Muscarine is an alkaloid found in the Amanita muscaria mushroom that causes only muscarinic effects. It can cause profuse salivation, lacrimation, sweating, blood vessel dilation and hypotension, miosis, and spasm of accommodation in the eyes. Mushroom poisoning may occur due to ingestion of poisonous mushrooms containing toxins like muscarine, amatoxins, or gyromitrins. Early onset poisoning features muscarinic symptoms like excessive sweating and salivation within 1-2 hours.

1. CHOLINERGIC SYSTEM AND
CHOLINERGIC DRUGS
Dr. D. K. Brahma
Associate Professor of Pharmacology
NEIGRIHMS, Shillong

2. SympatheticVs Parasympathetic
• SYMPATHETIC
Fight or Flight
• Increase BP & HR, glucose, perfusion
to skeletal muscles, Mydriasis, Bronchodilatation
• PARASYMPATHETIC
Rest and Digest
• Miosis, decreased HR, BP, bronchia secretion,
Insulin release, Digestion, excretion

3. Sympathetic
Nervous System
(Thoracolumbar
Outflow) -
paravertebral,
prevertebral and
terminal
Parasympathetic:
Craniosacral
outflow

4. Sites of CholinergicTransmission - Summary
Acetylcholine (ACh) is major neurohumoral transmitter at autonomic, somatic and
central nervous system:
1. All preganglionic sites (Both Parasympathetic and sympathetic)
2. All Postganglionic Parasympathetic sites and sympathetic to sweat gland and some
blood vessels
3. Skeletal Muscles
4. CNS: Cortex, Basal ganglia, spinal chord and others
Parasympathetic Stimulation – Acetylcholine (Ach) release at neuroeffector junction -
biological effects
Sympathetic stimulation – Noradrenaline (NA) at neuroeffector junction - biological effects

5. Cholinergic Transmission –
Synthesis:
• Cholinergic neurons contain large numbers of
small membrane-bound vesicles (containing
ACh) concentrated near the synaptic portion of
the cell membrane
• ACh is synthesized in the cytoplasm from
acetyl-CoA and choline by the catalytic action
of Choline acetyltransferase (ChAT)
• Acetyl-CoA is synthesized in mitochondria,
which are present in large numbers in the
nerve ending
• Choline is transported from the extracellular
fluid into the neuron terminal by a Na+-
dependent membrane choline cotransporter
(Carrier A). This carrier can be blocked by a
group of drugs called hemicholiniums
The action of the choline transporter
is the rate-limiting step in ACh
synthesis

6. Cholinergic Transmission –
Release:
• Synthesized, ACh is transported from the
cytoplasm into the vesicles by an antiporter that
removes protons (carrier B). This transporter can
be blocked by vesamicol
• Release is dependent on extracellular Ca2+
•and occurs when an action potential reaches the
terminal and triggers sufficient influx of Ca2+
ions
• The increased Ca2+
concentration "destabilizes"
the storage vesicles by interacting with special
proteins associated with the vesicular membrane
(VAMPs and SNAP- synaptosome associated
protein)
Fusion of the vesicular membranes with the
terminal membrane results in exocytotic expulsion
of ACh into the synaptic cleft
• The ACh vesicle release process is blocked by
botulinum toxin through the enzymatic removal of
two amino acids from one or more of the fusion
proteins. Black widow spider??

7. Cholinergic Transmission:
Destruction
• After release - ACh molecules may bind to
and activate an ACh receptor (cholinoceptor)
• Eventually (and usually very rapidly), all of
the ACh released will diffuse within range of
an acetylcholinesterase (AChE) molecule
• AChE very efficiently splits ACh into choline
and acetate, neither of which has significant
transmitter effect, and thereby terminates the
action of the transmitter.
• Most cholinergic synapses are richly
supplied with AChE; the half-life of ACh in the
synapse is therefore very short. AChE is also
found in other tissues, eg, red blood cells.
• Another cholinesterase with a lower
specificity for ACh, butyrylcholinesterase
[pseudo cholinesterase], is found in blood
plasma, liver, glial, and many other tissues

8. True Vs Pseudo AChE
True AChE Pseudo AChE
Distribution All cholinergic sites, RBCs, gray
matter
Plasma, liver, Intestine
and white matter
Action on:
Acetycholine
Methacholine
Very Fast
Slower
Slow
Not hydrolyzed
Function Termination of Ach actio Hydrolysis of Ingested
Esters
Inhibition More sensitive to Physostigmine More sensitive to
Organophosphates

9. Cholinergic receptors - 2 types
• Muscarinic (M) and Nicotinic (N):
Muscarinic (M)
- GPCR
Nicotinic (N) –
ligand gated

10. Types of Cholinergic Transmission
Site Receptor type Selective
agonist
Selective
antagonist
All postganglionic
Parasympathetic and few
postganglionic sympathetic
to sweat gland some blood
vessels
Muscarinic Muscarine Atropine
Ganglionic both symp. and
parasymp.
Nicotinic (NN) DMPP Heaxamethonium
Skeletal Muscle Nicotinic (NM) PTMA D-tubocurarine
CNS cortex, basal ganglia,
spinal chord etc.
Muscarinic
Nicotinic
Muscarine
Carbachol
Atropine
d-tubocurarine

11. Muscarinic Receptors ??
1. Selectively stimulated by Muscarine and blocked by Atropine – all are G-
protein coupled receptors
2. Primarily located in autonomic effector cells in heart, eye, smooth muscles
and glands of GIT and CNS
3. Subsidiary M receptors are also present in ganglia for modulation – long
lasting late EPSP
4. Autoreceptors (M type) are present in postganglionic prejunctional
cholinergic Nerve endings – inhibits ACh release
1.also in adrenergic nerve terminals (inhibits NA release) leading to vasodilatation when
ACh is injected
5. Blood vessels: All blood vessels have muscarninc receptors although no
cholinergic innervations – EDRF – SM relaxation -Vasodilatation

12. Muscarinic Receptors - Subtypes
• Pharmacologically - M1, M2, M3, M4 and M5
• M4 and M5 are present in certain areas of Brain and regulate other
neurotransmitters
• M1, M3 and M5 fall in one class, while M2 and M4 in another class
• However - M1, M2 and M3 are major ones and present in effector cells and
prejunctional nerve endings in Peripheral organs and CNS
• All subtypes have little agonist selectivity but selective antagonist selectivity
• Most organs usually have more than one subtype but one subtype predominates in
a tissue

13. Muscarinic Receptors - Location
• M1: Autonomic ganglion Cells, Gastric glands and Central Neurons (cortex,
hippocampus, corpus striatum)
• Physiological Role: Mediation of Gastric acid secretion and relaxation of LES (vagal)
• Learning, memory and motor functions
• M2: Cardiac Muscarinic receptors
• Mediate vagal bradycardia
• Also auto receptors in cholinergic nerve endings
• CNS –Tremor, analgesia
• M3: Visceral smooth muscles, glands and vascular endothelium. Also Iris and Ciliary
muscles

14. Muscarinic Receptor Subtypes
M1 M2 M3
Location Autonomic ganglia,
Gastric glands and
CNS
Heart and CNS SMs of Viscera, Eye,
exocrine glands and
endothelium
Functions Depolarization (late
EPSP) & Histamine
release & acid
secretion, relaxation of
LES, CNS learning and
motor functions
Less impulse generation,
less velocity of
conduction, decreased
contractility, less ACh
release (auto)
Visceral SM
contraction,
glandular secretions,
Constriction of
pupil, contraction of
Cilliary muscle and
vasodilatation (EDRF
- NO)Agonists Oxotremorine Methacholine Bethanechol
Antagonists Pirenzepine Methoctramine &
Triptramine
Darifenacin
Transducer IP3/DAG and PLA2
increase – Ca++ and
PG
K+ channel opening and
decresed cAMP
IP3/DAG and
increase – Ca++ and
PG synthesis

15. Acetylcholine (cholinergic receptors)
– Muscarinic Receptors
M1 M2 M3
Ganglia,
gastric
gland and
CNS
Heart
Cholinergic
Nerves
Visceral Smooth
Muscles, Iris and
cilliary muscle
Selectively stimulated by Muscarine and blocked by Atropine

16. Nicotinic (N) Receptors
• Nicotinic receptors: nicotinic actions of ACh are those that
can be reproduced by the injection of Nicotine (Nicotiana
tabacum)
– Can be blocked by tubocurarine and hexamethonium
• Ligand-gated ion channels
– activation results in a rapid increase in cellular permeability to Na+ and Ca++ resulting -
depolarization and initiation of action potential
• TWOTypes: NM and NN – based on location

17. Nicotinic Receptors - NM Vs NN
NM (Muscle type)
1. Location: Skeletal Muscle end plates
2. Function: Stimulate skeletal muscle
(contraction)
3. MOA: Postsynaptic and Excitatory
(opening of cations Na+, K+ etc.)
4. Agonists: ACh, carbachol (CCh),
suxamethonium
– Selective stimulation by phenyl trimethyl
ammonium (PTMA)
1. Antagonists: tubocurarine, Atracurium,
vecuronium and pancuronium
NN (Ganglion type)
1. Location: In autonomic ganglia of all type
(ganglion type) – Sympathetic,
Parasympathetic and also Adrenal Medulla
2. Function: Depolarization and postganglionic
impulse – stimulate all autonomic ganglia;
Adrenal Medulla – Catecholamine release
3. MOA: Opening of Na+, K+ and Ca+ channel
opening
4. Agonists: ACh, CCh, nicotine
– Selectively stimulated by Dimethyl
phenyl piperazinium (DMPP)
1. Antagonists: Trimethaphan,
Mecamylamine and Hexamethonium

18. Question ?
• A person is having severe cholinergic symptoms like vomiting, salivation and
lacrimation etc. after accidental consumption of poisonous mushroom.
What subtype of receptor is involved in the mediation of such reaction
….. ????
• Answer: M3

19. Question…?
• What side effects might you expect to see in a patient taking a cholinergic
drug?
• Hint…
• = “Colon-Urgent” ….Cholinergic

20. Cholinergic Drugs or Cholinomimetic or
Parasympathomimetics
Drugs producing actions similar to Acetylcholine by – 1) interacting
with Cholinergic receptors or 2) increasing availability of
Acetylcholine at these sites

21. Classifiction - Direct-acting (receptor agonists)
• Choline Esters
• Natural: Acetylcholine (ACh)
• Synthetic: Methacholine, Carbachol and Bethanechol
• Alkaloids: Pilocarpine, Muscarine, Arecholine
• Synthetic: Oxotremorine

22. Cholinergic Drugs – Indirect acting
• Cholinesterase inhibitors or reversible anticholinesterases:
1. Natural: Physostigmine
2. Synthetic: Neostigmine, Pyridostigmine, Distigmine, Rivastigmine,
Donepezil, Gallantamine, Edrophonium, Ambenonium, Demecarium
1.Irreversible anticholinesterases:
1. Organophosphorous Compounds (OPC) – Diisopropyl fluorophosphate
(DFP), Ecothiophate, Parathion, malathion, diazinon (insecticides and
pesticides)
2. Tabun, sarin, soman (nerve gases in war)
3. Carbamate Esters: Carbaryl and Propoxur (Baygon)

23. ACh actions –
Muscarinic
1. Heart: M2
– SA node hyperpolarization (decrease in rate of diastolic depolarizaton) - reduction in
impulse generation and Bradycardia
– AVN and PF – RP is increased – slowing of conduction – partial/complete heart block
– Atrial fibres: Reduction in force of contraction and RP in fibers abbreviated, APD
increase
– Atrial fibrillation and flutter – nonuniform vagal innervations and variation in intensity
of effect on RP in diferent atrial fibres
– Decrease in ventricular contractility (less prominent)
1. BloodVessels: M3
– Cholinergic innervations is limited – skin of face and neck - fall in BP and flushing
– But, M3 present in all type blood vessel –Vasodilatation by Nitric oxide (NO) release
(PLc-IP3/DAG)
– Penile erection

24. Muscarinic action
– contd.
3. Smooth Muscles: M3 - All are contracted
– Abdominal cramps, diarrhoea – due to increased peristalsis and relaxed sphincters
– Voiding of Bladder
– Bronchial SM contraction – dyspnoea, attack of asthma etc.
4.Glands: M3
– Increased secretions: sweating, salivation, lacrimation, tracheobronchial tree and gastric glands
– Pancratic and intestinal glands – less prominen
5.Eye: M3
– Contraction of circular fibres of Iris – miosis
– Contraction of Ciliary muscles – spasm of accommodation, increased outflow and reduction in
IOP

25. Ach actions –
Nicotinic
1. Autonomic ganglia:
– Both Sympathetic and parasympathetic ganglia are stimulated
– After atropine injection ACh causes tachycardia and rise in BP
1. Skeletal muscle
– IV injection – no effect
– Application causes contraction of skeletal muscle
3. CNS:
– Does not penetrate BBB
– Local injection in CNS – complex actions
(Acetylcholine is not used therapeutically – non specific)
Bethanecol Uses: Postoperative and postpartum urinary obstruction, neurogenic
bladder and GERD (10-40 mg oral), Congenital megacolon

26. Pilocarpine
• Alkaloid from leaves of Jaborandi (Pilocarpus microphyllus)
• Prominent muscarinic actions
• Profuse salivation, lacrimation, sweating
• Dilates blood vessels, causes hypotension
• High doses: Rise in BP and tachycardia (ganglionic action)
• On Eyes: produces miosis and spasm of accommodation
• Lowers intraocular pressure (IOP) in Glaucoma when applied as eye drops
• Too toxic for systemic use – CNS toxicity
• Diaphoretic (?), xerostomia and Sjögren’s syndrome

27. Pilocarpine – contd.
1. Used as eye drops in treatment of
narrow angle glaucoma to reduce IOP
2. To reverse mydriatic effect of atropine
3. To break adhesion between iris and
cornea/lens alternated with mydriatic
• Pilocarpine nitrate eye drops ( 1 to 4% )
• Atropine used as antidote in acute
pilocarpine poisoning ( 1-2 mg IV 8 hrly )

28. Pilocarpine in Glaucoma
• Constriction of circular muscle of Iris
• Contraction of ciliary muscle
• Spasm of accommodation – fixed at near vision

29. Muscarine
• Alkaloid from mushroom Amanita muscaria
• Only muscarinic actions
• No clinical use
• Mushroom poisoning due to ingestion of poisonous mushroom
1.Early onset mushroom poisoning (Muscarine type)
2.Late onset mushroom poisoning
3.Hallucinogenic type

30. Mushroom Poisoning
• After the ingestion of mushrooms that contain toxins
• Thousands of species of mushrooms, but only 100 species of mushrooms
cause symptoms
• 15-20 mushroom species are potentially lethal when ingested
• As a result of misidentification of the mushroom by an amateur
• Toxins: Amatoxin, Gyromitrins (monomethylhydrazine), Muscarine,
Muscimol & ibotenic acid, Nephrotoxins (norleucine), Myotoxins,
Immunoactive toxins, Hemolytic toxins and GI irritants

31. Mushroom Poisoning
• Early Onset Mushroom Poisoning: Occurs ½ to 1 hour
– Symptoms are characteristic of Muscarinic actions
– Inocybe or Clitocybe – severe cholinergic symptoms like vomiting, salivation,
lacrimation, headache, bronchospasm, diarrhoea bradycardia, dyspnoea, hypotension,
weakness, cardiovascular collapse, convulsions and coma
– Antidote is Atropine sulphate ( 2-3 mg IM every hrly till improvement)
• Hallucinogenic type: due to Muscimol or ibotenic acid present in A.
muscria. Blocks muscarinic receptors in brain and activate amino acid
receptors. No specific treatment – Atropine contraindicated.

32. Late Onset Mushroom
Poisoning
• Occurs within 6 - 15 hours
• Amanita phylloides (deadly nightcap), Galerina– due to peptide toxins – Inhibit
RNA and protein synthesis
• Irritability, restlessness, nausea, vomiting, bloody diarrhoea ataxia, hallucination,
delirium, sedation, drowsiness and sleep – Kidney, liver and GIT mucosal damage
• Maintain blood pressure, respiration
• Inj. Diazepam 5 mg IM
• Atropine contraindicated as it may cause convulsions and death - penicillin,
thioctic acid and silibinin (antidote?)
• Gastric lavage and activated charcoal
DELAYED ONSETType (more than 24 Hours) –
Nephrotoxic syndromes

33. Cholinergic Drugs – Indirect acting
• Cholinesterase inhibitors or reversible anticholinesterases:
1. Natural: Physostigmine
2. Synthetic: Neostigmine, Pyridostigmine, Distigmine, Rivastigmine, Donepezil,
Gallantamine, Edrophonium, Ambenonium, Demecarium
3. Acridine: Tacrine
1.Irreversible anticholinesterases:
1. Organophosphorous Compounds (OPC) – Diisopropyl fluorophosphate (DFP),
Ecothiophate, Parathion, malathion, diazinon (insecticides and pesticides)
2. Tabun, sarin, soman (nerve gases in war)
3. Carbamate Esters: Carbaryl and Propoxur (Baygon)
Carbamates

34. AChEs - Chemistry
• Either esters of Carbamic acid or
derivative of Phosphoric acid
• Carbamates: R1 – Nonpolar tertiary
amino N – physostigmine (lipid
soluble); Others – R1 quartenary
amino N+ (lipid insoluble)
• Organophosphates: All are highly lipid
soluble except ecothiophate
Carbamates
Organophosphates

35. AChEs - MOA
• Normally Acetylcholinesterase (AchE) hydrolyses
Acetylcholine
• The active site of AChE is made up of two
subsites – anionic and esteratic
• The anionic site serves to bind a molecule of
ACh to the enzyme
• Once the ACh is bound, the hydrolytic reaction
occurs at a second region of the active site called
the esteratic subsite
• The AChE itself gets acetylated at serine site
• Acetylated enzyme reacts + water = acetic acid
and choline
• Choline - immediately taken up again by the
high affinity choline uptake system presynaptic
membrane
Glutamate and
histidine
Tryptophan

36. AChEs - MOA
• Anticholinesterases also react with the enzyme ChEs in similar fashion like
Acetylcholine
• Carbamates – carbamylate the active site of the enzyme
• Phosphates – Phosphorylate the enzyme
• Both react similar fashion covalently with serine
• Carbamylated (reversible inhibitors) reacts with water slowly and the esteratic site
is freed and ready for action – 30 minutes (less than synthesis of fresh enzyme)
• But, Phosphorylated (irreversible) reacts extremely slowly or not at all – takes more
time than synthesis of fresh enzyme
– Sometimes phosphorylated enzyme losses one alkyl group and become resistant to
hydrolysis – aging
• Edrophonium and tacrine react only at anionic site – short acting while
Organophosphates react only at esteratic site

37. Anticholinesterases –
Pharmacological actions
• 2 (two) important clinically used drugs –
– Physostigmine – Muscarinic and CNS action, lipid soluble, ganglion acting and less action in skeletal
muscle
• Also organophosphates
– Neostigmine – lipid insoluble, skeletal muscle acting, stimulate ganglia, less muscarinic effect
• Ganglia: Stimulate ganglia – muscarinic action – less prominent action
• CVS: Complex; Muscarinic – bradycardia and hypotension; Ganglionic action – stimulation
– increase HR and BP; Medullary centre – stimulation followed by depression …overall
unpredictable
• Skeletal Muscle: Ach is not quickly destroyed – rebinds to same receptors – repetitive firing
– twitching and fasciculation; increases force of contraction in muscles

38. Physostigmine
• Alkaloid from dry ripened seed (Calabar bean) of African plant Physostigma
venenosum
• Tertiary amine, lipid soluble, well absorbed orally and crosses BBB
• Hydrolyzed in liver and plasma by esterases
• Long lasting action (4-8 hours)
• Penetrates cornea readily on local application in eye - Muscarinic action on
eye causing miosis and spasm of accommodation on local application
• Salivation, lacrimation, sweating and increased tracheobronchial secretions
• Increased heart rate & hypotension

39. Physostigmine - uses
1. Used as miotic drops to decrease IOP in Glaucoma
2. To antagonize mydriatic effect of atropine
3. To break adhesions between iris and cornea alternating with mydriatic
drops
4. Belladonna poisoning,TCAs & Phenothiazine poisoning
5. Alzheimer’s disease- pre-senile or senile dementia
6. Atropine is antidote in physostigmine poisoning.
ADRs – CNS stimulation followed by depression

40. Neostigmine
• Synthetic reversible anticholinesterase drug
• Quaternary ammonium compound and lipid insoluble
• Cannot cross BBB
• Hydrolysed by esterases in liver & plasma
• Short duration of action (3-5 hours)
• Direct action on nicotinic (NM) receptors present in neuromuscular junction (motor
end plate) of skeletal muscle
• Antagonises (reverses) skeletal muscle relaxation (paralysis) caused by
tubocurarine and other competitive neuromuscular blockers
• Stimulates autonomic ganglia in small doses - Large doses block ganglionic
transmission
• No CNS effects

41. Neostigmine – Uses and ADRs
• Used in the treatment of Myasthenia Gravis to increase muscle strength
• Post-operative reversal of neuromuscular blockade
• Post-operative complications – gastric atony paralytic ileus, urinary bladder
atony
• Cobra snake bite
• Produces twitchings & fasciculations of muscles leading to weakness
• Atropine is the antidote in acute neostigmine poisoning

42. Physostigmine Vs Neostigmine
Physostigmine Neostigmine
Source Natural Synthetic
Chemistry Tertiary amine Quaternary ammonium
compound
Oral absorption Good Poor
CNS action Present Absent
Eye Penetrates cornea Poor penetration
Effect Ganglia Muscle
Uses Miotic Mysthenia gravis
Dose 0.5-1 mg oral/parenteral
0.1-1% eye drop
0.5-2.5 mg IM/SC
15-30 mg orally
Duration of action 4-6 Hrs 3-4 Hrs

43. Other Drugs
• Pyridostigmine: Same as Neostigmine - less potent but longer
acting
• Edrophonium: Same as Neostigmine – shorter duration of action
(1- - 30 minutes) – diagnostic use in MG
• Tacrine: Acts like edrophonium, lipid soluble, crosses BBB –
increases brain ACh – symptomatic improvement in Alzheimer`s
disease (AD)
• Rivastigmine, donepezil, galantamine – all used in AD

44. Myasthenia gravis
(Myo + asthenia)
• Autoimmune disorder affecting 1 in
10,000 population (?) – reduction in
number of NM receptors
• Symptoms: Weakness and easy
fatigability – ptosis to diaphragmatic
paralysis
• Causes: Development of antibodies
directed to Nicotinic receptors in
muscle end plate – reduction in
number by 1/3rd of NM receptors
• Structural damage to NM junction

45. Myasthenia gravis – other drugs
• Neostigmine – 15 to 30 mg. orally every 6 hrly
• Adjusted according to the response
• Pyridostigmine – less frequency of dosing
• Other drugs: Corticosteroids (prednisolone 30-60 mg /day) –
immunosuppression
• Inhibits production of NR antibodies and may increase synthesis or NRs
• Azathioprin and cyclosporin also Plasmapheresis

46. Myasthenic crisis
• Acute weakness and respiratory paralysis
– Tracheobronchial intubation and mechnical ventilation
– Methylprednisolone IV with withdrawal of AChE
– Gradual reintroduction of AChE
– Thymectomy
• The problem – overtreatmentVs actual disease (opposite treatments)
– Diagnosis by various tests – TensilonTest
– Injection of Edrophonium – 2 mg (observe) – after half a minute 8 mg (observe)
• In MG – symptoms will improve
• In overtreatment – symptoms worsen

47. OverallTherapeutic Uses – cholinergic drugs
1. Myasthenia gravis: Edrophonium to diagnose and Neostigmine, Pyridostigmine
& Distigmine to treat
2. To stimulate bladder & bowel after surgery:
– Bethanechol, Carbachol, Distigmine.
1. To lower IOP in chronic simple glaucoma:
– Pilocarpine, Physostigmine
1. To improve cognitive function in Alzheimer’s disease: Rivastigmine,
Gallantamine, Donepezil.
2. Physostigmine in Belladonna poisoning
3. Cobra Bite

48. Pharmacotherapy of Organophosphate
Poisoning
• Complex effects – Muscarinic, Nicotinic and CNS
• Signs and symptoms:
1. Irritationof eye, lacrmation, salivation, tracheo-bronchial secretions, colic, blurring of vision,
defaecation and urination
2. Fall in BP, tachy or bradycardia and CVS collapse
3. Muscular fasciculations, weakness, and respiratory paralysis
4. Irritability, disorientation, ataxia, tremor, convulsins and coma
• Treatment:
1. Decontamination and termination of further exposure – gastric lavage if needed
2. Airway maintenance – endotrachial intubation
3. Supportive measures – for BP/fluid and electrolyte
4. Specifc antidote – Atropine – 2mg IV every 10 minutes till dryness of mouth or atropinization (upto
200 mg/day)

49. Cholinesterase
Reactivators – Oximes
• Pralidoxime (2-PAM) and Obidoxime Diacetyl monoxime (DAM)
• Oximes have generic formula R-CH=N-OH
• Provides reactive group OH to the enzymes to reactivate the phosphorylated
enzymes – million times faster
• PAM:
– Quaternary Nitrogen of PAM gets attaches to Anionic site of the enzyme and reacts with
Phosphorous atom at esteratic site
– Forms Oxime-phosphonate complex making esteratic site free
– Not effective in Carbamate poisoning
– Dose: 1-2 gm IV slowly maximum 12 gms/24 hrs and 20-30 mg/kg/hour continuous IV
infusion.

50. Summary
• Distribution of Muscarinic and Nicotinic receptors
• Classification of Anticholinesterases
• Mechanism of action of Anticholinesterases and Aging
• Action of cholinomimetics on eye
• PhysostigmineVs Neostigmine
• Myasthenia gravis
• Neostigmine and its uses
• Use of Edrophonium
• Organophosphate poisoning
• Oximes

51. Khublei Shibun/Thank you