Cardiovascular Pharmacology

Angiotensin-Converting Enzyme (ACE) Inhibitors: Examples include lisinopril, enalapril, and captopril. These medications work by inhibiting the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. By reducing angiotensin II levels, ACE inhibitors cause vasodilation, reduce aldosterone secretion (decreasing sodium and water retention), and decrease blood pressure. They are particularly beneficial for patients with diabetes or heart failure due to their renal protective effects.

Angiotensin II Receptor Blockers (ARBs): Drugs such as losartan, valsartan, and telmisartan block the angiotensin II type 1 receptor, preventing the vasoconstrictive and aldosterone-secreting effects of angiotensin II. They offer similar benefits to ACE inhibitors but are often used in patients who cannot tolerate the cough associated with ACE inhibitors.

Calcium Channel Blockers: Including amlodipine, diltiazem, and verapamil, these inhibit calcium influx into cardiac and smooth muscle cells. This reduces myocardial contractility, slows cardiac conduction, and causes vascular smooth muscle relaxation, leading to decreased blood pressure and reduced cardiac workload.

Beta-Blockers: Like propranolol, metoprolol, and atenolol, these antagonize beta-adrenergic receptors in the heart and blood vessels. By blocking the effects of catecholamines, they reduce heart rate, contractility, and cardiac output, as well as renin secretion from the kidneys, leading to decreased blood pressure.

Diuretics: Including hydrochlorothiazide, furosemide, and spironolactone, these increase urine output by acting on different segments of the nephron. Thiazide diuretics are commonly used as first-line therapy for hypertension, while loop diuretics are preferred in acute heart failure. By reducing blood volume, they decrease preload and afterload, effectively lowering blood pressure.

Class I (Sodium Channel Blockers): Subdivided into IA (quinidine, procainamide), IB (lidocaine, mexiletine), and IC (flecainide, propafenone) based on their effects on the action potential. These medications reduce sodium influx into cardiac cells, decreasing conduction velocity and membrane responsiveness.

Class II (Beta-Blockers): Propranolol, esmolol, and others in this class reduce sympathetic effects on the heart, slowing heart rate and conduction through the AV node.

Class III (Potassium Channel Blockers): Amiodarone, sotalol, and dofetilide prolong action potential duration and refractory period by blocking potassium channels. Amiodarone is particularly effective due to its multiple actions on ion channels.

Class IV (Calcium Channel Blockers): Verapamil and diltiazem primarily affect calcium channels in cardiac tissue and the conduction system, slowing heart rate and AV node conduction.

Other Anti-Arrhythmics: Digoxin increases vagal tone and intracellular calcium, while adenosine temporarily blocks AV node conduction and is used to terminate supraventricular tachycardias.

Antiplatelet Drugs: Aspirin irreversibly inhibits cyclooxygenase-1, reducing thromboxane A2 production and platelet aggregation. Clopidogrel, prasugrel, and ticagrelor inhibit the P2Y12 ADP receptor on platelets, preventing activation. These agents are crucial in preventing arterial thrombosis in coronary artery disease and after coronary interventions.

Anticoagulants: These prevent the formation of fibrin clots. Warfarin inhibits vitamin K-dependent clotting factors II, VII, IX, and X. Direct oral anticoagulants (DOACs) such as rivaroxaban, apixaban, dabigatran, and edoxaban directly inhibit thrombin or factor Xa, offering advantages in convenience and monitoring requirements compared to warfarin. Heparin and low molecular weight heparins enhance the activity of antithrombin III.

Thrombolytics: Including alteplase, reteplase, and streptokinase, these activate plasminogen to plasmin, which degrades fibrin clots. They are used in acute myocardial infarction, ischemic stroke, and pulmonary embolism to rapidly restore blood flow.

Statins: Atorvastatin, simvastatin, rosuvastatin, and others inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. They also have pleiotropic effects including improving endothelial function and stabilizing atherosclerotic plaques, making them fundamental in preventing and treating coronary artery disease.

Fibrates: Gemfibrozil and fenofibrate activate peroxisome proliferator-activated receptor-alpha (PPAR-), reducing triglycerides and increasing HDL cholesterol. They are used primarily for hypertriglyceridemia.

Ezetimibe: Inhibits intestinal absorption of cholesterol by blocking the NPC1L1 protein, often used in combination with statins when statin monotherapy is insufficient.

PCSK9 Inhibitors: Monoclonal antibodies like evolocumab and alirocumab bind PCSK9, preventing degradation of LDL receptors and significantly reducing LDL cholesterol levels, particularly useful for patients with familial hypercholesterolemia or statin intolerance.

RAS Inhibitors: ACE inhibitors and ARBs reduce afterload, prevent cardiac remodeling, and improve survival in heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors (ARNIs) like sacubitril/valsartan combine neprilysin inhibition with ARB action, showing superior outcomes in HFrEF.

Beta-Blockers: Bisoprolol, carvedilol, and metoprolol succinate reduce mortality and hospitalization in HFrEF by reducing sympathetic drive, decreasing heart rate, and preventing adverse remodeling.

Mineralocorticoid Receptor Antagonists: Spironolactone and eplerenone block aldosterone effects, reducing sodium retention, potassium excretion, and cardiac fibrosis in heart failure.

SGLT2 Inhibitors: Originally developed for diabetes, drugs like dapagliflozin and empagliflozin have shown remarkable benefits in heart failure, reducing hospitalizations and mortality, primarily through diuretic and cardioprotective effects.

Ivabradine: Inhibits the funny current (If) in the sinoatrial node, reducing heart rate without affecting contractility or blood pressure, beneficial in HFrEF patients who cannot tolerate beta-blockers or remain symptomatic despite maximal therapy.

Digoxin: Inhibits the Na+/K+ ATPase pump, increasing intracellular sodium and calcium, leading to increased cardiac contractility. It is used in symptomatic HFrEF and for rate control in atrial fibrillation.