作用于肾上腺素受体的药物(传出神经药理)课件

1、作用于肾上腺素受体的药物(传出神经药理),1,第十八章 作用于肾上腺素受体的药物,作用于肾上腺素受体的药物(传出神经药理),2,I.classification based on the selectivity for the main adrenoceptor subtypes.,-adrenoceptor agonists -Noradrenaline（去甲肾上腺素）、Metaraminol （间羟胺）、Phenylephrine（去氧肾上腺素） ,-adrenoceptor agonists - Adrenaline（肾上腺素）、Dopamine（多巴胺）、ephedrine（麻黄碱）

2、-adrenoceptor agonists -Isoprenaline（异丙甲肾上腺素）、Dobutamine （多巴酚丁胺）、Salbutamol（沙丁胺醇）etc.,第一节 肾上腺素受体激动药,1)儿茶酚胺(catecholamines)类 肾上腺素、去甲上腺素、多巴胺、异丙肾上腺素；作用强，维持时间短，易被COMT灭活。 2)非儿茶酚胺类 间羟胺、麻黄碱、甲氧明、苯肾上腺素(新福林）；作用弱，维持时间长（碳原子上的氢被-CH3取代），不易被MAO、COMT灭活。,构效关系,H,作用于肾上腺素受体的药物(传出神经药理),4,作用于肾上腺素受体的药物(传出神经药理),5,Noradrena

3、line（去甲肾上腺素）,acts mainly on receptors , few effects on 1;should be given by iv.,A. Pharmacological effects 1. Blood vessels very strong blood vessels constriction effect dilation（扩张）of coronary blood vessels（冠状血管） 2. Heart some effect as Adr.- weak,less likely to cause tachy-cardia（心动过速）,作用于肾上腺素受体的药

4、物(传出神经药理),6,3. Blood pressure increase systolic（心脏收缩的）and diastolic（心脏舒张的）pressure - increases BP B. Uses Hypotension（低血压） early phase of neurogenic shock（神经源性休克） upper gastrointestinal tract bleeding（上消化道出血） C. Side effects anxiety, respiratory difficulty, forceful heart beat and transient headache

5、, hypertension （高血压） necrosis（坏疽）of the site of intravenous injection（静脉注射） reduced blood supply to kidney and peripheries,作用于肾上腺素受体的药物(传出神经药理),7,D. contraindications and precautions Hypertension , atherosclerosis（动脉硬化症） , coronary heart disease（冠心病）, oliguria（少尿）and anuria（无尿）,Metaraminol（间羟胺，又称阿拉明

6、，Aramine）,acts on 1 receptor;causes NA release actions: increases BP and cardiac output;reflexly（反射性）decreases heart rate Uses: hypotensive states; attacks of supraventricular tachycardia（阵发性室上性心动过速）,作用于肾上腺素受体的药物(传出神经药理),8,Methoxamine（甲氧明）,acts on 1 receptor actions:inreceases BP;reflex decreases in

7、 heart rate;good for hypotension with tachycardia. uses: treat hypotensive states reflex decreases in heart rate;good for hypotension with tachycardia,作用于肾上腺素受体的药物(传出神经药理),19,Ephedrine（麻黄碱）,andagonist;enhances the release of NA indirect sympathomimetic（拟交感神经的） A.Pharmacological effect similar to adr

8、enaline action duration longer lower potency bronchial muscle relaxation less prominent but more sustained B. Uses prevent hypotension asthma nasal（鼻的） decongestant（消除充血药）,作用于肾上腺素受体的药物(传出神经药理),20,C. Side effects tachyphylaxis（快速耐受性）,hypertension,anxiety, insomnia, etc.,Isoprenaline（异丙肾上腺素）,synthetic

9、 derivative（衍生物） of noradrenaline A. Pharmacological effects Cardiovascular system 1,2 receptors agonist intravenous- lower peripheral vascular resistance increase heart rate, increase contractility increase cardiac output,作用于肾上腺素受体的药物(传出神经药理),21,cardiac effects may lead to palpitations（心悸）, sinus（窦

10、性）tachycardia and more serious arrhyth-mias 2. Bronchial smooth muscle relaxation of bronchial muscle(2) inhibit release of histamine and other mediators of inflammation- stronger than Adr. 3. Metabolism increase oxygen consumption,fatty acid,blood sugar.,作用于肾上腺素受体的药物(传出神经药理),22,B. Uses 1.asthma (tr

11、eat acute asthma) 2.cardiac arrest 3.shock- now seldom used C. Side effects palpitation, tachycardia, headache and flushed skin are common. cardiac ischemia（局部缺血）and arrhythmias may occur. D. Contraindication Coronary heart disease, myocarditis（心肌炎）, hyperthyroidism（甲状腺功能亢进）,讨论：比较几种拟交感胺类药的作用，分析其作用机制

12、。,作用于肾上腺素受体的药物(传出神经药理),24,I.classification,-Adrenoceptor Blocking Drugs -Nonselective Receptor BlockerPhentolamine（酚妥拉明）etc. -1-R blockerPrazosin（哌唑嗪） -2-R blockerYohimbine（育亨宾） -Receptor Blocking Drugs -Nonselective-R blocker propranolol（普萘洛尔） -Selective-R blocker atenolol（阿替洛尔） and -Receptor Block

13、ing Drugs - labetalol（拉贝洛尔）,第二节 肾上腺素受体阻断药,作用于肾上腺素受体的药物(传出神经药理),25,Phentolamine（酚妥拉明）,A. Pharmacological effects 1.Reduces peripheral resistance - block 1 2.Cardiac stimulation -reflex effect -blocks presynaptic（突触前的）2 enhanced NA release 3.Inhibits 5-HT 4.H1,H2 agonist B.Uses 1.Peripheral vascular d

14、iseases 2.Excess local vasoconstrictor 3.Shock,-Receptor Blocking Drugs,作用于肾上腺素受体的药物(传出神经药理),26,4.Myocardial（心肌的）infarction（梗死形成）and stubborn（顽固的）congestive heart failure 5. Pheochromocytoma（嗜铬细胞瘤）,Tolazoline（妥拉唑啉）,1. Effects similar to phentolamine but less potent. 2.Cholinomimetic（拟胆碱样作用）effect an

15、d histamine like effects are stronger.,A.Side effects postural hypotension（体位性低血压）, tachycardia (reflex), arrhythmia and angina（绞痛）,作用于肾上腺素受体的药物(传出神经药理),27,B.Uses 1.Peripheral vasospastic（血管痉挛的）disease 2.Extravasation（溢出）of iv. NA,Phenoxybenzamine（酚苄明，又名苯苄胺 dibenzyline）,1.Binds to receptors producin

16、g irreversible（不可逆的） blockade (14-48h). 2.Inhibits reuptake（再摄取）of NA 3.Blocks H1 and 5-HT receptors.,作用于肾上腺素受体的药物(传出神经药理),28,A.Pharmacological actions 1.Antagonizes（对抗） receptor 2.Blocks vasoconstriction but little fall in blood pressure 3.Cardiac output increased - reflex effect - blockade of pres

17、ynaptic 2 B.Uses 1.Peripheral vascular diseases 2.Shock 3.Pheochromocytoma（嗜铬细胞瘤）,作用于肾上腺素受体的药物(传出神经药理),29,C. Side effects 1.Nasal stuffiness（鼻塞） 2.Fatigue（疲乏）, sedation（嗜睡）, nausea（恶心） 3.Tachycardia 4.Postural hypotension,Prazosin（哌唑嗪）,1.Highly selective for 1 , low affinity for 2 2.Relaxation of bo

18、th arterial and venous smooth muscle - fall in blood pressure,作用于肾上腺素受体的药物(传出神经药理),30,3.Decreases preload and afterload of heart 4.Effective in the management of hypertension,Yohimbine（育亨宾）,-used as a tool in lab.,作用于肾上腺素受体的药物(传出神经药理),31,-Receptor Blocking Drugs,作用于肾上腺素受体的药物(传出神经药理),32,A. Pharmacolo

19、gical Effects 1.-blocking effects a. Heart (1)Decreases heart rate,cardiac contractility,and cardiac output (2)Decreases myocardial oxygen consumption b. Blood vessel and BP - decreases blood pressure in hypertension patients (1)heart 1-R blockade (2)smooth muscle of blood vessels 2 -R blockade (3)i

20、nhibits renin（肾素）- angiotensin（血管紧张素）system(RAS),作用于肾上腺素受体的药物(传出神经药理),33,c. Respiratory tract Increases airway resistance-2 -R blockade- patients with asthma d. Metabolic effects Inhibits lipolysis（脂解） and glycogenolysis（肝糖原分解） e. Other effects Blocks presynaptic 2 -R - decreases NA secretion 2. Int

21、rinsic sympathomimetic activity(ISA) partial agonistic action-Pindolol（吲哚洛尔）,作用于肾上腺素受体的药物(传出神经药理),34,3. Membrane stabilizing action Local anaesthetic effect - decreases membrane ion channel permeability ( Na+ channels) Needs high concentrations - 50-100 folds of the therapeutic concentrations 4. Antiplatelet aggregating（聚集）effect - induces platelet aggregation Propranolol B. Clinical Uses 1. Prevention of angina（心绞痛） 2. Prevention of Cardiac arrhythmias 3. Treatment of Hypertension,作用于肾上腺素受体的药物(传出神经药理),35,Others 1.Timolol（噻吗洛尔）used to treat glaucoma（青光眼）- r