Antianginal Medications Overview

Antianginal Medications

• Antianginal drugs manage angina pectoris, a condition of chest pain from reduced blood flow to the heart muscle. They balance oxygen supply and demand in the heart.

Nitrates (e.g., Nitroglycerin, Isosorbide dinitrate)

• Mechanism of Action: Nitrates are primarily vasodilators acting on the venous system, but also on the arterial system.
• They're converted to nitric oxide (NO), activating guanylate cyclase in smooth muscle cells, thus increasing cyclic GMP (cGMP).
• This causes smooth muscle relaxation, particularly in veins, reducing venous return (preload) and lowering the heart's oxygen demand.
• At higher doses, nitrates dilate coronary arteries, improving the heart's oxygen supply.
• Effect on Angina: By reducing preload and afterload (resistance heart pumps against), nitrates decrease myocardial oxygen demand, relieving angina.

Beta-Blockers (e.g., Metoprolol, Atenolol, Propranolol)

• Mechanism of Action: Beta-blockers block beta-adrenergic receptors (mainly β1 receptors in the heart), activated by catecholamines.
• This decreases heart rate (negative chronotropy), decreases myocardial contractility (negative inotropy), and reduces blood pressure (negative dromotropy).
• Effect on Angina: By reducing heart rate and contractility, beta-blockers lower the heart's oxygen demand, improving diastolic filling time, and reducing myocardial ischemia. This decreases angina frequency and severity.

Calcium Channel Blockers (e.g., Amlodipine, Verapamil, Diltiazem)

• Mechanism of Action: Calcium channel blockers block calcium ion influx through voltage-gated calcium channels (L-type channels) in smooth muscle and cardiac muscle.
• Dihydropyridines (e.g., Amlodipine) primarily dilate vascular smooth muscle, reducing systemic vascular resistance and lowering afterload.
• Non-dihydropyridines (e.g., Verapamil, Diltiazem) also dilate blood vessels and slow heart rate, reducing myocardial contractility.
• Effect on Angina: By reducing afterload and preload via coronary artery dilation, calcium channel blockers lower myocardial oxygen demand and improve oxygen supply to ischemic heart tissue to relieve angina. Non-dihydropyridines also lower heart's oxygen consumption by slowing heart rate.

Ranolazine

• Mechanism of Action: Ranolazine inhibits the late phase of sodium current (INa) in cardiac myocytes, reducing intracellular calcium overload. This lowers myocardial oxygen demand.
• Effect on Angina: Ranolazine improves the efficiency of the heart's oxygen utilization. It especially helps patients not well controlled by other medications.

Ivabradine

• Mechanism of Action: Ivabradine selectively inhibits the If ("funny" current) channels in the SA node, reducing heart rate without affecting myocardial contractility.
• Effect on Angina: By slowing heart rate, Ivabradine improves coronary perfusion, lowering myocardial oxygen demand, helping control angina, particularly in patients with elevated heart rates.

Antiplatelet and Anticoagulant Drugs (e.g., Aspirin, Clopidogrel, Heparin)

• Mechanism of Action: These drugs, while not directly reducing oxygen demand, reduce thrombus formation in coronary arteries by inhibiting platelet aggregation or clotting factors.
  -Aspirin inhibits cyclooxygenase (COX) and thromboxane A2 production.
  • Clopidogrel inhibits ADP-induced platelet aggregation by blocking the P2Y12 receptor.
  • Heparin (and other anticoagulants) inhibits thrombin and factor Xa, preventing clot formation.
• Effect on Angina: Used primarily in patients with unstable angina or acute coronary syndrome (ACS) to prevent worsening ischemia and reduce heart attack risk.

Heart Failure Drugs

• Heart failure (HF) is a condition where the heart's inability to pump blood effectively leads to symptoms like shortness of breath, fatigue, and fluid retention.

Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors)

• Mechanism of Action: ACE inhibitors block the enzyme angiotensin-converting enzyme (ACE), reducing angiotensin II levels, leading to vasodilation and reduced aldosterone secretion. They also reduce afterload and preload, lowering the heart's workload.
• Effect on Heart Failure: ACE inhibitors improve symptoms, reduce hospitalizations, and lower mortality in heart failure patients, particularly those with reduced ejection fraction (HFrEF).

Angiotensin II Receptor Blockers (ARBs)

• Mechanism of Action: ARBs selectively block the angiotensin II type 1 receptor (AT1), preventing angiotensin II binding.
• Effect on Heart Failure: ARBs function similarly to ACE inhibitors but do not increase bradykinin levels, making them a suitable alternative. They are also associated with reduced hospitalization and mortality in HFrEF.

Beta-Blockers

• Mechanism of Action: Beta-blockers block beta-adrenergic receptors, decreasing heart rate and myocardial contractility and lowering blood pressure.
• Effect on Heart Failure: Chronic beta-blocker use improves cardiac function, reduces heart remodeling (reverse remodeling), and reduces mortality in heart failure patients, especially in systolic heart failure (HFrEF).

Aldosterone Antagonists (Potassium-Sparing Diuretics)

• Mechanism of Action: These diuretics block aldosterone action, lowering blood pressure, reducing fluid retention, and preventing myocardial fibrosis.
• Effect on Heart Failure: Aldosterone antagonists improve survival and reduce hospitalizations in heart failure patients, particularly those with severe symptoms.

Diuretics

• Mechanism of Action: Diuretics promote sodium and water excretion by the kidneys, lowering fluid overload and blood pressure.
• Effect on Heart Failure: Diuretics relieve symptom management, addressing fluid retention, shortness of breath, and edema. They do not directly impact long-term mortality.

Hydralazine and Nitrates

• Mechanism of Action: This combination causes arterial (hydralazine) and venous vasodilation (nitrates), reducing afterload and preload.
• Effect on Heart Failure: This combination improves symptoms, reduces hospitalizations, and improves survival in HFrEF patients, especially in African Americans.

Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors

• Mechanism of Action: SGLT2 inhibitors block glucose reabsorption in the kidneys, promoting glucose excretion in the urine.
• Effect on Heart Failure: These agents improve symptoms, reduce hospitalizations, and lower mortality in HFrEF patients, particularly those with diabetes.

Ivabradine

• Mechanism of Action: Ivabradine selectively inhibits the If current in the SA node, decreasing heart rate without affecting myocardial contractility.
• Effect on Heart Failure: Ivabradine improves diastolic filling, reducing heart workload, aiding patients with elevated heart rates and symptomatic HFrEF who are already on optimal beta-blocker therapy.

Digoxin

• Mechanism of Action: Digoxin inhibits the Na+/K+ ATPase pump, increasing intracellular calcium and enhancing myocardial contractility (positive inotropy).
• Effect on Heart Failure: Digoxin improves symptoms and exercise tolerance in heart failure. It particularly benefits those with atrial fibrillation. While it does not improve survival, it can potentially reduce hospitalizations.

This quiz covers the fundamentals of antianginal medications, focusing on nitrates and beta-blockers. Learn about their mechanisms of action, effects on angina pectoris, and how they help manage heart conditions. Test your understanding of these critical cardiovascular drugs.