The document provides an overview of the autonomic nervous system and cholinergic system. It discusses how acetylcholine is the neurotransmitter of the parasympathetic nervous system and cholinergic fibers. It describes the two classes of cholinergic receptors - muscarinic and nicotinic receptors. It also summarizes several cholinergic drugs, including direct-acting cholinergic drugs like acetylcholine, and indirect-acting anticholinesterase drugs.

1. Introduction to
Autonomic Pharmacology
- DR. JERIN

3.  Autonomic nervous system innervates the heart, smooth muscle,
the glands & the viscera.
 Centres for the autonomic reflexes are present in the
hypothalamus, medulla & spinal cord.
 Hypothalamus coordinates the autonomic activity.
 Two major division : sympathetic & parasympathetic.
 These 2 divisions have opposing effects & normally their effects
are in a state of equilibrium.
 Sympathetic : flight & fight
 Parasympathetic : tissue building [rest & digest / feed & breed]

4.  The sympathetic divisions arise from thoracolumbar
region (T1 – L3 ) thoracolumbar outflow.
 Parasympathetic divisions arise from 2 regions.
Cranial outflow : Cranial nerves III, VII, IX & X
Sacral outflow : S2, S3 & S4

5. CHOLINERGIC SYSTEM

6. Introduction
 Acetylcholine is the neurotransmitter of parasympathetic
nervous system.
 Acetylcholine is the neurotransmitter of cholinergic system.
 The nerves that synthesize, stores & release acetylcholine are
called cholinergic.

7. Sites of release of acetylcholine
1. All preganglionic fibres of ANS : both sympathetic &
parasympathetic ganglia
2. Postganglionic parasympathetic nerve endings
3. Sweat glands : the sympathetic postganglionic nerve endings
supplying the sweat glands
4. Skeletal muscles : somatic nerve endings supplying skeletal
muscles
5. Adrenal medulla
6. CNS : brain & spinal cord

9. CHOLINERGIC RECEPTORS
 2 classes of cholinergic receptors
 Muscarinic & Nicotinic
 Muscarinic : 5 subtypes ; G protein coupled receptor
 M1 : autonomic ganglia, gastric glands, CNS
 M2 : Heart, smooth muscles
 M3 : smooth muscles, glands, eye
 M4 : CNS
 M5 : CNS
 Nicotinic : ion channels
 NM : neuromuscular junction
 NN : autonomic ganglia, adrenal medulla

10. Esters of
choline
• Acetylcholine
• Methacholine
• Carbachol
• Bethanechol
Cholinomimetic
alkaloids
• Pilocarpine
• Muscarine
• Arecoline
Carbamates
• Neostigmine
• Pyridostigmine
• Edrophonium
• Physostigmine
• Galantamine
• Ambenonium
Acridine
• Tacrine
Organo-
phosphorus
compound
• Parathion
• Malathion
• Echothiophate
• Sumithion
• Dyflos
• Toxic nerve
gas
• Sarin
• Tabun
Carbamate
insecticide
• Carbaryl
(SEVIN)
• Aldicarb
(TEMIK)
• Propoxure
(BAYGON)
Directly acting Indirectly acting
(anticholinesterases)
Reversible Irreversible

11. Acetylcholine
 Muscarinic action
 Heart : similar to vagal stimulation
 Depress the SA node ; reduces heart rate
 Decrease force of contraction
 Blood vessels
 Vasodilation : ↓ total peripheral resistance - ↓ BP
 Smooth muscles : ↑ tone of non vascular smooth muscles
 Gastrointestinal tract : tone & peristalsis enhanced, sphincters relax. (propulsion of intestinal contents)
 Urinary bladder : detrusor contracts & sphincters relax (promotes voiding)
 Bronchial smooth muscle : bronchoconstriction
 Secretory glands (↑ secretions of all glands)
 Salivary, lacrimal, nasopharyngeal, tracheobronchial, gastric, intestinal
 Eye
 Constriction of pupil (miosis) by contracting the circular muscles of the iris
 Drainage of aqueous humor
 Spasm of accommodation :Ciliary muscle contraction

12.  Nicotinic actions
 Neuromuscular junction
 Contraction of skeletal muscles
 Prolonged : paralysis
 Autonomic ganglia
 Stimulate sympathetic & parasympathetic ganglia & adrenal medulla
 CNS
 Ach does not cross BBB. Hence no CNS effect

13.  Acetylcholine is rapidly destroyed in gut, when given orally.
 IV administration : rapidly metabolised by pseudocholinesterase
in plasma & true cholinesterase at the site of action.
 Occasionally used as 1% eye drops to produce miosis.

14. Esters of choline : (carbachol, bethanechol)
 Effective orally
 Resistant to both cholinesterase
 Longer duration of action
 Uses :
 Hypotonia of bladder
 Hypotonia of GI smooth muscle
 Post operative paralytic ileus
 Urinary retention
 Adverse effects :
 Diarrhoea, salivation, sweating, bradycardia, hypotension, bronchospasm, syncope

15. Cholinomimetic alkaloids
Pilocarpine :
 Obtained from Pilocarpus microphyllus
 Tertiary amine, crosses BBB & cause CNS effects.
Actions :
 Muscarinic actions are more potent.
 Action on eyes are important
 Constriction of pupil (MIOSIS)
 Drainage of aqueous humor (↓ intraocular pressure)
 Contraction of ciliary muscle (spasm of accommodation)
 ↑ sweat (diaphoretic) ; ↑ salivary secretion (sialogogue)
 ↓ BP in therapeutic doses & ↑ BP & tachycardia in higher doses

16. Uses :
 Glaucoma : eye drops or ocusert
 Used alternately with mydriatics to break the adhesion between
iris & lens
 Dryness of mouth : radiation of head & neck
 Sjogren’s syndrome : dryness of mouth & lack of tears

17. Adverse effects :
 Eye drops :
burning sensation & painful spasm of accommodation, corneal edema
Long term use : retinal detachment
 Systemic use :
salivation, sweating, bradycardia, diarrhoea & bronchospasm

18. Indirectly acting cholinergic drugs :
Anticholinesterase :
 These drugs inhibit cholinesterase.
 MOA :
 They are structurally similar to ACh ; thus they bind to acetylcholinesterase &
inactivate them.
 This prevents the hydrolysis of ACh & accumulation of ACh.
 Thus ↑ its activity

19.  Acetylcholinesterase contains Anionic & Esteratic site.
 Acetylcholine & reversible anticholinesterase(except edrophonium)
bind to both anionic & esteratic site.
 Edrophonium binds to anionic site only. Its binding is quickly
reversible. Hence its very short acting.
 Organophosphorus compounds bind only to esteratic site. But the
enzyme gets phosphorylated (by covalent bond). Hence its stable.

20. Physostigmine :
 Obtained from Physostigma venenosum
 Its lipid soluble, tertiary ammonium compound : hence has better
penetration into tissue & crosses BBB.
Uses :
 Glaucoma
 Atropine & tricyclic antidepressant poisoning

21. Neostigmine
 Synthetic quaternary ammonium compound : poorly absorbed
from gut ; does not cross BBB.
Uses :
 Myasthenia gravis
 Post operative ileus
 Atony of urinary bladder

23.  Edrophonium
• Quaternary ammonium compound
• Binds only to anionic site
• Rapid & short acting (10-20min)
Use :
• diagnosis of Myasthenia gravis
• intravenously : snake bite & curare poisoning
• Edrophonium test : differentiate myasthenic crisis from cholinergic crisis.
on administering edrophonium 2mg IV
• If symptoms worsens : Cholinergic crisis – Rx. Atropine
• If symptoms improve : Myasthenic crisis – Rx. AntiChE

24.  Rivastigmine :
Longer acting carbamate
Selectively binds to AChE in the brain
Use : Rx of mild to moderate Alzheimer’s
 Pyridostigmine :
Used in myasthenia gravis

25. Organophosphorus poisoning
 Symptoms :
 Vomiting
 Abdominal cramps
 Diarrhoea
 Miosis
 ↑ Sweating
 ↑ salivation
 ↑ tracheal & bronchial
secretion
 Hypotension
 Muscular twitching, weakness
 convulsions

26. Treatment :
 Poisoning through skin :
 Remove clothing & wash skin with soap & water
 If consumed orally :
 Gastric lavage
 Patient should be put in prone position to avoid aspiration of
secretions.
 Maintain BP & airways patent
 DRUG OF CHOICE : ATROPINE IV 2mg every 10min till pupil dilates.
 Cholinesterase reactivators : Pralidoxime, obidoxime, diacteylmonoxime