L12 - Cholinergics II

University of Baghdad
College of Medicine
2022-2023
Title: Cholinergics II
Grade: 2nd Grade

Module: PP(Principles of Pharmacology)
Speaker: Assistant Proff. Dr. Mohammed Qasim Al Atrakji
Date: 10/11/2022
University of Baghdad/ College of Medicine 2022-2023
Dr.Mohammed Qasim
2022-2023
2nd Grade
Cholinomimetic Alkaloid
• Pilocarpine-
• Alkaloid obtained from the leaves of Pilocarpus microphyllus
• Systemic administration produce toxic effects, it can be given orally
(5-10 mg)
• USES:
• • Topical preparation for eye-0.5-4%,uses as miotic in
reversing angle closure glaucoma(contraction of
circular muscle of iris),break the adhesions of iris with
lens or cornea by alternating use with mydriatics.
• Cont…..
• • T for open angle glaucoma-contraction of
ciliary muscle of iris increases outflow facility
• ADR-
• Painful spasm of accommodation & brow pain
frequent side effects
• Systemic effects-nausea, diarrhoea, sweating &
• bronchospasm
MUSHROOM POISONING
• • Amanita muscaria, Inocybe, A.phalloides

• TYPES:
• • Muscarine Type-(Early Mushroom Poisoning)
• Inocybe species
• • Nausea, Vomiting , Diarrhoea, Bradycardia,
Salivation, Sweating, Bronchospasm, hypotension
• • Treated by Atropine IV
• Hallucinogenic Type:
• • Caused by Amanita muscaria
• Due to muscimol and other isoxazole compounds.
• Produces central effects
• Activates aminoacid receptor in Brain
• Block muscarinic receptor
• No specific tratment
• Atropine is C/I
• Another type Psilocybe mexicana whose active
psilocybine is a tryptaminergic
Anticholinesterase
• Indirectly acting cholinergic drugs (cholinesterase inhibitor)
• (A) Reversible anticholinesterase-
• • Carbamates
• (1) Tertiary amine- Physostigmine
• (2)Quaternary amine- Neostigmine, Pyridostigmine,
Edrophonium
• (3)Others-Rivastigmine, Donepezil, Galantamine
• • Acridine: Tacrine
• (B)-Irreversible anticholinesterase-
• • Organophosphorus compound
• (1)Therapeutically useful agents-Dyflos,
Echothiophate
• (2)Insecticides-Parathion, Malathion, Diazinon
• (3)War gases-Soman, Sarin, Tabun
FATE OF ACETYLCHOLINE
Reversible anticholinesterase(MOA)
• -ve charge anionic site attract (N+) nitrogen atom & esteratic site
attract COOH group of Ach.
• Enzyme substrate complex form.
• Acetylated enzyme react with water extremely rapidly & the esteratic
site free in milliseconds, acetic acid & choline is released.
• Reversible anticholinesterases structural resembles to Ach &
combines generally with anionic and esteratic site much less readily
hydrolyzed ,except edrophonium & Tacrine attach only to anionic site
& free from site by process of diffusion &action is brief.
Reversible Anticholinesterase
• Lipid soluble or tertiary amine crosses BBB. Where as lipid insoluble

quaternary ammonium derivative does not crosses BBB &more
marked effects on skeletal muscle
• They inhibit pseudocholinesterase equally. So increase Ach level at

cholinergic receptors
Physostigmine Neostigmine
Natural alkaloid obtained from Synthetic
Physostigma venenosum
(calabar bean)
Tertiary amine derivative Quaternary ammonium

compound
Oral absorption-good Poor

CNS action present CNS action absent
Cross BBB Does not cross BBB
Direct action on cholinoceptor
absent
Physostigmine Neostigmine
Uses- miotic in glaucoma Uses –Myasthenia gravis

-Atropine poisoning Post operative paralytic ileus
Duration of action- Duration of action-

Systemic-4-6 hrs 3-4 hrs
Eye – 6 to 24 hrs
Uses of reversible anticholinesterase
• (1)As miotic -Physostigmine-

• To counter act the effects of mydriatics after refraction error testing.
• (2)Glaucoma
• (3)Myasthenia gravis
• Autoimmune disorder
• 4 in 10000 population
• Twice in female than male
• Peak age -30 yrs
• Antibodies (IgG ) directed to NM receptor & reduces to 1/3 or less ,
Damage to neuromuscular junction leads to easy Fatiguability on
repeated activity with recovery after rest
CLINICAL FEATURES
• Fatiguability seen in many muscles

• Proximal limb muscles; extraocular muscles ;
Muscles of mastication, speech & facial expressions
• Respiratory difficulties may occour
• Complex extraocular palsies
• Ptosis
• Fluctuating proximal weakness
Myasthenia gravis
Treatment
• Neostigmine & its congener by inhibiting

cholinesterase enzyme, Ach release from nerve
ending & increases Ach at NM receptors & also
directly depolarises NM receptor.
• DOSE -15 mg QID
• Pyridostigmine claimed to better tolerated slightly longer duration of
action
• Dose-60 mg tab;1-3 tab every 6 hrs
• Corticosteroids-Inhibits production of NM RECEPTOR ANTIBODY &

increases synthesis of NM receptor
• AZATHIOPRINE & CYCLOSPORINEI nhibits NR- antibody synthesis
• PLASMAPHERESIS- Removal of antibodies from the body
• THYMECTOMY
Diagnostics tests for myasthenia gravis
• Ameliorative test-Edrophonium –2-10mg IV slowly

improve muscle strength in myasthenia gravis. Also
differentiate myasthenia crisis from cholinergic crisis
• • IMPROVEMENT- MYAESTHENIA CRISIS
• • WORSENING-CHOLINERGIC CRISIS
• Provocative test- d-tubocurarine 0.5 mg IV causes
• marked weakness in myasthenia gravis.
• Demonstration of anti – NR antibodies in plasma or
muscle biopsy specimen is more reliable.
Uses of reversible anticholinesterase University of Baghdad/ College of Medicine 2022-2023
cont..
• (4) Post operative paralytic ileus/urinary retention-0.5-1 mg S.C.

Neostigmine.
• (5) Postoperative decurarization –
Neostigmine –0.5-2 mg IV.
• (6) Belladonna poisoning- Consumption of seeds & berries of plant
Atropa belladonna &, Datura stramonium.→ Physostigmine 1-3mg
S.C.or I.V. antagonize both central & peripheral effects ,may repeat 4-
6 hourly.
• (7)Over dosages of drugs-

Tricylic antidepressants & many antihistaminics have anticholinergic
property
• (8)Alzheimer,s disease- Neurodegenerative disorder primarily
effecting cholinergic neurons in the brain & characterized by
progressive dementia Relatively cerebroselective anticholinesterase
• Tacrine, Rivastigmine, Donepezil have been recently approved for
clinical use FDA.
• (9) COBRA BITE

L12 - Cholinergics II

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University of Baghdad

Grade: 2nd Grade

• • Amanita muscaria, Inocybe, A.phalloides

• Lipid soluble or tertiary amine crosses BBB. Where as lipid insoluble

• They inhibit pseudocholinesterase equally. So increase Ach level at

Tertiary amine derivative Quaternary ammonium

Oral absorption-good Poor

Uses- miotic in glaucoma Uses –Myasthenia gravis

Duration of action- Duration of action-

Uses of reversible anticholinesterase

• (1)As miotic -Physostigmine-

• Fatiguability seen in many muscles

• Neostigmine & its congener by inhibiting

• Corticosteroids-Inhibits production of NM RECEPTOR ANTIBODY &

Diagnostics tests for myasthenia gravis

• Ameliorative test-Edrophonium –2-10mg IV slowly

• (4) Post operative paralytic ileus/urinary retention-0.5-1 mg S.C.

• (7)Over dosages of drugs-

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