交感舒血管神经纤维课件

血管活性药物概述 浙江大学医学院药理学系 卢韵碧 影响血管舒张收缩的因素 神经调节 心血管中枢（延髓心血管中枢） 心血管反射（baroreceptor reflex） 交感神经系统 副交感神经系统 体液调节 肾素-血管紧张素系统 局部具血管舒缩活性的多肽等活性物 质 血管的神经支配 缩血管神经纤维: 交感缩血管 纤维舒血管神经纤维： 交感舒血管神经纤维： 以乙酰胆碱为递质。 副交感舒血管神经纤维： 以乙酰胆碱为递质。 脊髓背根舒血管纤维： 以局部活性多肽如降钙素相 关基因肽介导。 Brain stem or Brain stem or spinal cordspinal cord Pre-Pre-ganglionicganglionic neuronneuron GanglionicGanglionic transmitter transmitter Post-Post-ganglionicganglionic neuronneuron NeuroeffectorNeuroeffector transmitter transmitter EffectorEffector organ organ Efferent neurons of ANSEfferent neurons of ANS Ach N1 receptor NE 1 1 2 2 receptor Clonidine（可乐定） 作用于血管运动中枢交感神经突出后膜 2 2 受体 Centrally acting Centrally acting sympathoplegicsympathoplegic drugs drugs （中枢性降压药） 可乐定 激动延髓嘴腹外侧核 I1咪唑啉受体 激动孤束核 2 2 受体 抑制外周交感神经活性 抑制去甲肾上腺素释放 抑制血管收缩 降低血压 Clinical uses Hypertension: mild to moderate hypertension that has not responded adequately to treatment with diuretics alone.minimal changes in renal blood flow and glomerular filtration, inhibit gastrointestinal secretion and mobility. Toxicity Central and atropine-like side effects Long-term uses: water and sodium retention rebound phenomenon Centrally acting Centrally acting sympathoplegicsympathoplegic drugs drugs： Clonidine The ganglion blocking agents block nicotinic cholinoceptors on postganglionic neurons in both sympathetic and parasympathetic ganglia. So the toxicities are intolerable. Trimethaphan camsilate（樟磺咪芬） : pool the blood in capacitance vessels. 使血管舒张，血压明显下降；仅用于手术中控制性降压。使血管舒张，血压明显下降；仅用于手术中控制性降压。 Ganglion blocking agents Ganglion blocking agents （神经节阻滞药）（神经节阻滞药） 血管的神经支配 缩血管神经纤维: 交感缩血管 纤维舒血管神经纤维： 交感舒血管神经纤维： 以乙酰胆碱为递质。 副交感舒血管神经纤维： 以乙酰胆碱为递质。 脊髓背根舒血管纤维： 以局部活性多肽如降钙素相 关基因肽介导。 Brain stem or Brain stem or spinal cordspinal cord Pre-Pre-ganglionicganglionic neuronneuron GanglionicGanglionic transmitter transmitter Post-Post-ganglionicganglionic neuronneuron NeuroeffectorNeuroeffector transmitter transmitter EffectorEffector organ organ Efferent neurons of ANSEfferent neurons of ANS Ach N1 receptor NE 1 1 2 2 receptor AdrenoceptorAdrenoceptor agonists agonists , , receptor agonistsreceptor agonists epinephrine (adrenaline)epinephrine (adrenaline)，dopamine, dopamine, ephedrineephedrine (2) (2) receptor agonists receptor agonists 1 1 2 2 receptor receptor agonists:agonists: norepinephrinenorepinephrine （升（升 压药）压药） 1 1 receptor receptor agonists:agonists: phenylephrinephenylephrine （升压药（升压药 ） 2 2 receptor agonists: receptor agonists: clonidineclonidine（抗高血压）（抗高血压） (3) (3) receptor agonistsreceptor agonists： 1 1 2 2 receptor agonists: receptor agonists: isoproterenolisoproterenol 1 1 receptor agonists: receptor agonists: dobutaminedobutamine 2 2 receptor agonists: receptor agonists: salbutenolsalbutenol Drug actions and classificationDrug actions and classification AdrenoceptorAdrenoceptor antantagonistsagonists （1 1） receptor antagonistsreceptor antagonists 1 1 2 2 receptor antagonists: receptor antagonists: short-acting:short-acting: phentolaminephentolamine long-acting:long-acting: phenoxybenzaminephenoxybenzamine （用于外周血管痉挛性疾病） 1 1 receptor receptor antagonists:antagonists: prazosinrazosin（抗高血（抗高血 压）压） 2 2 receptor antagonists: receptor antagonists: yohimbineohimbine Drug actions and classificationDrug actions and classification (1) Mechanism arrhythmiasOther uses: angina pectoris; arrhythmias (3) (3) Side effects Bradycardia or cardiac conduction disease (over inhibition); Asthma (Why); Peripheral vascular insufficiency Diabetes Withdrawal syndrome after prolonged regular use: nervousness, tachycardia, increased intensity of angina (even myocardial infarction), or increase of blood pressure; Receptor blockers: Propranolol Receptor blockers: Propranolol 影响血管舒张收缩的因素 神经调节 心血管中枢（延髓心血管中枢） 心血管反射（baroreceptor reflex） 交感神经系统 副交感神经系统 体液调节 肾素-血管紧张素系统 局部具血管舒缩活性的物质 Agents that block RAASAgents that block RAAS： Renin inhibitor enalkiren (依那克林) ACE Inhibitor (ACEI) captopril (卡托普利) AT1 receptor blocker (ARB) losartan (氯沙坦) 临床应用：抗高血压治疗 体液调节 肾素-血管紧张素系统 ：血管紧张素II（AT）收缩血管 the Adverse effects of ACE inhibitors: Severe hypotension (esp. hypovolemic due to diuretics, salt restriction, or gastrointestinal fluid loss). Acute renal failure (particularly in patients with renal artery stenosis肾动脉狭窄) Hyperkalemia Dry cough and angioedema(血管性水肿). During the second and third trimesters of pregnancy because of the risk of fetal hypotension, anuria, and renal failure, sometimes associated with fetal malformations or death. Captopril may cause neutropenia(中性粒细胞减少) or proteinuria（蛋白尿）. Minor toxic effects like altered sense of taste, allergic skin rashes, and drug fever ,NO,NO AutocoidsAutocoids HistamineHistamine 5-Hydroxytryptamine (serotonin, 5-HT)5-Hydroxytryptamine (serotonin, 5-HT) Lipid-derived Lipid-derived autocoidsautocoids Prostaglandins (PGs) Prostaglandins (PGs) LeukotrienesLeukotrienes ( (LTsLTs) ) Platelet activating factor (PAF) Platelet activating factor (PAF) VasoactiveVasoactive peptides peptides Substance P (SP)Substance P (SP)； KininsKinins ( (bradykininbradykinin, , etc.etc.) ) AngiotensinsAngiotensins (AT) (AT)； NatriureticNatriuretic peptides (NP) peptides (NP) VasoactiveVasoactive intestinal peptide (VIP) intestinal peptide (VIP) EndothelinsEndothelins (ET) (ET) CalcitoninCalcitonin gene related peptide (CGRP) gene related peptide (CGRP) Nitric oxide (NO)Nitric oxide (NO) AdenosineAdenosine 体液调节 血管加压素（ADH，抗利尿激素）：缩血管 肾上腺素和去甲肾上腺素 血管内皮生成的血管活性物质 舒张血管物质：NO，PGI2， 收缩血管物质：内皮素(ET)肌浆网释放Ca2+血 管收缩 激肽：缓激肽内皮释放NO 血管舒张 心房利尿肽(ANP)：舒张血管 前列腺素： PGI2、 PGE2舒张血管, PGF2收缩血管 组胺：舒张血管 Venous Nitrates Mixed Calcium Antagonists -adrenergic Blockers ACEI Nitroprusside Arterial Minoxidil Hydralazine VenousVenous VasodilatorVasodilator ArterialArterial VasodilatorVasodilator Classification of VasodilatorsClassification of Vasodilators Nitrates esters (硝酸酯类) 硝酸甘油(nitroglycerin) 作用：小剂量舒张静脉，大剂量舒张较大动 脉 机制：作为NO供体，释放NO激活细胞鸟苷 酸环化酶，使胞 内cGMP水平增高，抑制细胞 内Ca2+释放和外Ca2+内流，致血管平滑肌舒张 临床应用：抗心绞痛 VasodilatorsVasodilators Sodium Nitroprusside (硝普钠) Powerful parenterally (肠道外给药) administered vasodilator Dilates both arterial and venous vessels, resulting in reduced peripheral vascular resistance and venous return. The mechanism: produce NO and stimulate guanylyl cyclase (GC), thus increase cGMP, which relaxes vascular smooth muscle. Used in patients with hypertensive emergencies or severe heart failure. VasodilatorsVasodilators Hydralazine (肼屈嗪) Dilates arterioles but not veins. Disadvantage: tachyphylaxis to hypertensive effects developed rapidly. Combination therapy are now suggested. Especially in severe hypertension. Adverse effects Common: headache, nausea, anorexia, palpitations, sweating, and flushing. In patients with ischemic heart disease, reflex tachycardia and sympathetic stimulation may provoke angina or ischemic arrhythmias. High dose or in patients with slow acetylate: arthralgia(关节痛), myalgia(肌痛 ), skin rashes, and fever that resembles lupus erythematosus. Infrequency but severe: Peripheral neuropathy and drug fever VasodilatorsVasodilators Minoxidil (米诺地尔), a potassium channel opener Dilates arterioles but not veins. Can be used in patients with renal failure and severe hypertension, who do not respond well to hydralazine. Adverse effects Tachycardia, palpitations(心悸), angina, and edema are observed when doses of -blockers and diuretics are inadequate. Headache, sweating, and hirsutism, which is particularly bothersome in women VasodilatorsVasodilators Diazoxide (二氮嗪) Calcium Channel Blockers Verapamil(维拉帕米), diltiazem(地尔硫卓), and the dihydropyridine family (二氢吡啶类，amlodipine, felodipine, isradipine, nicardipine, nifedipine硝苯地平, and nisoldipine) Nifedipine and the other dihydropyridine agents are more selective as vasodilators and have less cardiac depressant effect than verapamil and diltiazem. Diltiazem has intermediate actions. 机制：抑制外Ca2+内流，使肌球蛋白轻链