pharmacology of cholinergic drugs with their indications and contraindications

1. PARASYMPATHOMIMETIC DRUGS
OR
CHOLINERGIC DRUGS
OR
CHOLINOMIMETIC DRUGS
OR
CHOLINOCEPTOR ACTIVATING DRUGS

2. 2patki10/9/2019

3. DEFINITION
These are the group of drugs which produce
effects resembling those produced by the
stimulation of parasympathetic autonomic
nervous system on the target organs

4.  Neurotransmitter
 Two types of activities
• Muscarinic
• Nicotinic

5. SYNTHESIS, STORAGE,
RELEASE & INACTIVATION

8. MECHANISM OF
ACTION
G –protein linked (Muscarinic)
Ion channel (Nicotinic)

9. PHOSPHO – INOSITOL SYSTEM
BINDING OF DRUG WITH RECEPTOR
(ALPHA-1 ADRENDERGIC, MUSCARINIC- CHOLINERGIC)
ACTIVATION OF PHOSPHOLIPASE-C
PHOSPHATIDYL INOSITOL 4-5 BIPHOSPHATE
DIACYL GLYCEROL INOSITOL 1.4.5 TRIPHOSPHATE
(CONFINEDTO MEMBRANE) (DIFFUSES INTO CYTOSOL)
ACTIVATION OF PROTEIN KINASEC RELEASE OF Ca++ FROM
INTRACELLULAR SOURCES
ENTRY OF Ca++ THROUGH THE CA++ FORMATION OF Ca++ CALMODULIN
COMPLEX
CHANNEL
ALTERATION IN THE ACTIVITY OF C
DEPENDENT ENZYMES
EFFECT

10. CHOLINERGIC RECEPTORS
Muscarinic
M1 = Nerves, Stomach, Brain
Antagonist: Pirenzepine
M2 = Heart, Nerves, Smooth Muscle.
Antagonist: Gallamine
M3 = Glands, Endothelium, Smooth Muscle.
M4 and M5 newly discovered, role not yet known

11. CLASSICIFICATION
A. Directly Acting
B. Indirectly Acting

12. A. Directly Acting Cholinergic
Drugs :
I. Choline Esters
Acetylcholine
Carbachol
Methacholine
Bethanechol

13. II. Cholinomimetic Alkaloids
a. Mainly Muscarinic Agonists
Natural Alkaloids:
Muscarine
Pilocarpine
Arecholine
Synthetic Alkaloid:
Oxotramorine
b. Mainly Nicotinic Agonists
Natural Alkaloids:
Nicotine
Lobeline
Synthetic Alkaloids:
Dimethylphenylpiperazinium(DMPP)

14. B. Indirectly Acting Cholinergic Drugs
(Anticholinesterases)
I- Reversible
a. Carbamates
b. Alcohols
II- Irreversible

15. I- Reversible
a. Carbamates
Tertiary amines
Physostigmine
Quaternary Ammonium compounds
Neostigmine
Pyridostigmine
Distigmine
Ambenonium
Demecarium
b. Alcohols
Edrophonium
c. Miscellaneous
Tacrine
Donepezil
Galantamine
Rivastigmine

16. II. Irreversible Anticholinesterases
(Organophosphorus Compounds)
1) Therapeutically useful:
Ecothiophate
2) War Gases:
Sarin
Tuban,
Soman
3) Insecticides:-
Parathion
Malathion
Diisopropyl Flurophosphate (DFP)
Tetramethyl Pyrophosphate (TMPP)
Octamethyl Pyrophosphotetraamide (OMPA)

17. ACETYLCHOLINE
NOT USED AS A DRUG

18. CHEMISTRY
CHEMISTRY

19. Pharmacological Actions/ 0rgan
system effects:
Muscarinic Actions
Nicotinic Actions

20. EYE:
• Miosis (constriction of pupil).
• Spasm of accommodation
• Decrease in intraocular pressure.
• Conjunctival hyperaemia
• Lacrimation

22. CVS (Heart & B.V)
Respiratory system
Gastro intestinal tract
Urinary bladder
Exocrine glands
Central Nervous System
Peripheral nervous system
N.M .Junction

23. CHOLINERGICS

24. CARBACHOL
 Ester of carbamic acid
 Has both muscarinic and nicotinic actions
 Muscarinic actions are prominent on eye, GIT &
urinary bladder
 DOA more than 30 min
 Therapeutic uses:
Glaucoma

25. METHACHOLINE
 Has methyl group in its structure
 Has both muscarinic and nicotinic actions
(very mild nicotinic actions )
 Muscarinic actions are prominent on CVS
 Longer DOA as compared to ACh
 Therapeutic uses: given SC for the relief
of paroxysmal atrial tachycardia

26. BETHANECHOL
 Structure related to Ach, acetate is replaced by
carbamate & choline is methylated
 Has no nicotinic actions
 Muscarinic actions are prominent on eye, GIT &
urinary bladder
 Prolonged DOA
 Therapeutic uses:
• Post operative Gastric distension
• Paralytic ileus
• Bladder atonia

27. MUSCARINE
 Quaternary amine (Amanita muscaria)
 Less complete absorption from the GIT
 Very toxic & can even enter the brain
 Rx : Atropine

28. PILOCARPINE
 Tertiary amine (Pilocarpus jaborandi leaves)
 Has muscarinic actions
 Therapeutic uses:
• Glaucoma
• To reduce the effect of mydriatics
• To break adhesions
Not used for systemic diseases increased
tracheobronchial secretions leading to
pulmonary oedema

29. NICOTINE & LOBELINE
 Plant derivatives
 Actions are mainly on nicotinic receptors (CNS,
PNS, NMJ)
 CNS, have important effects on brainstem and
cortex.
 PNS – autonomic ganglia.
 NMJ, immediate depolarization of the end plate
– increase in permeability to Na and K ions.

30. Myasthenia gravis (MG) is a disease affecting skeletal muscle
neuromuscular junctions. An autoimmune process causes
production of antibodies that bind to the a subunits of the
nicotinic receptor. This effect causes accelerated degradation
of the receptor and blockade of ACh binding to receptors on
muscle end plates. Frequent findings are ptosis, diplopia,
difficulty in speaking and swallowing, and extremity weakness.
Severe disease may affect all the muscles, including those
necessary for respiration.
The disease resembles the neuromuscular paralysis produced
by tubocurarine and similar nondepolarizing neuromuscular
blocking drugs. Patients with myasthenia are
sensitive to the action of curariform drugs and other drugs that
interfere with neuromuscular transmission e.g., aminoglycoside
antibiotics. Anti-ChEs are extremely valuable as therapy
for myasthenia. Almost all patients are also treated with
immunosuppressant drugs and some with thymectomy.
Edrophonium is used as a diagnostic test in myasthenia gravis.

31. Diagrams of (A) normal and (B) myasthenic
neuromuscular junctions. The MG junction
has a normal nerve terminal; a reduced number
of AChRs and a widened synaptic space.

32. • In the Alzheimer’s disease in the brain
tissue there are amyloid plaques and
neurofibrillarly tangles, as well as loss
of cholinergic neurons.
• Cholinacetyl trasferase activity
in the cortex and hippocampus
is reduced from 30% to 70%.
• Loss of cholinergic neurons contributes
for to much of the learning and memory deficit.
• The number of M-cholinoceptors is not
affected, but the number of N-receptors
is reduced.

33. Enlargement ventricles
Diminished hypothalamus
Thin brain cortex
Alzheimer's disease

34. Reversible anti-AChEs used in:
•Glaucoma: pilocarpine, demecarium
•Myasthenia gravis: edrophonium, galantamine,
neostigmine, physostigmine, pyridostigmine
•Alzheimer’ disease: donepezil, galantamine,
aminopyridine (Pymadine®), rivastigmine, tacrine
•Postoperative paralytic ileus or/and urinary
retention: galantamine, neostigmine
•Postoperative decurarization: galantamine,
neostigmine, pymadine (it releases ACh!)
•Belladonna poisoning: physostigmine,
neostigmine, galantamine
•Cobra bite (cobra venom has a curare-like
neurotoxin): galantamine, neostigmine

35. Reactivators of ChE used for the treatment
of intoxication with organophosphates
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