Pharmacology

1. AUTONOMICS Ma. Janetth B. Serrano, MD, DPBA

2. NERVOUS SYSTEM CENTRAL NERVOUS SYSTEM PERIPHERAL NERVOUS SYSTEM BRAIN SPINAL CORD EFFERENT Division AFFERENT Division AUTONOMIC N.S. SOMATIC N.S. Sympathetic N.S. Parasympathetic N.S. Enteric N.S.

6. Stimulation of adenyl cyclase ↑ cAMP Postsynaptic effector cells esp. lipocytes Beta 3 Stimulation of adenyl cyclase ↑ cAMP Posynaptic effector cells esp. sm. m. & cardiac m. Beta 2 Stimulation of adenyl cyclase ↑ cAMP Postsynaptic effector cells esp.heart, lipocytes, brain Presyn cholinergic & adrenergic terminals Beta 1 Inhibition of adenyl cyclase ↓ cAMP Presynaptic adrenergic n. terminals, platelets, lipocytes, sm.m. Alpha 2 Formation of IP 3 and DAG ↑ IC calcium Postsynaptic effector cells esp. smooth m. Alpha 1 RESULT OF LIGAND BINDING TYPICAL LOCATIONS RECEPTOR NAME

7. Inhibition of adenyl cyclase Brain, Cardiovascular System D 4 Inhibition of adenyl cyclase Brain D 3 Inhibition of adenyl cyclase ↑ K + conductance Brain, effector tissues, esp. smooth m., presynaptic nerve terminals D 2 (DA 2 ) Stimulation of adenyl cyclase ↑ cAMP Brain, effector tissues esp. sm.m. of the renal vascular bed D 1 (DA 1 ), D 5 RESULT OF LIGAND BINDING TYPICAL LOCATIONS RECEPTOR NAME

8. MUSCARINIC RECEPTORS Na + , K + depolarizing ion channel Postganglionic cell body, dendrites N N Na + , K + depolarizing ion channel Skeletal muscle NMJ N M IP 3 , DAG cascade ? CNS M 5 Inhibition of cAMP production ? CNS M 4 IP 3 , DAG cascade Glands, smooth muscle, endothelium M 3 Inhibition of cAMP prod’n, activation of K + channels Heart, nerves, smooth muscles M 2 IP 3 , DAG cascade Nerves M 1 Postreceptor Mechanism Location Receptor Type

10. METYROSINE COCAINE, TCA, IMIPRAMINE RESERPINE

11. HEMICHOLINIUM VESAMICOL BOTULINUM TOXIN

13. EFFECTOR ORGANS Autonomic Nervous System

14. Autonomic Nervous System Some Sweat glds & some BV RVSM Acetylcholine Acetylcholine Acetylcholine Dopamine Nicotinic Receptor Nicotinic Receptor Muscarinic Receptor D 1 Receptor

15. Somatic Nervous System

17. Autonomic Nervous System

18. Sympathetic N. S. relaxation  2 Lung bronchial m. ↑ Heart rate ↑ conduction velocity ↑ contraction  1  1  1 Heart SA node AV node Contractility Contraction (mydriasis) Relaxation α 1  2 Eye radial m. (iris) ciliary m. Action Receptor Effector Organs

19. Sympathetic N. S. Constriction Relaxation Ejaculation α 1  2 α 1 GUT sphincter bladder wall Penis, seminal v. Constriction Decrease α 1 α ,  2 GIT sphincter motility & tone Constriction Relaxation α 1  2 Blood Vessels most BV skeletal m. Action Receptor Effector Organs

20. Sympathetic N. S. Secretion of cathecolamines ↑ renin release Glycogenolysis ↓ insulin release Lipolysis N N  1  2 α 2  3 Metabolism adrenal medulla kidney skeletal m. Pancreas (B-cell) fat cells Localized secretion Inhibition - Moderate secretion α 1 α 2 - α Secretory glands sweat intestinal bronchial lacrimal Action Receptor Effector Organs

21. Parasympathetic N. S. contraction M 3 Lung bronchial m. ↓ Heart rate ↓ conduction velocity ↓ contraction M 2 M 2 M 2 Heart SA node AV node Contractility Contraction (miosis) Contraction (accomodation) M 3 M 3 Eye circular m. ciliary m. Action Receptor Effector Organs

22. Parasympathetic N. S. Relaxation Increase Erection M 3 M 3 M GUT trigone & sphincter m. bladder wall & detrusor m. Penis, seminal v. Relaxation Increase M 3 M 3 GIT sphincter motility & tone - - - - Blood Vessels most BV skeletal m. Action Receptor Effector Organs

23. Parasympathetic N. S. Generalized secretion ↑ secretion ↑ secretion Profuse secretion M M 3 M M Secretory glands sweat intestinal bronchial lacrimal Action Receptor Effector Organs

25. Sympathetic Agonists SYMPATHOMIMETICS

26. Sympathetic Agonists (Sympathomimetics) EPINEPHRINE NOREPINEPHRINE DOPAMINE IBOPAMINE AMPHETAMINE METHAMPHETAMINE EPHEDRINE PSEUDOEPHEDRINE DOBUTAMINE ISOPROTERENOL β 1 and β 2 α 1 and α 2 β 2 β 1 α and β α 2 α 1

27. Sympathetic Agonists (Sympathomimetics) PHENYLEPHRINE METHOXAMINE MEPHENTERMINE METARAMINOL MITODRINE β 1 and β 2 α 1 and α 2 β 2 β 1 α and β α 2 α 1

28. Sympathetic Agonists (Sympathomimetics) METHYLDOPA CLONIDINE GUANABENZ GUANFACINE β 1 and β 2 α 1 and α 2 β 2 β 1 α and β α 2 α 1

29. Sympathetic Agonists (Sympathomimetics) NAPHAZOLINE TETRAHYDROZOLINE β 1 and β 2 α 1 and α 2 β 2 β 1 α and β α 2 α 1

30. Sympathetic Agonists (Sympathomimetics) NAPHAZOLINE TETRAHYDROZOLINE OXYMETAZOLINE XYLOMETAZOLINE β 1 and β 2 α 1 and α 2 β 2 β 1 α and β α 2 α 1

31. Sympathetic Agonists (Sympathomimetics) METAPROTERENOL TERBUTALINE, ALBUTEROL RITODRINE ISOETHARINE, PILBUTEROL BITOLTEROL, FENOTEROL FORMOTEROL, SALMETEROL PROCATEROL β 1 and β 2 α 1 and α 2 β 2 β 1 α and β α 2 α 1

34. Sympathetic Antagonists SYMPATHOLYTICS

36. Sympathetic Antagonists (Sympatholytics) YOHIMBINE BUTOXAMINE LABETALOL CARVEDILOL Β 1 and β 2 α 1 and α 2 β 2 β 1 α and β α 2 α 1

37. Sympathetic Antagonists (Sympatholytics) PRAZOSIN, TERAZOSIN DOXAZOSIN, TRIMAZOSIN INDORAMIN, URADIPIL KETANSERIN, ALFUZOSIN BUNAZOSIN, TAMSULOSIN α 1 and α 2 β 1 and β 2 β 2 β 1 α and β α 2 α 1

38. Sympathetic Antagonists (Sympatholytics) PHENOXYBENZAMINE PHENTOLAMINE ERGOT ALKALOIDS NEUROLEPTIC DRUGS Β 1 and β 2 α 1 and α 2 β 2 β 1 α and β α 2 α 1

42. Sympathetic Antagonists (Sympatholytics) METOPROLOL ATENOLOL ACEBUTOLOL BETAXOLOL CELIPROLOL ESMOLOL Β 1 and β 2 α 1 and α 2 β 2 β 1 α and β α 2 α 1

43. Sympathetic Antagonists (Sympatholytics) PROPRANOLOL NADOLOL, TIMOLOL PINDOLOL, LEVOBUNOLOL CARTEOLOL, BISOPROLOL Β 1 and β 2 α 1 and α 2 β 2 β 1 α and β α 2 α 1

46. Properties of Beta-receptor blocking agents: 50 3-4 hrs Mod + - Metoprolol 70 4-5 hrs No data - + Celiprolol 0 8-10 min Low - - Esmolol 90 14-22 hrs Low Slight - Betaxolol 40 6-9 hrs Low - - Atenolol 50 3-4 hrs Low + + Acebutolol Selective β 1 blockers Approxi-mate Bioavai-lability Elimination Half-life Lipid Solu-bility Local Anesthetic Activity (MSA) Partial Agonist Activity ( ISA)

47. Properties of Beta-receptor blocking agents: 90 3-4 hrs Mod + + Pindolol 50 4-50 hrs Mod - - Timolol 33 14-24 hrs Low - - Nadolol 30 5 hrs Mod + + Labetalol 25-35 6-8 hrs No Data - - Carvedilol 85 6 hrs Low - + Carteolol 30 3.5-6 hrs High + - Propranolol NonSelective β 1 Blockers Approxi-mate Bioavai-lability Elimina-tion Half-life Lipid Solu-bility MSA (Local Anesthetic Activity) ISA (Partial Agonist Activity )

51. “ A heartfelt apology can’t change the past, but it can brighten the future.”