肾上腺素受体阻断药课件

单击此处编辑母版标题样式,*,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,Chapter 11,Adrenoceptor Blocking Drugs,Pharmacology,Instructor :,Lei Linsheng 雷林生,Chapter 11 PharmacologyInstr,1,The major pharmacologic effects of adrenoceptor blocking drugs are to occupy either,1,2,or,receptors outside the central nervous system and prevent their activation by catecholamines and related agonists.,The major pharmacologic ef,2,Since these drugs block adrenergic receptors, they are also called,sympatholytics or antiadrenergic drugs,Since these drugs block adrene,3,Adrenoceptor blocking drugs,block receptor, antagonize the effects of -agonists,after pretreatment with,-antagonist - Adr produces a decrease in BP called “,epinephrine reversal,”,Adrenoceptor blocking drugs,4,Adr,NA,ISO,Catech-lamine,control,After,-blocker,After,- blocker,200,100,0,200,100,0,200,100,0,AdrNAISOCatech-laminecontrolAf,5,Phenoxybenzamine,酚苄明,an agent related to the nitrogen mustards, forms a reactive ethyleneimonium,乙撑,亚胺离子,intermediate that covalently binds to,receptors.,Phenoxybenzamine 酚苄明,6,乙撑亚胺,ethylenimine;,aziridine,亚胺 imine,亚胺离子,iminium,（immonium）,onium,鎓,分子中含有碳-氮双键的化合物。通式R,2,CNR，其中R和R可以是烃基或氢。,乙撑亚胺亚胺 imine 亚胺离子 onium,7,binds to,receptors producing,irreversible blockade,(14-48 hs),long duration of action,slow onset of effect,Phenoxybenzamine 酚苄明,Phenoxybenzamine 酚苄明,8,Pharmacological actions,antagonizes receptor,blocks vasoconstriction induced by catecholamines,but little fall in blood pressure in hypertension patients.,increases cardiac output,- reflex effects,- blockade of presynaptic,2,Pharmacological actions,9,Uses,Pheochromocytoma(嗜铬细胞瘤),hypertensive crisis,A usually benign tumor of the adrenal medulla or the sympathetic nervous system in which the affected cells secrete increased amounts of epinephrine or norepinephrine.,Uses Pheochro,10,肾上腺髓质细胞和神经节细胞以及分,布在肾脏、卵巢、辜丸、肝脏、心脏和胃肠道的嗜铬样细胞胞质遇铬盐(重铬酸钾)后则变为棕色, 这种染色特性称为嗜铬反应。,只有细胞质内含有儿茶酚胺类物质的分泌颗粒才能与铬盐起反应。,肾上腺髓质细胞和神经节细胞以及分,11,Uses,peripheral vascular (vasospastic) diseases,(Raynauds disease, a vascular disorder that affects blood flow to the extremities when exposed to cold temperatures or in response to psychological stress. ),infectious shock,benign prostatic hyperplasia,Uses periphe,12,Side effects,postural hypotension, nausea, tachycardia,inhibition of ejaculation,Side effects,13,Phentolamine,酚妥拉明,a. Pharmacological effects,reduces peripheral resistance,- block ,1, direct relaxation of blood vessels.,cardiac stimulation,- reflex cardiac mechanisms,- blocks presynaptic ,2,-,enhances NA release ,1,Phentolamine 酚妥拉明,14,Cholinomimetic effect,stimulates gastrointestinal smooth muscle, increases the tone.,Agonist at H,1,and H,2,histamine receptors.,Cholinomimetic effect,15,b. Uses,1),peripheral vascular diseases,thromboangiitis,血栓(性)脉管炎,2),local vasoconstrictor excess-,- NA iv,3),shock,- dilates blood vessel , decreases peripheral resistance, increases cardiac output,b. Uses,16,4),Myocardial infarction and congestive heart failure,decrease peripheral vascular resistance, lower preload and after-load of the heart and left ventricular filling pressure,4) Myocardial infarction and c,17,5),Pheochromocytoma,preoperative managementfor acute hypertensive episodes,6),male erectile dysfunction,by injecting intracavernosally and when taken orally,5) Pheochromocytoma preopera,18,1,Receptor Blockers,prazosin,哌唑嗪,terazosin,特拉唑嗪,doxazosin,多沙唑嗪,highly selective for ,1, low affinity for,2,mainly used in the treatment of hypertension,peripheral vascular diseases,pheochromocytoma,shock,treatment of benign prostatic hyperplasia (BPH),1 Receptor Blockers,19,II.,-Receptor Blocking Drugs,1. Nonselectiveblockers,propranolol,普萘洛尔,2. Selective,1,blockers,atenolol,阿替洛尔, and blockers,labetalol,拉贝洛尔,II. -Receptor Blocking Drugs,20,1.,-blocking effects,a. Heart,decrease in heart rate, cardiac,contractility, and cardiac output,decrease in myocardial oxygen,consumption,Pharmacological Effects,1. -blocking effects Pharmac,21,b. blood vessel and BP,lower blood pressure in hypertension,patients,(1) heart,1,block,(2) inhibit renin release- angiotensin, decrease in resistance,b. blood vessel and BP,22,c. respiratory tract,increase airway resistance-,2,blockade - patients with asthma,metabolic effects,inhibit lipolysis and glycogenolysis,chronic use increase plasma concentrations of very-low-density lipoproteins (VLDL) and decrease concentrations of HDL cholesterol.,c. respiratory tract,23,intrinsic sympathomimetic activity (ISA),- receptor partial agonist,pindolol,吲哚洛尔,alprenolol,阿普洛尔,oxprenolol,氧烯洛尔,intrinsic sympathomimetic act,24,3.,Membrane stabilizing action,local anaesthetic effect- decrease membrane ion channel permeability ( Na,+,channels),needs high concentrations - 50-100 folds of the therapeutic concentrations,3. Membrane stabilizing action,25,Clinical Uses,Prevention of angina pectoris,- reduce the frequency, improve,exercise tolerance,- decrease cardiac work ,reduce oxygen demand,- slow heart rate,Clinical Uses,26,2.,Prevention of Cardiac arrhythmias,- supraventricular,- ventricular arrhythmias,3.,Treatment of Hypertension,alone or combined with diuretics or vasodilators,2. Prevention of Cardiac arrh,27,Side effects and Contraindications,inhibition,of cardiac function,induction,of asthma,rebound,- increase BP, severe arrhythmias, etc receptor up regulation - increase the sensitivity to catecholamine,(gradual tapering of the dosage),Constriction or spasm of vessels,rash, fever, drug allergy , nausea, vomiting,Side effects and Contraindicat,28,Specific Agents,Propranolol,普萘洛尔,-has extensive first-pass metabolism in the liver.,-has negligible effects at,and muscarinic receptors,.,-,used in the treatment of,angina pectoris,cardiac arrhythmias, hypertension, hyperthyroidism, migraine, glaucoma.,Specific Agents,29,Timolol,噻吗洛尔,-is a nonselective agent with no local anesthetic activity.,-has excellent ocular hypotensive effects when administered topically in the eye.,used to treat glaucoma - reduces aqueous humor formation,-oral dosage form used for treatment of hypertension and angina, to reduce mortality following myocardial infarction, and for prophylaxis of migraine,Specific Agents,Timolol 噻吗洛尔Specific Agents,30,Nadolol 纳多洛尔,-is noteworthy for its very long duration of action (t1/2: 20 to 24h );,-its spectrum of action is similar to that of,timolol.,-Treatment of hypertension and angina pectoris; prophylaxis of migraine headaches,Specific Agents,Nadolol 纳多洛尔Specific Agents,31,Metoprolol,美托洛尔, Atenolol,阿替洛尔,-Selective for,1 receptor.,-may be safer in patients who experience bronchoconstriction in response to propranolol.,-may be preferable in patients with diabetes or peripheral vascular disease since,2 receptors are probably important in liver (recovery from hypoglycemia) and blood vessels (vasodilation).,Specific Agents,Metoprolol 美托洛尔, Atenolol 阿替洛尔,32,Esmolol,艾司洛尔,-is an ultra-shortacting,1-selective adrenoceptor antagonist.,-has a short half-life (about 10,minutes).,steady state concentrations are achieved quickly, and the therapeutic actions of the drug are terminated rapidly.,Specific Agents,Esmolol 艾司洛尔Specific Agents,33,-,is potentially safer to use than longer-acting antagonists in critically ill patients.,-is useful in controlling supraventricular arrhythmias, arrhythmias associated with thyrotoxicosis, perioperative hypertension, and myocardial ischemia in acutely ill patients.,Specific Agents,Esmolol,-is potentially safer to use,34,Pindolol,吲哚洛尔, Acebutolol,醋丁洛尔,-have partial-agonist activity.,-are effective in the major cardiovascular applications (hypertension and angina).,-Although these partial agonists may be less likely to cause bradycardia and abnormalities in plasma lipids, the overall clinical significance of intrinsic sympathomimetic activity remains uncertain.,Pindolol 吲哚洛尔, Acebutolol 醋丁洛尔,35, Blocker,Labetalol,拉贝洛尔,block ,1, ,1, ,2,receptors,beta: alpha= 3:1,blood pressure lowered and ,1,blocked,heart rate , cardiac output no change, Blocker,36,Uses:,different types of hypertension, ventricular arrhythmias, angina,Side effects:,dizziness, general malaise全身倦怠, nausea,Contraindications,- asthma,- congestive heart failure,Uses: Side effects:,37,Drug list,Prototypes,:,phenoxybenzamine,propranolol,Major variants,:,phentolamine,prazosin,terazosin,metoprolol,timolol,pindolol,esmolol,Other significant agents,:,labetalol,Drug list,38,思考题,1.试比较酚苄明和酚妥拉明的药理学特点及临床应用。,2.与普萘洛尔相比, 噻吗洛尔、艾司洛尔、,吲哚洛尔、拉贝洛尔有哪些药理学及临床应用特点。,思考题1.试比,39,Scottish scientist James W. Black successfully developed propranolol in the late 1950s. In 1988, he was awarded the Nobel Prize in Medicine for this discovery.,He also developed cimetidine, which inhibits acid secretion in the stomach.,He was a very private man who was averse to publicity and was horrified to discover he had won the Nobel Prize.,Stories about Propranolol,Scottish scientist James W,40,Black died, aged 85, on the morning of 22 March 2010 after a long illness.,Stories about Propranolol,Black died, aged 85, on th,41,Principal and Vice-Chancellor of the University of Dundee said Black was a great scientist, but he was also a great man to know while the BBC said he was hailed as one of the great Scottish scientists of the 20th Century. He was described by The Daily Telegraph as the man who earned the most for the pharmaceutical industry through his drug development, though he received little personal financial gain from his work.,Stories about Propranolol,Principal and Vice-Chance,42,While once first-line treatment for hypertension, the role for beta-blockers was downgraded in June 2006 in the United Kingdom to fourth-line as they perform less well than other drugs, particularly in the elderly, and evidence is increasing that the most frequently used beta-blockers at usual doses carry an unacceptable risk of provoking type 2 diabetes.,Stories about Propranolol,While once first-line trea,43,Propranolol is often used by musicians and other performers to prevent stage fright. It has been taken by surgeons to reduce their own innate hand tremors during surgery.,Stories about Propranolol,Propranolol is often used b,44,Stories about Propranolol,Propranolol is one of the banned substances in the Olympics, presumably for its use in controlling stage fright and tremors. It was taken by Kim Jong Su 金钟秀, a North Korean pistol shooter who won two medals at the 2008 Olympic Games. He was the first Olympic shooter to be disqualified for drug use.,Stories about Propranolo,45,THE END,THE END,46,