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1、Chapter 9 Adrenoceptor agonists,肾上腺素受体激动药, 1 Introduction,basic chemical structure: -苯乙胺,catecholamines(CA类、儿茶酚胺类 ) : adrenaline 肾上腺素 noradrenaline 去甲肾上腺素 isoprenaline 异丙肾上腺素 dopamine 多巴胺 非CA类: ephedrine 麻黄碱 metaraminol 间羟胺,Classification (一)according to the structure,mainly (+) -R noradrenaline 去甲肾
2、上腺素 mainly(+) -R isoprenaline 异丙肾上腺素 (+)、-R adrenaline 肾上腺素,(二)according to the receptor, 2 -R agonists noradrenaline NA norepinephrine NE 去甲肾上腺素,1、 chemical characteristic is unstable: ineffective when given orally , should be given intravenous infusion 2、the effect is quick , strong and short: met
3、abolism mainly in the liver(COMT、MAO ),characteristics,()-R (+) 1-R cannot stimulate 2-R,mechanism,Pharmacological effect,1、Blood vessel: () 1-R constrict the vessel of the skin, mucous membrane, viscusincrease the peripheral resistance(外阻),()1-R ()heart dilation(扩张) of coronary blood vessels,2、Hear
4、t: ()1-R Force、 HR、conduction cardiac output(CO),In intact(整体) animal or human being : NA 1-R peripheral resistance HR NA 1-R peripheral resistance CO is unchangeable or degressive(下降),窦弓反射,3、blood pressure :BP heart(+) CO systolic blood pressure (SBP收缩压) constriction of blood vessel peripheral resi
5、stance diastolic blood pressure(DBP舒张压),low dosage: 血管收缩不剧烈 外阻略 DBP略 increase the pulse pressure(脉压) larger dosage: 血管剧烈收缩 外阻 DBP decrease the pulse pressure(脉压),1、Early phase of shock (休克早期) 2、Hypotension(低血压) induced by drug toxication 3、Upper gastrointestinal tract bleeding : PO 粘膜血管收缩止血,clinical
6、 use,2、acute renal failure(too long and too large dose) 用药间尿量应 25ml / h,1、 local necrosis(坏死) :静滴过久、药浓过高、外漏,Side effects,Contraindications 高血压、动脉硬化症、器质性心脏病、 少尿、无尿、严重微循环障碍病人,防治: 1)局部热敷 2)普鲁卡因局部浸润注射 3) R阻断剂:酚妥拉明,1、(+)-R ,effect is similar to NA, but weak and long 2、stimulates the release of NA : can c
7、ause tachyphylaxis(快速耐受性) 3、升压作用久、可靠,不易引起肾衰,Metaraminol 间羟胺(Aramine阿拉明),Clinical Use 各种休克早期、术后或脊椎麻醉后休克 NA代用品,缩血管药中首选,characteristics,Phenylephrine 去氧肾上腺素又名 新福林、苯肾上腺素,1. (+) 1-R 反射性HR下降 paroxysmal supraventricular tachycardia(阵发性室 上性心动过速) constrict smooth muscle of vessel antishock 2. (+) 1-R (+)瞳孔开大
8、肌扩瞳(无调节麻痹) 作用快、短-检查眼底, 3 、R agonists,1、heart:() 1Rforce、HR、conduction overdose: 心肌兴奋性提高、心肌耗氧 arrhythmia(可致室颤),adrenaline (Adr ) epinephrine 肾上腺素,mechanism,() 、1、 2 R,Pharmachological action,blood vessel (+)2R dilate the blood vessel of skeletal muscle and coronary artery (+) R constrict the blood ve
9、ssel of skin, mucous membrane and viscus,2、blood vessel and Bp,Blood pressure,Therapeutic dose,() R 皮肤、粘膜、 内脏血管收缩,Adr,()1R heart() COSBP,()2R 骨骼肌血管 舒张,()1R heart() COSBP,() R 皮肤、粘膜、 内脏血管收缩,Large dose,SBP DBP,() R 皮肤、粘膜、 内脏血管收缩,()1R heart() COSBP,(占优势),(占优势),DBP不变 或略,SBP,()2R 骨骼肌血管 舒张,()2R 骨骼肌血管 舒张,给
10、较大剂量Adr,随时间推移,血压发生什么变化?,Adr,()R,()2R,思考,3、smooth muscle,bronchia,(+)2R dilate the SM,(+) - R 支气管粘膜血管收缩 消除粘膜水肿,GI: relaxation bladder: relaxation(dysuria排尿困难、retention of urine尿潴留),4、 metabolism :血糖 、脂肪分解 可能与()1、 2 R 有关,1. Cardiac arrest (心跳骤停): induced by drowning(溺死), toxication of CNS inhibitors,
11、anesthesia, and acute infectious disease,Clinical Use,ABC approach A: airway B: breath C: circulation,Adr,() R血管收缩毛细血管通透性,(+) - R,改善心功、扩张冠脉,缓解支气管痉挛,减少过敏介质释放,消除支气管粘膜水肿,2. Allergic shock (过敏性休克),3. Bronchial asthma : 皮下、或肌肉注射,用于急性发作,4. Local usage(adrenaline+procaine普鲁卡因),局麻药中加Adr 收缩血管,延缓局麻药吸收 降低毒性,局麻
12、药麻醉时间,心悸、烦躁、头痛、BP、心律失常(重者室颤)、心肌缺血等,Side reaction,高血压、脑动脉硬化、器质心脏病、糖尿病、甲亢,contraindication,dopamine (DA) 多巴胺,mechanism,() 、 DA R,1、PO: destroyed easily 2、metabolized by MAO and COMT easily: 维时短 3、cannot pass BBB: 外源性DA无中枢作用,pharmacokinetics,1、 Cardiovascular system low concentration:(+) 肾、肠系膜血管 DA R血管
13、舒张 high concentration:() R 心脏() 对R作用弱舒张压无明显影响 Higher concentration: ()R血管收缩BP 2、kidney ()DA-R 肾血管扩张 肾血流 注意:低浓度时出现,pharmacological action,1、 various shock : cardiogenic and septicemic(败血病的) shock, hemorrhagic(出血) shock, especially with cardiac dysfunction, oliguria(尿少) or anuria(无尿). 2、 Acute renal f
14、ailure: particularly in patients with oliguria 3、 acute heart failure,Clinical Use,Ephedrine 麻黄碱,1、action is similar to Adr,(+) , -R, but slow, weak, long po 2、also has indirect effect:可促递质释放 tachyphylaxis(快速耐受性) 3、()CNS,characteristics,Clinical Uses,1、 Prevention of the asthma(哮喘) and treatment of
15、the moderate asthma 2、 Nasal decongestion ( 减轻鼻充血): 3、 Prevention and treatment of some hypotension(低血压) such as hypotention by spinal anesthesia(腰麻) 4、treatment of urticaria(荨麻疹), angioneurotic edema(血管神经性水肿), 4 R agonists,1、heart: () 1-Rforce、HR 、conduction 特点:1)作用强于肾上腺素 2 ) 也可引起心律失常,较少产生室颤,Isoprenaline 异丙肾上腺素,mechanism,(+) 1、 2R,Pharmachological action,3、bronchial SM: () 2-R 平滑肌舒张 特点:1) 作用略强于Adr 2) 也可抑制过敏介质释放 3) 久用可产生耐受性,2、blood vessel and blood press