A ppt Presentation on Cholinergic system aka Parasympathetic system and Cholinomimetic Drugs and Anticholinesterases.

1. CHOLINERGIC SYSTEM
DR. PAWAN KUMAR B

2. OVERVIEW OF NERVOUS
SYSTEM

3. Sympathetic Nervous System
- Adrenaline Rush
- Autonomic nervous system
response to fear, anger, stress

4. Parasympathetic Nervous System
- Rest and Digest
- Relax, Repair, Renew

5. Sympathetic Parasympathetic
Agonist
Antagonist

6. AUTONOMIC NS:
• CARRY MESSAGES FROM THE CNS TO SMOOTH
MUSCLE, CARDIAC MUSCLE AND ADRENAL MEDULLA.
• TWO SUBSYSTEMS:
1. PARASYMPATHETIC NERVES:
• FROM CNS TO SMOOTH MUSCLES.
• ACETYLCHOLINE IS THE N.T.
2. SYMPATHETIC NERVES:
• TO THE CARDIAC MUSCLES AND MOST OF INTERNAL ORGANS.
• USING NORADRENALIN AND ACETYLCHOLINE AS N.T

9. PARASYMPATHETIC
RESPONSES

10. ACH PRODUCTION

12. .
Subtypes of M
receptors
M1
Neural
M2
Cardiac
M3
Glandular, Smooth
muscles
M4
CNS
M5
CNS
Main location CNS, Gastric & Salivary
glands
Heart , GIT, CNS Gastric & salivary glands,
GIT, Eye
CNS CNS
Cellular response Increase IP3, DAG,
Depolarization, excitation,
increase potassium
conductance
Decrease in
a) cAMP inhibition,
b) Ca++ conductance,
Increase K+
conductance
Increase IP3, Ca++
conductance,
As M2 As M3
Functional
responses
CNS excitation, gastric
secretion
Cardiac inhibition,
neural inhibition
Gastric & saliva secretion, GI
smooth muscle contraction,
ocular accommodation
Enhanced
locomotion
Not
known

13. CHOLINOMIMETICS /
CHOLINERGIC /
PARASYMPATHOMIMETIC
• DIRECT ACTING - ACT ON THE RECEPTORS TO ACTIVATE A
TISSUE RESPONSE
• INDIRECT ACTING - INHIBIT THE ACTION OF THE ENZYME
ACETYLCHOLINESTERASE:
• MAJOR USES = STIMULATE BLADDER & GI TONE, CONSTRICT
PUPILS (MIOSIS), NEURO-MUSCULAR TRANSMISSION

19. DRUG EFFECTS OF CHOLINERGIC
AGENTS
“SLUDGE”
• Salivation
• Lacrimation
• Urinary incontinence
• Diarrhea
• Gastrointestinal cramps
• Emesis

20. CHOLINE ESTERS
• Uses: Rarelyused(evanescentand
nonselectiveaction)
•Bethanechol:MORE SELECTIVE
ON MUSCARINIC RECEPTOR.
•non-obstructiveurinaryretention,
neurogenicbladder,Paralyticileus
Sideeffects:
belching,colic
involuntary
urination/defecation
flushing,sweating
fallinBP
bronchospasm

21. CHOLINOMIMETIC ALKALOIDS
PILOCARPINE
source: pilocarpus microphyllus
• prominent muscarinic actions; ganglionic action via M1 receptors •
CVS effects: • small dose – fall in BP (muscarinic, ?M2)
• higher dose – rise in BP and tachycardia (ganglion mediated; M1)
•
Eyes: • local application – penetrates cornea, miosis, ciliary muscle
contraction,
fall in intraocular tension (M3)
• use: as miotics (counteract mydriatics used for refraction, along with
mydriatics to prevent/break adhesions), in open angle glaucoma,

22. • Arecholine – from betel nut areca • muscarinic as
well as nicotinic actions • no therapeutic use
• Muscarine •source: mushrooms amanita
muscaria, inocybe sps. •Only muscarinic
actions
• Not used therapeutically, has toxicological
importance cholinomimetic alkaloids

24. INDIRECTLY ACTING
CHOLINERGIC /
ANTICHOLINESTERASES
• Inhibit enzyme cholinesterases

26. PHYSOSTGMINE:
• Alkaloid found in plants, physiostigma venenosum
• Reversible inhibitor of acetylcholinesterase and
potentiate cholinergic activity through out the body.
• Its duration of action is 2-4 hours, it can enter and
stimulate CNS.• CLINICAL USES:
1. BLADDER AND INTESTINAL ATONY (INCREASE THEIR
MOTILITY).
2.GLAUCOMA ( DECREASE INTRAOCULAR PRESSUE).
3.OVERDOSE OF ANTICHOLINERGIC DRUGS LIKE ATROPINE,
PHENOTHIAZINES, AND TRICYCLIC ANTIDEPRESSANTS.

27. SIDE
EFFECTS:
1.CONVULSION AT HIGH DOSES.
2. BRADYCARDIA.
3. SKELETAL MUSCLE PARALYSIS DUE TO INHIBITION OF
ACETYLCHOLINESTERASE AT NEUROMUSCULAR JUNCTION
AND ACH ACCUMULATION

28. NEOSTIGMINE:
Synthetic compound reversibly inhibits acetylcholinesterase,
Does not enter CNS , greater effect on skeletal muscle that can increase
contractility then paralysis.
Uses:
1.Stimulate atonic bladder and intestine.
2.Antidote for neuromuscular blocking agents like tubocurarine.
3.Symptomatic treatment in myasthenia gravis.
Side effects:
salivation, flushing, hypotension, nausea, abdominal pain, diarrhea, and
bronchospasm.

29. • PYRIDOSTIGMINE:
USED IN CHRONIC TREATMENT OF MYASTHENIA GRAVIS, ITS
DURATION OF ACTION 3-6 HOURS.
•
EDROPHONIUM:
HAS SHORT DURATION OF ACTION (10-20 MINUTES) USED IN
DIAGNOSIS OF MYASTHENIA GRAVIS (I.V INJECTION OF
EDROPHONIUM LEAD TO RAPID INCREASE IN MUSCLE
STRENGTH).

30. IRREVERSIBLE
ANTICHOLINESTERASE
• Synthetic organophosphorus compounds bind
acetylcholinesterase covalently and inhibit it irreversibly, so
there will be increase in ACH at all the sites of its release.
• These drugs are extremely toxic and used in military as
nerve agents (soman, sarin, VX), some agents like
parathion and malathion used as insecticides.

32. ORGANOPHOSPHOR
US POISONING
• Acute intoxication must be recognized
and treated promptly .
The dominant initial signs are those of
muscarinic excess
• Central nervous system involvement
(cognitive disturbances, convulsions,
and coma) usually follows rapidly,
accompanied by peripheral nicotinic
effects.

33. OP POISONING
Treatment:
1. Maintenance of vital signs - respiration in particular may be
impaired
2. Decontamination to prevent further absorption—this may
require removal of all clothing and washing of the skin in cases
of exposure to dusts and sprays
3. Atropine parenterally in large doses, given as often as
required to control signs of muscarinic excess.
Therapy often also includes treatment with pralidoxime and
administration of benzodiazepines for seizures.

34. • CHOLINERGIC
• CHOLINOMIMETIC
• PARASYMPATHOMIMETIC
• INDIRECT ACTING CHOLINOMIMETIC
• ANTICHOLINESTERASE (REVERSIBLE / REVERSIBLE)
• ACETYLCHOLINESTARE
• ANTICHOLINERGICS

35. •TobecontinuedwithAnticholinergics.
•Reviseandcome(P.S.–Justincaseyouneed
attendancefortomorrow’sclass.)
Pheww…!! That will be all for today