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

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Presentation on theme: "Introduction to Autonomic Nervous System Pawitra Pulbutr M.Sc. In Pharm (Pharmacology)"— Presentation transcript:

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

2 Objectives สามารถอธิบายพื้นฐานทางกายวิภาค และสรีรวิทยาของระบบประสาทซิมพา เทติก รวมทั้งเป้าหมายการออกฤทธิ์ ของยาที่มีผลต่อระบบประสาทซิมพา เทติก สามารถอธิบายพื้นฐานทางกายวิภาค และสรีรวิทยาของระบบประสาทพารา ซิมพาเทติก รวมทั้งเป้าหมายการออก ฤทธิ์ของยาที่มีผลต่อระบบประสาท พาราซิมพาเทติก

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 Skeletal Muscle Posture/ Movement >>> Skeletal Muscle

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

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 Basic plan of ANS Medullary Cervical Thoracic Lumbar Sacral

8 A highly simplified diagram of some of the circuitry of the enteric nervous system (ENS) 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 ACh Synthesis & release ACh All Pre-ganglionic autonomic fiber (both SNS & PNS) Somatic fiber (innervate skeletal M.) All Parasympathetic All Parasympathetic postganglionic fiber Some sympathetic Some sympathetic postganglionic fiber (innervate eccrine sweat gland)

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

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

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

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

15 Degradation of NE Less Less are metabolized in synaptic cleft Major degradation Simple diffusion 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) N N, N M 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 OrganEffect of Sympathetic ActivityParasympathetic Activity ActionReceptorActionReceptor EyeIris  Radial muscle  Circular muscle Ciliary muscle Contracts….[Relaxes]  1 ….….ContractsContracts….M3M3 Heart Sinoatrial node Ectopic pacemakers ContractilityAcceleratesAcceleratesIncreases  1,  2 Decelerates…. Decreases (atria) M2….M2

19 OrganEffect of Sympathetic ActivityParasympathetic Activity ActionReceptorActionReceptor Blood vessels Skin, splanchnic vessels Skeletal muscle vessels EndotheliumContractsRelaxes [contract ] Relaxes  2 M*….….….…. Release EDRF ….….….….M3** Bronchiolar smooth muscle Relaxes 2222ContractsM3 GI tract Smooth muscle Walls Walls Sphincter SphincterSecretion Myenteric plexus RelaxesContracts….  2#,  2  1 ….ContractsRelaxesIncreasesActivatesM3M3M3M1

20 OrganEffect of Sympathetic ActivityParasympathetic Activity ActionReceptorActionReceptor Genitourinary smooth muscle Bladder wall Sphincter Uterus, pregnant Penis, Seminal vesicle RelaxesContractsRelaxesContractsEjaculatn 221122221122ContractsRelaxes…ContractsErectionM3M3….M3MSkin Pilomotorsmooth muscle Sweat glands Thermoregulatory Apocrine (stress) Apocrine (stress)ContractsIncreasesIncreasesM………………

21 Metabolic functions LiverLiver Fat cells KidneyGluconeogenesisGlycogenolysisLipolysis Renin release  2,   3  1 …………………… Autonomic nerve endings SympatheticParasympathetic… Decrease ACh release … Decrease NE release …M##… OrganEffect of Sympathetic ActivityParasympathetic Activity ActionRCActionReceptor

22 Baroreceptor Reflex Chart Stand up quickly BP falls in upper body Aortic ArchCarotid Sinus Medulla Oblongata Nucleus Tractus Solitarius Neutral Integration Effectors Veins & Arterioles Heart MuscleSA node Vasoconstriction Increased SV Increased HR Increased TPR Increased CO Increased BP = CO x TPR

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

24 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

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

26 Main process of transmitters 1. uptake of precursors 2. synthesis of transmitters 3. storage in vesicle 4. degradation of surplus 5. depolarization 6. Ca ++ influx 7. exocytosis 8. diffusion to postsynp RC 9. activation of postsynp RC 10.inactivation of transmitters 11. reuptake or degradation 12. interact with presynp RC

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