Cardiovascular Drugs PDF

Cardiovascular drugs 1. Antihypertensive drugs 2. Anti- heart failure drugs 3. Antianginal drugs 4. Anti-hyperlipidemic drugs 5. Antiarrhythmic drugs 6. Antiplatelets, anticoagulants and thrombolytic drugs  Cardiovascular drugs 1. Antihypertensive drugs 2. Anti- heart failure...

Cardiovascular drugs 1. Antihypertensive drugs 2. Anti- heart failure drugs 3. Antianginal drugs 4. Anti-hyperlipidemic drugs 5. Antiarrhythmic drugs 6. Antiplatelets, anticoagulants and thrombolytic drugs  Cardiovascular drugs 1. Antihypertensive drugs 2. Anti- heart failure drugs 3. Anticoagulants and thrombolytic drugs 4. Anti-hyperlipidemic drugs  Drugs Used in the Treatment of Hypertension Hypertension is the medical term for high blood pressure (BP) which is defined in adult as BP greater than or equal to 140 mmHg systolic pressure, or greater that or equal to 90 mmHg diastolic pressure  Hypertension Hypertension results from the increased tone of the peripheral vascular arteriolar smooth muscle, which leads to increased arteriolar resistance and reduced capacitance of the venous system. 4  Factors that contribute to high blood pressure Controllable risk factors : ⚫ obesity, ⚫ sodium intake, ⚫ alcohol, ⚫ lack of exercise, ⚫ stress  Factors that contribute to high blood pressure Uncontrollable risk factors: ⚫ Age, ⚫ Race, ⚫ Heredity.  Treatment of Hypertension A. Non- Pharmacological ⚫ Reduction of weight ⚫ Restriction of salt ⚫ Moderation use of alcohol ⚫ Eating health foods  Anti hypertensive Drug ⚫ Diuretics ⚫ Beta adrenergic Blockers ⚫ Calcium channel blockers ⚫ Angiotensin- converting enzyme(ACE) inhibitors ⚫ Angiotensin II antagonist ⚫ Alpha-adrenergic blockers ⚫ Vasodilators ⚫ Centrally acting agents  1. Diuretics ⚫ Diuretics are drugs that promote a net loss of sodium ions and water from the body, the result an increase in urine flow. ⚫ Different diuretics act at different sites of the nephron, the functional unit of the kidney  Main uses of Diuretics Diuretics are frequently used for clinical management of disorders involving abnormal fluid distribution such as: Hypertension, Heart failure, Pulmonary edema Cerebral edema Peripheral edema Acute renal failure. Stroke Myocardial infarction Glaucoma Increased intracranial pressure  Types of diuretics 1. thiazide diuretics 2. loop diuretics Used in hypertension 3. K+ sparing diuretics 4. osmotic diuretics, 5. carbonic anhydrase inhibitors. 11  Thiazide Diuretics Chlorothiazide, Hydrochlorothiazide ⚫ They interfere with the re-absorption of Na, K and water and cause a diuresis from distal convoluted tubules. ⚫ Used to treat chronic edema, essential hypertension. ⚫ Adverse effects: hypokalemia, hyperglycemia, postural hypotension  Loop (High-Ceiling) Diuretics Furosemide, Bumetanide & Ethacrynic acid ⚫ interfere with the re-absorption of salt and water from ascending loop of Henle. ⚫ They increases the excretion of potassium. ⚫ They are the most potent oral diuretic agent available. ⚫ Useful for the treatment of acute episodes of pulmonary edema. ⚫ Adverse effects: fluid and electrolyte imbalances, hypokalemia  Potassium (K+)-Sparing Diuretics Triamterene, Spironolactone, Amiloride, Triamterene ⚫ They block the action of aldosterone on the kidney and leads Na and water diuresis and K retention ⚫ Thiazide or loop diuretics can be combined with K sparing diuretics in one tablet to prevent K loss ⚫ Used in edema. ⚫ Adverse effect hyperkalemia.  2. Beta adrenergic blocking agents Propranolol, Atenolol, Metoprolol, Metoprolol, Timolol, Nadolol ⚫ They block the action of beta – adrenergic receptors (selective & nonselective) ⚫ They are recommended as first line therapy.  3. Calcium Channel Blockers Nifedipine, Diltiazem, Verapamil, Amlodipine, Isradipine, Lercanidipine ⚫ They act by blocking calcium channel in smooth muscle, reducing or preventing muscle contraction, they have vasodilation property. ⚫ Adverse effects: dizziness, peripheral edema, hypotension, asystole  4. Angiotensin-converting enzyme inhibitors Captopril, Enalapril, Lisinopril, Perindopril ⚫ They act by blocking the conversion of angiotensin I to angiotensin II and so prevent the vasoconstrictive effect of angiotensin II and sodium retention caused by aldosterone. ⚫ Adverse effects: dry cough, taste disorder, hypokalemia. Renin angiotensin aldosterone system (RAAS)  5. Angiotensin II antagonist Losartan, Candesartan, Valsartan, Irbesartan, Telmisartan ⚫ They act by preventing the effects of angiotensin II which lead to relax smooth muscle and promoting vasodilatation, increase renal salt and water excretion, reduce plasma volume. ⚫ Two of the adverse effect of ACE inhibitors angioedema and cough have not been associated with angiotensin II antagonists.  6. Alpha-adrenergic blockers Prazosin, Phenoxybenzamine, Phentolamine ⚫ They block the action of  - adrenergic receptors in small blood vessels leading to vasodilatation. ⚫ The main adverse effect is tachycardia.  7. Vasodilators Nitroprusside, Hydralazine, Minoxidil ⚫ They directly relaxes blood vessels and thus reduce arterial blood pressure. ⚫ They are reserved for emergency situations.  8. Centrally Acting Agents Methyldopa, Clonidine ⚫ They act centrally on the vasomotor center of the brain. ⚫ Clonidine is reserved for patients not controlled with other less toxic antihypertensive agents. ⚫ Methyldopa is used in pregnancy-induced hypertension ⚫ adverse effects are sedation, drug fever, anemia, hypotension  HYPERTENSIVE EMERGENCY Hypertensive emergency is a rare but life-threatening situation characterized by severe elevations in blood pressure (>180/120 mm Hg) with evidence of impending or progressive target organ damage (for example, stroke, myocardial infarction). Hypertensive urgency is a severe elevation in blood pressure without evidence of target organ damage. Treatment is directed by the type of target organ damage present and/or comorbidities present. Hypertensive emergencies require immediate lowering of blood pressure with intravenous drug such as: ⚫ Nicardipine, nitroprusside, nitroglycerine, phentolamine, Esmolol, labetalol, hydralazine, or fenoldopam to prevent or limit target organ damage. 23  Cardiovascular drugs 1. Antihypertensive drugs 2. Anti- heart failure drugs 3. Anticoagulants and thrombolytic drugs 4. Anti-hyperlipidemic drugs  What is heart failure (HF) HF is a complex, progressive disorder in which the heart is unable to pump sufficient blood to meet the needs of the body. Main symptoms are dyspnea, fatigue, and fluid retention. Measurement of the percentage of blood leaving the heart each time it contracts is called ejection fraction (EF). EF is usually measured in the left ventricle (LV). LVEF ejection fraction of 50% or higher is considered normal. Types of heart failure (HF)  1. Systolic heart failure This type of failure is the result of the ventricle being unable to pump effectively. In this type of heart failure, LVEF ≤ 40% and is called systolic HF or HF with reduced ejection fraction (HFrEF).  2. Diastolic heart failure Less commonly, patients with HF may have “diastolic dysfunction,” a term applied when the ability of the ventricles to relax and accept blood is impaired by structural changes such as hypertrophy. In this case, the ventricle does not fill adequately. The clinical syndrome in which patients have clinical features of heart failure in the presence of normal or near-normal left ventricular ejection fraction, is called diastolic HF or HF with preserved ejection fraction (HFpEF).  Underlying causes of HF include: 1. Arteriosclerotic heart disease 2. Myocardial infarction 3. Hypertensive heart disease 4. Valvular heart disease 5. Dilated cardiomyopathy 6. Congenital heart disease The donkey analogy for HF  The donkey analogy for HF The heart is like a poor donkey pulling a heavy load of sandbags. The high preload and afterload are represented by the sandbags The result  To help the donkey Either increase its heart efficiency to coup or Reduce the extra load it is carrying To make the poor donkey feel better, we may remove some of those sandbags! It is simply like taking a load off the wagon making the work of the donkey much easier This is like the heart after some good diuresis, and afterload/preload reduction with ACEIs or ARBs.  How about slowing down! They are like saying to the donkey "Slow down a bit and rest. Don't work so hard! Regain your strength!" Beta-blockers reduces the sympathetic nervous system and reduces heart rate  How about if we give the donkey some incentive to work harder? There are two types of drugs used in congestive heart failure that can do this by directly increasing the cardiac output: Digoxin and sympathomimetics (dobutamine and milrinone).  II. PHYSIOLOGY OF MUSCLE CONTRACTION The myocardium, like smooth and skeletal muscle, responds to stimulation by depolarization of the membrane, which is followed by shortening of the contractile proteins and ends with relaxation and return to the resting state (repolarization).  Cardiac Myocytes Cardiac myocytes are interconnected in groups that respond to stimuli as a unit, contracting together whenever a single cell is stimulated. Large mitochondria (Cell powerhouse) account for 25–35% of the volume of cardiac cells (compared with only 2% in skeletal muscle), a characteristic that makes cardiac cells highly resistant to fatigue  Action potential Cardiac myocytes are electrically excitable and have a spontaneous, intrinsic rhythm generated by specialized “pacemaker” cells located in the sinoatrial and atrioventricular (AV) nodes. Cardiac myocytes also have an unusually long action potential, which can be divided into five phases (0 to 4).  Phases of action potential Figure 19.2 illustrates the major ions contributing to depolarization and repolarization of cardiac myocytes.  Cardiac contractions The force of contraction of the cardiac muscle is directly related to the concentration of free (unbound) cytosolic calcium. Therefore, Agents that increase intracellular calcium levels (or) That increase the sensitivity of the contractile machinery to calcium increase the force of contraction (inotropic effect).  Management of HF Experts have classified HF into four stages, from least severe to most severe. As the disease progresses, polytherapy is initiated.  Pharmacologic intervention provides the following benefits in HF: Reduce myocardial workload Decrease extracellular fluid volume Improve cardiac contractility Reduce rate of cardiac remodeling Summary of drugs used to treat HF  Actions of angiotensin converting enzyme (ACE) inhibitors in HF ACE inhibitors are indicated for patients with all stages of left ventricular failure. (LVHF) Depending on the severity of HF, ACE inhibitors may be used in combination with diuretics, β- blockers, digoxin, aldosterone antagonists, and vasodilators. Examples of ACEIs: Captopril, Enalapril, Fosinopril, Perindopril, Benazepril  ANGIOTENSIN RECEPTOR BLOCKERS (ARBs) ARBs are competitive antagonists of the angiotensin II type 1 receptor. The actions of ARBs and ACE inhibitors are similar. Their use in HF is mainly as a substitute for ACE inhibitors in those patients with severe cough or angioedema. Examples of ARBs: Irbesartan, Valsartan, Telmisartan, Candesartan, Losartan  Aldosterone antagonists Patients with advanced heart disease have elevated levels of aldosterone due to angiotensin II stimulation and reduced hepatic clearance of the hormone. Spironolactone and eplerenone are aldosterone antagonists indicated in patients with more severe stages of HFrEF.  𝝱-BLOCKERS The benefit of β-blockers is attributed, in part, to their ability to prevent the changes that occur because of chronic activation of the sympathetic nervous system. These agents decrease heart rate and inhibit release of renin in the kidneys. β–blockers are recommended for all patients with chronic, stable HF. Carvedilol is a nonselective αβ- adrenergic receptor antagonist. Bisoprolol and metoprolol are β1- selective antagonists.  DIURETICS Diuretics relieve pulmonary and peripheral edema. Pulmonary edema is often caused by congestive heart failure. When the heart is not able to pump efficiently, blood can back up into the veins that take blood through the lungs. As the pressure in these blood vessels increases, fluid is pushed into the air spaces (alveoli) in the lungs  DIURETICS These agents are also useful in reducing the symptoms of volume overload, including orthopnea and paroxysmal nocturnal dyspnea. Diuretics decrease the plasma volume and cardiac output. This decreases cardiac workload and oxygen demand. Loop diuretics like frusemide, torsemide, bumetanide and ethacrynic acid are the most used diuretics in HF.  VASO- AND VENODILATORS Nitrates and hydralazine are venous and arterial dilators (respectively). They are used for patients with chronic HF. If the patient is intolerant of ACE inhibitors or ARBs, a combination of hydralazine and isosorbide dinitrate may be used. A fixed-dose combination of these agents has been shown to improve symptoms and survival in patients with HFrEF on standard HF treatment (β- blocker plus ACE inhibitor or ARB). Headache, dizziness, and hypotension are common adverse effects with this combination.  INOTROPIC DRUGS Positive inotropic agents enhance cardiac contractility and, thus, increase cardiac output. Medications in this group include: ⚫ Digitalis glycosides (digoxin) ⚫ B- receptor agonists (dobutamine and dopamine) ⚫ Phosphodiesterase inhibitors (milrinone) Although these drugs act by different mechanisms, the inotropic action is the result of an increased cytoplasmic calcium concentration that enhances the contractility of cardiac muscle. All positive inotropes (except digoxin) are only used for a short period and in the inpatient setting.  Digitalis glycosides Most drugs of the cardiac glycosides come from the digitalis (foxglove) plant. Digitalis glycosides have a low (narrow) therapeutic index, The most widely used agent is digoxin. Digitoxin is seldom used due to its considerable duration of action.  Pharmacokinetics: Digoxin is available in oral and injectable formulations. It has a large volume of distribution. The dosage is based on lean body weight. Digoxin has a long half-life of 30 to 40 hours. It is mainly eliminated intact by the kidney, requiring dose adjustment in renal dysfunction.  Therapeutic uses: Digoxin therapy is indicated in patients with severe HFrEF after initiation of ACE inhibitor, β- blocker, and diuretic therapy. Patients with mild to moderate HF often respond to treatment with ACE inhibitors, β-blockers, aldosterone antagonists, direct vaso- and venodilators, and diuretics and may not require digoxin.  Adverse effects: Digoxin toxicity (because digoxin has a very narrow therapeutic index) leading to hospitalization. ⚫ Anorexia, nausea, and vomiting may be initial indicators of toxicity. ⚫ Hypokalemia predispose a patients to digoxin toxicity, since digoxin normally competes with potassium for the same binding site on the Na+/K+-ATPase pump. ⚫ Management of toxicity: discontinue digoxin, determine serum potassium levels, and, if indicated, replenishing potassium. ⚫ Severe toxicity necessitate the use of antibodies to digoxin (digoxin immune Fab), which bind and inactivate the drug. Yellowish vision (xanthopsia), and various cardiac arrhythmias.  Β -ADRENERGIC AGONISTS β-Adrenergic agonists improve cardiac performance by causing positive inotropic effects and vasodilation. Medications: dobutamine and dopamine, β-Adrenergic agonists ultimately lead to increased entry of calcium ions into myocardial cells and enhanced contraction Dobutamine is the most used inotropic agent other than digoxin. Both drugs must be given by intravenous infusion and are primarily used in the short-term treatment of acute HF in the hospital setting.  Phosphodiesterase inhibitors Milrinone is a phosphodiesterase inhibitor that increases intracellular calcium and therefore, cardiac contractility (like β- adrenergic agonists), Milrinone is usually given by intravenous infusion for short-term treatment of acute HF.  Cardiovascular drugs 3. Antianginal drugs  I. What is Angina Angina is chest pain or discomfort caused when the heart muscle doesn't get enough oxygen-rich blood. It may feel like pressure or squeezing in the chest. The discomfort also can occur in the shoulders, arms, neck, jaw, or back. Angina pain may even feel like indigestion.  Is angina a disease? Angina is NOT a disease. Angina is a symptom of an underlying heart problem, (usually coronary heart disease (CHD), also called ischemic heart disease (IHD) or coronary artery disease). This usually happens because one or more of the coronary arteries is narrowed or blocked  Causes of Angina 1. Atherosclerotic disease of the coronary arteries, also known as coronary artery disease (CAD) or ischemic heart disease (IHD), is the most common cause of mortality worldwide. 2. Spasms of vascular smooth muscle may also impede cardiac blood flow, reducing perfusion and causing ischemia and anginal pain.  Cardiac ischemia Cardiac ischemia due to atherosclerotic lesion or coronary spasm leads to an imbalance in myocardial oxygen supply and demand presenting as anginal pain  Types of angina Angina pectoris has three patterns: 1. Stable angina, also called (effort-induced angina, classic angina, or typical angina); 2. Unstable angina; and 3. Prinzmetal angina, also called variant angina, vasospastic angina, or rest angina. They are caused by varying combinations of increased myocardial demand and decreased myocardial perfusion.  Stable angina Stable (classic, typical, effort-induced) angina is the most common form of angina. It is usually characterized by a short-lasting burning, heavy, or squeezing feeling in the chest. Some ischemic episodes may have atypical presentation like extreme fatigue, nausea, or diaphoresis while others may have no symptoms (silent angina). Typical angina pectoris is promptly relieved by: rest or nitroglycerin.  Unstable angina Unstable angina is classified between stable angina and myocardial infarction (MI). In unstable angina, chest pain occurs with increased frequency, duration, and intensity. This chest pain can be precipitated by progressively less effort. The symptoms of unstable angina are not relieved by rest or nitroglycerin.  Unstable angina Any episode of rest angina having any of the below criteria is suggestive of unstable angina. ⚫ longer than 20 minutes, ⚫ any new-onset angina, ⚫ any increasing (crescendo) angina, or ⚫ even sudden development of shortness of breath Unstable angina is a form of acute coronary syndrome and requires hospital admission and more aggressive therapy to prevent progression to MI and death.  Prinzmetal, variant, vasospastic, or rest angina Prinzmetal angina is an uncommon pattern of episodic angina that occurs at rest and is due to coronary artery spasm. Symptoms are caused by decreased blood flow to the heart muscle from the spasm of the coronary artery. Prinzmetal angina generally responds promptly to coronary vasodilators, such as nitroglycerin and calcium channel blockers.  Acute coronary syndrome Acute coronary syndrome is an emergency that commonly results from rupture of an atherosclerotic plaque and partial or complete thrombosis of a coronary artery. If the thrombus occludes most of the blood vessel, and, if the occlusion is untreated, necrosis of the cardiac muscle may ensue (myocardial infarction, MI).  Treatment strategies Four types of drugs, used either alone or in combination, are commonly used to manage patients with stable angina: ⚫ β-blockers, ⚫ Calcium channel blockers, ⚫ Nitrates, ⚫ Sodium channel blocking drug, (ranolazine).  These agents help to balance the cardiac oxygen supply and demand equation by affecting blood pressure, venous return, heart rate, and contractility. Major sites of actions of antianginal drugs  Treatment strategies For prevention and relief of acute angina, ⚫ Sublingual nitroglycerin (the primary drug of choice). ⚫ Sublingual isosorbide dinitrate may also be used For long-term prevention or management of recurrent angina, ⚫ oral or topical nitrates, ⚫ β-adrenergic blocking agents, or ⚫ calcium channel blocking agents can be used. Double or triple therapy is often needed to control chronic stable angina since patients with IHD and angina can have several comorbidities  Lifestyle modifications All patients with IHD and angina should receive guideline-directed medical therapy with emphasis on: 1. Lifestyle modifications (smoking cessation, physical activity, weight management) and, 2. Management of modifiable risk factors (hypertension, diabetes, dyslipidemia) to reduce cardiovascular morbidity and mortality. Treatment Algorithm  𝛃-ADRENERGIC BLOCKERS The β-adrenergic blockers decrease the oxygen demands of the myocardium by blocking β1 receptors, resulting in decreased heart rate, contractility, cardiac output, and blood pressure. These agents reduce myocardial oxygen demand during exertion and at rest. As such, they can reduce both the frequency and severity of angina attacks. β-Blockers can be used to increase exercise duration and tolerance in patients with effort- induced angina.  𝛃-ADRENERGIC BLOCKERS β-Blockers are recommended as initial antianginal therapy in all patients unless contraindicated. The exception to this rule is vasospastic angina, in which β-blockers are ineffective and may worsen symptoms. Medications used: ⚫ Propranolol ⚫ Metoprolol ⚫ Atenolol  Calcium channel blockers In effort-induced (stable) angina, calcium channel blockers reduce myocardial oxygen consumption by decreasing vascular resistance, thereby decreasing afterload. In vasospastic angina, their efficacy is due to relaxation of the coronary arteries. Medications used: Amlodipine Diltiazem Verapamil  ORGANIC NITRATES These compounds cause reduction in myocardial oxygen demand, followed by relief of symptoms. They are effective in stable, unstable, and variant angina. Nitrates such as nitroglycerin cause dilation of the large veins, which reduces venous return to the heart and, therefore, reduces the work of the heart. Nitrates also dilate the coronary vasculature, providing an increased blood supply to the heart muscle.  Nitrates Nitrates differ in their onset of action and rate of elimination. The onset of action varies from 1- 5 minute for sublingual (SL) preparations to 30-35 minutes for oral and transdermal preparations. For prompt relief of an angina attack sublingual (or spray form) nitroglycerin is the drug of choice. All patients suffering from angina should have nitroglycerin SL on hand to treat acute angina attacks.  Sodium channel blocker (Ranolazine) Ranolazine inhibits the late phase of the sodium current (late INa), improving the oxygen supply and demand equation. Ranolazine is indicated for the treatment of chronic angina alone or in combination with other therapies It is usually used in patients who have failed other antianginal therapies.  Cardiovascular drugs 1. Antihypertensive drugs  Drugs used in the treatment of Hyperlipidemia Hyperlipidemia is an increase in the lipids, which are a group of fats or fat-like substances in the blood. ⚫ Cholesterol and the triglycerides are the two lipids in the blood. ⚫ Elevation of one or both lipids is seen in hyperlipidemia. ⚫ Serum cholesterol levels above 240 mg/dL and triglyceride levels above 150 mg/dL are associated with atherosclerosis.  Low-density lipoproteins (LDL) ⚫ Low-density lipoproteins (LDL) transport cholesterol to the peripheral cells. When the cells have all of the cholesterol they need, the excess cholesterol is discarded into the blood. ⚫ This can result in an excess of cholesterol, which can penetrate the walls of the arteries, resulting in atherosclerotic plaque formation. ⚫ Elevation of the LDL increases the risk for heart disease.  High-density lipoproteins (HDL) ⚫ High-density lipoproteins (HDL) take cholesterol from the peripheral cells and bring it to the liver, where it is metabolized and excreted. ⚫ The higher the HDL, the lower the risk for development of atherosclerosis. ⚫ Therefore, it is desirable to see an increase in the HDL (the “good” lipoprotein) because of the protective nature of its properties against the development of atherosclerosis and a decrease in the LDL.  Triglycerides ⚫ Elevated triglycerides are independently associated with increased risk of CHD. ⚫ Diet and exercise are the primary modes of treating hypertriglyceridemia. ⚫ If indicated, niacin and fibric acid derivatives are the most efficacious in lowering triglycerides. ⚫ Omega-3 fatty acids (fish oil) in adequate doses may be beneficial. Lipid profile  Risk factors Risk factors, besides cholesterol levels, play a role in the development of hyperlipidemia ⚫ Family history of early heart disease ⚫ Cigarette smoking ⚫ High blood pressure ⚫ Age (men older than 45 years and women older than 55 years) ⚫ Low HDL levels ⚫ Obesity ⚫ Diabetes  Drugs used to treat hyperlipidemia ⚫ HMG-CoA reductase inhibitors (Statins) ⚫ Fibric acid derivatives ⚫ Niacin ⚫ Bile acid sequestrants  1. HMG-CoA reductase inhibitors (Statins) Atorvastatin, Lovastatin, Pravastatin, Rosuvastatin, Simvastatin ⚫ 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are indicated for: patients with hypercholesterolemia who are at high risk of myocardial infarction, useful in patients with combined elevated cholesterol and triglycerides. ⚫They act by inhibiting the enzyme (HMG-CoA) responsible for cholesterol synthesis in the liver. ⚫ They cause myopathy and are contraindicated in pregnancy, lactation and in children  2. Fibric acid derivative Gemfibrozil, fenofibrate and clofibrate ⚫ lower serum triglycerides and increase HDL. ⚫ Fibrates are known to decrease triglyceride levels to the extent of 20% to 50%. ⚫ Adverse effects: G.I irritation, arrhythmias  3. Niacin ⚫ Niacin is called vitamin B3 or Pellagra- preventing vitamin. ⚫ Pellagra is a systemic disease that results from severe vitamin B3 (Niacin) deficiency ⚫ Niacin can reduce LDL-C by 10% to 20% and is the most effective agent for increasing HDL-C. ⚫ It lowers triglycerides by 20% to 35% at typical doses of 1.5 to 3 grams/day. ⚫ Adverse effect: cutaneous flush, itching diarrhea  4. bile acid sequestrants Cholestyramine, Colestipol, Colesevelam that reduce elevated LDL levels ⚫ These drugs bind to bile acids to form an insoluble substance that cannot be absorbed by the intestine, so it is secreted in the feces. ⚫ With increased loss of bile acids, the liver uses cholesterol to manufacture more bile. ⚫ This is followed by a decrease in cholesterol levels.  Cardiovascular drugs 5. 1. Antiarrhythmic drugs Antihypertensive drugs  Cardiac arrhythmias An arrhythmia, or irregular heartbeat, is a problem with the rate or rhythm of the heartbeat and arise from a defect in impulse generation or impulse conduction. An arrhythmia may occur as a result of: ⚫ A heart disease ⚫ A disorder that affects cardiovascular function. ⚫ Conditions such as emotional stress, hypoxia, and electrolyte imbalance.  Arrhythmia The clinical implications of disordered cardiac activation range from harmless premature contractions to lethal arrhythmia.  Electrocardiogram (ECG) An electrocardiogram (ECG) provides a record of the electrical activity of the heart. Careful interpretation of the ECG along with a thorough physical assessment is necessary to determine the cause and type of arrhythmia.  Electrocardiogram (ECG) Enlarged R wave indicates enlarged ventricles S-T segment elevation or depression indicates cardiac ischemia P-R interval reflects conduction through the AV node. P-R segment reflects the time delay between atrial and ventricular activation. Prolonged Q-T interval reveals a repolarization abnormality that increases the risk of ventricular arrhythmias  Management of Arrhythmia Pharmacological management of arrhythmias uses drugs that exert effects directly on cardiac cells by inhibiting the function of specific ion channels or by altering the autonomic input into the heart. Non-drug strategies of arrhythmia management include transcatheter radiofrequency ablation, intraoperative cryoablation, implanted pacemakers, and defibrillation.  Antiarrhythmic drugs Successful antiarrhythmic drug therapy requires a combination of: ⚫ understanding the pathophysiology of the arrhythmia, ⚫ identification of a drug that can influence the relevant electrophysiological parameters, and ⚫ careful titration of the drug’s dose to correct the abnormal electrophysiological events giving rise to the arrhythmia.  Goal of antiarrhythmic therapy The goal of antiarrhythmic drug therapy is to restore normal cardiac function (sinus rhythm) and to prevent life-threatening arrhythmias. Action potential  Refractory periods After an action potential initiates, the cardiac cell is unable to initiate another action potential for some duration of time. This period is referred to as the refractory period, which is 250ms in duration and helps to protect the heart.  Classification of antiarrhythmic drugs The antiarrhythmic drugs are classified according to their effects on the action potential of cardiac cells and refractory period to four classes: ⚫ Class I: Sodium channel blockers ⚫ Class II: ß-adrenoceptor antagonists ⚫ Class III: Potassium channel blockers ⚫ Class IV: Calcium channel blockers  Class I antiarrhythmic drugs Class I antiarrhythmic drugs are sodium channel blockers and is subdivided to: ⚫ Class IA represented by Quinidine, disopyramide and procainamide ⚫ Class IB represented by lidocaine, phenytoin and mexiletine ⚫ Class IC represented by flecainide and propafenone  Class II antiarrhythmic drugs Class II antiarrhythmic drugs are ß- adrenoceptor antagonists and are represented by: ⚫ Propranolol ⚫ Metoprolol ⚫ Atenolol ⚫ Esmolol  Class III antiarrhythmic drugs Class III antiarrhythmic drugs are potassium channel blockers and are represented by: ⚫ Amiodarone ⚫ Dronedarone ⚫ Dofetilide ⚫ Ibutilide ⚫ Sotalol  Class IV antiarrhythmic drugs Class IV antiarrhythmic drugs are the calcium channel blockers and are represented by: ⚫ Verapamil ⚫ Diltiazem  Cardiovascular drugs 6. Antiplatelets, 1. Antihypertensive anticoagulants drugs 2. Anti- and heart failure thrombolytic drugs drugs 3. Anti-Antihypertensive demic drugs  Antiplatelets, anticoagulants and thrombolytic Drugs Antiplatelets, anticoagulants and thrombolytic drugs are used to prevent and/or treat thrombotic disorders Major thrombotic disorders caused by a clot formation (thrombus or embolus) are: 1. Acute myocardial infarction (MI) 2. Pulmonary embolism (PE) 3. Acute ischemic stroke 4. Deep vein thrombosis (DVT).  Antiplatelets (platelet aggregation inhibitors Platelet aggregation inhibitors decrease the formation of a platelet rich clot Examples of antiplatelet drugs: ⚫ Aspirin ⚫ Clopidogrel ⚫ Ticlopidine ⚫ Dipyridamol  Anticoagulant Drugs Anticoagulants either: 1. Inhibit the action of the coagulation factors (for example, heparin) or 2. interfere with the synthesis of the coagulation factors (for example, vitamin K antagonists such as warfarin).  1. Heparin ⚫ Unfractionated heparin is administered parentally. ⚫ Prepared from bovine or porcine origin, ⚫ Prolongs the clotting time of blood ⚫ Inhibits thrombin formation ⚫ Used as prophylaxis of venous thrombosis. ⚫ Main anticoagulant used during pregnancy ⚫ The aPTT is the test to monitor the extent of anticoagulation with heparin ⚫ Adverse effects: hemorrhage, osteoporosis ⚫ Antidote is protamine sulfate  2. Warfarin Sodium ⚫ Warfarin is an oral anticoagulant drug used in prophylactic treatment of venous thrombosis and pulmonary embolism. ⚫ Warfarin interfere with the manufacturing of vitamin K-dependent clotting factors by the liver. ⚫ This results in the depletion of clotting factors II (prothrombin), VII, IX, and X. ⚫ The INR is the standard test to monitor the extent of anticoagulation with warfarin. ⚫ Main side effect is hemorrhage ⚫ Antidote is vitamin K. ⚫ It is contraindicated during pregnancy  3. Other anticoagulant drugs ⚫ Low molecular weight heparins ⚫ Argatroban ⚫ Bivalirudin ⚫ Fondaparinux ⚫ Dabigatran ⚫ Rivaroxaban ⚫ Apixaban  Thrombolytic therapy ⚫ They are available for intravenous administration in the treatment of coronary artery thrombosis associated with myocardial infarction. ⚫ Adverse effect includes serious bleeding, arrhythmia. ⚫ Available drugs Streptokinase, urokinase, and tissue type plasminogen activator (t-PA) Alteplase Reteplase tenecteplase