IVMS-CV Pharmacology -Anti-Aniginal Agents

CV PharmacologyAnti-Anginal AgentsPrepared and Presented: Marc Imhotep Cray, M.D.Professor PharmacologyRecommended Reading:AntianginalDrugsFormative AssessmentPractice questionClinical:E-Medicine ArticleAngina PectorisCoronary Artery Disease9/29/20092Coronary heart disease(CHD) Defined (Etiologic Dx)Coronary heart disease(CHD) is a condition in which proper circulation of blood and oxygen are not provided to heart and surrounding tissue. Result is due to a narrowing of small blood vessels, which normally supply heart with blood and oxygen. Coronary heart disease, a type of cardiovascular disease, is the leading cause of death for both men and women in the United States. 9/29/20093Causes(Anatomic Dx)The typical cause of coronary heart disease is atherosclerosis, which takes place with plaque and fatty build up on the artery walls, narrowing the vessels. http://en.wikipedia.org/wiki/Atherosclerosis9/29/200949/29/20095CAD Risk FactorsCertain conditions are considered to put an individual at greater risk for coronary heart disease. The following are some risk factors: 1.Age (particularly 40+)2.Diabetes3.Genetics (heredity)4.High blood pressure5.High bad cholesterol (LDL)6.Increased levels of C-reactive protein, fibrinogen, or homocysteine7.Lack of sufficient physical activity8.Low good cholesterol (HDL)9.Menopause 10.Obesity11.Smoking 9/29/20096SymptomsSome more frequent symptoms of coronary heart disease include: 1.Angina (ischemic pain)2.Myocardial Infarction3.Shortness of breath9/29/20097DiagnosisDiagnosis of coronary heart disease may be accomplished by a variety of means: 1.Coronary angiography2.Coronary arteriography3.Coronary CT angiography4.Echocardiogram5.Electrocardiogram (ECG)6.Electron-beam CT (EBCT)7.Exercise stress test8.Magnetic resonance angiography9.Nuclear scan 9/29/20098TreatmentCoronary heart disease treatment methods may include: (depends on the presenting Physiologic Dx) 1.Angioplasty with stenting2.Coronary artery bypass surgery3.Medication4.Minimally invasive heart surgery5.Proper diet and exercise6.Quitting smoking 9/29/20099Coronary ArteryO2 Supply and Demand9/29/200910Angina Pectoris (Chest Pain)When the supply of oxygen and nutrients in the blood is insufficient to meet the demands of the heart, the heart muscle achesThe heart demands a large supply of oxygen to meet the demands placed on itThe myocardial supply:demand ratio--a critical review.[Am J Cardiol. 1978]9/29/200911R/O MI AlgorithmContemporary Diagnosis and Management of Unstable AnginaGUYS. REEDER, MDFrom the Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minn.http://www.mayoclinicproceedings.com/inside.asp?AID=1529&UID=9/29/200912Antianginal Pharmacologic AgentsNitratesBeta blockersCalcium channel blockers9/29/200913Types of AnginaChronic stable angina (also called classic or effort angina)Unstable angina(also called preinfarction or crescendo angina)Vasospastic angina(also called Prinzmetal’s or variant angina)9/29/200914Antianginal Agents:Therapeutic ObjectivesIncrease blood flow to ischemic heart muscleand/orDecrease myocardial oxygen demand9/29/200915Antianginal Agents:Therapeutic ObjectivesMinimize the frequency of attacks and decrease the duration and intensity of anginal painImprove the patient’s functional capacity with as few side effects as possiblePrevent or delay the worst possible outcome, MI9/29/200916Antianginal Agents: 1)NitratesAvailable forms:SublingualOintmentsBuccalTransdermal patchesChewable tabletsInhalable spraysCapsulesIntravenous solutions9/29/200917Antianginal Agents: NitratesCause vasodilation due to relaxation of smooth musclesPotent dilating effect on coronary arteriesUsed for prophylaxis and treatment of angina9/29/200918Antianginal Agents: Nitrates NitroglycerinPrototypical nitrateLarge first-pass effect with PO formsUsed for symptomatic treatment of ischemic heart conditions (angina)IV form used for BP control in perioperative hypertension, treatment of CHF, ischemic pain, and pulmonary edema associated with acute MI9/29/200919Antianginal Agents: Nitrates isosorbide dinitrate (Isordil, Sorbitrate, Dilatrate SR)isosorbide mononitrate(Imdur, Monoket, ISMO)Used for:Acute relief of anginaProphylaxis in situations that may provoke anginaLong-term prophylaxis of angina9/29/200920Antianginal Agents: Nitrates Side EffectsHeadacheUsually diminish in intensity and frequency with continued useTachycardia, postural hypotensionTolerance may develop9/29/200921Antianginal Agents: 2)Beta Blockersatenolol (Tenormin)metoprolol (Lopressor)propranolol (Inderal)nadolol (Corgard)9/29/200922Antianginal Agents: Beta BlockersMechanism of ActionDecrease the HR, resulting in decreased myocardial oxygen demand and increased oxygen delivery to the heartDecrease myocardial contractility, helping to conserve energy or decrease demand9/29/200923Antianginal Agents: Beta BlockersTherapeutic UsesAntianginalAntihypertensiveCardioprotective effects, especially after MI9/29/200924Antianginal Agents: Beta BlockersSide EffectsBody System EffectsCardiovascularbradycardia, hypotensionsecond-or third-degree heart blockheart failureMetabolicAltered glucose and lipidmetabolism9/29/200925Antianginal Agents: Beta BlockersSide EffectsBody System EffectsCNSdizziness, fatigue, mental depression, lethargy,drowsiness, unusual dreamsOtherimpotencewheezing, dyspnea9/29/200926Antianginal Agents: 3) Calcium Channel Blockersverapamil (Calan)diltiazem (Cardizem)nifedipine (Procardia)•Dihydropyridines•Amlodipine (Norvasc), Felodipine (Plendil)•Nimodipine•Isradipine•Nicardipine•Nifedipine•Non-Dihydropyridines•Bepridil (Vascor)•Diltiazem (Cardiazem)•Verapamil (Isoptin, Calan)9/29/200927Antianginal Agents: Calcium Channel BlockersMechanism of ActionCause peripheral arterial vasodilationReduce myocardial contractility (negative inotropic action)Result:decreased myocardial oxygen demand9/29/200928Antianginal Agents: Calcium Channel BlockersTherapeutic UsesFirst-line agentsfor treatment of angina, hypertension, and supraventricular tachycardiaShort-term management of atrial fibrillation and flutterSeveral other uses9/29/200929Antianginal Agents: Calcium Channel BlockersSide EffectsVery acceptable side effect and safety profileMay cause hypotension, palpitations, tachycardia or bradycardia, constipation, nausea, dyspnea9/29/200930Cardiovascular Animations and Interactive TutorialsCardiovascular System Topicsby ADAM Basic Heart CirculationBristol-Myers Squibb Heart Structureby Nucleus Communications Heart functions and ProblemsCardiology Associates Electrocardiogram -ECG TechnicianNobel eMuseum Hyper heartby Knowlege Weavers The Arrhythma CenterHeartCenterOnline Cardiac Cell DeathSan Diego State University Prenatal HeartHeartCenterOnline Congenital Heart DiseaseHeartCenterOnline 9/29/200931Cardiovascular Animations and Interactive Tutorials(2)Valvular Functions and DiseasesHeartCenterOnline Electro Cardio Gramby Knowlege Weavers Mammal Fetal Circulation by HHMI Cardiology -Visible Heartby HHMI The Electrocardiogram BasicsMcGill University Heart AnimationsScience Museum of Minnesota Operation Heart Transplantfrom PBS Interpeting an EKGEKG TutorialRnCeus Interactive Blaufuss Medical Multimedia Heart Valves Movieby Marcy Thomas at Wellesley Aninations of Common Heart Defects and RepairMiami Children's Hospital Cadaver Dissection of the Human HeartVirtual AutopsyHBO 9/29/200932Free Useful 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