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Introduction to Autonomic Nervous System

Introduction to Autonomic Nervous System. Pawitra Pulbutr M.Sc. In Pharm (Pharmacology). Objectives. สามารถอธิบายพื้นฐานทางกายวิภาคและสรีรวิทยาของระบบประสาทซิมพาเทติก รวมทั้งเป้าหมายการออกฤทธิ์ของยาที่มีผลต่อระบบประสาทซิมพาเทติก

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Introduction to Autonomic Nervous System

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  1. Introduction to Autonomic Nervous System Pawitra Pulbutr M.Sc. In Pharm (Pharmacology)

  2. Objectives • สามารถอธิบายพื้นฐานทางกายวิภาคและสรีรวิทยาของระบบประสาทซิมพาเทติก รวมทั้งเป้าหมายการออกฤทธิ์ของยาที่มีผลต่อระบบประสาทซิมพาเทติก • สามารถอธิบายพื้นฐานทางกายวิภาคและสรีรวิทยาของระบบประสาทพาราซิมพาเทติก รวมทั้งเป้าหมายการออกฤทธิ์ของยาที่มีผลต่อระบบประสาทพาราซิมพาเทติก

  3. Motor (Efferent) portion of nervous system • Autonomic portion… Autonomic Nervous System (ANS) • Involuntary control • CVS, GI, Iris, Genitourinary function • Somatic portion • Voluntary control • Commanded by brain • Posture/ Movement >>> Skeletal Muscle

  4. Preganglionic neuron Postganglionic neuron Difference between ANS VS Somatic nervous system

  5. Drugs acting on ANS • Act on receptor of NTs • Agonist • Antagonist • Interfere biosynthesis of NTs • Inhibit precursor uptake • Inhibit enzyme for biosynthesis • Interfere degradation of NTs • Inhibit degradation enzyme • Inhibit NTs reuptake

  6. Autonomic Nervous System (ANS) • Sympathetic Nervous System (Thoracolumbar division) • Parasympathetic Nervous System (Craniosacral division) • Named after anatomy origin NOT after type of action or NTs !!

  7. Medullary Cervical Thoracic Lumbar Sacral Basic plan of ANS

  8. Enteric Nervous System (ENS) A highly simplified diagram of some of the circuitry of the enteric nervous system (ENS)

  9. Neurotransmitters of ANS • Major (Primary) NTs • Acetylcholine (ACh) • “Cholinergic fiber” • Norepinephrine (NE) • ”Noradrenergic or Adrenergic fiber” • Co-transmitters • Peptide, etc.

  10. Cholinergic fiber • Synthesis & release ACh • All Pre-ganglionic autonomic fiber (both SNS & PNS) • Somatic fiber (innervate skeletal M.) • All Parasympathetic postganglionic fiber • Some sympathetic postganglionic fiber (innervate eccrine sweat gland)

  11. Adrenergic fiber • Synthesis & release NE • Most Postganglionic sympathetic fiber • Adrenal medulla = Modified postganglionic sympathetic neuron release both NE & Epinephrine (Epi)

  12. Hemicholiniums Cholinergic transmission precursor Choline acetyl transferase (ChAT) • ACh receptor = Cholinergic receptor • Postsynaptic RC >>> Action • Presynaptic RC • Autoreceptor • Heteroreceptor Action potential vesamicol Botulinum toxin AChE

  13. Acetylcholine ACh hydrolysis via AChE Anionic site Esteratic site AChE enzyme Acetylated enzyme Free AChE

  14. Adrenergic transmission Tyrosine Tyrosine hydroxylase RLS Metyrosine Dopamine -hydroxylase Reserpine Action Potential Cocaine / Tricyclic antidepressant (TCA) 1 Bretylium/ Guanethidine Metabolism via MAO & COMT 2

  15. Degradation of NE • Less are metabolized in synaptic cleft • Major degradation • Simple diffusion away from synapse • Metabolize in plasma & liver • Uptake via uptake • Uptake 1 into presynaptic nerve • Uptake 2 into perisynaptic glia & smooth muscle

  16. Drugs acting on adrenergic transmission • Direct acting • Adrenergic Agonist • Adrenergic Antagonist • Indirect acting… increase NE at synaptic cleft • Reuptake inhibitors • Cocaine, TCA • Increase NE release from vesicle • Amphetamine, Tyrosine

  17. Autonomic receptor • Acetylcholine receptor (Cholinergic receptor) • Nicotinic receptor (N receptor) • NN, NM • Ion channel linked receptor • Muscarinic receptor (M receptor) • M1, M2, M3 • GPCR • Noradrenergic receptor (Adrenergic receptor) • Alpha receptor • Alpha1, Alpha2 • GPCR • Beta receptor • Beta1, Beta2, Beta3 • GPCR

  18. Direct effects of ANS activity on some organ systems

  19. Baroreceptor Reflex Chart Stand up quickly BP falls in upper body Aortic Arch Carotid Sinus Medulla Oblongata Nucleus Tractus Solitarius Neutral Integration Effectors Veins & Arterioles Heart Muscle SA node Vasoconstriction Increased SV Increased HR Increased CO Increased TPR Increased BP = CO x TPR

  20. BP = TPR * CO CO = HR * SV SV = Contractility force * Venous return Venous return = Venous tone * Blood volume Blood volume = Aldosterone regulation Autonomic and Hormonal Control of CVS function

  21. Presynaptic regulation • Negative feedback control • “Autoreceptor” • Receptor of their own secreted NTs • Alpha 2-receptor at presynaptic nerve • Inhibit NE release from presynaptic • “Heteroreceptor” • Receptor of other NTs • Cholinergic receptor at sympathetic nerve • Inhibit NE release from presynaptic

  22. Postsynaptic regulation • Receptor dynamic • Receptor upregulation • Surgical denervation… increase No. of RC • Increase response …“denervation supersensitivity” • Pharmacologic denervation supersensitivity … drug that decrease NTs >>> reserpine • Receptor downregulation • Receptor desensitization

  23. Main process of transmitters • uptake of precursors • synthesis of transmitters • storage in vesicle • degradation of surplus • depolarization • Ca++ influx • exocytosis • diffusion to postsynp RC • activation of postsynp RC • inactivation of transmitters • reuptake or degradation • interact with presynp RC

  24. Questions & Answers

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