The document discusses the nervous system, specifically focusing on the peripheral nervous system (PNS) and its divisions - the autonomic nervous system (ANS) and somatic nervous system. The ANS can be further divided into the sympathetic and parasympathetic nervous systems, which have opposing effects. The parasympathetic system uses acetylcholine as its main neurotransmitter and targets organs via muscarinic receptors to induce relaxation responses. Cholinergic drugs that act on muscarinic receptors are used to treat various conditions like glaucoma and myasthenia gravis.

1. Nervous system
Peripheral Nervous System
CNS
PNS

3. Peripheral nervous system

4. ANS
• Auto: Self; Nomos:Governing
involuntary and maintain
homeostasis
• Each autonomic fibres made
up of two neurons
• It innervates the heart,
smooth muscles and
endocrine glands
• ANS controls visceral
functions such as circulation,
digestion, excretion etc.,
Somatic nervous system
• Voluntary control
• Somatic fibres made up of
single motor neuron, connect
CNS to skeletal muscle
• It innervates skeletal muscle
• Controls skeletal muscle
tone
E

5. Divisions:-
–Sympathetic
–Parasympathetic

6. Arise from
Length of pre /
postganglionic fibres
Ganglion

7. Branching of axons
NT released by preganglionic axons
NT released by post ganglionic axons

8. Anger, Alert,
Aggressive
Flushing of Face
Bronchodilatation
Mydriasis
In. Cardiac output
Inc. Muscle tone
Lipolysis-Energy
Liver
Glucogenolysis
More energy prod
Large B vessels
dilate to speed
up blood flow

9. Anger, Alert,
Aggressive
Flushing of Face
Bronchodilatation
Mydriasis
In. Cardiac output
Inc. Muscle tone
Lipolysis-Energy
Liver
Glucogenolysis
More energy prod
Large B vessels
dilate to speed
up blood flow

10. Parasympathetic system
• ACh is a first neurotransmitter discovered
• It is synthesized from two common chemicals
Acetyl Co enzyme A and Choline.
• Cholinomimetics, mimic the action of Ach
c/s parasympathomimetics”
• External Ach is no therapeutic value due to its ultra
short acting.
• Hypothalamus is major controlling centre
• It is metabolized by Acetylcholine esterase.

11. Parasympathetic

12. Ach release

13. Ach release

14. • Hemicholinium: It acts by blocking choline
uptake.
• Vesamicol: It acts by inhibiting active transport
of ACh into synaptic vesicle by interfering with
VAT
• Botulinum toxin : It acts by inhibiting release of
ACh from synaptic vesicle.
• Black widow spider: It acts by inducing
massive release and causes depletion of ACh.

15. Metabolism:- In synaptic cleft, Ach is rapidly hydrolyzed by
acetyl cholinesterase (AChE) enzyme
Two type of cholinesterases.
True And Pseudo cholinesterase
True cholinesterase:
• Found in cholinergic neurons, ganglia, RBCs and NMJ.
• Highly specific for Ach, other acetylesters (methacholine
and bethanechol)

16. Pseudo cholinesterase/ butyrylcholinesterase /
Plasma choline esterase :
• Synthesized in liver
• found in plasma and intestine .
• Actions are non specific
• It hydrolyzed Ach, benzoylcholine and butyrylcholine esters
• Genetically variation
• atypicalcholine esterase slowly hydrolyzesis
• Typical choline (Fast acetylates)

18. N receptors
• The cholinergic receptors are divided into
Nicotinic and Muscarinic.
• Nicotinic receptors located
– NMJ and Autonomic ganglia
– brain (located presynaptically)  facilitator role in
release of other NT like DA and Glutamate.
• N receptor subtypes are muscle type (NM),
neuronal type (NN) and central nicotinic
receptors.

19. Nicotinic receptors
NM NN Central N
Location Skeletal NMJ
post synaptic
All autonamic
ganglia and
adrenal medulla
Sensory nerve
terminals
presynaptically
Function Contraction
of Sk. muscle
NE & E from
adrenal medulla
Facilitate
release of
Dopamine,
glutamate
Mechanism Ligand gated
channel
Ligand gated
channel

20. • N receptors are inotropic receptors
• Quaternary structure indicate five sub
units (two alpha, beta, delta and gamma)
• Ach binding sites between α and γ subunit,
and α and δ subunit

21. Mechanism of action
• Ach interacts with nicotinic Ach receptor, it
opens Na+ channel and Na+ ions flow into
the membrane
• Causes a depolarization, and result in
EPP.
• It cause excitatory on skeletal muscle.
Response is fast and short lived.

22. Muscarinic
• Parasympathetic neuro effector junction of all smooth muscle
and glands.
• M receptors are linked to G-protein (metabotrophic)
• Responses are slower and longer lived
• Serpantain receptor(7phosphtidil )

23. Types of M receptors
• 5 types of “M” receptors
• M1,M3,M5 (Odd) are excitatory effect through
IP3,DAG.
• M2,M4 are inhibitory effect cAMP and opening of
K+ channels.
• M1,M2,M3 are well characterized. M
1 3
2

24. Mechanism -M1,3,5

25. Mechanism –M2,4

26. M1 (Neuronal
and gastric)
M2 (Cardiac) M3(Glandular) M4 M5
Distrib
ution
Ganglia,
Gastric (parietal) ,
CNS (cortex,
hippocampus)
Myocardium,
presynaptic CNS
Glands
GIT smooth muscle
Bladder
Bronchus
CNS
Neostriatum Substanti
a nigra
Functi
on
Gastric acid
secretion, GI
motility, CNS
excitation
SA node rate of
impulse generation
AV node velocity
and decrease atrial
and ventricular
contraction
Exocrine
secretions.
Smooth muscle
contraction
(expect urinary,
Blood vessels
- -
Mech G protein (Gq),
IP3,DAG,depolari
zation
Gi cAmp, opening
of K+ channels
G protein (Gq),
IP3,DAG,depolari
zation
Gi cAmp,
opening of
K+ channels
G (Gq),
IP3,DAG,
depolariz

27. • Ach is more effective with “M” receptors.
• “N” receptor activation require larger
doses.
• At high dose it acts on “N” receptors cause
release of NE & Epinephrine from adrenal
medulla.
M N

28. Ach- contraction circular
muscle of iris- Miosis . (M3)
Contraction of ciliary muscle (M3)
- suspensory ligaments loose-
eye accommodated for near
vision
Miosis
Accommodated for near vision
Inc. drainage
Lacrimal gland (M3) inc. secretion
LENS
Ciliary
muscle
Circular
muscle
Radial
muscle

29. • Parasympathetic supply only up to
SA node, atria and AV node.
• Ventricular myocardium has M receptors
but no innervation.
• SA node M2 receptors activation:
– heart rate (-ve chronotrophic)
– contractile strength(-ve inotrophic)
• AV node M2 activation:
conduction velocity and
refractory period

30. RP RP

31. • Bronchial smooth muscle
mucous gland contain
M3 receptors
Bronchoconstriction
Inc. bronchial secretions

32. Gastric parietal cells M1- Acid secretion
GIT smooth muscle, gastric gland – M3
• Sphincters – Relaxation
• Glands – secretions
Pancreas – Acini cells M3 secretion of
pancreatic juice.

33. Detrusor muscle (M3)- Contraction
Relaxation of sphincter .
Emptying of urinary bladder.
Vascular bed of erectile tissue is
dilated,
venous sphincters closed.
Erection of penis.

34. • Arteries have no parasympathetic, but M
receptors.
• Release EDRF, cause vasodilatation.
• Exogenous Ach cause fall in BP, it evoke
baroreceptor reflex, result sympathetic
discharge at heart.
• Bardycardia initial, after followed by
tachycardia.

35. CENTRAL NERVOUS SYSTEM
Brain
PARASYMPATHETIC
Spinal
cord
Stimulates salivation VII
Constricts bronchi X
Slows heartbeat X
Stimulates activity
Contracts bladder
Stimulates erection
of sex organs S
Stimulates gallbladder
Gallbladder
Contracts pupil III

36. Parasympathomimetics
Directly acting Indirectly acting
1. Ach
2. Synthetic choline esters Reversible Irreversible
Methacholine Carbamates
Carbachol 1. Natural alkaloids 1. Organophosphates
Bethanechol
3. Natural alkaloids 2. Quaternary
4.Miscellaneous 2. Carbamates
Acridine
Tacrine
• Edrophonium
• Neostigmine
• Pyridostigmine
• Ambenonium
• Demecarium
• Rivastigmine • Popoxour
• Carbaryl
• Tremorine
• Oxotremorine
• Muscarine
• Nicotine
• Pilocarpine
• Arecoline
• Physostigmine • Ecothophate
• Isoflurophate
• Paraoxon
• Parathion
• Malathion
• Diazon

37. Methacholine:- Seldom used therapeutically
Use to supra ventricular tachycardia but now not
using better drugs available.
Muscarinic Mycocardium (3Ms)
Bethanechol:- (Urocholine) resistant to
True/Pseudocholinestrase , t½ long (M action)
• Uses:-
i) To reverse post operative atony of baldder
ii) To treat GIT atony, inc motility, tone
iii) to treat salivary gland malfunction
iv) intra cerebroventricular inj beneficial effect in
Alzheimer's disease

38. Carbachol:
– Totally resistances to true/Pseudo chE
– N and M action
– Avoided therapeutic use bcoz of Large nicotinic action
Precautions : for all cholinesters
– Never give IV
• Sudden rise  cardiac collapse
CI:
– Bronchial asthma
– Peptic ulcers
– MI
– Hyperthyrodism

39. Pilocarpine (natural)
• Obtained from the leaves of Pilocrapus
microphyllus.
• Tertiary amine cross BBB
• Prominent Muscarinic action.
• Increases all the secretions .
• Have complex effect on CVS, small doses
decreases BP but larger doses have opposite
action. (Ganglionic stimulation NN stimulation)

40. • Penetrates cornea
• Promptly causes miosis
• Ciliary muscle contracts and IOP reduces.
• Uses:
 0.5 - 4% eye drops for open angle glaucoma.
 To counteract mydriatics after refraction testing.
 To prevent or break adhesions of iris with lens
• A/E: stinging sensations, painful spasms of
accomodation.

41. • Muscarine :source Amantia muscaria
Not used therapeutically
• Arecoiline: Found in Beetel nuts Areca
catechu
Muscrinic as well as nicotinic action
Not used therapeutically

42. Side effects:- result of over stimulation
of the parasympathetic system .
• Cardiovascular:
– Bradycardia, hypotension, conduction
abnormalities (AV block and cardiac arrest)
• CNS:
– Headache, dizziness, convulsions
• Gastrointestinal:
– Abdominal cramps, increased secretions,
nausea, vomiting

43. • Respiratory:
– Increased bronchial secretions,
bronchospasms
Other:
– Lacrimation, sweating, salivation, loss of
binocular accommodation, miosis

44. Physostigmine
Physostigma venenosum

45. Physostigmine and Neostigmine
Physostigmine Neostigmine
Source Natural alkaloid Synthetic
Chemistry Tertiary amine Quaternary amine
CNS action Present Absent
Oral absorption Good Poor
Applied to eye Cross cornea No
Action on cholino receptors Absent Present
Prominent effect on Autonomic effectors Skeletal muscles (Post
operative decurization)
Post operative paralytic ileus /
urinary retention (1mg SC)
Use Glaucoma Myasthenia gravis

46. Belladona (Atropine) poison
• Physostigimine specific antidote for
atropine
• It cross BBB dec central action and
peripheral action
• Poison :- 0.5- 1mg IM dose.
• 2mg IV/IM initially and additional dose if
required

47. Rivastigmine & Tacrine
• Lipophilic
• Cross BBB
• Cerebroselective ChE
• Used for Alzheimer’s Disease

48. Myasthenia gravis
• Autoimmuno disorder
• Occurs 1 in 10,000
• It is associated with production of IgG
antibody that binds to Ach receptors at
post junctional motor end plate
• Fast moving muscles are affected first

49. Symptoms
–Ptosis
–Diplopia
–Slurring of speech
–Difficulty in swallowing
Diagnosis
Edrophonium test: 1-2mg IV
Very shorting anti ChE (5min)
Improve –Myasthenia crisis
Worsen - Cholinergic crisis

51. R Myasthenia gravis
Tab. Neostigmine 15mg – 6hrly
Or
Tab. Pyridostigmine 60mg – 8hrly
Tab. Prednisolone 20mg 1tab 8hrly
Tab. Atropine 0.5mg OD
Plasmapheresis-removal antibodies
Glucocorticoids (Prednosolone 10mg /OD)
Immunosuppresants (Azathioprine 2.5mg/kg/OD)
Thymectomy-Produce antibodies

52. Glaucoma
• Glaucoma is an increased intraocular
pressure. (>21mm/Hg)
• If persistent it leads to optic nerve damage
result in blindness.
• Glaucoma is caused
• drainage
• aqueous humor production

53. LENS

54. Primary glaucoma is subdivided to 2 types
1. Narrow angle
2. Open angle

55. • Narrow angle (Closed angle, Acute congestive)
• Iris physically blocking canal of Schlemm
• It is medical emergency, drugs may control acute
attack but long term surgical (partial iridectomy)

56. • Wide angle (Open angle, Chronic simple):-
• Angle is remain wide but trabecular
meshwork losses patency due to
degeneration.
• So outflow of aqueous humor is impeded.
• surgery is not useful.

57. Cholinomimetics decrease the IOP in both types.
In closed angle:- Pulling the Iris, opening of angle
In open angle : contraction of longitudinal Ciliary
muscle  inc. drainage

59. Group Mech Dose
Directly acting
Cholinomimetics
Pilocarpine
Ciliary muscle contraction,
opening of trabecular
meshwork, Inc drainage
0.5 - 4% topical 3times a day
or ocular inserts
Reversible Anti AChE
Physostigmine
Demecuronium
Same 0.25 - 5% topical 2 a day
0.25 - 5% topical 2 a week
Irreversible
Ecothiophate
Only one drug used clinically
Same 0.05 - 0.25% once in 2weeks
0.03% topically
Beta blockers (DOC for Open)
Timolol
Betaxolol
Levobunolol
Carteolol
Dec. aqueous humor by
blocking β2 present in
ciliary epithelium
0.25% - 0.5% topical 2 a day
0.25% - 0.5% topical 2 a day
0.25% - 0.5% topical 1 a day
1% solution topically
Non seletive α agonist
Epinephrine
Dipivefrine
α1 Blood
α 2 Aqueous secretion 0.5 - 2% topically
0.1%opically 2 or 3 a day
Seletive α2 agonist
Apraclonidine
Brimonidine
Dec formation by α2 agonist
Potent ocular hypotensive
≠ BBB no systemic side
effects
0.5 -1% topically
0.5 -1% topically
Restricted use for acute IOP

60. Group Mech Dose
Carbonic anhydrase
inhibitors
Acetazolamide
Dorzolamide
Reduce aqueous humor by
dec. formation of HCO3 ions in
ciliary epithelium
250 – 500mg 3 a day orally
2% soln. 3 a day
Hypertonic solutions ©
Manitol (20%)
Glycerol (10%)
Reduce IOP  intaocular
dehydration by osmatic action
IV Infusion
Prostaglandins (O)
Latanopost
Facilitate outflow via
uveoscleral
Acute
glaucoma
Pilocarpine nitrate 4%
eye drops with
physostigmine
salicylate1%
Install 2drops every
10min initially then
longer intervals 2Hrs
+ Inj. Manitol 20%
100ml slow IV +
Acetazolamide
500mg orally
1tab 2 a day

61. Advantage of β Blockers
• No cahnge in pupil size
• No myopia
• No head ache/brow pain due to persistent
spasmof iris
• No fluctuations in iot (occurs with pilocarpine)
• Convenient twice/once daily
Open
angle B-blockers
Alpha-
Blcokrs
PG
Latanoprost
CAI
Acetazolami
de

62. Organophosphates
INSECTICIDES
• Echothiophate
• Isoflurophate
• Parathion, Malathion
CHEMICAL WEAPONS
Chemical warfare agents-nerve gases
• Tabun
• Serin
• Soman

63. Mechanism of Action
Phosphorylating the active
Site
Covalent modification
Duration: days
Irreversible action
By the loss of one of the
alkyl group the
phosporylated enzyme may
become resistant to
hydrolysis thus causing
irreversibility.

64. Uses of AChE
Ecothiophate
• Quaternary compound
• Water soluble
• Don’t cross BBB
• Used as miotic and management of
glaucoma (Ophthalmic solution 0.05- 0.25%)
• Potent and longer acting
• No local irritation
Isofluorophosphate :
• oil in character cause local irritation

65. Effects
• Cardiovascular:
Bradycardia, hypotension
• Gastrointestinal:
Nausea, vomiting, diarrhea
• Urinary tract:
Incontinence, urinary urgency
• Glands:
Salivation, lacrimation, sweating
• Eye:
Miosis, blurred vision
• Respiratory
bronchoconstriction, bronchial secretion

66. Toxicity of AChE Inhibitors
2. Skeletal Muscle: Fasciculations, weakness, paralysis
3. CNS: Ataxia, confusion, convulsions, coma, paralysis
4. Death:
Respiratory depression due to bronchoconstriction, increased
secretions, paralysis of diaphragm and intercostals muscles and
central respiratory depression

67. Treatment of AChE Poisoning
Atropine
Reverses muscarinic but not nicotinic
AchE reactivating drugs
Pralidoxime (Pyrindine 2-Aldoxime Methylcholride 2-PAM):

68. HON=CH
H20
N=CH
Oxime
Oxime Phosphonate complex

69. General supportive
Removal of clothes, washing of contaminated skin,
gastric lavage , artificial respiration,
If convulsions  Diazeepam
Pradlidoxime 1-2g Slow IV infusion over 15-
30min to reactive and regeneration of AChE
2 mg IV repeated every 10 mins till signs of full
atropinization
i.e. dilatation of pupils, tachycardia
R Organo Phosphorus poison
Diacetylmonoxime cross BBB

70. Thank Q

72. N M
Choline + Acetate
Pyu
PDH
Ac Co A
Ach by exocytosis
Hemicholine
-
AChE
PDH: Pyruvate dehyrogenase
AChE: Acetylcholine esterase

73. PNS
• Consists of bundles of sensory and motor
neurons
• It relaying information between the central
nervous system and muscles or sensory
organs.