2adrenergicantagonists教材.ppt

AUTONOMIC DRUGS CHAPTER 11 ADRENOCEPTOR ANTAGONISTS 肾上腺素受体阻断药 Part I Alpha adrenergic receptor antagonists 能选择性地与α肾上腺素受体结合，其本身不激动或较少激动肾上腺素受体，却能妨碍去甲肾上腺素能神经递质及肾上腺素受体激动药与α受体结合，从而产生抗肾上腺素作用。 “肾上腺素作用的翻转”（adrenaline reversal） Alpha adrenergic receptor antagonists --phentolamine 【 Mechanism 】 Pentolamine has similar affinity for both ?1 and ?2 receptors. It is a competitive antagonist. It has wide spectrum of pharmacological specificities. Short-term ? blocker. Alpha adrenergic receptor antagonists --phentolamine Effects on cardiovascular system Vasodilation: decrease peripheral resistance Cardiac stimulation: increase cardiac output. reflex sympathetic nerve stimulation Alpha adrenergic receptor antagonists --phentolamine 【therapeutic uses】 peripheral vascular disease: vasospasm of Raynauds disease and frostbite pheochromocytoma shock Hypertensive emergency Myocardial infarction and heart failure Local vasoconstrictor excess 酚妥拉明（phentolamine） 药理作用： （1）舒张血管—阻断α受体和直接作用 （2）兴奋心脏—反射性兴奋和阻断突触前 膜α2受体 临床应用： （1）外周血管痉挛性疾病（2）嗜铬细胞瘤的诊断和治疗（3）休克（4）心肌梗死和心衰（5）静滴NA外漏 Alpha adrenergic receptor antagonists -- phenoxybenzamine Irreversibly block ?1 and ?2 receptors. Long-term ? blocker. 【pharmacological properties】 attenuates catecholamine-induced vasoconstriction 【therapeutic uses】 pheochromocytoma peripheral vascular disease: Septic shock Part II Beta adrenergic receptor antagonists Beta-adrenergic receptor antagonists-- propranolol 【ADME】 a. Well absorbed after oral administration; peak concentrations occur 1-3 hours after ingestion. Sustained-release preparations of propranolol and metoprolol are available. b. Propranolol undergoes first-pass elimination. Its bioavailability is relatively low. c. Propranolol is rapidly distributed and readily cross the BBB. d. Propranolol is extensively metabolized in the liver, with little unchanged drug appearing in the urine. Beta-adrenergic receptor antagonists-- propranolol 【Pharmacological effects】 Blockade of β receptors Effe