Adrenomimetic drugs adrenoceptor agonists

1. Adrenomimetic drugs adrenoceptor agonists Department of pharmacology Zhu ling (朱玲) 2010.3

2. Adrenomimetic drugs adrenoceptor agonists • A kind of drugs that mimic the actions and the chemistry structure （amine） of epinephrine or norepinephrine. • Because the action similar to sympathetic effects that stimulation are mediated by release of norepinephrine sympathomimetic drugs

3. Adrenomimetic drugsadrenoceptor agonists

4. αreceptor： blood vessels of skin, gut contracts β1receptor：heart function enhancement β2receptor： bronchial smooth muscles: relaxation skeletal muscle vessels: relaxation coronary artery: relaxation

6. Adrenomimetic drugsadrenoceptor agonists Commonness 1 Basic structure :β--phenylethylamine 2 main effects in the cadiovascular systerm 3 elimination from uptake, MAO, COMT 4 main application: shock

7. Noradrenaline synthesize and elimination

8. Adrenomimetic drugsadrenoceptor agonists • individuality 1 structure: different substituted groups 2 different of receptor selectivity 3 different effects mostly on the systolic and diastolic blood pressure (pulse pressure)

9. αβreceptor agonist Adrenaline Ad 肾上腺素 Epinephrine E • Rooted in adrenal gland medulla，instability • Pharmacokinetics： absorption : is poor with oral administration ， sc or i.m injection . distrbution: the area of noradrenergic nerve domination； elimilation: uptake，or inactivation by MAO, COMT

10. αβreceptor agonist --adrenaline Effects a very potentαβreceptor agitated action 1 heart : β1receptor excitement 2 blood vessels: α1 and β2 receptor skin vessels, mucous membrane vessels, viscus vessels contraction； brain, pulmonary blood vessels feeble vasoconstriction; skeletal muscle vessels ,coronary artery dilation

11. αβreceptor agonist --adrenaline β2 receptor agitate blood pressure coronary artery perfusion pressure flux adenosine increase • 3 blood pressure systolic blood pressure increase, diastolic pressure steadiness or slightly fall pulse pressure

12. αβreceptor agonist --adrenaline 4 bronchia smooth muscle relaxation 5 metabolism: activates fat lipolysis, blood glucose↑ 6 CNS application 1 anaphylactic shock first choose drug 2 bronchial asthma( urgent outbreak) 3 sudden cardiac arrest 4 local application local anesthetics and rhinorrhagia

13. αβreceptor agonist --adrenaline Adverse reaction heart-throb, headache, arrhythmia (extensions of their receptor effects in the cardiovascular ) Contraindication hypertension , hyperthyroid etc

14. αβreceptor agonist --ephedrine pharmacokinetics： substitution on benzene ring(Absence of ring-OH groups) and substitution on alpha carbon preferably lipid-soluble, stabilization, orally active, increase the distribution, prolong the action(resistant to COMT,MAO) effects： Agitate, accelerate NA release 1 peripheral effects like Ad but the function is slow, feeble, long duration 2 CNS effects elevation of mood

16. Methyl-benzedrine甲基苯丙胺(冰毒)

17. αβreceptor agonist --ephedrine application ： • bronchial asthma • congestive snuffle (as a nasal decongestant ) • Prevent some hypotension (as a pressor agent) arachnoid below cavity and outside putamen anesthesia, local anesthetics poisoning • Some disease induced by allergic reaction Adverse reaction： like Ad, further insomnia (CNS effects)

18. αreceptor agonist --noradrenaline Pharmacokinetics chemical quality like Ad， orally taking easily be destroyed， maybe ischemia or putrescence with sc or im ， only can be applied by iv

19. αreceptor agonist --noradrenaline Effect mostly agitateαβ1 receptor 1 heart positive klinotropic effect, positive chronotropic effect positive inotropic effects 2 blood vessel vasoconstriction except coronary artery peripheral resistance 3 blood pressure both diastolic and systolic blood pressure

20. αreceptor agonist --noradrenaline Clinical uses： ① shock and hypotension ② hemorrhage of the upper alimentary tract oral administration (local application) Adverse reaction： marked vasoconstriction , arrhythmia ① local tissues necrosis ② acute kidney failure

21. αreceptor agonist • metaraminal direct and indirect action weak, long-duration substitute of NA • Phenylephrine and methoxamine kidney blood vessels contract ＞NA treatmemt of paroxysmal atrial tachycardia and effictive mydriatic agent (Phenylephrine)

22. βreceptor agonist Isoproterenol (Isoprenaline 异丙肾上腺素) • Isoproterenol （Isoprenaline） 1 pharmacokinetics： absorption: low bioavailability of oral administration，usually iv, sublingua administration, aerosol inhalation （through capillary vessel , rapid absorption ) biotransformation: main metabolized by COMT，some by MAO，some by uptake

23. βreceptor agonist Isoproterenol (Isoprenaline 异丙肾上腺素) effects：more active βreceptor agonist ① heart exciting ② blood vessels potent vasodilator ③ blood pressure systolic pressure slightly increased, diastolic pressure decreased • bronchia smooth muscle: relaxation • metabolism glycogenolysis and lipolysis ↑ increased oxygen consumption

24. βreceptor agonist Isoproterenol (Isoprenaline 异丙肾上腺素) Therapeutic application： ① Sudden cardiac arrest： (cause: ventricular automaticity slowness, severity atrioventricular block and SA nodes function failure) ② atrioventricular block ③ bronchial asthma acute outbreak ④ Infected shock Adverse reaction： heart-throb, arrhythmia etc

26. β1 receptor agonist Dobutamine 多巴酚丁胺 • effects： relatively β1 selective synthetic catecholamine， positive inotropic effects characteristic: in low to moderate doses, it can increase, constriction and cardiac output , but slightly influence on the heart rate, cause relatively little peripheral vasoconstriction and little increase oxygen consumption

27. β1 receptor agonist Therapeutic application： 1 shock well curative effect when companying with weak contract or renal failure 2 congestive heart failure 3 acute renal failure always with diuretic Adverse reaction： tachycardia, hypertension, angina， inducing tolerance

28. αβDA receptor agonist – Dopamine多巴胺 Dopamine（ DA 多巴胺） • the immediate metabolic precursor of norepinephrine • Exist in peripheral nerve, ganglion and central nerve pharmacokinetics： absorption: low bioavailability of oral administration，usually iv distribution: difficult pass through blood-brain barrier

29. αβDA receptor agonist – Dopamine多巴胺 effect：agitate αβDA receptor 1 heart β1 R 2 blood vessel and blood pressure • low doses activate D1 receptor in several vascular beds vasodilation, reduce peripheral resistance • moderate doses β1R systolic pressure↑ diastolic pressure -unchanged • higher doses α β1R systolic pressure ↑ diastolic pressure ↑ 3 kidney renal vascular dilation blood flow↑ (raise glomerulus filtration rate) (clinical value)

30. αβDA receptor agonist – Dopamine多巴胺 Therapeutic application： 1 shock especially oliguria 2 congestive heart failure 3 acute renal failure (with diuretic) Ibopamine （异波帕胺） heart failure (difficult controlling)

31. Sympathomimetic drugs