Antianginal Drugs Mechanism of Action

Antianginal Drugs Mechanism of Action

Antianginal drugs work through various mechanisms to alleviate angina symptoms by either increasing oxygen supply to the heart or decreasing myocardial oxygen demand. Understanding these mechanisms is crucial for effective management of angina pectoris. Here's a detailed look at the mechanisms of action for different classes of antianginal drugs:

Nitrates:

Mechanism: Nitrates are prodrugs that release nitric oxide (NO) in vascular smooth muscle cells. NO activates guanylate cyclase, increasing cyclic GMP levels, which leads to:

Venodilation: Reducing preload and left ventricular end-diastolic pressure

Arterial vasodilation: Reducing afterload

Coronary vasodilation: Improving blood flow to ischemic areas

Inhibition of platelet aggregation

These effects collectively reduce myocardial oxygen demand and increase oxygen supply.

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Beta-blockers:

Mechanism: Beta-blockers competitively inhibit the binding of catecholamines to beta-adrenergic receptors, resulting in:

Decreased heart rate

Reduced myocardial contractility

Lowered blood pressure

These effects reduce myocardial oxygen demand and increase diastolic filling time, improving coronary perfusion.

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Calcium Channel Blockers:

Mechanism: These drugs block L-type calcium channels in cardiac and vascular smooth muscle cells, leading to:

a. Dihydropyridines (e.g., amlodipine):

Peripheral and coronary vasodilation

Reduced afterload

b. Non-dihydropyridines (e.g., verapamil, diltiazem):

Decreased heart rate

Reduced myocardial contractility

Coronary vasodilation

Both subclasses reduce myocardial oxygen demand and improve oxygen supply.

Potassium Channel Openers (Nicorandil):

Mechanism: Nicorandil has a dual mechanism of action:

Activation of ATP-sensitive potassium channels in vascular smooth muscle, causing vasodilation

Nitrate-like effects, releasing NO and causing venodilation

These actions reduce preload and afterload, decreasing myocardial oxygen demand.

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Fatty Acid Oxidation Inhibitors (Trimetazidine):

Mechanism: Trimetazidine inhibits the long-chain 3-ketoacyl-CoA thiolase enzyme, leading to:

Shift from fatty acid oxidation to glucose oxidation in cardiac metabolism

Improved cardiac efficiency and reduced oxygen consumption

This metabolic modulation improves myocardial function without affecting hemodynamics.

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If Channel Inhibitors (Ivabradine):

Mechanism: Ivabradine selectively inhibits the funny current (If) in sinoatrial node cells, resulting in:

Reduced heart rate without affecting myocardial contractility or conduction

This decreases myocardial oxygen demand while preserving coronary dilation and contractility.

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Late Sodium Current Inhibitors (Ranolazine):

Mechanism: Ranolazine inhibits the late sodium current in cardiac cells, leading to:

Reduced intracellular calcium overload

Improved diastolic relaxation

Enhanced coronary blood flow

These effects improve myocardial oxygen supply-demand balance without significant hemodynamic changes.

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Antiplatelet Agents:

Mechanism: While not directly antianginal, these drugs prevent platelet aggregation:

Aspirin: Irreversibly inhibits cyclooxygenase-1 (COX-1), reducing thromboxane A2 production

Clopidogrel: Inhibits ADP-induced platelet aggregation by irreversibly binding to P2Y12 receptors

By preventing thrombotic events, these agents help maintain coronary blood flow.