Angina, Heart Failure PDF

Angina, Heart Failure Antianginal Medications Antianginal drugs are used to manage angina pectoris, a condition characterized by chest pain due to reduced blood flow to the heart muscle (myocardium). These drugs work by improving the balance between oxygen supply and demand in the heart Nitrates (...

Angina, Heart Failure Antianginal Medications Antianginal drugs are used to manage angina pectoris, a condition characterized by chest pain due to reduced blood flow to the heart muscle (myocardium). These drugs work by improving the balance between oxygen supply and demand in the heart Nitrates (e.g., Nitroglycerin, Isosorbide dinitrate) ​ Mechanism of Action: ○​ Nitrates are vasodilators, primarily acting on the venous system, but also on the arterial system to some extent. ○​ They are converted to nitric oxide (NO), which activates guanylate cyclase in smooth muscle cells, leading to an increase in cyclic GMP (cGMP). ○​ This results in smooth muscle relaxation, especially in veins, reducing venous return (preload) and consequently lowering the heart's oxygen demand. ○​ At higher doses, nitrates also dilate coronary arteries, improving oxygen supply to the heart. ​ Effect on Angina: By reducing preload (the amount of blood returning to the heart) and afterload (resistance against which the heart has to pump), nitrates decrease myocardial oxygen demand, helping relieve angina. Beta-Blockers (e.g., Metoprolol, Atenolol, Propranolol)  ​ Mechanism of Action: ○​ Beta-blockers work by blocking beta-adrenergic receptors (mainly β1 receptors in the heart), which are activated by catecholamines (epinephrine and norepinephrine). ○​ This leads to a decrease in heart rate (negative chronotropy), decreased myocardial contractility (negative inotropy), and reduced blood pressure (negative dromotropy). ○​ By reducing heart rate and contractility, beta-blockers lower the heart’s oxygen demand, which is especially beneficial during exertion or stress. ○​ They also improve diastolic filling time and can reduce myocardial ischemia. ​ Effect on Angina: By reducing the workload of the heart, beta-blockers reduce the frequency and severity of angina attacks. Calcium Channel Blockers (e.g., Amlodipine, Verapamil, Diltiazem) ​ Mechanism of Action: ○​ Calcium channel blockers block the influx of calcium ions 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) not only dilate blood vessels but also slow the heart rate and reduce myocardial contractility.  ​ Effect on Angina: ○​ By reducing afterload and preload, calcium channel blockers lower myocardial oxygen demand. ○​ By dilating coronary arteries, they improve oxygen supply to ischemic heart tissue, thus relieving angina. ○​ Non-dihydropyridines also reduce the heart's oxygen consumption by slowing the heart rate. Ranolazine ​ Mechanism of Action: ○​ Ranolazine is an anti-ischemic agent that works by inhibiting the late phase of sodium current (I_Na) in cardiac myocytes. ○​ This action reduces intracellular calcium overload, which in turn reduces myocardial oxygen demand. ○​ Unlike other antianginals, ranolazine does not significantly affect heart rate or blood pressure. ​ Effect on Angina: It is used to relieve angina by improving the efficiency of the heart’s oxygen utilization, especially in patients who are not adequately controlled on other medications. Ivabradine ​ Mechanism of Action: ○​ Ivabradine selectively inhibits the If ("funny" current) channels in the sinoatrial (SA) node, reducing heart rate without affecting myocardial contractility. ○​ By slowing the heart rate, Ivabradine allows more time for coronary perfusion, which may be beneficial in angina, especially in patients with elevated heart rates.  ​ Effect on Angina: By reducing heart rate, Ivabradine decreases myocardial oxygen demand, thereby helping to control angina. Antiplatelet and Anticoagulant Drugs (e.g., Aspirin, Clopidogrel, Heparin) ​ Mechanism of Action: ○​ While not directly reducing oxygen demand or improving oxygen supply, these drugs reduce thrombus formation in coronary arteries by inhibiting platelet aggregation or clotting factors. ○​ Aspirin inhibits cyclooxygenase (COX) and the production of thromboxane A2, which is involved in platelet aggregation. ○​ 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: These drugs are used primarily in patients with unstable angina or in the context of acute coronary syndrome (ACS) to prevent the worsening of ischemia and reduce the risk of a heart attack. Heart Failure Drugs Heart failure (HF) is a condition where the heart is unable to pump blood effectively to meet the body's demands, leading to symptoms like shortness of breath, fatigue, and fluid retention. The management of heart failure involves several classes of drugs that target different mechanisms to improve heart function, reduce symptoms, and improve survival. Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors) ​ Examples: Enalapril, Lisinopril, Ramipril ​ Mechanism of Action: ○​ ACE inhibitors block the enzyme angiotensin-converting enzyme (ACE), which normally converts angiotensin I to the potent vasoconstrictor angiotensin II. ○​ By inhibiting ACE, these drugs reduce angiotensin II levels, which leads to vasodilation, reduced aldosterone secretion, and lowered blood pressure. ○​ They also reduce afterload (the resistance the heart must overcome to pump blood) and decrease preload(the volume of blood returning to the heart), which decreases the heart’s workload. ○​ ACE inhibitors also increase the availability of bradykinin, which promotes vasodilation. ​ Effect on Heart Failure: ACE inhibitors improve symptoms, decrease hospitalization, and have been shown to reduce mortality in heart failure patients, especially in those with reduced ejection fraction (HFrEF). Angiotensin II Receptor Blockers (ARBs) ​ Examples: Losartan, Valsartan, Candesartan ​ Mechanism of Action: ○​ ARBs selectively block the angiotensin II type 1 receptor (AT1), preventing the binding of angiotensin II.  ○​ This results in vasodilation, reduced aldosterone secretion, and lowered blood pressure, similar to ACE inhibitors, but without increasing bradykinin levels (which can cause a cough). ​ Effect on Heart Failure: ARBs are used as an alternative to ACE inhibitors in patients who cannot tolerate ACE inhibitors due to side effects. They also reduce hospitalization and mortality in HFrEF. Beta-Blockers ​ Examples: Metoprolol, Carvedilol, Bisoprolol ​ Mechanism of Action: ○​ Beta-blockers block beta-adrenergic receptors (mainly β1 receptors) in the heart and vasculature, reducing the effects of the sympathetic nervous system, which is often overactive in heart failure. ○​ They decrease heart rate, reduce myocardial contractility (negative inotropy), and reduce blood pressure. ○​ Chronic use of beta-blockers leads to improved cardiac function, decreased remodeling of the heart (reverse remodeling), and increased survival. ​ Effect on Heart Failure: Beta-blockers improve symptoms, reduce hospitalizations, and have been shown to reduce mortality in patients with HFrEF. They are particularly important in the management of systolic heart failure. Aldosterone Antagonists (Potassium-Sparing Diuretics) ​ Examples: Spironolactone, Eplerenone  ​ Mechanism of Action: ○​ Aldosterone antagonists block the action of aldosterone, a hormone that promotes sodium and water retention, leading to fluid buildup and increased blood pressure in heart failure. ○​ By inhibiting aldosterone, these drugs reduce fluid retention, lower blood pressure, and prevent myocardial fibrosis (scarring of the heart muscle). ○​ Spironolactone also has anti-inflammatory and antifibrotic effects, which are beneficial in heart failure. ​ Effect on Heart Failure: Aldosterone antagonists improve survival and reduce hospitalizations in patients with heart failure, particularly in those with severe symptoms or after a myocardial infarction (MI). Diuretics ​ Examples: Furosemide, Bumetanide, Torsemide (loop diuretics); Hydrochlorothiazide, Chlorthalidone (thiazide diuretics) ​ Mechanism of Action: ○​ Diuretics promote the excretion of sodium and water by the kidneys, which reduces fluid overload (edema) and lower blood pressure. ○​ Loop diuretics (e.g., furosemide) work in the loop of Henle in the kidneys, inhibiting sodium, chloride, and potassium reabsorption, leading to significant diuresis. ○​ Thiazide diuretics (e.g., hydrochlorothiazide) work in the distal tubule of the kidney, inhibiting sodium reabsorption to a lesser degree.  ​ Effect on Heart Failure: Diuretics are primarily used for symptom management in heart failure by relieving fluid retention and reducing edema, shortness of breath, and fatigue. They do not affect long-term mortality but are critical for improving quality of life. Hydralazine and Nitrates (Vasodilators) ​ Examples: Hydralazine, Isosorbide dinitrate, Isosorbide mononitrate ​ Mechanism of Action: ○​ Hydralazine causes direct arterial vasodilation, reducing afterload (resistance the heart must pump against). ○​ Nitrates cause venodilation, reducing preload (the volume of blood returning to the heart). ○​ When used together, hydralazine and nitrates have a complementary effect by reducing both preload and afterload, improving myocardial perfusion and decreasing the workload of the heart. ​ Effect on Heart Failure: This combination has been shown to improve symptoms, reduce hospitalizations, and improve survival in patients with HFrEF, especially in African American patients (who may have a more pronounced response). Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors ​ Examples: Empagliflozin, Dapagliflozin, Canagliflozin ​ Mechanism of Action: ○​ SGLT2 inhibitors block the sodium-glucose cotransporter 2 in the kidneys, reducing glucose reabsorption and promoting glucose excretion in the urine.  ○​ They also cause osmotic diuresis, reducing fluid retention and lowering blood pressure. ○​ These drugs have additional cardioprotective effects, including reducing inflammation, oxidative stress, and fibrosis in the heart. ​ Effect on Heart Failure: SGLT2 inhibitors have been shown to improve symptoms, reduce hospitalizations, and decrease mortality in heart failure patients, particularly in those with HFrEF and diabetes. Ivabradine ​ Mechanism of Action: ○​ Ivabradine selectively inhibits the If (funny) current in the sinoatrial node, which slows the heart rate without affecting myocardial contractility. ○​ This results in lower heart rate and allows for improved diastolic filling, leading to better oxygen delivery to the heart. ​ Effect on Heart Failure: Ivabradine is used in patients with HFrEF who are symptomatic despite optimal beta-blocker therapy, particularly in those with elevated heart rates. It reduces hospitalization for heart failure and may improve survival. Digoxin ​ Mechanism of Action: ○​ Digoxin is a cardiac glycoside that inhibits the Na+/K+ ATPase pump, leading to an increase in intracellular calcium in cardiac muscle cells.  ○​ The increased calcium enhances myocardial contractility (positive inotropy), helping the heart pump more effectively. ○​ Digoxin also slows the heart rate by inhibiting the AV node, which is beneficial in patients with atrial fibrillation and heart failure. ​ Effect on Heart Failure: Digoxin is used to improve symptoms and exercise tolerance in heart failure, particularly when associated with atrial fibrillation. It does not improve survival but may reduce hospitalizations.