Drugs for Angina Pectoris PDF

Coronary Artery Disease aka Ischemic Heart Disease or Coronary...

Coronary Artery Disease aka Ischemic Heart Disease or Coronary Heart Disease Pathophysiology a condition where insufficient blood DRUGS FOR of Angina flow occur in one or more coronary arteries ANGINA PECTORIS Pectoris can produce characteristic pain in the chest but pain may not necessarily occur Prepared by: Charina Gail B. Isidoro, MSc. can be temporary, lasting for a few minutes, or permanent leading to death of tissue Atherosclerosis: A Progressive Disease Atherosclerosis Coronary Artery Plaque rupture Disease The buildup of plaque on the arteries' inner walls causing: Monocyte LDL-C Adhesion molecule Macrophage Oxidized Narrowing of arteries, greatly reducing blood flow to the Foam cell LDL-C Causes of low blood flow: heart CRP Coronary Formation of blood clots that partially or totally block the Thrombosis/Embolism arteries Vasospasm Smooth muscle cells Fixed Stenosis CRP=C-reactive protein; LDL-C=low-density lipoprotein cholesterol. It is a progressive, multifaceted condition. Transition from healthy arterial endothelium to chronic then acute disease Plaque instability Endothelial dysfunction Inflammation Oxidation and thrombus Atherosclerosis: A Progressive Disease Initiation Progression Complication Coronary Artery Disease Angina Infiltration of LDL into Continued LDL infiltration, Increased inflammation and artery wall lipid core oxidation and endothelial May lead to: Oxidation of LDL dysfunction Fewer SMCs and fibrous a characteristic chest pain or Involvement of monocytes Formation of foam cells material Myocardial Ischemia discomfort due to myocardial Decreased endothelial SMC migration & fibrous Unstable plaque formation and function production rupture Reversible changes in the myocardial cells due to hypoxia ischemia or infarction Plaque rupture leads to spilling Vascular inflammation and occurs when blood flow to heart muscle is decreased by a formation of lipid core of plaque materials and acute thrombosis partial or complete blockage of coronary arteries may be regarded as an expression of a coronary blood Myocardial Infarction supply–demand mismatch Results from permanent loss of myocardial oxygenation/perfusion Underlying Disease: CAD Endothelium Cellular necrosis/death (irreversible) Normal Artery Intimal Dysfunction Thickening Atheroma Unstable Ruptured Scarring of tissues Formation Plaque Plaque  Risk Factors Diagnosis Decrease Coronary Blood Flow (Supply) Coronary Thrombosis/Embolism Vasospasm Age: male (> 45yrs), female Hypercholesterolemia ECG/ EKG (Electrocardiogram) Fixed Stenosis (> 55yrs) Sedentary lifestyle Detects and records hearts electrical activity ANGINA Note: Some people with angina may have a normal EKG/ECG Family history of MI Chronic inflammation Increased Oxygen Demand Hypertension Stress Testing ↑ Heart rate Elevated serum homocysteine ↑ Contractility Treadmill, dobutamine ↑ Afterload Obesity levels Nuclear heart scanning or echocardiography for patients who can’t ↑ Preload Diabetes mellitus perform physical exercise. Chest X-Ray Diagnosis Diagnosis Coronary Angiography and Cardiac Catheterization Blood Tests Dye; special x-rays show the coronary arteries (cardiac C-reactive protein (hs-CRP) – studies suggest that high levels of catheterization) hs-CRP increases the risk of CAD and heart attack Hemoglobin Types of Angina Cholesterol Pectoris Sugar Normal Narrowing/Blockade Unstable Non-STEMI STEMI Types of Angina Pectoris Acute Coronary Syndrome Occlusion Partial/Minimal Severe Complete Cardiac enzyme Normal Elevated Elevated Chest pain lasting for at least 20 minutes Acute Coronary Chronic Stable Prinzmetal Angina levels Unrelieved by rest nor SL nitrates CK-MB test Syndrome Angina Cause: coronary plaque rupture resulting in thrombosis = ↓O2 Troponin I or T Thrombus Fixed Stenosis Vasospasm supply ECG Supply ischemia Demand ischemia Supply ischemia 3 conditions related to ACS: a. STEMI (ST Segment Elevation Myocardial Infarction) b. NSTEMI (Non-ST Segment Elevation Myocardial Infarction) Normal, ST Depression or T Inversion ST Elevation c. Unstable Angina Pectoris Non-STEMI and STEMI are Acute MI. Chronic Stable Angina Pectoris Prinzmetal Angina Prinzmetal Angina aka Effort Angina or Classic Angina aka Variant Angina, Vasospastic Angina or Angina Inversa Other causes of spasms in the coronary arteries are: Most common type rare Exposure to cold Cause: Fixed Stenosis = ↓peripheral pooling of blood = ↑preload = Cause: vasospasm coronary arteries = ↓O2 supply Emotional stress ↑O2 demand No atherosclerosis Medicines that tighten or narrow blood vessels Chest pain lasting for 2-5 minutes Usually occurs while at rest, usually unprecipitated by physical Smoking Precipitated by physical exertion, emotional stress, exposure to cold, exertion or smoking Cocaine use No increase in severity, duration and frequency for the last 1-2 Can cause significant myocardial ischemia and severe pain months Usually happens between midnight and early morning Relieved by resting and SL nitrates Can be relieved by drugs Therapeutic Goal Vasodilation by NO To restore the balance between myocardial O2 supply and demand + NO by: a. Decrease O2 demand by decreasing cardiac workload (CSAP) GTP Guanylyl cyclase cGMP ↑ Drugs for Angina β-blockers + Nitrovasodilators Pectoris Ca2+–channel blockers Myosin-LC-PO4 dephosphorylation Myosin-LC b. Increase O2 supply by vasodilation (Unstable/Prinzmetal Angina) Actin Nitrovasodilators Ca2+–channel blockers Contraction Relaxation Nitrovasodilators Nitrovasodilators Clinical Uses MOA: activation of guanylyl cyclase (direct and/or via release of 1. Ultrashort acting (