第23章 肾素-血管紧张素系统药理ACEIs.pptVIP

Renin-Angiotensin System Inhibitors肾素-血管紧张素系统抑制药 Angiotensin Converting Enzyme Inhibitors (ACEIs) Mechanism of Action: Competitive inhibition of angiotensin converting enzyme (ACE) reduces circulating and local Ang II. Reduction of the hydrolysis of bradykinin. Reduction of the tone of sympathetic nerve system. Effect of scavenging free radicals Types of ACEIs (-prils) Active molecules: Captopril卡托普利, Lisinopril, Enalaprilat Prodrugs: Enalapril依那普利, Benazepril, Fosinopril, Quinapril, Ramipril雷米普利, Moexipril, Spirapril Effects of ACEIs on cardiovascular system Reduction in systemic arteriolar resistance, systolic, diastolic and mean arterial pressure. Increase in regional blood flow in proportion to Ang II sensitivity of the vascular bed Cardiac output and heart rate unchanged Aldosterone secretion reduced Improvement of endothelial vasomotor dysfunction, increase in large artery compliance Therapeutic Uses 1. Hypertension One of the initial choices for monotherapy of mild to moderate hypertension ACEIs are superior to other antihypertensive drugs in hypertensive patients with diabetes Most effective in high renin hypertension Excellent for patients with concomitant congestive heart failure, left ventricular hypertrophy (LVH), cardiac arrhythmias or diabetes mellitus, consider in asthma instead of ?-blockers Efficacy enhanced by diuretics Therapeutic Uses 2. Chronic Heart Failure ACEIs should be given to all patients with impaired left ventricular systolic function whether or not they have symptoms of overt heart failure. 1. reduce preload/afterload 2. reverse ventricular remodeling and improve ventricular diastolic dysfunction by preventing the growth effects of angiotensin II on myocytes, attenuating cardiac fibrosis induced by angiotensin II and aldosterone Therapeutic Uses 3. Acute Myocardial Infarction High Risk of Cardiovascular Events ACEIs significantly decrease the rate of myocardial infarction, stroke, and death in a b