverses all cardiac de-pressant effects of propranolol, and its use is associated with a minimum of side effects. The inotropic agents amrinone (Inocor) and milrinone (Primacor) provide alternative means of augmenting cardiac contractile function in the presence of β-adrenoceptor blockade . Propranolol may also stimulate bron-chospasm in patients with asthma.

Since propranolol crosses the placenta and enters the fetal circulation, fetal cardiac responses to the stresses of labor and delivery will be blocked. Additionally, propranolol crosses the blood-brain barrier and is associ-ated with mood changes and depression. School difficul-ties are commonly associated with its use in children. Propranolol may also cause hypoglycemia in infants.


Propranolol is contraindicated for patients with de- pressed myocardial function and may be contraindicated in the presence of digitalis toxicity because of the possi-bility of producing complete A-V block and ventricular asystole. Patients receiving anesthetic agents that tend to depress myocardial contractility (ether, halothane) should not receive propranolol. Propranolol should be used with extreme caution in patients with asthma.

Up-regulation of β-receptors follows long-term therapy, making abrupt withdrawal of β-blockers dan-gerous for patients with ischemic heart disease.

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