From the Guidelines
Mechanism of Action of Propranolol
Propranolol, a non-selective beta-adrenergic receptor blocker, exerts its mechanism of action by competitively inhibiting the binding of catecholamines, such as epinephrine and norepinephrine, to beta-1 and beta-2 adrenergic receptors 1.
- This inhibition reduces myocardial contractility, sinus node rate, and AV node conduction velocity, thereby decreasing heart rate and cardiac output.
- The primary benefits of beta blockers, such as propranolol, are due to inhibition of beta-1 adrenergic receptors, which results in a decrease in cardiac work and myocardial oxygen demand 1.
- Slowing of the heart rate also has a favorable effect, acting not only to reduce MVO2 but also to increase the duration of diastole and diastolic pressure-time, a determinant of forward coronary flow and collateral flow.
- At typical oral doses of 20-160 mg, propranolol reduces sympathetic nervous system activity, resulting in decreased heart rate, contractility, and cardiac output, as well as vasodilation and decreased peripheral resistance.
- The medication's effects are dose-dependent and typically occur within 30 minutes to 1 hour after administration, with peak effects observed at 1-3 hours and a duration of action ranging from 6-12 hours. Key points about propranolol include:
- Non-selective beta blocker: Propranolol blocks both beta-1 and beta-2 adrenergic receptors.
- Competitive inhibition: Propranolol competitively inhibits the binding of catecholamines to beta-adrenergic receptors.
- Decreased myocardial oxygen demand: Propranolol reduces cardiac work and myocardial oxygen demand by inhibiting beta-1 adrenergic receptors.
- Slowed heart rate: Propranolol slows the heart rate, increasing diastole and diastolic pressure-time, which improves coronary flow.
From the FDA Drug Label
Propranolol is a nonselective, beta-adrenergic receptor-blocking agent possessing no other autonomic nervous system activity. It specifically competes with beta-adrenergic receptor-stimulating agents for available receptor sites When access to beta-receptor sites is blocked by propranolol, the chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation are decreased proportionately.
The mechanism of action of Propranolol is through beta-adrenergic blockade, where it competes with beta-adrenergic receptor-stimulating agents for available receptor sites, decreasing the chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation. 2
From the Research
Mechanism of Action of Propranolol
The mechanism of action of propranolol, a beta blocker, involves the antagonism of beta-adrenergic receptors, which are stimulated by endogenous catecholamines 3. Propranolol is a nonselective beta blocker, meaning it blocks both beta 1 and beta 2 receptors 4, 5.
Effects on Beta 1 and Beta 2 Receptors
- Beta 1 receptors are primarily found in the heart, and their blockade by propranolol reduces heart rate, cardiac output, and arterial pressure, while increasing peripheral vascular resistance 4.
- Beta 2 receptors are found in the lungs, liver, and other tissues, and their blockade by propranolol can cause bronchoconstriction and peripheral vasoconstriction 4.
- Propranolol has a higher affinity for beta 2 receptors than beta 1 receptors, with an equilibrium dissociation constant (KB) of 8.6 for beta 1 receptors and 8.9 for beta 2 receptors in atrial preparations 5.
Clinical Implications
The nonselective beta blockade by propranolol can have both beneficial and disadvantageous effects. For example, in patients with heart failure, nonselective beta blockade by propranolol can reduce cardiac sympathetic activity, which may be beneficial 6. However, the blockade of beta 2 receptors can also cause bronchoconstriction, which may be disadvantageous in patients with asthma or chronic obstructive pulmonary disease.
Stereoselectivity of Propranolol
Propranolol is administered as a racemic mixture of (R)- and (S)-enantiomers, but only the (S)-enantiomer has beta blocking activity 7. The (R)-enantiomer has other effects, such as inhibiting the conversion of thyroxine to triiodothyronine, and may be useful in certain indications without causing beta blockade 7.