Cardiovascular Agents Lecture Notes PDF

PHARMACOLOGY LECTURE CARDIOVASCULAR AGENTS CARDIAC GLYCOSIDES HEART FAILURE Drugs in these groups regulate heart contraction, The causes of HF i...

PHARMACOLOGY LECTURE CARDIOVASCULAR AGENTS CARDIAC GLYCOSIDES HEART FAILURE Drugs in these groups regulate heart contraction, The causes of HF include chronic hypertension, heart rate, and rhythm, and blood flow to the myocardial infarction (MI), coronary artery disease myocardium (heart muscle) (CAD), valvular heart disease, congenital heart a. Cardiac Glycosides disease, and arteriosclerosis. b. Antianginals Heart failure can be left-sided or right- sided. c. Antidysrhythmics The patient has left-sided HF when the left ventricle Naturally occurring cardiac glycosides are found in does not contract sufficiently to pump the blood a number of plants, this group of drugs inhibits the returned from the lungs and left atrium out through the sodium potassium pump, resulting in an increase in aorta into the peripheral circulation; this causes intracellular sodium. excessive amounts of blood to back up into the lung This increase leads to an influx of calcium, causing tissue. Usually the patient has shortness of breath the cardiac muscle fibers to contract more (SOB) and dyspnea efficiently. Are also used to correct atrial fibrillation (cardiac Right-sided HF occurs when the heart does not dysrhythmia with rapid uncoordinated contractions of sufficiently pump the blood returned into the right atrial myocardium) and atrial flutter (cardiac atrium from the systemic circulation. dysrhythmia with rapid contractions of 200 to 300 beats/ As a result, the blood and its constituents are backed min). up into peripheral tissues, causing peripheral This is accomplished by the negative chronotropic edema. Left-sided heart failure may lead to effects (decreased heart rate) and negative right-sided failure and vice versa. Myocardial dromotropic effects (decreased conduction through hypertrophy resulting in cardiomegaly (increased the atrioventricular [AV] node). heart size) can be a major problem associated with When digoxin cannot convert atrial fibrillation to normal progressive HF. heart rhythm, the goal is to slow the heart rate by decreasing electrical impulses through the AV node. GENEIL H. RIVA O. NEIL P. ALLAIN S. LYBERICA Y. 1  TRANS: Module 5 4 STAGES OF CONGESTIVE HEART FAILURE PHARMACOKINETICS The absorption rate of digoxin in oral tablet form is 70%. The rate is 90% in liquid and capsule form. The protein binding power for digoxin is 30%. The half-life is 30 to 40 hours. Because of its long half-life, drug accumulation can DIGITALIS occur. Side effects should be closely monitored to detect digitalis toxicity. Digitalis began being used as early as 1200 ad, making Serum digoxin levels are most commonly drawn when it one of the oldest drugs. actual Digi toxicity is suspected. Digitalis is obtained from the purple and white Thirty percent of digoxin is metabolized by the liver, foxglove plant, and it can be poisonous. and 50% to 70% is excreted by the kidneys mostly In 1785, William Withering of England used digitalis to unchanged. alleviate “dropsy,” edema of the extremities caused Kidney dysfunction can affect the excretion of by kidney and cardiac insufficiency. digoxin. Thyroid dysfunction can alter the Withering and his medical colleagues did not realize that metabolism of cardiac glycosides. dropsy was the result of heart failure, however. For patients with hypothyroidism, the dose of Digitalis preparations have come to be known for their digoxin should be decreased; in hyperthyroidism, effectiveness in treating heart failure (HF), also known the dose may need to be increased. as cardiac failure (CF), and previously referred to as congestive heart failure (CHF). PHARMACODYNAMICS When the heart muscle (myocardium) weakens and enlarges, it loses its ability to pump blood through In patients with a failing heart, cardiac glycosides the heart and into the systemic circulation. increase myocardial contraction, which increases This is called heart failure, or pump failure. cardiac output and improves circulation and tissue When compensatory mechanisms fail and the perfusion. peripheral and lung tissues are congested, the Because these drugs decrease conduction through condition is CHF. the AV node, the heart rate decreases. DIGITALIS (DIGOXIN) TOXICITY Overdose or accumulation of digoxin causes digitalis toxicity. Signs and symptoms include anorexia, diarrhea, nausea and vomiting, bradycardia (pulse rate below 60 beats/min), premature ventricular contractions, cardiac dysrhythmias, headaches, malaise, blurred vision, visual illusions (white, green, yellow halos around objects), confusion, and delirium. Older adults are more prone to toxicity. Antidote: Digoxin Immune Fab (Brand Name: Ovine, Digibind) OTHER AGENTS USED TO TREAT HEART FAILURE THREE EFFECTS ON HEART MUSCLE: OTHER DRUG GROUPS PRESCRIBED TO TREAT 1. Positive inotropic action (increases myocardial HF: contraction stroke volume), ○ Vasodilators 2. Negative chronotropic action (decreases heart ○ Angiotensin-converting enzyme (ACE) rate) inhibitors 3. Negative dromotropic action (decreases ○ Angiotensin II receptor antagonists conduction of heart cells). (blockers) ○ Diuretics (thiazides, furosemide) GENEIL H. RIVA O. NEIL P. ALLAIN S. LYBERICA Y. 2  TRANS: Module 5 ○ Spironolactone (Aldactone) either plaque occlusions within or spasms of the ○ Some beta blockers coronary arteries. The vasodilators decrease venous blood return to With decreased blood flow, there is a decrease in the heart resulting in a decrease in cardiac filling, oxygen to the myocardium, which results in pain. ventricular stretching (preload), and oxygen demand Anginal pain is frequently described by the patient as on the heart. tightness, pressure in the center of the chest, and Arteriolar dilators act in three ways: pain radiating down the left arm. ○ (1) to reduce cardiac afterload, which Referred pain felt in the neck and left arm commonly increases cardiac output occurs with severe angina pectoris. ○ (2) to dilate the arterioles of the kidneys, which improves renal perfusion and increases fluid loss ○ (3) to improve circulation to the skeletal muscles. TYPES OF ANGINA PECTORIS Classic (stable): Occurs with predictable stress or exertion Unstable (preinfarction): Occurs frequently with progressive severity unrelated to activity; unpredictable regarding stress/exertion and intensity ○ The most dangerous type; often indicates an ACE inhibitors are usually prescribed for HF. ACE impending myocardial infarction or heart inhibitors dilate venules and arterioles, improving attack renal blood flow and decreasing blood fluid Variant (Prinzmetal, vasospastic): Occurs during volume. rest The first two types are caused by a narrowing or They also moderately decrease the release of partial occlusion of the coronary arteries; variant angina aldosterone, which in turn reduces sodium and fluid is caused by vessel spasm (vasospasm). retention. ○ Narrowing - plaque ACE inhibitors can increase potassium levels, so ○ Variant - spasm serum potassium levels should be monitored, JNN especially if potassium sparing diuretics (e. g. , TYPES OF ANTIANGINAL DRUGS spironolactone [Aldactone]) are being taken concurrently. Antianginal drugs increase blood flow either by Angiotensin II receptor blockers (ARBs), such as increasing oxygen supply or by decreasing oxygen valsartan (Diovan) and candesartan (Atacand ) have demand by the myocardium. been approved for HF in patients who cannot THREE TYPES OF ANTIANGINAL: tolerate ACE inhibitors. ○ Nitrates Diuretics are the first-line drug treatment for ○ Beta blockers reducing fluid volume. They are frequently ○ Calcium channel blockers prescribed with digoxin or other agents. The major systemic effect of nitrates is a reduction of Spironolactone (Aldactone), a potassium-sparing venous tone, which decreases the workload of the diuretic, is used in treating moderate to severe HF. heart and promotes vasodilation. Aldosterone secretions are increased in HF. This ○ Venous tone - resistance/pressure in the promotes body loss of potassium and magnesium vein needed by the heart and increases sodium and water Beta blockers and calcium channel blockers retention. — where sodium goes water follows decrease the workload of the heart and decrease Spironolactone blocks the production of oxygen demands. aldosterone. Nitrates and calcium channel blockers are effective in treating variant (vasospastic) angina pectoris. Beta blockers are not effective for this type of angina ANTIANGINAL DRUGS and may aggravate it. Antianginal drugs are used to treat angina pectoris ○ With stable angina, (chest pain). ○ beta blockers can effectively be used to This is a condition of acute cardiac pain caused by prevent angina attacks. inadequate blood flow to the myocardium due to ○ With unstable angina, immediate medical care is necessary. GENEIL H. RIVA O. NEIL P. ALLAIN S. LYBERICA Y. 3  TRANS: Module 5 Nitrates are usually given sublingually (faster absorption = effect immediately) and intravenously as BETA BLOCKERS needed. Beta-adrenergic blockers block the beta1- and If the cardiac pain continues, a beta blocker is given beta2-receptor sites. intravenously, and if the patient is unable to tolerate Beta blockers decrease the effects of the sympathetic beta blockers, a calcium channel blocker may be nervous system by blocking the action of the substituted. catecholamines (epinephrine and norepinephrine), thereby decreasing the heart rate and blood pressure. They are used as antianginal, antidysrhythmic, and antihypertensive drugs. NITRATES Beta blockers are effective as antianginals because by decreasing the heart rate and myocardial contractility, Nitrates, developed in the 1840s, they reduce the need for oxygen consumption and were the first agents used to relieve angina. consequently reduce anginal pain. They affect coronary arteries and These drugs are most useful for classic (stable) blood vessels in the venous circulation. angina Nitrates cause generalized vascular and coronary vasodilation, which CALCIUM CHANNEL BLOCKERS increases blood flow through the Calcium channel blockers (CCBs), or calcium blockers, coronary arteries to the myocardial cells. were introduced in 1982 for the treatment of stable and This group of drugs reduces variant angina pectoris, certain dysrhythmias, and myocardial ischemia (lack of oxygen hypertension. supply) but can cause hypotension. Calcium activates myocardial contraction, increasing NR: check BP prior to the workload of the heart and the need for more administration oxygen. The sublingual (SL) nitroglycerin tablet, which is CCBs relax coronary artery spasm (variant angina) and absorbed under the tongue, comes in various dosages, relax peripheral arterioles (stable angina), decreasing but the average prescribed dose is 0.4 mg following cardiac oxygen demand. cardiac pain. They also decrease cardiac contractility (negative If pain has not subsided or worsened, then 911 should inotropic effect that relaxes smooth muscle), decrease be called. The effects of SL nitroglycerin last for 10 afterload, decrease peripheral resistance, and reduce minutes. the workload of the heart, which decreases the need After a dose of nitroglycerin, the patient may experience for oxygen. = decreased need for oxygen dizziness, faintness, or headache as a result of the peripheral vasodilation. Sublingual (SL) nitroglycerin is the most commonly used ANTIDYSRHYTHMIC DRUGS nitrate. A cardiac dysrhythmia (arrhythmia) is defined as any It is not swallowed, because it undergoes first-pass deviation from the normal rate or pattern of the metabolism by the liver, which decreases its heartbeat. effectiveness. This includes heart rates that are too slow (bradycardia), It is readily absorbed into the circulation through the too fast (tachycardia), or irregular. SL vessels. The terms dysrhythmia (disturbed heart rhythm) and Can be given up to 3 times at an interval of 5 minutes arrhythmia (absence of heart rhythm) are used each dose. interchangeably, despite the slight difference in meaning Nitro patch ○ NR: never touch the center; do not expose to heat because it is made out of foil ○ 16 hours on; 8 hours off PHARMACOKINETICS Nitroglycerin, taken SL, is absorbed rapidly and directly into the internal jugular vein and the right atrium. Approximately 40% to 50% of nitrates absorbed through the gastrointestinal (GI) tract are inactivated by first-pass metabolism in the liver. PHARMACODYNAMICS 4 CLASSES OF ANTIDYSRHYTHMICS Nitroglycerin acts directly on the smooth muscle of blood vessels, causing relaxation and dilation. It decreases cardiac preload (amount of blood in the CLASS I: SODIUM CHANNEL BLOCKERS ventricle at the end of diastole) and afterload (peripheral A sodium channel blocker decreases sodium influx vascular resistance) and reduces myocardial O2 into cardiac cells. Responses to the drug are decreased demand. conduction velocity in cardiac tissues; suppression of With dilation of the veins, there is less blood return to automaticity, which decreases the likelihood of ectopic the heart, and with dilation of the arteries, there is less vasoconstriction and resistance. GENEIL H. RIVA O. NEIL P. ALLAIN S. LYBERICA Y. 4  TRANS: Module 5 foci; and increased recovery time (repolarization or Diabetes refractory period). Obesity 3 SUBGROUPS OF SODIUM CHANNEL BLOCKERS: Aging ○ Class IA slows conduction and prolongs Stress repolarization (quinidine, procainamide, Excessive Smoking and Alcohol Ingestion disopyramide). ○ Class IB slows conduction and shortens repolarization (lidocaine, mexiletine HCl). RENIN-ANGIOTENSIN ALDOSTERONE SYSTEM ○ Class IC prolongs conduction with little to no The Kidneys and the Blood Vessels strive to regulate effect on repolarization (flecainide). and maintain a “normal” blood pressure. The Kidneys regulate blood pressure via CLASS II: BETA BLOCKERS (—OLOLS) Renin-Angiotensin Aldosterone System (RAAS). The drugs in the second class, beta blockers, decrease conduction velocity, automaticity, and recovery time (refractory period). Examples are propranolol (Inderal), acebutolol (Sectral), esmolol (Brevibloc), and sotalol (Betapace). Beta blockers are more frequently prescribed for dysrhythmias than sodium channel blockers. CLASS III: DRUGS THAT PROLONG REPOLARIZATION Drugs in the third class prolong repolarization and are used in emergency treatment of ventricular dysrhythmias when other antidysrhythmics are ineffective. Amiodarone (Cordarone) increases the refractory period (recovery time) and prolongs the action potential duration (cardiac cell activity). ○ Ex.: given when there is rapid AF CLASS IV: CALCIUM CHANNEL BLOCKER The fourth class consists of the calcium channel blockers verapamil (Calan, Isoptin) and diltiazem (Cardizem). Verapamil is a slow (calcium) channel blocker that 1.0 DIURETICS blocks calcium influx, thereby decreasing the “Water pill” excitability and contractility (negative inotropic) of the Promotes sodium depletion, which decreases myocardium. = decrease HR extracellular fluid volume (ECFV) It increases the refractory period of the AV node, Are effective as first-line drugs for treating mild which decreases ventricular response. Verapamil is hypertension. contraindicated for patients with AV block or HF. Hydrochlorothiazide (HydroDiuril), a thiazide, is the most frequently prescribed diuretic to control hypertension. It can be used alone for recently ANTIHYPERTENSIVE diagnosed or mild hypertension or with other antihypertensive drugs. Is an increase in blood pressure such that the systolic Many antihypertensive drugs can cause fluid pressure is greater. than 140 mmHg and the diastolic retention; therefore diuretics are often pressure is greater than 90 mmHg administered with antihypertensive drugs. Thiazide diuretics should not be used for clients with renal insufficiency (creatinine clearance level