Agents for Treating Heart Failure PDF

Agents for Treating Heart Failure Heart Failure – a condition that was once called “dropsy” or decompensation, is a syndrome that usually involves dysfunction of the cardiac muscle, of which the sarcomere is the basic unit. The sarcomere* contains two contractile proteins, actin and myosin, which ar...

Agents for Treating Heart Failure Heart Failure – a condition that was once called “dropsy” or decompensation, is a syndrome that usually involves dysfunction of the cardiac muscle, of which the sarcomere is the basic unit. The sarcomere* contains two contractile proteins, actin and myosin, which are highly reactive with each other but at rest are kept apart by the chemical troponin. Heart Failure can result from conditions that damage or overwork the heart muscle, this may include: Coronary Artery Disease – reduces blood flow to the heart muscle, causing it to become oxygen-deficient and function poorly. If it progresses to MI or heart attack, heart muscles die, further impairing the heart’s ability to pump blood. Cardiomyopathy – this heart ,muscle disease can lead to an enlarged heart and eventually complete heart failure. It can be caused by viral infections, alcoholism, steroid abuse or collagen disorders. This condition alters the heart muscle, making contraction and pumping ineffective. Hypertension – high blood pressure forces the heart to work harder, eventually leading to enlarged heart muscle. This increased workload can eventually cause heart failure. Valvular Heart Disease – leads to an overload of the ventricles because the valves do not close tightly, which allows blood to leak backward into the ventricles. CARDIOTONIC AGENTS Cardiotonic drugs increase calcium levels in heart muscle, boosting contraction strength and cardiac output. This increased output leads to higher renal blood flow, reduced renin release, increased urine production, and decreased blood volume. The overall effect is reduced heart workload and felief from heart failure. Cardiac Glycosides These were originally derived from the foxglove or digitalis plant. These plants were once ground up to make digitalis leaf, today digoxin(Lanoxin) is the drug most often used to treat heart failure. Actions and Indications: Digoxin increases calcium in heart muscles, leading to stronger contractions (positive inotropic effect) and a slower heart rate (negative chronotropic effect). This reduces the heart’s workload. It also increases urine output, lowering blood volume. Digoxin is used to treat heart failure, atrial flutter, atrial fibrillation, and paroxysmal atrial tachycardia. However, it has a narrow safety margin, meaning the therapeutic dose is close to the toxic dose, requiring careful monitoring. Pharmacokinetics: Digoxin is available in oral and parenteral administration. It has a rapid onset of action and rapid absorption (30-120 mins when taken orally, 5 to 30 mins in IV). Widely distributed throughout the body, excreted unchanged in the urine. Caution for those with renal impairment because the drug may not be excreted and could accumulate, causing toxicity. Contraindications and Cautions: Contraindicated in patients with: allergy to any component of the drug, patients with ventricular tachycardia or fibrillation (potentially fatal heart rhythm problems), heart block or sick sinus syndrome, idiopathic hypertrophic subaortic stenosis (IHHS), acute MI, renal insufficiency and electrolyte abnormalities, ex: high calcium, low potassium, low magnesium. Digoxin should be used cautiously in pregnant or lactating women due to potential adverse effect on fetus or neonate, though the effect on the neonate are not fully known. Pediatric and geriatric patients are at higher risk for adverse effects and require close monitoring. Adverse Effects: Adverse effects with cardiac glycosides include, headache, weakness, drowsiness, and vision changes (yellow halo around objects) GI upset and anorexia commonly occurs. Arrythmias may develop because the glycosides affect the action potential and conduction system of the heart. The patient may also present nausea, vomiting, malaise, depression, irregular heart rhythms including heart block, atrial arrythmias and ventricular tachycardia. ANTIARRYTHMIC AGENTS Arrhythmias are abnormal rhythms of the heart that occur when the electrical impulses that coordinate heartbeats don't work properly, causing the heart to beat too fast, too slow, or irregularly. Types of Arrhythmias 1.Tachycardia: A fast heart rate, typically over 100 beats per minute. 1. Examples: Atrial fibrillation (AFib), ventricular tachycardia. 2.Bradycardia: A slow heart rate, typically under 60 beats per minute. 1. Examples: Sinus bradycardia, heart block. 3.Irregular Rhythms: Variations in heart rhythm that are not necessarily fast or slow. 1. Examples: Atrial fibrillation, premature ventricular contractions (PVCs). Class I Antiarrhythmics Class 1 Antiarrhythmics are sodium-channel blockers that inhibit the fast sodium channels in non-nodal myocardial tissues. They are subdivided into three categories based on their speed of dissociation from the sodium channels and electrophysiologic effects: These drugs are generally used to treat atrial and ventricular arrhythmias Pharmacokinetics: Class IA: Quinidine and Procainamide are well absorbed orally and have a relatively long half-life. Class IB: Lidocaine is often administered intravenously and has a rapid onset and short duration of action. Class IC: Flecainide and Propafenone are also well absorbed orally and have a longer duration of action. Contraindications and Cautions: Class IA: Contraindicated in patients with a history of heart block or severe myocardial dysfunction. Class IB: Caution in patients with severe liver disease Class IC: Contraindicated in patients with structural heart disease, such as a history of myocardial infarction Adverse Effects: Class I antiarrhythmic adverse effects: These drugs can cause a range of side effects affecting the central nervous system (CNS), gastrointestinal (GI) system, cardiovascular system, and respiratory system. CNS: Dizziness, drowsiness, fatigue, twitching, numbness, slurred speech, vision changes, and potentially convulsions. GI: Changes in taste, nausea, and vomiting. Cardiovascular: Proarrhythmic effects (leading to arrhythmias and heart blocks), hypotension (low blood pressure), vasodilation, and potentially cardiac arrest. Respiratory: Respiratory depression, potentially leading to respiratory arrest. Other: Rash, hypersensitivity reactions, hair loss, and bone marrow depression. Specific drug examples: Moricizine (Class Ia) and Flecainide (Class Ic) have been linked to increased cardiac death risk due to their proarrhythmic effects. Class II Antiarrhythmics Class 2 antiarrhythmics work by blocking beta-adrenergic receptors, which inhibits the effects of norepinephrine and epinephrine on the heart. This results in decreased heart rate, reduced cardiac contractility, and prolonged atrioventricular (AV) node conduction time. Actions and Indications: They are commonly used to treat: Atrial fibrillation and flutter, Supraventricular tachycardia, Ventricular arrhythmias, Sinus tachycardia. Pharmacokinetics: Beta-blockers are typically well-absorbed orally, with variable bioavailability depending on the specific drug. They undergo hepatic metabolism and are excreted in the urine. The onset of action varies, with some drugs like esmolol having a rapid onset and short duration, while others like propranolol have a longer duration of action. Contraindications and Cautions: Class 2 antiarrhythmics should be used with caution in patients with: Severe bradycardia, Heart block, Severe heart failure (unless specifically indicated), Bronchospastic diseases (e.g., asthma), Hypotension. Adverse Effects: Common adverse effects include: Bradycardia, Hypotension, Fatigue, Dizziness, Bronchospasm, Fluid retention Class III Antiarrhythmics Actions and Indications: These drugs block potassium channels and slow the outward movement of potassium during phase 3 of the action potential, prolonging it. All of these drugs are proarrhythmic and have the potential of inducing arrythmias. Pharmacokinetics: These drugs are well absorbed after oral administration and are immediately available after IV administration and widely distributed. They are metabolized in the liver and excreted in the urine. Contraindications and Cautions: When these drugs are used to treat life-threatening arrythmias for which no other drug has been effective, there are no contraindications. Adverse Effects: The adverse effects associated with these drugs re related to the changes they cause in action potentials. Nausea, vomiting, and GI distress, weakness and dizziness; and hypotension, heart failure and arrythmias are common. Amiodarone has been associated with a potentially fatal liver toxicity, ocular abnormalities and the development of very serious cardiac arrythmias. Class IV Antiarrhythmics Actions and Indications: These drugs block the movement of calcium ions across the cell membrane, depressing the generation of action potentials and delaying phases 1 and 2 of repolarization, which slows automaticity and conduction. Other Antiarrhythmics ANTIANGINAL AGENTS Antianginal agents are medications used to relieve and prevent angina, which is chest pain or discomfort caused by reduced blood flow to the heart. These agents work by either increasing the oxygen supply to the heart or decreasing the heart's oxygen demand. Antianginal agents are primarily used to manage angina pectoris and improve the quality of life for patients with coronary artery disease. They help balance the oxygen supply and demand of the heart, reducing the frequency and severity of angina attacks. Types of Antianginal Agents 1.Nitrates: Examples: Nitroglycerin, Isosorbide Mononitrate, Isosorbide Dinitrate Mechanism: Dilate blood vessels, increasing blood flow to the heart Uses: Immediate relief of angina attacks 2. Beta-Adrenergic Blockers: Examples: Propranolol, Metoprolol, Atenolol Mechanism: Reduce heart rate and contractility, decreasing oxygen demand Uses: Prevent angina attacks, manage hypertension 3. Calcium Channel Blockers: Examples: Amlodipine, Diltiazem, Verapamil Mechanism: Inhibit calcium entry into cells, relaxing blood vessels and reducing heart workload 4. Ranolazine: Mechanism: Inhibits ion channels during cardiac repolarization, reducing oxygen demand Uses: Chronic angina management Side Effects Nitrates: Headache, hypotension, dizziness Beta-Adrenergic Blockers: Bradycardia, fatigue, bronchospasm Calcium Channel Blockers: Peripheral edema, constipation, dizziness Ranolazine: Dizziness, nausea, constipation LIPID LOWERING AGENTS Lipid-lowering agents, also known as antihyperlipidemic agents, are medications used to lower levels of lipids (fats) in the blood, particularly cholesterol and triglycerides. These agents are crucial in managing and preventing cardiovascular diseases. Lipid-lowering agents are used to manage dyslipidemia (abnormal lipid levels) and reduce the risk of cardiovascular events such as heart attacks and strokes. They are often prescribed based on individual lipid profiles and cardiovascular risk factors. Types of Lipid-Lowering Agents 1.Statins (HMG-CoA Reductase Inhibitors) Mechanism: Inhibit the enzyme HMG-CoA reductase, which is involved in cholesterol synthesis Indications: High LDL cholesterol, prevention of cardiovascular events Side Effects: Muscle pain, increased liver enzymes, potential for diabetes in rare cases 2. Fibrates Mechanism: Activate peroxisome proliferator-activated receptors (PPARs), which increase the oxidation of fatty acids and reduce triglyceride levels Indications: High triglycerides, low HDL cholesterol Side Effects: Gastrointestinal issues, myopathy, liver dysfunction 3. Bile Acid Sequestrants Mechanism: Bind bile acids in the intestine, preventing their reabsorption and promoting their excretion Indications: High LDL cholesterol Side Effects: Gastrointestinal discomfort, constipation, possible nutrient malabsorption 4. Cholesterol Absorption Inhibitors Mechanism: Inhibit the absorption of cholesterol from the small intestine Indications: High LDL cholesterol, often used in combination with statins Side Effects: Diarrhea, abdominal pain 5. PCSK9 Inhibitors Examples: Evolocumab, Alirocumab Mechanism: Monoclonal antibodies that inhibit PCSK9, increasing the number of LDL receptors on liver cells Indications: Severe hypercholesterolemia, familial hypercholesterolemia Side Effects: Injection site reactions, potential for neurocognitive effects 6. Niacin (Nicotinic Acid) Mechanism: Inhibits lipolysis in adipose tissue, reducing free fatty acids and VLDL production Indications: High triglycerides, low HDL cholesterol Side Effects: Flushing, hyperglycemia, liver toxicity Monitoring and Considerations Regular Monitoring: Lipid levels, liver function tests, and muscle symptoms should be monitored regularly. Lifestyle Modifications: Diet, exercise, and weight management are essential components of lipid management. DRUGS AFFECTING COAGULATION Drugs affecting coagulation are used to prevent or treat blood clots and are categorized into three main groups: anticoagulants, antiplatelets, and thrombolytics. These drugs play a vital role in managing and preventing thromboembolic disorders, but they must be used carefully to balance the benefits of preventing clots with the risks of bleeding. Anticoagulants Purpose: Prevent the formation of new clots and the growth of existing clots. Indications: Atrial fibrillation, deep vein thrombosis (DVT), pulmonary embolism (PE), and after certain surgeries to prevent clot formation. Side Effects: Bleeding, bruising, and in rare cases, heparin-induced thrombocytopenia (HIT). Antiplatelets Purpose: Prevent platelets from clumping together to form clots. Indications: Coronary artery disease, after a heart attack, and in patients with stents to prevent clotting. Side Effects: Increased risk of bleeding, gastrointestinal issues, and in rare cases, thrombotic thrombocytopenic purpura (TTP). Thrombolytics Purpose: Dissolve existing clots. Indications: Acute myocardial infarction (heart attack), acute ischemic stroke, and massive pulmonary embolism. Side Effects: Bleeding, including intracranial hemorrhage, and allergic reactions. Monitoring and Considerations Regular Monitoring: Patients on anticoagulants often require regular blood tests to monitor their coagulation status (e.g., INR for warfarin). Patient Education: Educating patients on the signs of bleeding and when to seek medical attention is crucial. Drug Interactions: Be aware of potential interactions with other medications, foods, and supplements that can affect coagulation. OTHER DRUGS AFFECTING CLOT FORMATION DRUGS USED TO TREAT ANEMIAS Anemia is a medical condition characterized by a deficiency in the number or quality of red blood cells (RBCs) or hemoglobin in the blood. Hemoglobin is the protein in red blood cells that carries oxygen from the lungs to the rest of the body. When you have anemia, your body does not get enough oxygen-rich blood, which can lead to a variety of symptoms and complications. Drugs used to treat anemias are tailored to the specific type and cause of anemia. Iron Supplements Purpose: Treat iron deficiency anemia by replenishing iron stores. Examples: Ferrous sulfate, ferrous gluconate, ferrous fumarate. Indications: Iron deficiency anemia due to blood loss, poor dietary intake, or increased need (e.g., pregnancy). Side Effects: Constipation, nausea, dark stools. Vitamin B12 and Folate Supplements Purpose: Treat anemias caused by vitamin B12 or folate deficiencies. Examples: Cyanocobalamin (Vitamin B12), Folic acid. Indications: Pernicious anemia, dietary deficiencies, malabsorption syndromes. Side Effects: Rare, but may include allergic reactions or gastrointestinal issues. Erythropoiesis-Stimulating Agents (ESAs) Purpose: Stimulate the production of red blood cells. Examples: Epoetin alfa, Darbepoetin alfa. Indications: Anemia due to chronic kidney disease, chemotherapy-induced anemia. Side Effects: Hypertension, thrombosis, bone pain. Blood Transfusions Purpose: Provide immediate increase in red blood cell count. Indications: Severe anemia requiring rapid correction, such as in acute blood loss or severe hemolysis. Side Effects: Risk of transfusion reactions, infections. Medications for Hemolytic Anemias Purpose: Treat anemias caused by the destruction of red blood cells. Examples: Corticosteroids, Rituximab. Indications: Autoimmune hemolytic anemia, hereditary spherocytosis. Side Effects: Immunosuppression, increased infection risk. Medications for Thalassemia and Sickle Cell Anemia Purpose: Manage symptoms and complications. Examples: Hydroxyurea, Luspatercept. Indications: Thalassemia, sickle cell anemia. Side Effects: Bone marrow suppression, increased infection risk. Medications for Anemia of Chronic Disease Purpose: Address underlying inflammation or infection. Examples: Erythropoiesis-stimulating agents, iron supplements. Indications: Anemia associated with chronic infections, inflammatory diseases. Side Effects: Similar to those of ESAs and iron supplements. Each type of anemia requires a specific approach to treatment, and the choice of medication depends on the underlying cause and severity of the condition. It's important to consult a healthcare provider for a proper diagnosis and treatment plan.