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Introduction to Autonomic Nervous System

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Presentation on theme: "Introduction to Autonomic Nervous System"— Presentation transcript:

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 Difference between ANS VS Somatic nervous system
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 Cholinergic transmission
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 ACh hydrolysis via AChE
Acetylcholine ACh hydrolysis via AChE Anionic site Esteratic site AChE enzyme Acetylated enzyme Free AChE

14 Dopamine -hydroxylase Metabolism via MAO & COMT
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 Beta receptor Beta1, Beta2, Beta3

18 Direct effects of ANS activity on some organ systems
Effect of Sympathetic Activity Parasympathetic Activity Action Receptor Eye Iris Radial muscle Circular muscle Ciliary muscle Contracts …. [Relaxes] 1 M3 Heart Sinoatrial node Ectopic pacemakers Contractility Accelerates Increases 1,2 Decelerates Decreases (atria) M2

19 Parasympathetic Activity
Organ Effect of Sympathetic Activity Parasympathetic Activity Action Receptor Blood vessels Skin, splanchnic vessels Skeletal muscle vessels Endothelium Contracts Relaxes [contract] 2 M* …. Release EDRF M3** Bronchiolar smooth muscle M3 GI tract Smooth muscle Walls Sphincter Secretion Myenteric plexus 2#, 2 1 Increases Activates M1

20 Parasympathetic Activity
Organ Effect of Sympathetic Activity Parasympathetic Activity Action Receptor Genitourinary smooth muscle Bladder wall Sphincter Uterus, pregnant Penis, Seminal vesicle Relaxes Contracts Ejaculatn 2 1 Erection M3 …. M Skin Pilomotorsmooth muscle Sweat glands Thermoregulatory Apocrine (stress) Increases

21 Parasympathetic Activity
Organ Effect of Sympathetic Activity Parasympathetic Activity Action RC Receptor Metabolic functions Liver Fat cells Kidney Gluconeogenesis Glycogenolysis Lipolysis Renin release 2, 3 1 Autonomic nerve endings Sympathetic Parasympathetic Decrease ACh release Decrease NE release M##

22 Baroreceptor Reflex Chart Nucleus Tractus Solitarius
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

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 Autonomic and Hormonal Control of CVS function

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

25 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

26 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

27 Questions & Answers

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