1. CHOLINERGIC TRANSMISSION
A:- Precursor - Choline B :- Enzyme- Synthesizing - Choline Acetylase Degrading - Acetycholine Esterase (TRUE) - Butyrylcholine Esterase(PSEUDO) C :- 300,000 vesicles Quantum to 0.3 mv - 1mepp/sec

2. CHOLINERGIC TRANSMISSION (CONTD.)
RECEPTORS
N - Ligand gated ion channels Nn & Nm
M - Through G- protein signalling systems
M1 – Stomach Glands - Release of hist.
- Secretion of acid
M2 – (i) Myocardium
- ↓ generation of impulses –SA
- ↓ conduction of impulse – AV
- ↓ contractility –Atria & Ventricle

3. CHOLINERGIC TRANSMISSION (CONTD.)
(ii) Pre-synaptic
↓ Ach from cholinergic neurons
↓ NA Postgang. sym. Neurones
M3 - Smooth muscle – Contraction
- Exocrine glands – ↑ secretion
- Vascular Endothelium – ↑ NO secretion

4. CLASSIFICATION CHOLINE ESTERS - Acetylcholine - Methacholine
- Carbachol
- Bethanechol
- Cevimeline
NATURAL ALKALOID - Muscarine
- Pilocarpine
- Arecoline
- Nicotine

5. ANTI- CHOLINESTERASES
A) Reversible - Physostigmine
- Neostigmine
- Pyridostigmine
- Edrophonium
- Rivastigmine
- Donepezil

6. ANTI- CHOLINESTERASES(contd.)
B) Irreversible - Parathion (agricultural insecticides) - Malathion - Diazinon (Household) - Propoxur - Tabun - Sarin (Chemical warfare) - Soman

7. PHARMACOLOGICAL ACTIONS
CVS (M2)
a) Heart :-
↓ G/C /C in Myocardium (PR ↑ – AV)
b) Blood Vessel(M3)
Dilatation – ↓ BP → Reflex tachycardia
innervation is only on face to neck
2) Exocrine glands (M3)
Sweating > Salivation > Lacrimation = TBT
secretion >> Gastric secretion

8. PHARMACOLOGICAL ACTIONS(contd.)
3) Smooth Muscle a) G.I. – ↑ Tone & Peristalsis b) Urinary System – ↑ Tone , Voiding c) Bronchi – ↑ Tone (Bronchial Asthma) 4) Eye- Cont. of circular mus. of iris →Miosis. - Cont. of ciliary mus.→ thickening of lens

9. PHARMACOLOGICAL ACTIONS(contd.)
5) Skeletal muscles (NM)
Twitching & fasciculation
6) Autonomic ganglia(Nn)
Both Ad & Ch- unpredictable
7) CNS (M+N)
Rapid destruction + min. entry
→unpredictable response.
8) Stomach (M1) – ↑ acid+ Pepsin

10. USES OF CHOLINE ESTERS
1) Cardiac – PSVT – Methacholine 2) Intestinal – Paralytic ileus ,Megacolon (carbachol / bethanechol) 3) Urinary - Retention of urine (carbachol /bethanechol) 4) Lacrimal Secretion & Sialogogue – Cevimeline

11. CHOLINOMIMETIC ALKALOIDS
Pilocarpine :-
- As eye drops – Miosis
- Ch. simple glaucoma – Drops Vs. Ocusert
- To prevent and break adhesions between
iris / lens and iris / cornea
Muscarine, Arecoline and Nicotine

12. CHOLINESTERASE INHIBITORS
Reversible
Physostigmine (Eserine) :-
-Natural ,lipid soluble compound
-Rapidly absorbed and crosses BBB – CNS
effects
-Poisoning with Atropine , Phenothiazines &
Tricyclic Antidepressants

13. CHOLINESTERASE INHIBITORS(contd.)
Neostigmine –
-Synthetic, much less lipid soluble
-Does not cross BBB – No central effects
- ACh action on NMJ – Myasthenia gravis
- If intolerable M effects – Atropine
-Steroids – ↓ production of Nm antibodies
-Thymectomy
Also in paralytic ileus & bladder atony.

14. CHOLINESTERASE INHIBITORS (contd.)
Pyridostigmine - Less potent , Long duration
Edrophonium - Very short duration
- To identify between “Myasthenic” and “Cholinergic” crisis
Rivastigmine Newer agents, AD, Long acting,
Donepezil Well tolerated

15. b) Decurarisation after G.A c) Curare & other poisonings
OTHER USES :- a) Cobra bite –venom
b) Decurarisation after G.A
c) Curare & other poisonings
d) Edrophonium (PSVT)

16. ChE INHIBITORS – IRREVERSIBLE
High efficacy Toxicity (cross BBB)
High lipid soluble – Rapid absorption from all
routes
Poisoning occurrence - Accidental , suicidal, homicidal

17. Muscarinic Effects
- Inhalation / ingestion/ vapours (Eye)
Miosis , lacrimation
- ↑ secretion – Dehydration
- Fall in BP – Reflex Tachycardia
- ↑ dose –VMC at medulla (Bradycardia)
- ↑ contraction of smooth muscle
- Ataxia, convulsion , coma , death due to
Respiratory Failure

18. TREATMENT Change clothes. Wash skin , eyes. Gastric lavage.
Fresh air, Patent airway, PPR, Hydration
Maintenance of BP- vasopressor agent
CONVULSION – Diazepam i.v
Atropine
Enzyme Reactivator – Oximes
DAM, Pralidoxime, Obidoxime