第23章 肾素-血管紧张素系统药理ACEIs.ppt

Renin-Angiotensin System Inhibitors肾素-血管紧张素系统抑制药
Role of RAS in cardiovascular pathology
Majority of the physiological effects of angiotensin II is due to the function of the AT1 receptor.
Associated with essential hypertension
Associated with increased risk of cardiac ischemia, coronary artery spasm, hypertrophic cardiomyopathy, aortic stiffness
Associated with chronic renal failure, especially in patients with diabetes mellitus
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 pliance
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 itant congestive heart failure, left ventricular hypertrophy (LVH), cardiac arrhythmias or diabetes mellitus, consider in asthma instead of ß-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 ventricul