1、chapter 10chapter 10 Adrenoceptor blocking drugs肾上腺素受体阻断药肾上腺素受体阻断药classification-adrenoceptor blocking drugs-adrenoceptor blocking drugs、-adrenoceptor drugs1 -adrenoceptor blocking drugsreversible(short effect):phentolamine 酚妥拉明酚妥拉明irreversible(long effect):phenoxybenzamine 酚苄明酚苄明 nonselectiveselect
2、ive(-)1-R:prazosin 哌唑嗪哌唑嗪 (-)2-R:yohimbine 育亨宾育亨宾 phentolamine 酚妥拉明酚妥拉明 regitine 立其丁、瑞支亭立其丁、瑞支亭 Competitive antagonist 可使可使 R激动剂量效曲线平行右移,最大效应激动剂量效曲线平行右移,最大效应不变。不变。characteristicsmechanism ()1、2 Rpharmacological effect1.blood vessel dilation decrease the blood pressure low dosage:directly dilate Larg
3、e dosage:(-)-R2.Heart excite blood pressure (+)heart (-)突触前膜突触前膜 2-R 取消负反馈调节取消负反馈调节NA释放释放(+)M-R(+)smooth muscle of GI(+)H1 and H2 histamine receptors increase the secretion of acid3、others:Clinical uses1.Peripheral vascular diseases雷诺病又称雷诺病又称“肢端动脉痉挛病肢端动脉痉挛病”,发作时指端苍白,继而发紫,发作时指端苍白,继而发紫,伴局部冷感、麻木、疼痛,数分钟
4、后缓解,局部皮肤转为潮红伴有烧伴局部冷感、麻木、疼痛,数分钟后缓解,局部皮肤转为潮红伴有烧灼、刺痛感,然后恢复正常。灼、刺痛感,然后恢复正常。病情严重者,长期发作可致皮肤萎缩、病情严重者,长期发作可致皮肤萎缩、增厚、溃疡,甚至指端坏死。增厚、溃疡,甚至指端坏死。1.Peripheral vascular diseases2.Excess local vasoconstrictor(e.g.NA)3.Shock 4.Myocardiac infarction(心肌梗塞心肌梗塞)and stubborn congestive heart failure 5.Pheochromocytoma(嗜铬细
5、胞瘤嗜铬细胞瘤)Side reaction1.Hypotension 2.Tachycardia(心动过速心动过速),arrhythmia3.abdominal pain,nausea,and exacerbation(恶化恶化)of peptic ulcer(胃溃疡胃溃疡)思考题:给酚妥拉明后,再给予较大剂量思考题:给酚妥拉明后,再给予较大剂量Adr,BP会会发生什么改变?发生什么改变?()()R()()2RAdrenaline reversal肾上腺素作用的翻转:肾上腺素作用的翻转:R阻阻断药可阻断断药可阻断Adr 的(的(+)R 的的作用,保留其(作用,保留其(+)R作用,作用,从而使从
6、而使Adr的升压作用翻转为降的升压作用翻转为降压的现象。压的现象。phentolamineAdr 1、()R 作用与酚妥拉明相似而弱作用与酚妥拉明相似而弱 2、主要用于血管痉挛性疾病:新生儿持续性、主要用于血管痉挛性疾病:新生儿持续性 肺动脉高压症肺动脉高压症Tolazoline 妥拉唑啉(苄唑啉)妥拉唑啉(苄唑啉)characteristics1.可使可使 R激动剂量效曲线右移,最大效应下降。激动剂量效曲线右移,最大效应下降。noncompetitive antagonistphenoxybenzamine 酚苄明酚苄明mechanism()1、2 R2.effect is slow,str
7、ong and long3.clinical uses:similar to phentolamine2 -adrenoceptor blocking drugsclassification:nonselective:(:(-)1、2 Rselective:(-)1 Rselectivity propranolol 普萘普萘 洛尔洛尔(心得安心得安)atenolol 阿替洛尔阿替洛尔metoprolol 美多洛尔美多洛尔Mechanism pharmacological action(一)(一)(-)R 1、cardiovascular system:(-)1、2 R(-)1 R (-)hea
8、rtforceHRconduction CO、oxygen consumption(-)2 R constrict the blood vessel of skeletal muscle and coronary arterydecrease the blood flow3、Metabolism:(-)R 脂肪分解脂肪分解 不影响血糖,但可掩盖低血糖症状不影响血糖,但可掩盖低血糖症状2、bronchia:(-)2 R bronchoconstriction particularly in patients with asthma4、renin 肾素:肾素:(-)1 R inhibit the
9、release of renin BP(二二)intrinsic sympathomimetic activity,ISAISA(内在拟交感活性(内在拟交感活性)Some-adrenergic antagonists,after combining with and blocking-receptors,may have partial agonistic action具具ISA的药,的药,R阻断作用弱于无阻断作用弱于无ISA类药类药(二二)membrane stabilizing action 膜稳定作用:膜稳定作用:Some-adrenergic antagonists have loca
10、l anaesthetic effects.They decrease the membraneion channel permeability(渗透性渗透性).(三)(三)other effects:antiplatelet aggregating effect(抗血小板聚集抗血小板聚集)some-blockers may decrease intraocular pressure 1、tachycardiac arrhythmia2、angina pectoris心绞痛心绞痛3、hypertension高血压高血压4、others:hyperthyroidism甲亢、偏头痛等甲亢、偏头痛等
11、clinical usagecontraindicationheart failure、sinus bradycardia(窦性心动过缓窦性心动过缓)、serious atria-ventricular blockade、bronchial asthmaSide reaction1.Inhibition of cardiac function2.Inducement or exacerbation of asthma 3.Withdrawal(rebound)action propranolol 普奈洛尔普奈洛尔1.用药应个体化。用药应个体化。2.无内在拟交感活性无内在拟交感活性(ISA)atenolol 阿替洛尔、阿替洛尔、metoprolol美美托洛尔托洛尔(倍他乐克倍他乐克):selectively(-)1 R:哮喘病人仍应慎用哮喘病人仍应慎用 timolol 噻吗洛尔:噻吗洛尔:1.the strongest R blocking drug2.clinical use:glaucoma 无缩瞳及调节痉挛无缩瞳及调节痉挛 3 、-adrenoceptor agonists Labetalol 拉贝洛尔拉贝洛尔:1.(-)-R(-)-R2.Clinical use:hypertension