ANS, CHOLINERGIC AGONIST /PARASYMPATHOMIMETICS/ CHOLINERGIC DRUGS As per the PCI syllabus

1. AUTONOMIC NERVOUS SYSTEM

2. AUTONOMIC NERVOUS SYSTEM
“ANS FUNCTIONS BELOW THE LEVEL OF
CONSCIOUSNESS AND CONTROLS VISCERAL
FUCTIONS”
The ANS is majority divided into two types
PARASYMPATHETIC NERVOUS SYSTEM
&
SYMPATHETIC NERVOUS SYSTEM

3. PARASYMPATHETIC NERVOUS SYSTEM
also known as Cholinergic Nervous System.

4. CHOLINERGIC RECEPTORS:
There are 2 types of receptors.
MUSCARINIC RECEPTORS & NICOTINIC RECEPTORS
MUSCARINIC RECEPTORS:
They are belonging to G-PROTEIN COUPLED RECEPTORS
Stimulated by: Acetylcholine, Muscarine
Inhibited (blocked)) by: Atropine
SUBTYPES:
There are 5 subtypes are present in the muscarinic
receptors
M1, M2, M3, M4, M5,
M1, M2, M3 - are major subtypes present on effector
cells and pre junctional nerve endings.
M4 & M5- Present mainly on nerve endings in certain
areas of brain and regulate the release of
neurotransmitters.

6. M1- (Muscarinic-1) RECEPTORS:
Present in:
AUTONOMIC GANGLIA,
GASTRIC GLANDS,
CNS - Cortex, Hippocampus & Corpus Striatum
Transducer Mechanism:
IP3 / DAG, PLA2↑
Role / functions:
Mediating gastric acid secretion.
Relaxation of lower esophageal sphincter,
In learning, memory &
Motor functions.

8. M2 (Muscarinic-2) RECEPTORS:
Present in:
Heart,
Cholinergic nerve endings,
Visceral smooth muscle
Transducer mechanism:
K+ Channel Opening, ↓cAMP
Role / functions:
Mediate bradycardia
Visceral smooth muscle contraction.

10. M3 (Muscarinic-2) RECEPTORS:
Present in:
Visceral smooth muscles,
Iris,
Exocrine glands
Vascular endothelium.
Transducer Mechanisms:
IP3 / DAG↑, PLA2↑
Role / functions:
Visceral smooth muscle contraction
Glandular secretion
Vasodilatation by NO release
Constriction of pupils

11. NICOTINIC RECEPTORS
They belongs to the ION CHANNEL RECEPTORS
Activated by - Ach, Nicotine
Blocked by - Tubocurarine
SUBTYPES:
There are two subtypes of nicotinic receptors
NM RECEPTOR & NN RECEPTOR.

12. NM RECEPTOR:
Present in:
• Skeletal muscles endplate
Transducer mechanism:
• Opening of Na+, K+ channels.
Role / functions:
• Skeletal muscle contraction.

13. NN RECEPTOR:
Present in:
• Ganglionic cells,
• Adrenal medullary cells
• Spinal cord
• Some areas of brain.
Transducer mechanism:
• Opening of Na+, K+, Ca2+ channels.
Role / functions:
• Catecholamine release & CNS - excitation /
inhibition.

14. CHOLINERGIC DRUGS
(PARASYMPATHOMIMETIC, CHOLINERGIC DRUGS)
• These drugs produce the action similar to that of ACETYLCHOLINE.
• The act either by directly interacting with cholinergic receptors or
by increasing availability of acetylcholine at these sites.
CHOLINERGIC AGONISTS:
CHOLINE ESTERS:
• ACETYLCHOLINE
• METHACHOLINE
• CARBACHOL
• BETHANECHOL
ALKALOIDS:
• MUSCARINE
• PILOCARPINE
• ARECOLINE

15. ACETYL CHOLINE:
• It is a Quaternary Ammonium Compound which cannot
penetrate membranes.
• It is a neurotransmitter of parasympathetic and somatic
nerves also in autonomic ganglia.
• Acetylcholine has both Muscarinic & Nicotinic Activity.
PHARMACOLOGICAL ACTIONS:
HEART:
ACETYLCHOLINE
↓
HYPERPOLARIZES – SA NODAL CELLS AND DECREASE THE
RATE OF DIASTOLIC DEPOLARISATION
↓
RATE OF IMPULSE GENERATION IS REDUCED
↓
BRADYCARDIA / CARDIAC ARREST

16. BLOOD VESSELS:
• M3 receptors present on vascular endothelial
cells, Vasodilatation due to NO release.
• All the blood vessels are dilated
• Fall In BP & Flushing
• Causes Erection in penis
SMOOTH MUSCLES:
• Contraction (due to M3 receptors)
• Increase in peristalsis in GIT
• Sphincters Relax – Abnominal Cramp &
Evacuation of Bowel
• Bronchial muscle – Constriction – dyspnoea,
precipitation of asthmatic attack.

17. GLANDS:
• Secretions of all glands are increased, Via M2 &
M3 receptors.
• Eg: Sweating, Salivation, Lacrimation, Tracheo
Bronchial & Gastric Secretions
EYE:
• Contractions of circular muscle of iris - Miosis
SKELETAL MUSCLE:
• Application of Ach to muscle end plate cause –
Contraction of muscle Fibre (Due to NM receptor)
CNS:
• IV injection → does not cross BBB → No central
effect
• Direct Injection → Stimulation followed by
Depression.

18. CHOLINOMIMETIC ALKALOIDS:
• Eg. PILOCARPINE, MUSCARINE, ARECOLINE
PILOCARPINE:
• It is obtained from the natural sources.
• It is less potent, which penetrates the CNS at therapeutic
doses.
• Pilocarpine exhibits Muscarinic Activity.
• This is primarily used in Ophthamology.
ACTIONS:
• Increase Sweating, Salivation & Secretion
• Smaller dose → Fall in BP
• Higher dose → Increase in BP & Tachycardia.
• Applied topically to the Cornea - produces a rapid miosis
& spasm of accommodation vision is fixed at a particular
distance.

19. USE IN GLAUCOMA:
• It is the drug of choice in the emergency
lowering of intraocular pressure of both narrow
angle & wide angle glaucoma.
• This causes an immediate drop in intraocular
pressure As a result of the increased drainage of
aqueous humor.
MUSCARINE:
• Present in poisonous mushrooms.
• Currently it is not used therapeutically.

20. ANTI CHOLINESTERASE

21. • Acetylcholinesterase is an enzyme that specifically cleaves
ACETYLCHOLINE → ACETATE + CHOLINE
• There by Acetylcholinesterase terminates the actions of
acetylcholine.
ANTI CHOLINESTERASE
↓
INHIBITS ACETYLCHOLINESTERASE
↓
PROLONGING THE LIFE TIME OF ACETYLCHOLINE AT THE
CHOLINERGIC NERVE ENDING
↓
ACCUMULATION OF ACH AT THE SYNAPTIC SPACE
↓
INCREASE IN ACTIVITY

22. CLASSIFICATION:
REVESIBLE INHIBITORS OF ACETYLCHOLINESTERASE:
• PHYSOSTIGMINE,
• NEOSTIGMINE,
• PYRIDOSTIGMINE
• RIVASTIGMINE,
• GALANTAMINE,
• DONEPEZIL.
IRREVESIBLE INHIBITORS OF ACETYLCHOLINESTERASE:
• PARATHION,
• MALATHION,
• DIAZONIUM,
• DYFLOS.

23. PHYSOSTIGMINE:
• It is found naturally in plants.
• It is a substrate for acetylcholinesterase.
• It forms a relatively stable carbamoylated
intermediate with the enzyme & become
reversibly inactivated.
• Only Tacrine , Rivastigmine , Donepezil &
Galantamine have been approved for clinical
used.

24. PHARMACOLOGICAL ACTIONS
ACTIONS OF CHOLINOMIMETRIC AGENTS=ACTIONS
OF ANTICHOLINE ESTERASE.
• Lipid soluble agents like Physotigmine &
Parathione have more marked Muscarinic & CNS
effects.
• Lipid insoluble agents like Neostigmine
&Quaternary ammonium compounds have more
marked effects on skeletal muscles.
CVS:
• Muscarinic action – Bradycardia & Hypotension.
• Ganglionic stimulant-Increase in the heart rate &
BP

25. USES:
• MIOTIC,
• used in Glaucoma.
• MYASTHENIA GRAVIS (Autoimmune disorder. due
to the development of antibodies to the nicotinic
receptors, Therefore reduction in the number of
free Nm. i.e 1/3 of normal or less)
• URINARY RETENTION
• POST OPERATIVE DECURARIZATION
• COBRA BITE.
• Cobra venom has – Curare like Neurotoxin, specific
antivenom serum is the primary treatment
• Neostigmine +Atropine prevent respiratory
paralysis.

26. • ALZHEIMER’S DISEASE:
• Neuro degenerative disorder, affecting
cholinergic neurons in the brain.
• Various measures to cholinergic transmission
in brain have been tried.

27. THANK YOU