9第九章肾上腺素受体激动药文档资料.ppt

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 agonistsnoradrenaline 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：metabolism 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、Heart：（）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 resistance 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 toxication3、Upper gastrointestinal tract bleeding：PO 粘膜血管收缩止血,clinical 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 cause 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 antishock2.(+)1-R(+)瞳孔开大肌扩瞳(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 vessel of skin,mucous membrane and viscus,2、blood vessel and Bp,Blood pressure,Therapeuticdose,（）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,Largedose,SBPDBP,（）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：relaxationbladder：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,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 easily2、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 failure：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 po2、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 the moderate asthma2、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 pressure：（）2-Rdilatation of blood vessel BP：SBP DBP 略,4、others：不透BBB，中枢作用弱（）-R心脏（+）组织耗氧,1、Bronchial asthma(for controlling the attack)2、A-V conduction blockade(II,III)3、Hear arrest：适用于心脏自身原因引起的骤停4、Septicemic(败血症的)shock：suitable for high central vein pressure（中心静脉压）and lower cardiac output(低排高阻型),Clinical Uses,心悸、头晕、心律失常,adverse action,冠心病、心肌炎、甲亢等,contraindication,1、Stimulate 1 receptor selectively：positive inotropic(变力的)effect HR 不明显，心肌耗氧增加不明显 2、clinical uses:cardiogenic shock and congestive(充血)heart failure,Dobutamine 多巴酚丁胺,