Autonomic nervous system , specially about parasympathetic system. its agonists and antagonists.

1. Dr. Asif Hussain
JNMCH
A.M.U, Aligarh

2.  Autonomic nervous system
◦ Afferent neurons
◦ Efferent neurons
◦ Preganglionic and post ganglionic neurons
◦ Involuntary in nature
1) Parasympathetic nervous system
2) Sympathetic nervous system

3.  Somatic nervous system
◦ Sensory neurons
◦ Motor neurons
◦ Voluntary in nature
◦ Somatic motor neurons are myelinated
◦ Somatic motor neurons are cholinergic

4. Parasympathetic System

5.  Ganglia close to or on target organs
• Preganglionic neurons - long
• Post ganglionic neurons - short

6.  Acetic acid ester of choline
 Synthesis, storage , release and degradation

7. (1) Nicotinic cholinergic
1. Nicotine = agonist
2. Directly opens a Na+ Ca + K+ channels
3. Curare = antagonist
4. NM : Skeletal muscle endplate
5. NN : Ganglionic cells, adrenal medulla,
CNS
receptor

8. Ionotropic Receptors
1. Work very fast; important role in fast neurotransmission
2. Each is made of several subunits (together form the complete receptor)
3. At center of receptors is channel or pore to allow flow of neurotransmitter
4. At rest - receptor channels is closed
5. When neurotransmitter bind -- channel immediately opens
6. When ligand leaves binding site -- channel quickly closes

9. Nicotinic Receptor signal transduction pathway
Ionotropic : ligand
gated ion channel
Composed of 5 subunits
ACh binds to extracellular
domains of α subunits
Receptor opens a central
transmembrane ion
channel
Changes in membrane potential
or ionic concentration within cell

10.  Selectively stimulated by muscarine and
blocked by atropine.
 Located primarily on autonomic effector
cells of heart, smooth muscles, respiratory
tract etc and CNS.
 Subtypes are M1 ,M2, M3, M4 & M5

11. Muscarinic Receptor signal transduction pathways
NH3
COOH
Gq
Phospho -
lipase C
(+)
PIP2
IP3 Diacylglycerol
Increase Ca 2+ Activate Protein
Kinase C
Response
M3 muscarinic
receptor
C
O
O
CH3
CH2 CH2 N
CH3
CH3
CH3
Acetylcholine

15. Choline esters
◦ Acetylcholine
◦ Methacholine
◦ Carbachol
◦ Bethanechol
Alkaloids
Muscarine
Pilocarpine
Arecoline

16.  Blocks action of Ach on autonomic effectors and in
CNS exerts through muscarinic rceptors.
 Atropine is prototype drug of this class is highly
selective for muscarinic receptors.
 All anticholinergics are competitive antagonists.

17.  Natural alkaloid
◦ Atropine
◦ Hyoscine
 Semisynthetic derivatives
◦ Homatropine
◦ Ipratropium bromide
◦ Tiotropium bromide

18.  Synthetic compounds
Mydriatics: cyclopentolate, tropicamide
Antisecretory-antispasmodics:
◦ Propantheline
◦ Oxyphenonium
◦ Glycopyrrolate
◦ Dicyclomine
◦ Pirenzepine
Vesicoselective :oxybutynin, flavoxate, tolterodine
Antiparkinsonian: trihexyphenidyl, biperiden

19. CVS Affect heart’s conduction system
Low Doses High Doses
↓ ↓
Slows heart rate
Block inhibitory vagal
effects on SA & AV Nodes
Atropine (0.05 – 1 mg/ml injection)
1. Sinus Bradycardia
2. Sympatomatic 2nd degree heart block

20. CNS
1.Parkinson’s Disease 3.Motion Sickness
Deficiency in the Dopaminergic
activity in Basal ganglia-Striatum
system
Parkinsonian tremor & rigidity results
from Relative Excess of Cholinergic
activity
This vestibular disturbance
involve muscarinic
cholinergic transmission
2.Drug induced extra-pyramidal
symptoms
Centrally acting Antimuscarinic Agents
Benzhexol,
Benztropine
Scopolamine

21. Respiratory system
Both smooth muscle & secretory glands of Airway
receive Vagal innervation & contain Muscarinic
receptors
Decreased secretions from pharynx ,bronchi &
bronchioles
Relaxes smooth muscles in bronchi & bronchioles
1. Asthma
2. COPD
3. Exercise-induced
bronchospasm
Ipratropium, Tiotropium

22. Gastrointestinal System
Blockade of muscarinic receptors affect
motility & secretory functions of the gut
1.Decreased secretions
2. Relaxation of smooth muscle
3. Decreased tone & peristalsis
1.To facilitate endoscopy & GI radiology by relaxing smooth
muscles ( Hyoscine)
2. As an antispasmodic in IBS & colonic divericula ( Dicyclomine)
3. Peptic ulcer disease ( Pirenzepine – selective M1 antagonist)
4. Traveler's diarrhea (atropine + diphenoxylate, Lomotil)

23. Genitourinary system
Relaxes smooth muscles of ureters & bladder
wall
1.Bladder spasm after urologic surgery
2. Reduces involuntary voiding in neurological disorder
-Oxybutinin
-Derifenacin
-Solifenacin
-Toltrodine

24. Eye
Pupillary constrictor mucle depends on
muscarinic cholinoceptor activation
Constrictor papillae muscle is blocked by
Atropine
Results in unopposed sympathetic dilator
activity
1
2 Weaken the contraction of ciliary muscle (
Cycloplegia)
1.Referactive error measurement
2. Fundoscopic examination
3. To prevent synechia(adhesion) formation in uveitis &
iritis
Atropine,homatropine,
tropicamide,cyclopentolate

25. Cholinergic poisoning
- Cholinesterase inhibitors insecticide in rural
communities
- Consumption of wild mushrooms
1.Antimuscarinic
therapy
1-2 mg Atropine sulphate i/v every 5-15 minutes
until signs (dry mouth, reversal of miosis) appears
2.Cholinisterase regenerator compounds
Pralidoxime (PAM) & Diacetylmonoxime(DAM)
(1-2 gm i/v infusion over 15-30 mins)

26. Body System Side/Adverse Effects
Cardiovascular Increased heart rate,
dysrhythmias
CNS CNS excitation, restlessness,
irritability,
disorientation, hallucinations,
delirium

27. Body System Side/Adverse Effects
Eye Decreased visual
accommodation, increased intraocular
pressure
Gastrointestinal Decreased salivation,
decreased gastric secretions,
decreased motility
Genitourinary Urinary retention

28.  Antihistamines, phenothiazines,
tricyclic antidepressants, MAOIs
 When given with cholinergic blocking
agents, cause ADDITIVE anticholinergic
effects, resulting in increased effects

29. Ganglion blocking drugs
Competitively block action of Acetylcholine & similar agonist at nicotinic
receptors of both parasympathetic & sympathetic ganglia
Effects are numerous & complex as both divisions
of ANS are blocked indiscriminately
Hexamethonium –historically 1st effective antihypertensive agent
Mecamylamine ---reducing nicotine craving in patients quitting
smoking
Trimethaphan ---occasionally used in hypertensive
emergency & dissecting aortic aneurysm---to produce
controlled hypotension