Mechanism of Antianginal Action
The antianginal effect of these drugs is based on the blockade of cardiac $\beta_1$-adrenergic receptors. This leads to two key outcomes:
- Negative inotropic effect — reduction in the force of cardiac contractions;
- Negative chronotropic effect — reduction in heart rate.
As a result, overall cardiac work decreases, and myocardial oxygen demand drops significantly. With prolonged use (more than a week), blood pressure also decreases, further unloading the heart muscle.
Classification and Drug Characteristics
Depending on their receptor affinity, these agents are divided into two main groups:
- Cardioselective ($\beta_1$): atenolol, metoprolol, bisoprolol, talinolol. The cardiac mechanism described is fully manifested in these agents.
- Non-selective ($\beta_1, \beta_2$): propranolol. This agent is characterized by a unique ability to redistribute coronary blood flow in favor of ischemic areas by increasing the tone of healthy vessels.
Nebivolol deserves special mention; it features superselective $\beta_1$-receptor blockade and the ability to stimulate endothelial nitric oxide production for additional vasodilation.
Side Effects and Safety
The use of these agents carries the risk of certain adverse reactions:
- Cardiac effects: suppression of AV conduction, excessive bradycardia, decreased contraction force, and arterial hypotension.
- Specific risks of non-selective agents: bronchospasm and peripheral vascular spasms with a sensation of cold in the extremities.
Abrupt discontinuation of therapy is unacceptable because it triggers withdrawal syndrome — a sudden intensification and increased frequency of angina attacks.
Combination Therapy with Nitrates
Co-administration with nitrates is considered a classic and highly beneficial example of drug synergy:
- Beta-blockers completely eliminate the reflex tachycardia induced by nitrates.
- Nitrates, in turn, neutralize the potential vasospastic effect of beta-blockers and reduce left ventricular end-diastolic pressure and volume.