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