Here are the answers to the quiz questions: 1. Norepinephrine 2. A 3. B 4. A 5. B 6. A 7. B 8. A 9. A 10. A

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.

3. NERVOUS SYSTEM SOMATIC N.S. Skeletal, motor, voluntary No ganglias or plexuses Motor n. to skeletal muscles myelinated Interruption of impulses  paralysis & atrophy AUTONOMIC N.S. Visceral, vegetative, involuntary Efferent n. supply all except skeletal m. Peripheral ganglias & plexuses Postganglionic fibers unmyelinated Interruption of transmission  spontaneous activity

4. NEUROTRANSMITTERS: Sympathetic: ADRENERGIC Central: EPINEPHRINE Peripheral: NOREPINEPHRINE Parasympathetic: CHOLINERGIC Acetylcholine

5. RECEPTORS: Sympathetic: ADRENOCEPTORS Alpha  α 1 , α 2 Beta   1 ,  2 ,  3 Parasympathetic: CHOLINOCEPTORS Muscarinic Nicotinic Dopaminergic: D 1 , D 2

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

9. SUMMARY OF NEUROHUMORAL TRANSMISSION PROCESS: Synthesis and Storage of Neurotransmitter Release of Neurotransmitter Interaction with Postjunctional Cell and Initiation of Activity Deactivation

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

16. Enteric Nervous System Third division of the ANS Innervates GIT, pancreas, gallbladder Includes: Myenteric plexus (Plexus of Auerbach) Submucous plexus (Plexus of Meissner)

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

24. Site and Mode of Action: 1. Direct Acting - Epinephrine - Dobutamine - Phenylephrine - Norepinephrine - Isoproterenol - Clonidine 2. Indirect Acting Tyramine, Amphetamine, Cocaine 3. Mixed Acting Agonists - Dopamine - Ephedrine - Amphetamine - Metaraminol - Phenylpropanolamine SYMPATHETIC DRUGS

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

32. Special sympathomimetics: COCAINE Local anesthetic Inhibits uptake 1  Peripheral sympathomimetic action CNS  inhibits reuptake of dopamine into neurons in the “pleasure centers” of the brain Sympathetic Agonists (Sympathomimetics)

33. Special sympathomimetics: TYRAMINE Normal by-product of tyrosine metabolism Fermented foods  cheese, red wine Metabolized by MAO Release of stored catecholamines  indirect sympathomimetic action Sympathetic Agonists (Sympathomimetics)

34. Sympathetic Antagonists SYMPATHOLYTICS

35. Adrenergic Neuron Blockers (ANB) Guanethedine, Reserpine Adrenergic Receptor Blockers (ARB) Reversible – Prazosin, Phentolamine, Tolazoline, Labetalol, Ergot alkaloids Irreversible – Phenoxybenzamine, Dibenamine 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

39. PHENOXYBENZAMINE irreversible noncompetetive blockade (14-48 hrs) inhibits NE reuptake Blocks H 1 , Ach and serotonin receptors Blocks catecholamine-induced vasoconstriction Epinephrine- reversal Cl. Indication: pheochromocytoma male erectile dysfunction peripheral vascular diseases Adv. Eff: postural hypotension, tachycardia

40. PHENTOLAMINE Competetive antagonist (4 hrs) Epinephrine- reversal reduce PVR Cardiac stimulation  baroreflex & ↑ NE release Inhibits serotonin responses Indic: Pheochromocytoma, male erectile dysfunction Adv. Eff: severe tachycardia, arrhythmia, myocardial ischemia, GI stimulation

41. Beta-Adrenergic Blocking Agents BETA - BLOCKERS

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

44. Beta- blockers Pharmacokinetics: oral: peak in 1-3 hrs extensive first-pass metabolism half- lives: 3 to 10 hrs * Esmolol – 8 – 10 min * Nadolol – 24 hrs

45. PHARMACODYNAMICS: CVS: (-) chronotropic, (-) inotropic effects Respiratory: bronchoconstriction Eye: reduce IOP Metabolic & Endocrine: inhibits lipolysis partial inhibition of glycogenolysis ↑ VLDL and ↓ HDL ↓ HDL: LDL ratio ISA; MSA Beta- blockers

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 )

48. CLINICAL INDICATIONS: Hypertension Cardiac arrhythmias Angina CHF: Metoprolol, Bisoprolol, Carvedilol Glaucoma: Timolol, Betaxolol, Carteolol, Levobunolol, Metipranolol Neurologic: Migraine, somatic mgt. of anxiety, alcohol withdrawal Misc: reduce portal vein pressure in cirrhosis Beta- blockers

49. Clinical toxicities: Drug allergy – rare CNS effects – sedation, sleep disturbances, depression, psychotic rxns Worsening of preexisting asthma & airway obstruction Depress myocardial contractility & excitability Hypoglycemic episodes Beta- blockers

50. DRUG INTERACTION: Calcium- channel VERAPAMIL Severe hypotension Bradycardia CHF arrhythmia Beta- blockers

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

52. QUIZ Major neurotransmitter of the Sympathetic Nervous System Write A if Agonist or B if Antagonist: 2. Epinephrine 7. Phentolamine 3. Labetalol 8. Cocaine 4. Clonidine 9. Phenylephrine 5. Prazosin 10. Ephedrine 6. Terbutaline