1. Chapter 9 adrenoceptor blocking drugs (Adrenoceptor antagonists) α-R antagonists β-R antagonists α 、 β-R antagonists

2. Section 1 α-R antagonists α 1, α 2 -R antagonists α 1 -R antagonists α 2 -R antagonists

3. Basic actions of α-R antagonists 1.CVS effects (1)α 1 -R antagonistic effects: Endogenous CA blockage: BP↓ (Postural hypotension) Exogenous CA blockage: “adrenaline reversal” (2) α 2 -R antagonistic effects: presynaptic  2 antagonism –NE release ↑ CNS  2 antagonism - sympathetic activity ↑

5. Basic actions of α-R antagonists 2.other effects (1) Prostate and bladder sphincter α 1 -R antagonism: dilation (2) insular α 2 -R antagonism: insulin ↑

6. Classification Ⅰ. α 1, α 2 -R antagonists  1.short-term acting: phentolamine ( 酚妥拉明 ), tolazoline ( 妥拉唑啉 )  2. long-term acting: phenoxybenzamine( 酚苄明 ) Ⅱ. α 1 -R antagonists: prazosin ( 哌唑嗪 ) Ⅲ. α 2 -R antagonists: yohimbine( 育亨宾 )

7. α 1, α 2 -R antagonists phentolamine ( 酚妥拉明, regitine, 立其丁 ) competitive α-R antagonists pharmacological actions 1.vessels : dilation; BP ↓  Mechanism: (1) direct action (2)  1 -R blockade: “adrenaline reversal”

9. pharmacological actions 2.heart: excitation, CO ↑ HR ↑ Mechanism: (1) BP ↓  excite heart (2)  2-R blockade 3.other effects: cholinergic action histamine-like action

10. clinical uses 1. peripheral vasospasmatic disorders:  eg. Raynaud’s syndrome, 雷诺氏综合征 2. local vasoconstrictor excess (eg, NA) 3. shock : a. dilate vessel  peripheral resistance↓ ( 肺血管 ) b. excite heart  Co↑ c. pulse pressure↑  improve viscera hemoperfusion, relief microcirculation disturbance Phentolamine+ NE

11. 4. CHF and AMI Pathophysiology: Cardia insufficiency  arteriovenous reflex contraction Phentolamine: dilate vessel  cardiac load↓  Co↑ 5. diagnosis and treatment of pheochromocytoma 6. others: male sexual dysfuction  甲磺酸酚妥拉明分散片（伟哥）

12. adverse reactions 1.cardiovascular reaction:  Postural hypotension, tachycardia, angina, arrhythmia 2.gastrointestinal reaction:  stomachache, diarrhea, vomiting, ulceration

13. Tolazoline( 妥拉唑啉 )  Characteristics (compared with phentolamine ) weaker in  antagonism, stronger in cholinergic and histamine-like effects.  Used to treat peripheral vasospasmatic disorders and pheochromocytoma

14. phenoxybenzamine( 酚苄明 )  Noncompetitive antagonism  Pharmacokinetics : Slow onset(1h), long duration(3-4d)

15. pharmacological actions 1.α 1 -R antagonistic effects : slow, strong and long. (Postural hypotension) 2. HA-R antagonistic effects

16. clinical uses 1. peripheral vasospasmatic disorders 2. pheochromocytoma 3. Shock 4. Urinary obstruction caused by benign prostatic hyperplasia

17. adverse reactions Postural hypotension, tachycardia (palpitation), nasal congestion CNS inhibition

18. α 1 -R antagonists Prazosin( 哌唑嗪 ) Terazosin （特拉唑嗪） Doxazosin （多沙唑嗪） Actions: decrease BP, but weak influence on HR Clinical uses: 1. HBP 2. CHF 3. Urinary obstruction caused by benign prostatic hyperplasia

19. Tamsulosin ( 坦洛新 ) Block α 1A -R ( prostate ) > α 1B -R (blood vessel) High effect on prostatic hyperplasia (compare with phenoxybenzamine and prazosin) Phenoxybenzamine: ↓BP, palpitation Prazosin: ↓BP Tamsulosin: have no effect on BP and HR

20. α 2 -R antagonists Yohimbine ( 育亨宾 ) uses 1. tool agent for research 2. impotence ( 阳痿 ) ：痿必治

21. Section 2 β-R antagonists β 1,β 2 -R antagonist β 1 -R antagonist α 、 β -R antagonist

22. classification  1.β 1,β 2 -R antagonist 1A ： Propranolol( 普萘洛尔 ), Timolol （噻吗 ~ ） 1B ： pindolol （吲哚 ~ ）  2.β 1 -R antagonist 2A ： atenolol （阿替 ~ ）, metoprolol （美托 ~ ） 2B ： Acebutolol( 醋丁 ~)  3. α,, β -R antagonist Labetalol （拉贝 ~ ）, carvedilol( 卡维地洛 )

23. Intrisic sympathomimetic activity (ISA) partial agonistic activity (PAA)

24. Characteristics of Pharmacokinetics: affected by liposolubility 1.absorption: first pass elimination (propranolol is obvious, atenolol is not ) 2.distribution:BBB (propranolol, atenolol) 3.elimination: hepatic metabolism and Kidney excretion (propranolol, atenolol) 4. individual variation

25. basic actions of β-R antagonist 1. β-R blocking action: 1) cardiovascular effects:  heart : depression ( β1 )  vessels: contraction a. blockβ 2 -R b. Co ↓  vasoconstriction  BP↓

27. basic actions of β-R antagonist 2) bronchial smooth muscle : β2 3) metabolism: β2 a. Delay recovery of blood glucose after insuline (insuline  hypoglycemia  increase CA release  activate α, β  glycogenolysis  blood glucose↑) b. Inhibit lipoclasis

28. 4) Renin release: β 1 (propranolol) 5) ↓intraocular pressure (timolol)

29. basic actions of β-R antagonist  2.intrinsic sympathominetic activity(ISA) partial agonistic activity (PAA) Characteristic of drugs with ISA

30. basic actions of β-R antagonist 3.membrane stabilizing action: in large dose (local anesthetic action )

31. clinical uses  1.arrhythmias ( tachyarrhythmia)  2. hypertension  3. angina pectoris, myocardial infarction  4.CHF  5.others: hyperthyroidism, glaucoma

32. adverse actions  1. bronchial asthma  2. cardiovascular reaction  3. induce Raynaud’s syndrome  4. rebound phenomenon:  5. others: hypoglycemia, depression

33. Some β-R antagonists 1A Propranolol( 普萘洛尔 ), Timolol （噻吗洛尔） 1B Pindolol （吲哚洛尔） 2A Atenolol （阿替洛尔） Metoprolol （美托洛尔） 2B Acebutolol( 醋丁洛尔 ) 3 Labetalol （拉贝洛尔）

34. 1A ： nonselective, no ISA Propranolol( 普萘洛尔 ), 1.pharmacokinetics: high liposolubility 2.uses: HBP, arrhythmia, CHF, myocardial ischemia, hyperthyroidism Timolol （噻吗洛尔） 1.actions: strongest 2.uses: glaucoma (block β-R of ciliary body  aqueous humor ↓)

35. 1B:nonselective, ISA Pindolol （吲哚洛尔） Actions: stronger than propranolol Uses: HBP

36. 2A: selective, no ISA Atenolol （阿替洛尔, 氨酰心安 ） : long t1/2 Metoprolol （美托洛尔, 美多心安 ）

37. 3: α 、 β-R antagonists Labetalol （拉贝洛尔, 柳胺苄心定 ） 1.β-R blockage>α-R blockage 2. β-R blockage<propranlol 3.α-R blockage<phentolamine 4. ISA (β2-R) 5. used in HBP, angina pectoris

38. 3: α 、 β-R antagonists carvedilol ( 卡维地洛 ) 1.β-R blockage>α-R blockage 2. used in HBP, CHF