药理学教学课件：Chapter11 AdrenoceptorBlockingDrugs

1、Chapter 11 Adrenoceptor Blocking Drugs Abstract Section 1 -Adrenoceptor Blocking Drugs 1. Nonselectively -Adrenoceptor Blockers Short acting class： Phentolamine、 Tolazoline; ; Long acting class：Phenoxybenzamine 2. Selectively 1-Adrenoceptor Blockers Prazosin 3. Selectively 2-Adrenoceptor Blockers Yo

2、himbine Section 2 -Adrenoceptor Blockers 1. Nonselectively -Adrenoceptor Blockers Propranolol 2. S2. Selectively 1-Adrenoceptor Blockers Atenolol and Metoprolol Section 3 、-Adrenoceptor Blockers Labetalol Section 1 -Adrenoceptor Blocking Drugs 1、2 -Receptor Blockers Phentolamine 【The In Vivo Process

3、】 Bioavailability by p.o. is only 20 of injection. 【Pharmacological Effects】 1 Blood Vessels Diastole，B.P. 2 Heart Excited Cardiac contractility H.R. 3 Others a Stimulation of gastrointestinal smooth muscle Quasi ACh effects b Gastric acid secretion c Cutaneous flushing 【Clinical Uses】 1 Convulsive

4、disease of peripheral vessels 2 Anti leakage of NA by i.v. Anti-Hypertetion induced by Adr 3 Diagnosis and treatment of adrenal pheochromocytoma 4 Anti-Shock of infectious、cardiogenic、 nervous 5 Acute myocardial infarction and congestive heart failure which other drugs have not effects on 6 Male ere

5、ctile dysfunction The Mechanism of Antishock for Phentolamine Cardiac Contractility Phentolamine Peripheral Vein (Expansion) Peripheral Arteries (Expansion) (mainly) Cardiac Output Tissue Perfusion Resistance（R） After Load Front Load Cardiac Oxygen Consumption Pulmonary Congestion Improvement 【Adver

6、se Reaction】 1 Hypotention 2 Abdominal Pain、Diarrhea、Vomiting、 Induced Ulcer 3 Intravenous Injection HR， Arrhythmia， Cardiac Angina Tolazoline 1. The effects of blocking -receptor is similar to Phentolamine，but weaker； Also has stronger effects of quasi acetylcholine and quasi histamine. 2. Has more

7、 adverse reaction. 3. May be Used in： A. Convulsive disease of peripheral vessels B. Anti leakage of NA by i.v.gtt.(drip) Effects of CA to the BP of Dog Before and Post the Treatment of Adr-R blocking Drugs CA P r i o r t r e a t m e n t No blockers Given blocker Given blocker Adr * NA ISO Phentolam

8、ine Phenoxybenzamine （Competitive -R Blocker） （Uncompetitive -R Blocker ） （ Short Acting Class） （ Long Acting Class ） Characteristics Fast，Short； Last, Strong Little Specificity Quasi Ach R blocking effects become weaker because of ISA III. Membrane Stabilizing Action 1. Reduce the permeability of c

9、ell membrane towards Na+、K and Ca2 2. Probably have no relationship with the treatment. IV. Others Inhibit aggregation of platelet Lower intraocular pressure 【Clinical Applications】 1 Anti-Arrhythmia Effective to tachycardia type 2 Anti-Cardiac Angina Have good effects，larger dose . 3 Anti-Hypertent

10、ion Reduce BP with HR 4 Congestive Heart Failure 【Others】 Hyperthyroidism、 Thyroid Crisis Glaucoma Migraine Pheochromocytoma etc 【Adverse Reaction】 Generally： Nausea、Vomiting、Mild Diarrhea Seriously： Acute Heart Failure、 Induced Asthma Rarely Seen： Rash、Platelet、WBC 【Contraindication】 Not permitted

11、to： Heart Failure，Sinus Bradycardia ， Severe Atrioventricular Block Be carefully used in： a. patients with myocardial infarction b. drugs selectively blocking 1R for the patients of bronchial asthma. c. drugs metablized in liver for patients with liver dysfunction 【Classifications】 1 、 、2 R Blockers

12、 Propranolol、Nadolol 1 R Blockers Metoprolol、Atenolol 、 R Blockers Labetalol etc. Propranolol 【The In Vivo Process】 Absorption： Absorbed totally by P.O.，but bioavailability is not high. Distribution： Combinated in 90 with plasma protein，easy to enter brain and placenta Metabolism：Liver，Big individua

13、l differences；20 times at same dose. Excretion：90 Metabolites kidney 【 Pharmacological Characteristics 】 1. Stronger blocking effects of R; 2. Has no ISA; 3. Stronger membrane stabilizing action 【Clinical Applications】 1. Anti-Arrhythmia 2. Anti-Cardiac Angina 3. Anti-Hypertention 4. Hyperthyroidism

14、 【Medication Attention】 1. Given small dose at beginning and gradually increace the dose because of large individual differences. 2. Can not stop medication suddenly in long period of drug-therapy，otherwise the oringinal symptoms will reoccur even aggravate. Nadolol The time for blocking effects las

15、t longer； Excretion mainly from kidney with the prototype. Timolol Strongest blocker of R in known compounds; Inhibiting the production of aqueous water，used in the treatment of glaucoma. Pindolol Stronger ISA; Has certain activating effects of 2 R and useful to the treatment of hypertention. Select

16、ively 1 R Blockers Atenolol Weaker blocking effects of 2 R, Milder effect of increasing breath-track resistance， Used mainly in the treatment of BP Metoprolol Shorter lasting time of effects than atenolol Labetalol 1. Can be absorbed by p.o. , larger individual differences in bioavailability; 2. R b

17、locking effects is stronger 5-10 times than R blocking effects ; 3. Used often in moderate or severe hypertension and cardiac angina. Also used in hypertention crisis by i.v. Arotinolol 1. Stronger R blocking effects than R blocking effects compared with labetalol; 2. Used in the treatment of hypert

18、ention、cardiac angina、supraventricular tachycardia and essential tremor，especially in the patients with hypertention combinated with coronary heart disease; 3. Has synergistic effects combinated with the drugs reducing blood sugar, calcium channel blockers, etc. Carvedilol 1. Has the activity of blocking1、1、2 R，and the eff