Antianginal Therapies: Mechanisms, Classes, and Side Effects

Angina, marked by chest pain due to reduced blood flow to the heart, is managed with medications that improve oxygen supply or reduce demand. These therapies help prevent attacks and enhance quality of life for those with coronary artery disease.

Different classes of antianginal drugs work through distinct mechanisms. Understanding their functions, benefits, and potential side effects is essential for optimizing treatment choices.

Mechanisms Of Action

Antianginal therapies address the imbalance between myocardial oxygen supply and demand, which leads to ischemic symptoms. The heart’s oxygen consumption is influenced by factors such as heart rate, contractility, and ventricular wall tension. By enhancing coronary perfusion or reducing cardiac workload, these medications alleviate chest pain and prevent ischemic episodes.

Vasodilation plays a key role by improving blood flow to ischemic myocardial tissue. Coronary vasodilation expands arterial diameter, reducing resistance and facilitating perfusion, particularly in vessels narrowed by atherosclerosis. Systemic vasodilation decreases afterload and preload, lowering myocardial oxygen demand. By reducing venous return, some agents decrease ventricular filling pressure, leading to lower end-diastolic volume and myocardial wall stress.

Beyond vascular effects, certain medications modulate autonomic control. By slowing heart rate and reducing contractility, they decrease ischemic episodes. A slower heart rate prolongs diastole, the phase when coronary perfusion occurs, improving oxygen delivery. Reduced contractility further lowers myocardial energy expenditure and oxygen consumption, particularly benefiting patients with stable angina.

Classes Of Agents

Antianginal medications are categorized by their effects on the cardiovascular system. The primary classes include nitrates, beta blockers, and calcium channel blockers. Additional agents with unique mechanisms are used in specific cases.

Nitrates

Nitrates, such as nitroglycerin and isosorbide mononitrate, function as vasodilators by releasing nitric oxide, which increases cyclic guanosine monophosphate (cGMP) levels in vascular smooth muscle, promoting relaxation and vasodilation. Their primary effect is reducing myocardial oxygen demand by decreasing preload, as venodilation lowers venous return and left ventricular end-diastolic pressure. Nitrates also improve oxygen supply by dilating coronary arteries, particularly useful in vasospastic angina.

Sublingual nitroglycerin provides rapid relief within minutes, while long-acting formulations like transdermal patches or oral isosorbide mononitrate manage chronic symptoms. Continuous use can lead to tolerance, necessitating nitrate-free intervals. Clinical guidelines recommend a 10-12 hour nitrate-free period to maintain efficacy.

Beta Blockers

Beta blockers, including metoprolol, atenolol, and propranolol, reduce myocardial oxygen demand by inhibiting beta-adrenergic receptors, primarily β1 receptors in the heart. This decreases heart rate, myocardial contractility, and blood pressure. By slowing heart rate, beta blockers prolong diastole, improving coronary perfusion.

These medications are particularly effective for stable angina and are often first-line therapy in patients with a history of myocardial infarction or left ventricular dysfunction. Cardioselective agents like bisoprolol and metoprolol are preferred in patients with respiratory conditions, as they carry a lower risk of bronchoconstriction compared to non-selective options like propranolol.

Calcium Channel Blockers

Calcium channel blockers (CCBs) are divided into dihydropyridines (e.g., amlodipine, nifedipine) and non-dihydropyridines (e.g., verapamil, diltiazem). These agents inhibit L-type calcium channels, reducing calcium influx into vascular and myocardial cells, leading to vasodilation, decreased myocardial contractility, and, in the case of non-dihydropyridines, reduced heart rate.

Dihydropyridines primarily act as vasodilators, decreasing systemic vascular resistance and afterload, which reduces myocardial oxygen demand. They are particularly useful in vasospastic angina. Non-dihydropyridines also lower heart rate and contractility, making them an alternative for patients who cannot tolerate beta blockers.

Additional Agents

Other options include ranolazine, ivabradine, and nicorandil, each with distinct mechanisms. Ranolazine inhibits late sodium current (INa) in cardiac myocytes, reducing intracellular sodium and calcium overload, which improves myocardial relaxation and decreases oxygen consumption. It is particularly useful for refractory angina.

Ivabradine selectively inhibits the sinoatrial node’s If current, reducing heart rate without affecting contractility or blood pressure, making it suitable for patients who cannot tolerate beta blockers. Nicorandil, a potassium channel opener with nitrate-like properties, provides arterial and venous vasodilation, improving coronary blood flow and reducing oxygen demand.

These agents are considered when standard therapies are insufficient or contraindicated. Clinical trials have demonstrated ranolazine’s effectiveness in reducing angina episodes and improving exercise tolerance.

Potential Side Effects

The benefits of antianginal medications must be weighed against their potential side effects, which vary by drug class, dosage, and individual patient factors. While most adverse reactions are mild, some can impact treatment adherence and cardiovascular health.

Vasodilation, common among many antianginal agents, can lead to hypotension, dizziness, lightheadedness, and syncope. This effect is particularly pronounced with nitrates and dihydropyridine calcium channel blockers. Reflex tachycardia may also occur as a compensatory response, potentially aggravating ischemia in certain individuals.

Beta blockers, which reduce heart rate and contractility, can cause bradycardia and fatigue, particularly in those with conduction abnormalities. Some patients experience exercise intolerance due to reduced cardiac output. Non-selective beta blockers like propranolol may provoke bronchospasm, posing challenges for those with asthma or chronic obstructive pulmonary disease (COPD).

Calcium channel blockers, particularly non-dihydropyridines like verapamil and diltiazem, may cause constipation due to their effects on gastrointestinal smooth muscle. Edema, primarily in the lower extremities, is another frequent complaint with dihydropyridines like amlodipine. This occurs due to capillary leakage from arteriolar dilation and may require dose adjustment or drug substitution.