About cholinergic Drugs Introduction Pharmacological Actions Therapeutic Uses Pharmacotherapy of Myasthenia Gravis

1. (Parasympathomimetic Drugs)
(Cholinomimetic Drugs)
Dr. Mohd. Furkan
Pharmacy Practice
NIMS University Rajasthan

2.  Introduction
 Pharmacological Actions
 Therapeutic Uses
 Pharmacotherapy of Myasthenia Gravis

3.  These are drugs which produce action similar to that of ACh,
either by directly interacting with cholinergic receptor
(Cholinergic agonist) or by increasing availability of ACh at
these sites(Anticholinesterases).
 Dale Principle : A mature neurons release the same
neurotransmitter at all of its synapses.

4. Receptor Locations Mechanism
NM Neuromuscular junction Ion channel
NN Autonomic ganglia
Adrenal medulla
CNS
Ion channel
Mohd. Furkan
(Doctor of pharmacy)

5. Receptor Locations Mechanism
M1 ANS, CNS Gq
M2 Heart, ganglia Gi
M3 Smooth muscle, glands,
Vascular endothelium
Gg
M4 CNS Gi
M5 CNS Gq

7. gg
Cholinergic drugs
Direct acting Indirect acting
Muscarinic Nicotinic
Organophosphates
(very low acting)
Carbamates
(Intermediate)
Edrophonium
(Short Acting)
Choline esters
Alkaloids

8.  Choline esters : Acetylcholine
Methacholine
Carbachol
Bethanechol
 Natural Alkaloids : Muscarine
Pilocarpine
Arecoline
 Synthetic Agonists : Cevemiline
Varenicline
Oxotremorine
Tremorine

9. ORGAN SYSTEM EFFECT/ACTION
Central nervous system Complex stimulating effects
Autonomic nervous system Sympathetic and Parasympathetic ganglia
stimulating
Skeletal Muscle Contraction

10. ORGAN SYSTEM ACTIONS
EYE Sphincter pupillae
Ciliary muscle
Miosis
Cyclospasm, accomodation
of near vision
HEART SA node
Atria
AV node
Ventricles
Negative chronotropy
Negative ionotropy
Negative dromotropy
Negative ionotropy
BLOOD VESSELS Dilatation via realease of
EDRF from endothelium
(NO)
BRONCHI Bronchoconstriction
GI TRACT Motility
Sphincter
Increases peristalsis
Relaxation
URINARY BLADDER Detrusor
Trigone & Sphincter
Contraction
Relaxation
GLANDS Increases secretion

11. CHOLINE ESTER
 Bethanechol – (Dose – 10-40 mg oral, 2.5-5mg s.c )
 USES
• Postoperative/postpartum nonobstructive urinary retention,
neurogenic bladder to promote urination.
 Side effects-
• Sweating, Intestinal Colic, fall in BP, Bronchospasm.
 Contraindication-
• Hyperthyroidism
• Bronchial asthma
• Peptic ulcer
• Myocardial infraction
• Pregnancy or breastfeeding

12.  Pilocarpine –(Dose- 0.5 - 4% eye drops )
• It is a third line drug in open angle glaucoma.
• It is used to lower high eye pressure.
 Side effects
• Sweating, salivation, increase in other secretions.
 Contraindication-
• Inflammation of the front portion of he eye.
• Inflammation of the cornea of the eye.
• Pupillary block glaucoma.
• Inflammation of the iris – the colored part of the eye.

13. • Plant alkaloid – Nicotiana tobaccum
• Fatal dose of nicotine - 40 mg
• Smoking cessation therapy: nicotine patches, chewing gums
 VARENICLINE-
• Partial agonist at NN receptor and α4β2
• Act on mesolimbic – Dopamine system ; reduce craving
 Side effects
• Nausea
• headache
• insomnia

14. Anticholinesterases (anti-ChEs) are agent which inhibit ChE,
protect ACh from hydrolysis – produce cholinergic effects in
vivo and potentiate ACh both in vivo and in vitro.
ANTICHOLINESTERASES
Reversible Irreversible
Carbamates Acridine
Organophosphates Carbamates

15.  CARBAMATES- ORGANOPHOSPHATE -
• Physostigmine (Eserine) Dyflos (DFP)
• Neostigmine Echothiophate
• Pyridostigmine Malathion*
• Edrophonium Diazinon*
• Rivastigmine Tabun`, Sarin`, soman`
• Donepezil
• Galantamine
CARBAMATES-
 ACRIDINE- Carbaryl*
• Tacrine Propoxur*
* Insecticides
` Nerve gases for
chemical warfare

16. S.n
o Physostigmine Neostigmine
1. Source Natural Alkaloid from
Physostigma venenosum
Synthetic
2. Chemistry Tertiary amine derivative Quaternary ammonium compound
3. Oral absorption Good Poor
4. CNS action Present Absent
5. Applied to eye Penetrates cornea Poor penetration
6. Direct action on NM
cholinoceptors
Absent Present
7. Prominent effect on Autonomic effectors Skeletal muscles
8. Important use Miotic (Glucoma) Myasthenia gravis
9. Dose 0.5-1 mg oral/parental
0.1-1.0% eye drops
0.5-2.5 mg i.m/s.c
15-30 mg orally
10
.
Duration of Action Systemic 4-6 hrs
In eye 6- 24 hrs
3-4 hrs

17. • Myasthenia gravis is an
autoimmune disorder
Characterized by
progressive weakening of
Skeletal muscle.
• Development of antibodies
directly to the nicotinic
receptor (NR)
• Diagnosis ;
• Tensilon Test : Myasthenia crisis
Cholinergic crisis
• Treatment –
• Neostigmine (0.5-2.5 mg i.m/s.c, 15-30 mg orally)
• Pyridostigmine (60 mg orally)