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. It provides details on the ANS, including its sympathetic and parasympathetic divisions. The parasympathetic system uses acetylcholine as its neurotransmitter which acts on nicotinic and muscarinic receptors. Cholinergic drugs that act as parasympathomimetics are used to treat various conditions like glaucoma. Pilocarpine is commonly used as a parasympathomimetic eye drop to reduce intraocular pressure in glaucoma by contracting the ciliary muscle and increasing drainage of aqueous humor through the trabecular

1. Nervous system
Peripheral Nervous System
CNS
PNS

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

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. ANS
• Afferent (Sensory) Sensory organs to CNS
• Efferent (Motor) CNS to effector cells.
• Motor responses are auto regulatory in nature.
Regulates unconscious body functions such as:
– All exocrine and some endocrine secretions
– heart rate
– Blood pressure
– Some metabolic functions

6. Divisions:-
–Sympathetic
–Parasympathetic

7. Arise from
Length of pre /
postganglionic fibres
Ganglion

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

9. Sympathetic Para sympathetic
Arise from thoracolumbar division
T1 –L2
craniosacral division
III,VII,IX,X, S2-S4 of spinal
Length of postganglionic
fibres
long postganglionic fibres short postganglionic fibres
Ganglion Away from effector organ Near or on effector organ
Pre ganglion fibres Myelinated Myelinated
Post ganglion fibres NonMyelinated Myelinated – Ciliary muscle
Non myelinated to other
Neurotransmitter released by
preganglionic axons
cholinergic Cholinergic
Neurotransmitter released by
post ganglionic axons
adrenergic cholinergic
Branching of axons highly branched
Influences many organs
few branches Localized
effect

10. 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

11. Parasympathetic system
• ACh is a first neurotransmitter to be discovered
• It a main NT at the neuromuscular junction
• It is synthesized from two common chemicals
Acetyl Co enzyme A and Choline.
• It is metabolized by Acetylcholine esterase.

12. • Cholinomimetics, mimic the action of Ach
c/s parasympathomimetics”
• All parasympathetic fibres release Ach.
• External Ach is no therapeutic value due to its ultra
short acting.
• Hypothalamus is major controlling centre

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

14. 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)

15. 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)

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

17. 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

18. • 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

19. 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.

20. Muscarinic
• Parasympathetic neuroeffector junction of all smooth muscle
and glands.
• M receptors are linked to G-protein (metabotrophic)
• Responses are slower and longer lived
• More sterospecific and structure specific then „N‟

21. 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.

22. M1 (Neuronal
and gastric)
M2 (Cardiac) M3(Glandular) M4 M5
Distrib
ution
Ganglia, gastric
parietal cells,
CNS (cortex,
hippocampus)
Myocardium,
smooth muscle,
presynaptic
PNS,CNS
Exocrine glands,
visceral smooth
muscle, vascular
endothelium
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
Agoni
st
Oxotremorine Methacholine Bethanechol
- -
Anta
gonist
Pirenzepine,
Telenzepine
Methoctramine,Tripi
tramine
4-DAMP, Hexa
hydrosiladifenidol

23. • 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

24. 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

25. • Parasympathetic supply only upto
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

26. RP RP

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

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

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

30. • 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.

31. 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

32. 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

33. • 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
• Uses:-
i) To reverse post operative atony of baldder
ii) To treat GIT atony
iii) to treat salivary gland malfunction
iv) intra cerebroventricular inj beneficial effect in
Alzheimer's disease

34. 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

35. 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)

36. • 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.

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

38. 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

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

40. Physostigmine
Physostigma venenosum

41. 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

42. Belladona (Atropine) poision
• 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

43. Rivastigmine & Tacrine
• Lipophilic
• Cross BBB
• Cerebroselective ChE
• Used for Alzheimer‟s Disease

44. Glaucoma
• Glaucoma is an increased intraocular
pressure.
• If persistent it leads to optic nerve damage
result in blindness.
• Glaucoma is caused by impaired drainage
or inc. aqueous humor.

45. • Out flow of aqueous humor:
Produced by ciliary epithelium Posterior chamber
Flow to anterior chamber by passing betn lens and iris
Out through pupil
Leaves anterior chamber by flowing through
trabecu-lar- mesh work
Drainage through canal of Schlemm
Episcleral venous plexus
Systemic circulation

46. LENS

47. 3 Types of glaucoma
1.Primary (after trauma)
2.secondary (followed by cataract operation)
3.congenital.(By birth)
-Primary / secondary glaucoma Physostigmine in
combination with pilocarpine used.
-Congenital glaucoma hardly respond to drug
therapy, except surgery.
Primary glaucoma is subdivided to 2 types
1. Narrow angle
2. Open angle

48. • 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)

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

50. 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

52. 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

53. 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

54. 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

55. 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

57. R Myasthenia gravis
Tab. Neostigmine 15mg – 6hrly
Or
Tab. Pyridostigmine 60mg – 8hrly
Tab. Prednisolone 20mg 1tab 8hrly
Tab. Atropine 0.5mg OD(to dec M action)
Plasmapheresis-removal antibodies
Thymectomy-Produce antibodies

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

59. Mechanism of Action
Phosphorylating the active
Site of serine.
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.

60. 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

61. 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

62. 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

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

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

65. 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

66. Thank Q