1. Part 4 Adrenoceptor agonists §1. ,  receptor agonists §2.  receptor agonists §3.  receptor agonists

2. Bronchial smooth muscle Overview of catecholamine actions on CVS & respiratory systems Adrenal medulla

3. Overview of catecholamine actions on blood presure

4. Action site of catecholamines

5. Tyrosine Dopa Dopamine Norepinephrine Epinephrine Tyrosine hydroxylase Dopa decarboxylase Dopamine  -hydroxylase Phenylethanolamine N-methyltransferase Catecholamine biosynthesis

6. Catecholamines ( 儿茶酚胺 ) 去甲肾上腺素 肾上腺素 异丙肾上腺素 多巴胺

7. Structure-activity relationship of catecholamines and related compounds Substitution on the aromatic nucleus Substitution on the aromatic nucleus COMT, central activity COMT, central activity Substitution on the  -carbon atom Substitution on the  -carbon atom MAO, uptake-1, NE release MAO, uptake-1, NE release Substitution on the amino group Substitution on the amino group sensitivity to the subunits of receptors sensitivity to the subunits of receptors

8. 1，21，2

9. Metabolism of catecholamines

10. Effect patterns of sympathomimetics

11. Subtypes of adrenoceptors

12. Effects of catecholamines （ therapeutic doses ）

13. BP  antagonist  antagonist epinephrine Epinephrine reversal （ adrenaline reversal ） epinephrine

14. Epinephrine reversal (adrenaline reversal)

15. The  -adrenoceptor action of epinephrine on cardiovascular system

17. 1. ,  receptor agonists Epinephrine 肾上腺素, Adrenaline Short action because of rapid metabolism

18. 1. ,  receptor agonists §1.1 Pharmacological effects §(1) Cardiac effects §  1 : HR , output , § oxygen consumption , inducing arrhythmia §(2) Vascular effects §  1 ： vasoconstriction, especially at larger doses §  2 ： vasodilatation of skeletal muscles and coronary vessels

19. §(3) Blood pressure § SP , DP  (at therapeutic doses) §(4) Bronchodilatation §  2 ： dilatation of bronchial smooth muscles §  1 ： reducing congestion and edema of bronchial mucosa §(5) Metabolic effects § blood glucose  ; free fatty acids  1. ,  receptor agonists

20. §1.2 Clinical uses §(1) Cardiac arrest §(2) Anaphylactic shock & other sever allergy §(3) Acute bronchial asthma §(4) Local uses adjuvant for local anesthetics; control of bleeding § adjuvant for local anesthetics; control of bleeding 1. ,  receptor agonists

21. Clinical uses of epinephrine Systmatic uses: Cardiac arrest Anaphylactic shock Acute bronchial asthma Topical uses: Adjuvant of local anesthesia Bleeding

22. §1.3 Adverse effects §(1) Cardiac arrhythmia: BP , arrhythmia §(2) Excessive rise of BP: cerebral or subarachnoid hemorrhage §(3) Central excitation ： anxiety §(4) Contraindications: heart diseases, hypertension, coronary arterial disease, arteriosclerosis, hyperthyroidism 1. ,  receptor agonists

23. Ephedrine 麻黄碱 Ephedrine麻黄碱 Epinephrine肾上腺素 1. ,  receptor agonists

24. §1.1 Pharmacological effects §Promoting release of NE, weak agonist effects on  1,  2,  1,  2 receptors §Properties ： § chemically stable, orally effective ； § central stimulating ； § less potent and longer action duration; § tachyphylaxis. 1. ,  receptor agonists

25. §1.2 Clinical uses §(1) Prevention of hypotension: anesthetics §(2) Nasal decongestion: nasal drop §(3) Bronchial asthma: mild, chronic cases §(4) Relieving allergic disorders: urticaria, angioneurotic edema 1. ,  receptor agonists

26. §1.3 Adverse effects §(1) Central stimulation §(2) CVS effects §(3) Dependence §Pseudoephedrine ( 伪麻黄碱 ） §usually used in the compounds for treatment of cold 1. ,  receptor agonists

27. Dopamine 多巴胺 1. ,  receptor agonists

28. §1.1 Pharmacological effects §(1) Cardiac effects ：  1 receptor, weak §(2) Vascular effects and blood pressure ： § DA receptor ： dilatation of renal and mesenteric arteries, blood flow  (small doses); §  1 receptor ： vasoconstriction of skin, mesenteric vessels (larger doses) §(3) Renal effects ： renal vasodilatation; natriuretic effects 1. ,  receptor agonists

29. Vasodilatation (DA receptor) Vasoconstriction (  -adrenoceptor) Effects of dopamine on CVS

30. §1.2 Clinical uses §(1) Shock §cardiac and septic shock: low output, urinary volume , to be used after fully adequate replacement of intravascular fluid §(2) Acute renal failure § combined with furosemide （呋塞米） §1.3 Adverse effects § tachycardia, arrhythmia, renal vasoconstriction 1. ,  receptor agonists

31. 2.  receptor agonists § 2-1  1,  2 receptor agonists Norepinephrine 去甲肾上腺素, noradrenaline noradrenaline

32.  -adrenoceptor-mediated signal transduction

33. 2.  receptor agonists §2.1 Pharmacological effects §(1) Vascular effects ： §  1 ： vasoconstriction (skin, renal, brain, hepatic, mesenteric, etc.) § vasodilatation of coronary arteries  2 ： inhibiting endogenous NE release §  2 ： inhibiting endogenous NE release

34. Actions of norepinephrine on post-synaptic (  1 ) and pre-synaptic (  2 ) receptors

35. §(2) Cardiac effects ： weak direct stimulation (  1 ); § weak direct stimulation (  1 ); § inhibition via reflex, HR  §(3) Blood pressure ： § SP , DP  ( especially at larger doses ), larger doses:pulse pressure , tissue blood flow  § larger doses: pulse pressure , tissue blood flow  2.  receptor agonists

36. §2.2 Clinical uses §(1) Shock § BP , tissue blood flow , tissue damage  § used in early phase of some types of shock or BP rise too slow after treatment: small doses and shorter duration 2.  receptor agonists

37. §(2) Hypotension due to drug poisoning § for example: chlorpromazine §(3) Hemorrhage in upper alimentary tract § orally given after dilution with cold saline 2.  receptor agonists

38. §2.3 Adverse effects §(1) Ischemia and necrosis at the site of iv administration relieved by filtration with procaine or phentolamine §(2) Acute renal failure avoiding larger doses and longer duration; monitoring urinary volume §(3) Withdrawal hypotension §(4) Contraindication hypertension, arteriosclerosis, heart diseases, severe urinary volume , microcirculation disorders 2.  receptor agonists

39. §Acting on  receptors directly, promoting NE release indirectly ； §Weaker effects and longer duration than NE, §weak for renal vessels; §Used in early phase of shock, hypotension Metaraminol 间羟胺, Aramine 2.  receptor agonists

40.  2-2  1 receptor agonists § §used in hypotension, paroxysmal supraventricular tachycardia (by reflex) ； §Mydriasis (phenylephrine): pupillary dilator muscles, no or less effect on intraocular pressure, short-acting (for several hours) Phenylephrine 去氧肾上腺素 Phenylephrine 去氧肾上腺素 Methoxamien 甲氧明 Methoxamien 甲氧明 2.  receptor agonists

42. 3.  receptor agonists §3-1  1,  2 receptor agonists Isoproterenol 异丙肾上腺素, Isoprenaline Isoprenaline

43.  -adrenoceptor-mediated signal transduction PKA PKA (cAMP-dependent protein kinase)

44. 3.  receptor agonists §3.1 Pharmacological effects §(1) Cardiac effects §  1 receptor stimulation §(2) Vascular effects and blood pressure §  2 receptor: dilatation of skeletal muscles and coronary vessels ； § SP , DP  or , pulse pressure 

45. §(3) Bronchodilatation §  2 receptor ， no effect on edema of mucosa §(4) Metabolism § Promoting effects as epinephrine 3.  receptor agonists

46. Effects of isoproterenol

47. 3.2 Clinical uses §(1) Cardiac arrest §(2) A-V block §(3) Septic shock ： low-output §(4) Acute bronchial asthma ： § generally use  2 receptor agonists 3.  receptor agonists

48. 3.3 Adverse effects §(1) Heart stimulation, arrhythmia §(2) Contraindications: § coronary heart disease, myocarditis, hyperthyroidism 3.  receptor agonists

49. §3-2  1 receptor agonists § Heart failure § Cardiac stimulation Dobutamine 多巴酚丁胺 3.  receptor agonists

50. §3-3  2 receptor agonists Bronchial asthma § Bronchial asthma Salbutemol 沙丁胺醇 3.  receptor agonists