1. Sympathetic Nervous System Needed for studying SNS PHARMACOLOGY
PREREQUISITE
Sympathetic Nervous System
PHYSIOLOGY
Needed for studying SNS PHARMACOLOGY

2. Differ in:
Site of ganglia
Length of pre & postganglionic fiber
Mediators of postganglionic fiber
Ramifies adrenal medulla and its mediator circulate in blood

3. Heart - parasympathetic Arterioles/arteries - sympathetic
PREDOMINANT TONES OF MAJOR ORGAN SYSTEMS
Heart - parasympathetic
Arterioles/arteries - sympathetic
Veins - sympathetic
Iris - parasympathetic
Ciliary muscle - parasympathetic
GI tract (ENS) - parasympathetic
Smooth muscle - parasympathetic
Bladder - parasympathetic
Sweat glands - sympathetic
Salivary glands – parasympathetic
Lacrimal glands – parasympathetic

4. Mainly norepinephrine [NE] Rarely Ach  M2 or Dopamine  D1
Transmitter is
Mainly norepinephrine [NE]
Rarely Ach  M2
or Dopamine  D1
Transmitter is
Mainly epinephrine [E ]  circulates and acts a1, a2, b1 , b2 , b3
Gland cells

5. POSTGANGLIONIC SYMPATHETIC NERVE ENDINGNa
Norepinephrine (NE)
Tyrosine
Dopa
Tyrosine
SYNTHESIS DA
STORAGE NE
RELEASE Ca
ACTION
REUPTAKE
NET
DEGRADE
NE  E
Dopamine (DA) E
ADRENAL MEDULLA
COMT

6. Autoregulatory Function
ADRENOCEPTORS [ADRs] D1
Postsynaptic
Presynaptic
a1 ADRs.
a2 ADRs.
b1 ADRs.
b2 ADRs.
b3 ADRs. a2 a1 b2 b1 b3
Autoregulatory Function a2

7. ADRENOCEPTORS [ADRs]

8. a1 ADRs couple to Gq to stimulate PLC Ca++ intracellular.
ADRENOCEPTORS [ADRs]
a1 ADRs couple to Gq to stimulate PLC Ca++ intracellular.
a2 ADRs couple to Gi to inhibit AC  cAMP .
B1,2 &3 ADRs couple to Gs to stimulate AC  cAMP

9. Some smooth muscles [SMC] 
ADRs
a1 ADRs
Coupled to Gq Activates PLC  IP3 Ca++ & PKC
Some smooth muscles [SMC] 
Vascular [VSMC]
N-VSMC [ Lung / GIT & UB (sphincters) / eye (dilator) ….etc ]
Adr
a1 Adrenoceptor Gq
PLC
a1 ADRs
[VSMC]
↑Ca ++
At VSMCs VASOCONSTRICTION

10. Couple to Gi  Inhibit AC  cAMP
ADRs
a2 ADRs
Couple to Gi  Inhibit AC  cAMP
At presynaptic nerve ending
At some VSMCs & N-VSMC [GIT motility]
In pancreas   insulin
Adr Gi
a2 ADRs AC
a 2 NE
cAMP
At VSMCs a2 ADRs activation postsynaptic
cAMP leaves Ca signaling unopposed  Vasoconstriction
At Presynaptic Nerve Ending
NE release ????

11. + ADRs Couple to Gs  stimulate AC  cAMP Gs ↑cAMP b1 ADRs b2 ADRs
CARDIAC STIMULATION
Renal (renin release)
VSMCs Vasodilatation (cardiac,skeletal)
N-VSMCs  RELAXATION = Bronchodilatation
+ GIT, UB, pregnant uterus, (motility)
 glucagon secretion (glycogenolysis, glycolysis)
Adipose T. (Lipolysis)

12. SNS ACTIVATION on VSMCs1 2 2
VASOCONSTRICTION
VASOCONSTRICTION
VASODILATATION
NET SUMMATION will dictate the FINAL ACTION

13. SNS actions at b receptors in organs controlling metabolism
b2 ADRs
b3ADRs

14. Eye Mydriasis IOP Accomodation
Kept by a balance between formation & drainage
Paralysis of constrictor pupilli (M)
Contraction of dilator pupilli (a1)
Accomodation
If balance disturbed by increasing formation or decreasing drainage  IOP glaucoma
Parasymp mimetics  glucoma (trabecular)
Parasymp lytics   glucoma
Sympathomimetics  ??? effect
b blockers  glucoma (uveoloscleral)
For near vision (M)
For far vision (b2)

15. SYMPATHETIC ACTIONS Fight & Flight a receptors b1 receptors
EYE: Contract
Dilator Pupilli
EYE: Relax
Ciliary m.
SALIVARY GLANDS
 Salivation
BLOOD VESSELS
Vasoconstriction
VESSELS
Vasodilatation
HEART
 Force Inotropic
HR Chronotropic
AV conduction
Dromotropic
BRONCHUS
Bronchodilatation
GIT
Contraction of sphincters
GIT & G. Bladder
Motility
PANCREAS
 Insulin secretion
LIVER
 Glucose
KIDNEY
Renin from Juxta-glomerular cells
URINARY BLADDER
Contraction of sphincters
BLADDER
Detrusal m.:Relax
UTERUS
Relax :Tocolysis
PENIS
Ejaculation

16. Sum up of physiological actions of Epinephrine (adrenaline)
Acts on all ADR; b =/> a
Heart  inotropic, chronotropic, dromotropic & lusiotropic (excitability)(b1)
BP  systolic (b1) / diastolic   low dose (b2) &  high dose (a1)
Vascular SMC; constrict skin + peripheral (a1) / dilate coronary+skeletal (b2)
Non vascular SMC;
Lung  bronchiodilatation (b2)
GIT  motility (b2) / contract sphincter (a1)
Bladder   detrusor m. (b2) / contract trigone & sphincter (a1)
Pregnant uterus  tocolytic (b2)
Eye  mydriasis (a1)
 accommodation for far vision & little effect on IOP
Metabolism insulin (a2) , glucagon (b2),  liver glycogenolysis + sk m. glycolysis (b2) /   adipose lipolysis (b3 /b2)
CNS little, headache, tremors & restlessness

17. GOOD LUCK

18. Adrenergic receptor subtypes and actions
Alpha
GPCRs
Two subtypes
A1 – Gq protein coupled
A2 – Gi protein coupled
Beta
Three subtypes
B1-3 – Gs protein coupled

21. Autonomic regulation of organ systems

22. Autonomic regulation of CVS function
Baroreceptor reflex
Increase in MAP
Increased baroreceptor firing
Increase parasympathetic tone
Decrease sympathatic tone
Decrease in MAP
Decreased baroreceptor firing
Decrease parasympathetic tone
Increase sympathetic tone

23. Regulation of the heart
Dominant tone = parasympathetic
Sympathetic
Increases heart rate and contractility via beta-1 and 2 (primarily beta-1)
Parasympathetic
Decreases heart rate and atrial contractility via M2

24. Regulation of the blood vessels
Veins
Dominant tone = parasympathetic
Arterioles/arteries
Dominant tone = sympathetic
Contraction via alpha1
Relaxation via beta-2

25. Regulation of bronchi
In autonomic ganglia there is cholinergic N and M1 receptors
At postganglionic parasympathetic fibres there is M2 receptors and is also controlled by B2 ADRs fibres
On bronchiolar SMCs there is M3 and B2 ADRs

26. Postganglionic Cholinergic
Regulation of bronchi
Adrenal Medulla
ADRENERGIC
Vasodilatation
Exudation
Mucous secretion
Medulla
Cholinergic Ganglia
Postganglionic Cholinergic
Ach M2 M1
CHOLINERGIC N
SNS Ganglia
ß2-AR AD
Vagus n. AD
Adrenaline is coming to bronchi mainly humoral AD AD
ß2-AR
Bronchodilatation
Bronchoconstriction M3
Epithelial Irritation Shedding

27. Enteric Nervous System
Large and highly organized system of neurons located in the walls of the gastrointestinal system
It is often considered a third division of the autonomic nervous system
Includes the myenteric plexus (of Auerbach) and the submucous plexus (of Meissner)

28. Enteric nervous system
Parasympathetic
Longitudinal muscle
Myenteric plexus
Circular muscle layer
Submucosal plexus
Walls constricted and sphincters relaxed via M3
Secretions increased via M3

29. Autonomic regulation of eye structures
Dominant tone = Parasympathetic
Iris radial – contracted via alpha-1
Iris circular – contracted via M3
Ciliary muscle – contracted via M3

30. Regulation of the liver
Sympathetic
Increase gluconeogenesis and glycogenolysis
Provide glucose to fuel “flight or fight” response
Primarily beta-2, possibly alpha-1

31. Control of stomach acid
Parasympathetic
Increase histamine release from ECL cell via M3
Increase H+ production from parietal cell in fundus via M3
Decrease somatostatin release from D cell in antrum
Increases gastrin release from G cell

32. Regulation of the bladder
Parasympathetic
Bladder wall
Constriction via M3
Relaxation via beta- 2
Sphincter
Relaxation via M3
Constriction via alpha-1

33. Lacrimal gland (tear production) – increased via M
Glandular secretion
Sweat
Salivary
Increased via M3
Appocrine – increased via alpha-1
Eccrine – increased via M
Lacrimal gland (tear production) – increased via M

34. PHYSIOLOGICAL EFFECTS OF ANS INNERVATION AND RECEPTORS THAT GOVERN SUCH EFFECT
PARASYMPATHETIC
SYMPATHETIC
Contracts the iris radial muscle via alpha-1
Relaxes the ciliary muscle via beta
Accelerates the sinoatrial node via beta-1,2
Accelerates ectopic pacemakers via beta-1,2
Increases cardiac contractility via beta-1,2
Relaxes bronchiolar smooth muscle via beta-2
Relaxes GI walls via alpha-2, beta-2
Contracts GI sphincters via alpha-1
Relaxes bladder wall via beta-2
Contracts bladder sphincter via alpha-1
Contracts uterus via alpha, relaxes uterus via beta-2
Contracts pilomotor smooth muscle via alpha
Activates sweat glands via alpha, M
Increases gluconeogenesis and glycogenolysis in liver via beta-2 and alpha
Induces lipolysis via beta-2
Increases renin release from kidney via beta-1
Semine ejaculation alpha-1
Contracts the ciliary muscle via M-3
Decelerates the sinoatrial node via M-2
Decreases heart contractility via M-2
Releases EDRF in the endothelium via M-3, M-5
Contracts bronchiolar smooth muscle via M-3
Contracts GI walls via M-3
Relaxes GI sphincters via M-3
Increases GI secretions via M-3
Contracts the uterus via M-3
Causes erection of the penis via M