CHAPTER 24 ANTIANGINAL DRUGS.ppt

CHAPTER 24 ANTIANGINAL DRUGS section 1 introduction 1.Angina pectoris 2.The types of angina (1)Stable angina (2)Unstable angina (3)Variant angina 3.The pathologic physiological mechanism of angina: an imbalance between the myocardial oxygen supply and demand  major determinants of myocardial oxygen consumption: myocardial basic metabolism heart rate contractility wall tension ejection time blood pressure (peripheral resistance) 4.The mechanism of antianginal drugs (1)Decease myocardial oxygen consumption (2)Increase myocardial blood and oxygen supply (3)antiplatelet、antithrombosis Section 2 Organic nitrates 1.Drugs: Nitroglycerin (硝酸甘油) , isosorbide dinitrate(硝酸异山梨酯) isosorbide mononitrate(单硝酸异山梨酯) 2.Pharmacological mechanism Organic nitrates NO  guanylyl cyclase cGMP cGMP dependent protein kinase intracellular Ca2+ vascular smooth muscle relaxation 3. Pharmacological action (1) decrease myocardiac oxygen consumption dilate venous decrease blood returning to heart decrease ventricular end-diastolic volume and pressure (large dose) dilate arterial decrease peripheral resistance decrease afterload (2) increase blood supply to ischemia area (3) redistribution of coronary blood flow (4) Inhibite of platelet aggregation, increase the release of PGI2 and CGRP 4.pharmacokinetics first pass elimination is large, bioavailability is very low. sublingual route is a preferred. 5.Clinical uses (1) all types of angina (2) acute myocardia infarction (3) CHF isosorbide dinitrate used in prophylaxis attack and CHF after myocardia infarction 5. adverse effects and tolerance tachycardia, flushing, throbbing headache, orthostatic hypotension, methemoglobinemia section 3. β-adrenoceptor blocking drugs 1.The mechanism of antiangina decrease myocardial oxygen consumpation block β-adrenoceptor inhibit myocardial contractility and heart rate