Mechanism of Action of Antianginal Drugs

Mechanism of Action of Antianginal Drugs

Antianginal drugs work through various mechanisms to improve the balance between myocardial oxygen supply and demand, thereby reducing the frequency and severity of anginal episodes. The primary classes of antianginal drugs include nitrates, beta-blockers, calcium channel blockers, and ranolazine. Here's a detailed look at their mechanisms of action:

Nitrates:

Nitrates, such as nitroglycerin and isosorbide dinitrate, act as nitric oxide (NO) donors. Their mechanism involves:

a) NO release: Nitrates are metabolized to release NO in vascular smooth muscle cells.

b) Activation of guanylate cyclase: NO stimulates guanylate cyclase, increasing cyclic guanosine monophosphate (cGMP) levels.

c) Smooth muscle relaxation: Elevated cGMP leads to smooth muscle relaxation and vasodilation.

d) Venodilation: Primarily affects the venous system, reducing preload and left ventricular end-diastolic pressure.

e) Arterial dilation: To a lesser extent, dilates arteries, including coronary arteries, improving blood flow.

f) Reduced myocardial oxygen demand: By decreasing preload and afterload.

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Beta-blockers:

Beta-blockers, such as metoprolol and atenolol, work by blocking beta-adrenergic receptors. Their mechanism includes:

a) Decreased heart rate: Blocking beta-1 receptors in the sinoatrial node slows heart rate.

b) Reduced myocardial contractility: Beta-1 blockade in ventricular muscle decreases contractility.

c) Lowered blood pressure: Due to decreased cardiac output and reduced renin release.

d) Increased diastolic filling time: The slower heart rate allows more time for coronary perfusion.

e) Reduced myocardial oxygen demand: Result of decreased heart rate, contractility, and blood pressure.

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Calcium Channel Blockers (CCBs):

CCBs, including amlodipine (dihydropyridine) and verapamil (non-dihydropyridine), work by:

a) Inhibiting calcium influx: Block L-type calcium channels in vascular smooth muscle and cardiac cells.

b) Vasodilation: Reduced intracellular calcium causes relaxation of vascular smooth muscle.

c) Decreased afterload: Systemic vasodilation reduces peripheral vascular resistance.

d) Coronary vasodilation: Improves coronary blood flow.

e) Reduced myocardial oxygen demand: Due to decreased afterload and, for some CCBs, reduced heart rate and contractility.

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Ranolazine:

Ranolazine has a unique mechanism of action:

a) Late sodium current inhibition: Blocks the late sodium current in cardiac cells.

b) Reduced calcium overload: By inhibiting the sodium-calcium exchanger.

c) Improved diastolic relaxation: Leads to better coronary perfusion.

d) Reduced myocardial oxygen demand: Without significantly affecting heart rate or blood pressure.

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Additional Mechanisms:

Some antianginal drugs have secondary mechanisms that contribute to their effectiveness:

a) Antioxidant effects: Some beta-blockers and CCBs may have antioxidant properties, protecting against ischemia-reperfusion injury.

b) Improved endothelial function: Nitrates may enhance endothelial function.

c) Antiplatelet effects: Nitrates can inhibit platelet aggregation.

In clinical practice, these drugs are often used in combination to leverage their complementary mechanisms of action. For example:

Nitrates provide rapid symptom relief and can be combined with beta-blockers or CCBs for long-term management.

Beta-blockers and CCBs may be used together in patients who don't achieve adequate control with monotherapy.

Ranolazine can be added to standard therapy in patients with refractory angina.