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

Objectives สามารถอธิบายพื้นฐานทางกายวิภาคและสรีรวิทยาของระบบประสาทซิมพาเทติก รวมทั้งเป้าหมายการออกฤทธิ์ของยาที่มีผลต่อระบบประสาทซิมพาเทติก สามารถอธิบายพื้นฐานทางกายวิภาคและสรีรวิทยาของระบบประสาทพาราซิมพาเทติก รวมทั้งเป้าหมายการออกฤทธิ์ของยาที่มีผลต่อระบบประสาทพาราซิมพาเทติก

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

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

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

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 !!

Medullary Cervical Thoracic Lumbar Sacral Basic plan of ANS

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

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

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)

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

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

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

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

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

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

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

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

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

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

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##

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

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

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

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

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

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