1. PHARMACOLOGY OF THE AUTONOMIC NERVOUS SYSTEM YORAM ORON, PhD PROFESSOR OF PHARMACOLOGY SACKLER FACULTY OF MEDICINE TEL AVIV UNIVERSITY

2. ANATOMY OF ANS - I

4. OUTLINE OF THE ANS S P CERV THOR LUMB SACRAL VAGUS

5. ANATOMY OF ANS - II TARGET TISSUES

6. Responses to ANS Stimuli Effector Organ Sympathetic Response Parasympathetic Response Heart SA node Rate Contractility Conduction Velo. Rate Contractility Conduction Velo. AV node Conduction Velo. Conduction Velo. Heart Ventricles Contractility Conduction Velo. ----- Lungs Relaxation of bronchial muscle Contraction of bronchial muscle

7. Responses to ANS Stimuli Effector Organ Sympathetic Response Parasympathetic Response - Arterioles Skin Constriction ----- Mucosa Constriction ----- Abdominal viscera Constriction ----- Skeletal muscle Dilation ----- Coronary Dilation Dilation Glands Constriction Dilation

8. Responses to ANS Stimuli Effector Organ Sympathetic Response Parasympathetic Response - Veins (systemic) Constriction ----- Gastrointestinal tract Motility and tone Contraction of sphincters Motility and tone Relaxation of sphincters Skin Pilomotor muscles Piloerection ----- Sweat glands Secretion ----- Spleen capsule Contraction

9. Responses to ANS Stimuli Effector Organ Sympathetic Response Parasympathetic Response - Eye Radial muscle of iris Contraction -> mydriasis ----- Sphincter muscle of iris ----- Contraction -> miosis Ciliary muscle Relaxation for far vision Contraction for near vision

10. Responses to ANS Stimuli Effector Organ Sympathetic Response Parasympathetic Response - Glands Gastrointestinal Inhibition of secretion Secretion Lacrimal ----- Secretion Nasopharyngeal ----- Secretion Respiratory Inhibition of secretion Secretion Salivary Thick secretion Thin secretion

11. ANATOMY OF ANS - III PRE- AND POST-GANGLIONIC FIBERS

12. SCHEMATICS OF ANS GANGLIA

19. SIGNAL TRANSMISSION IN THE ANS - I PRINCIPLES

22. ACETYLCHOLINE NOREPINEPHRINE

23. SIGNAL TRANSMISSION IN THE ANS - II TRANSMITTER SYNTHESIS

28. SIGNAL TRANSMISSION IN THE ANS - III TRANSMITTER REMOVAL

35. SIGNAL TRANSMISSION IN THE ANS - IV TRANSMITTER RELEASE

38. ADRENERGIC SYNAPSE Beta1-receptor + M2-receptor

40. SIGNAL TRANSMISSION IN THE ANS - V TARGET TISSUE RECEPTORS

45. AUTONOMIC DRUGS CHOLINERGIC

49. AUTONOMIC DRUGS ADRENERGIC

58. AUTONOMIC DRUGS ORGAN CONTROL - CVS

59. AUTONOMIC CONTROL OF CVS

60. AUTONOMIC CONTROL OF CVS ISO – VASODILATION, INCREASED HR, DECREASED MEAN BP, SYMPATHETIC REFLEX NE – VASOCONSTRICTION, INCREASED MEAN BP, VAGAL REFLEX, DECREASED HR EPI – VASODILATION & VASOCONSTRICTION, NO CHANGE IN MEAN BP, NO REFLEX, INCREASED HR

61. AUTONOMIC CONTROL OF CVS DOPAMINE – (LOW - DARs) VASODILATION OF SPLANCHNIC BED, DECREASED PERIFERAL RESISTANCE, INCREASED URINE OUTPUT DOPAMINE – (MEDIUM -betaRs) VASODILATION OF SEVERAL BEDS, DECREASED PERIFERAL RESISTANCE, INCREASED URINE OUTPUT & CO DOPAMINE – (HIGH - alphaRs) VASODILATION & VASOCONSTRICTION, DECREASED PERIFERAL RESISTANCE, INCREASED URINE OUTPUT, INCREASED CO, INCREASED BP

62. GLAUCOMA THERAPY Primary Open-Angle Glaucoma (POAG)

63. GLAUCOMA CILLIARY BODY LENS IRIS CORNEA SCLERA PUPIL TRABECULAR MESH AQUEOUS OUTFLOW

64. GLAUCOMA THERAPY Primary Open-Angle Glaucoma (POAG) ETHIOLOGY? INCREASED IOP (BUT ALSO NORMOTENSIVE GLAUCOMA ) (BUT ALSO INCREASED IOP W/O GLAUCOMA – OCULAR HYPERTENSION ) PROGRESSIVE DEATH OF GANGLION CELLS PROGRESSIVE DAMAGE TO OPTIC NERVE HEAD PROGRESSIVE LOSS OF VISION NEURODEGENERATIVE SYNDROME?

65. PROGRESSIVE LOSS OF VISION

66. POAG THERAPY DRUG CLASS – BETA BLOCKERS BRONCHOSPASM HEART FAILURE SIDE EFFECTS BETAXOLOL TIMOLOL AQUEOUS OUTFLOW AQUEOUS PRODUCTION DRUGS

67. POAG THERAPY DRUG CLASS – MUSCARINIC STIMULATION PHYSOSTYGMINE IMPAIRED VISION MIOSIS BROW ACHE SIDE EFFECTS CARBACHOL PILOCARPINE (PA) AQUEOUS OUTFLOW AQUEOUS PRODUCTION DRUGS

68. POAG THERAPY DRUG CLASS – ALPHA AGONISTS MACULAR EDEMA PUPIL DILATION SIDE EFFECTS CONTACT ALLERGY HYPOTENSION (CHILDREN) TACHYCARDIA EPINEPHRINE DIPIVEFRINE (PRO) BROMONIDINE APRACLONIDINE AQUEOUS OUTFLOW AQUEOUS PRODUCTION DRUGS

69. POAG THERAPY DRUG CLASS – CARBONIC ANHYDRASE INHIBITORS CONFUSION RENAL STONES APLASTIC ANEMIA MALAISE GI SIDE EFFECTS DORZOLAMIDE (TOPICAL) ACETAZOLAMIDE AQUEOUS OUTFLOW AQUEOUS PRODUCTION DRUGS

70. POAG THERAPY DRUG CLASS – PROSTAGLANDINS IRIS COLOR CHANGE LASH GROWTH SIDE EFFECTS LATANOPROST AQUEOUS OUTFLOW AQUEOUS PRODUCTION DRUGS

71. ESSENTIAL HYPERTENSION THERAPY

72. ESSENTIAL HYPERTENSION