6. 6
Ganglion : A collection of neuronal bodies.
- accepts action potential, regenerates and
propagates to organ of interest.
- located closer to organs in Parasympathetic nervous
system
- located closer to vertebra in Sympathetic nervous system
●In Parasympathetic Nervous system : preganglionic fibres
are
longer postganglionic fibres
●In Sympathetic Nervous system : postganglionic fibres are
longer preganglionic fibres
7. MECHANISHM OF PROPOGATION OF ACTION POTENTIAL.
- Action Potential traverses along 1st Neuron
Depolarises Presynaptic Membrane and opens Ca2+ channel
Ca2+ ions move in and cause contraction of proteins on vesicles
Vesicales move foreward, fuse with Presynaptic membrane
Exocytosis of Neurotransmitter = Ach
Acts on Post synaptic receptor (Nicotinic)
Na+ ion channels open followed by Influx of Na+ AP generated
7
14. 14
PILOCARPINE
History- Obtained from leaves
of Pilocarpus microphyllus
Effect-
Eyes
• Miosis
• Ciliary muscle
contraction
• Fall in the intraocular
tension
USES
• Closed angle
Glaucoma
• Sjogren syndrome
Glands
• Increase in Sweat
and salivary
secretions
Adverse effects-
Accomodation Spasm
leading to headache and
retinal detatchment
Dose:
In Rx of Sjogren
Syndrome- 5-10
mg thrice daily.
Contrainidcations-
Asthama
COPD
GI/ Urinary Obstruction
15. Muscarine type/ early
type (30-60 minutes)
Hallucinogenic type Phalloidin type (late
onset type)
Toxic agent Inocybe in Inocyte
species
Muscimol present
in A. muscaria
Psilocybine in
Psilocybe mexicana
Peptide toxins found
in Amanita
phalloides, Galerina
species.
Effect Muscarinic- salivation,
bronchospasm,
nausea, vomiting,
abdominal pain,
bradychardia and
hypotension.
• Neurological
symptoms like
irritability,
ataxia, delirium,
sedation
• Muscimol,
Ibotenic acid,
isoxazole
derivative-
Hallucinations
• Most serious type.
>90% fatalities.
• Late onset,
patient may be
symptom free
upto 24 hours
except diarrhoea
and abdominal
cramp.
• Hepatic & renal
failure.
Treatment Atropine 2mg i.v. and
1-2 mg repeated every
half an hour till
resolves
No specific
treatment. Atropine
is C/I
Supportive measures.
15
17. Acetylcholinesterase Butyrylcholinesterase
/Pseudocholinesterase
(BuChE)
Distribution All cholinergic sites,
erythrocytes, Brain
(Grey matter)
Plasma, liver, skin,
brain(white matter)and
gastrointestinal smooth
muscles
Substrate hydrolysed
Acetylcholine
Butyrylcholine
Hydrolysed (ultra fast)
Not hydrolysed
Hydrolysed (slow)
Hydrolysed
Inhibition Relatively more sensitive
to physostigmine
Relatively most sensitive
to Organophosphates
Function Degrades acetylcholine Degrades exogenous
esters
17
18. 18
• Anionic site- binds with choline moiety of ACh
• Esteratic site- binds with acetyl moiety of ACh
• Hydrolysis of Ach occurs by transferring acetyl group to
Serine hydroxyl group, leaving behind free choline.
• Acetylated enzyme reacts freely with water to release
acetic acid and liberate free enzyme.
19. 19
• Carbamates + Esteratic site --- Enzyme is Carbamylated releasing
choline, BUT carbamylated enzyme reacts slowly with water and
enzyme is freed slowly.
• Half life of reactivation of carbamylated enzyme Is about 30 minutes
• Edrophonium + anionic site of enzyme AChE and the ionic bond is
readily reversible and thus, it has very short action, about 10 minutes
20. Parameter Physostigmine Neostigmine and other
quaternary compounds
Source Physostigma
venenosum
( dried ripe seeds of
Calabar beans)
Synthetic
Oral Absorption Good Poor
Penetration to
cornea
Good Poor
Penetration to
CNS
Good Poor
Additional
direct action on
cholinergic
receptors
Abesnt Present
20
21. Parameter Physostigmine Neostigmine and other
quaternary compounds
Predominant
effect
Parasympathetic effectors NM Junction, GIT,CVS
and Eye.
Preferred
Clinical use
• Glaucoma (0.25-0.5%)
• Belladona Poisoning
Dose- 2 mg sc/i.v. and
repeated initially every
15-20 minutes and later
every 2 hours.
• Diagnosis & treatment
of Myasthenia Gravis.
• Non depolarizing
muscle relaxant
(NDMR) reversal
• Cobra bite
• Bladder atony
21
22. long acting drug as compared to Neostigmine, though
less potent.
Onset is delayed and peak effect occurs after 2 hours.
Better compliance than Neostigmine
Safe in Pregnancy and lactation
Dose: 60-120 mg TDS
22
Pyridostigmine.
23. Ultra short acting ( ~10 minutes) as it combines with anionic site of
AchE and forms ionic bond which is readily reversible
Has mainly peripheral actions.
Drug of choice in Myasthenia Gravis
Used to differentiate between myasthenic crisis and cholinergic crisis
Edrophonium test: Premedication with Atropine.
If Symptoms improve --- Myasthenia Gravis
If Symptoms worsen --- Cholinergic crisis
23
Edrophonium
24. Highly lipid soluble, cross BBB
Inhibit AChE in CNS and thus can be used for trratment of Alzhimer’s
disease.
It has a long half life, and thus can be used only once a day.
Can cause hepatoxicity.
Delays the progress of disease upto one year.
Dose: 5 mg OD at Bed time (maximum 10 mg OD)
24
Donepezil
25. Autoimmune disorder, occurring due to development of antibodies
directed to Nicotinic receptors at muscle end plate.
Number of free Nm cholinoceptors may be reduced to 1/3rd of normal
Symptoms- Weakness and easy fatigability on repeated activity with
recovery after rest.
Treatment- Neostigmine- increases the availability of Ach from
prejunctional endings to accumulate and act on receptors over a large
area. Dose: 15 mg orally 6 hourly
Prednisolone 30-60 mg/day produces remission in 80% of advanced
cases. After tapering the dose, 10 mg daily or alternate days.
Plasmaphersis.
25
Myasthenia gravis
26. Condition Drugs used
Glaucoma Pilocarpine, Physostigmine
Testing of Myasthenia gravis Edrophonium
Treatment of Myasthenia gravis Neostigmine & Pyridostigmine
Cobra bite Edrophonium ( prevents
respiratory paralysis)
Atropine Poisoning Physostigmine
TCA, Phenothiazines overdose Physostigmine
Post operative paralytic ileus Neostigmine
26
27. Organophosphate Poisoning
Caused by irreversible cholinesterase inhibitors
Route of entry- Eye, skin, respiratory system and GI tract
they are- Organophoshate insecticides (malathion, parathion) or
nerve gases (sarin, tabun, soman)
They cause excessive cholinergic stimulation (muscarinic) and
neuromuscular blockade producing symptoms of
- increased salivation, rhinorrhoea and sweating, excessive bronchial
secretion and difficulty in respiration due to Bronchoconstriction.
- Miosis, vomiting, diarrhoea and abdominal pain
- Muscle twitching begins with eyelids, tongue.
27
28. Peripheral neuromuscular blocking action and excessive
bronchial secretion --- respiratory paralysis – Death.
Cholinergic crisis occurs because the irreversible
anticholinesterase poison binds to the enzyme
acetylcholinesterase and inactivates it. Thus, acetylcholine
remains in the cholinergic synapses causing excessive
stimulation of muscarinic and nicotinic receptors.
28
29. Treatment of OP Poisoning
GENERAL SUPPORTIVE MEASURES.
Prevention of further exposure to poison.
Decontamination of clothing
Flushing poison from the skin and eyes
Activated charcoal and lavage for GI ingestion
29
30. Specific Treatment.
A. ATROPINE- Drug of choice.
Dose- 2mg i.v. to start with and same dose repeated until full
atropinisation is achieved.
Atropinisation is assessed by degree of dilatation of pupil and pulse
count, i.e. increased pulse rate should be seen.
Tachycardia upto 120 beats per minute is allowed.
30
31. B. Cholinesterase reactivators.
Phosphorylated cholinesterase enzyme does not react with water at
all and therefore, action is irreversible.
So, if compounds possessing highly reactive hydroxyl group (OH) is
used, cholinesterase enzyme is reactivated very fast.
OXIMES- Pralidoxime, obidoxime, diacetyl monoxime.
Pralidoxime Dose- administered slow IV infusion for 15-30 minutes.
Adults- 1-2 gm
Children- 20-40 mg/kg
Pralidoxime should be administered as early as possible.
31
32. 32
Pralidoxime combines with anionic site of the phosphorylated
enzyme, and comes in close proximity with phosphorylated
Esteratic site.
Oxime end reacts with Phosphorous atom of Organophosphate at
Esteratic site and enzyme is reactivated.
Oximes not useful in treatment of Carbamate poisoning.
33. References
1. Wessler I, Kilbinger H, Bittinger F, Unger R, Kirkpatrick CJ. The non-
neuronal cholinergic system in humans: Expression, function and
pathophysiology. Life Sciences. 2003;72:2055–2061
2. Goodman & Gilman’s The Pharmacological basis of therapeutics
3. SK Srivastava Rohan Srivastava, Pharmacology for MBBS
4. Essentials of Medical Pharmacology, KD Tripathi.
33