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Cardiovascular and Hematology Drugs 중점 요약 1. 심장의 해부학적 구조와 기능 (생리학 강의 이수 간주) • • • • Right & left atria and ventricles Interatrial and interventricular septum Heart wall 의 구성 근육(epicardium, myocardium, endocardium Pulmonary semilunar, aortic semilunar, tricuspid, biscuspid valves 2. Circulation (혈류 순환) • • • • Pulmonary circulation and systemic circulation Coronary circulation Two atria full with blood and then contract simultaneously. This is followed by the simultaneous contraction of both ventricles, which sends blood through the pulmonary and systemic circulations. The AV valves close when the ventricles contract and the semilunar valves close when ventricles relax, producing the heart sounds. Contraction of the myocardium results from electrical excitation, which can recorded as an electrocardiogram (ECG or EKG) The heart contraction phase is called systole and the relaxation phase is called diastole. 3. Heart Beats and Electrical activity of Heart • SA node (sinoatrial node) 의 역할은? • 개구리 심장을 떼어내서 생리영양액에서 관찰할 경우 myocardial cells 이 생존하는 동안 심장 박동은 계속된다. 이를 automaticity 라 함. 즉 체내 신경조직과 절단된 상태에 서도 심장박동은 계속되는 점은 자율신경계가 심장박동의 주된 요인이 아니고 부가적 요인으로 작용함을 실험적으로 관찰한 것이다. • • Ion channel (Na+, Ca++, K+)의 역할은? Autonomic nerves (sympathetic & parasympathetic nerves)가 부가적으로 심장박동을 빠르게 또는 늦추는 경 우와 기전? 4. 심장의 박동에 의한 혈액 펌프 작용은 수 십년 계속된다. • 많은 에너지 소모를 위한 O2 소모와 mitochonria 분포가 타 세포와 비교하여 많다. • Coronary vessels의 기능은? Blood Pressure 1. 2. The pressure of the arterial blood is regulated by the blood volume, total peripheral resistance, and the cardiac rate. Regulatory mechanisms adjust these factors in negative feedback manner to compensate for deviations. Arterial pressure rises and falls as the heart goes through systole and diastole. Three most important variables affecting BP are the cardiac rate, stroke volume, and total peripheral resistance. Cardiac output x total peripheral resistance =BP Increased pressure Decreased pressure Constriction A constriction increaes blood pressure upstream (analogous to the arterials pressure) and decreases pressure downstream (analogous to capillary and venous pressure). Clinical consideration 1. Arrhythmias (abnormal heart rhythms) • Bradycardia < 60 beats/min • Tachycardia > 100 beats/min 2. Structural Heart Disorders • Heart murmurs; congenital and acquired Valves defects (not significant clinically) • Congenital Artrial septal and ventricular septal defects (tetralogy of Fallot) • Bacterial endocarditis (Valve area’s infections) 3. Atherosclerosis (hardening of the arteries); most common • Localized plaques(artheromas)-protrude into the lumen of artery—reduce blood flow • Sites for thrombus (blood clot) formation, which occuled the blood supply to an organ. • Smoking, hypertention, high blood cholesterol (LDL) and diabetes. • LDLs (low-density lipoproteins) particles produced by the liver a core of cholesterol surrounded by a layer of phospholipid and protein. Cells in various organs contain receptors for the protein in LDL. When LDL attaches to its receptors, the cells engulfs the LDL by receptor-mediated endocytosis and utilizes the cholesterol. When endothelial cells engulf LDL they oxidize it to a product called oxidized LDL. injury endothelial cells (migration of monocytes and lymphocytes conversion of monocytes machophages and progression of atherosclerosis. some antioxidant drugs are effective in some degree (vitamin C, E, and Beta-carotene. HDLs do not have their own receptors. 4. Ischemic Heart Disease • inadequate supply of oxgen (blood flow) • commonly myocardial ischemia is atherosclerosis of coronary arteries associated with increased lactic acid in ischemic tissue (anaerobic a few minutes necrosis myocardial infarction (Heart Attack) severe pain (left shoulder): angina pectoris : takes nitorglycerin 5. Cardiac Output and Hypertension The pumping ability of a heart is a function of the number of beats per minute (cardiac rate) and the volume of blood ejected per beat (stroke volume). The cardiac rate and stroke volume are regulated by autonomic nerves and by mechanisms intrinsic to the cardiovascular system. The cardiac output is equal to the volume of blood pumped per minute by each ventricle. The average resting cardiac rate in an adult is 70 beats/min. and the average stroke volume is 70~80 ml/beat. Cardiac output (5.5 L/min)=stroke volume X cardiac rate * Average blood volume = 5.5 L. Thus each ventricle pumps total blood volume per minute under resting condition thru pulmonary and systemic circulation. Action potential No neural effects Pacemaker potential Sympathetic parasympathetic Effects autonomic nerve activity on the heart Region affected Sympathetic Parasympathetic SA node (Incr) cardiac rate diastolic depolarization (Incr) conduction rate (Incr) contraction strength (Incr) contraction strength (Dcr) diastolic depolarization cardiac rate (Dcr) conduction rate (Dcr) contraction strength (Dcr) contraction strength AV node Arterial Muscle Ventricular muscle Antihypertensive drugs 1. Diuretics 2. Antiadrenergics: • suppress adrenergic effects by inhibiting release of agonists or antagonizing adrenergic receptors Presynaptic adrenergic release inhibitors (central and peripheral) Alpha and beta blockers 3. Vasodilators • By blocking a1-mediated vasoconstriction • By inhibiting other endogenous vasoconstrictors • By activating a vasodilation pathway Inhibition of Angiotensin Converting Enzyme Calcium entry blokers Direct vasodilators Angina and Heart Failure 1. Stable angina • • • Aspirin Beta-blokers Calcium channel blocker 2. Unstable angina • • • • Nitroglycerin Isosorbide Heparin Together with the above drugs for stable angina Arrhythmias 1. 2. 3. 4. 5. Atropine, isoproterenol, epinephrine Propranolol Verapamil, quinidine Digoxin Procinamide **see Class I, II, III and unclassified cases Lipid-lowering agents 1. To prevent arteriosclerosis • Cholestyramine, colestipol • Niacin • Lovastatin, pravastatin, simvastain, fluvastatin atrovastatin • Gemfibrozil, clofibrate • Probucol • Fenofibrate Anticoagulants • Inhibit blood coagulation; heparin and wafarin Antithrombic agents • Prevent platelet aggregation: aspirin, clopidogrel, cilostazol, dipyridamole, abciximab, eptifibatide, tirofiban Thrombolytic agents • Degrade blood clots: streptokinase, urokinase, anisteplase, tissue plasminogen activator (TPA), alteplase, retepplase P T QS 0 0.2 milivolts R 0.6초