Pharmacology of Antianginal Drugs

Pharmacology of Antianginal Drugs

Antianginal drugs are a diverse group of medications used to treat angina pectoris, a condition characterized by chest pain due to inadequate blood supply to the heart muscle. The pharmacology of these drugs involves various mechanisms of action, pharmacokinetics, and pharmacodynamics. Here's an overview of the pharmacology of major classes of antianginal drugs:

Nitrates:

Mechanism of Action:

Nitrates are converted to nitric oxide in the body, which activates guanylate cyclase.

This leads to increased cyclic GMP, causing smooth muscle relaxation and vasodilation.

Primarily dilate venous vessels, reducing preload and cardiac workload.

Also dilate coronary arteries, improving blood flow to the heart.

Pharmacokinetics:

Rapid absorption through mucous membranes (sublingual) or skin (transdermal).

Short-acting forms (e.g., nitroglycerin) have a half-life of minutes.

Long-acting forms (e.g., isosorbide mononitrate) have longer half-lives and duration of action.

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Beta-Blockers:

Mechanism of Action:

Block beta-adrenergic receptors in the heart and blood vessels.

Reduce heart rate, contractility, and blood pressure, decreasing myocardial oxygen demand.

Pharmacokinetics:

Most are well-absorbed orally.

Lipophilic beta-blockers (e.g., metoprolol) are extensively metabolized by the liver.

Hydrophilic beta-blockers (e.g., atenolol) are primarily excreted unchanged in urine.

Half-lives vary from a few hours to 24 hours, depending on the specific drug.

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Calcium Channel Blockers:

Mechanism of Action:

Block L-type calcium channels in vascular smooth muscle and cardiac tissue.

Cause vasodilation and reduce cardiac contractility.

Dihydropyridines (e.g., amlodipine) primarily affect vascular smooth muscle.

Non-dihydropyridines (e.g., verapamil, diltiazem) have more significant cardiac effects.

Pharmacokinetics:

Generally well-absorbed orally but undergo significant first-pass metabolism.

Highly protein-bound in plasma.

Metabolized primarily by the liver.

Half-lives vary widely, from a few hours to over 24 hours.

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Ranolazine:

Mechanism of Action:

Inhibits the late sodium current in cardiac cells.

Reduces intracellular calcium overload, improving diastolic function.

Does not significantly affect heart rate or blood pressure.

Pharmacokinetics:

Oral bioavailability of about 70%.

Extensively metabolized in the liver, primarily by CYP3A enzymes.

Half-life of about 7 hours.

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Ivabradine:

Mechanism of Action:

Selectively inhibits the If current in the sinoatrial node.

Reduces heart rate without affecting blood pressure or contractility.

Pharmacokinetics:

Rapidly and almost completely absorbed after oral administration.

Extensively metabolized by the liver, primarily by CYP3A4.

Half-life of about 11 hours.

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Trimetazidine:

Mechanism of Action:

Metabolic modulator that shifts cardiac energy metabolism from fatty acid to glucose oxidation.

Improves cardiac efficiency without affecting hemodynamics.

Pharmacokinetics:

Well-absorbed orally.

Primarily eliminated by renal excretion.

Half-life of about 6 hours.

General Pharmacological Considerations:

Drug Interactions:

Many antianginal drugs are metabolized by liver enzymes, leading to potential interactions with other medications.