Lecture

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CHOLINOMIMETICS
Dr Igor Khalin

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Druds acting on ANS
• Parasympathomimetics Sympathomimetics
(cholinomimetics) (adrenomimetics)
• Parasyimpatholythics Sympatholythics
(cholinoblockers) (adrenoblockers)

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Drugs acting on ANS
• Parasympathomimetics
(cholinomimetics)
• Sympatholythics
(adrenoblockers)

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Drugs acting on ANS
• Sympathomimetics
(adrenomimetics)
• Parasympatholythics
(cholinoblockers)

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Cholinomimetics
• Eye
 accommodation for near vision, miosis, IOP
• Saliva
 copious, liquid
• Bronchi
 constriction, secretion
• Heart
 rate, blood pressure
• GIT
 secretion, peristalsis sphincter tone
• Bladder
 detrusor sphincter tone

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Cholinergic neuron
ATP
ATP
negative
feedback

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Cholinergic receptors
MUSCARINIC NICOTINIC
M1 M2 M3 M4 M5 NM NN
Eye
Heart
Smooth muscles
Exocrine glands
CNS
Ganglions
Carotid sinus
Skeletal muscles
Adrenal glands
CNS

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Muscarinic receptors
• High affinity for muscarine
• M1 – gastric parietal cells, saliva, CNS
• M2 - cardiac cells, smooth muscle,
CNS
• M3 - bladder, exocrine glands, smooth muscle, eye, CNS
• M1&M3 – Gq
• M2 - Gi
Amanita muscaria

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Muscarinic receptors
M1
M3

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Cholinergic Agonists
Direct acting Indirect acting
Acetylcholine
Bethanecol
Carbachol
Pilocarpine
Edrophonium
Physostigmine
Neostigmine

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ACETYLCHOLINE - Pharmakokinetics

12. Direct acting cholinergic agonists
1. Decrease in heart rate and cardiac output 2. Decrease in blood pressure
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ACETYLCHOLINE - Effects

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Organ system effects
ACETYLCHOLINE
• 3. Eye
– Contraction of sphincter (Miosis)
– Contraction of cilliary muscle (Myopia)

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ACETYLCHOLINE
4. Other actions
diarrhea
sweating
nausea
4. Clinical use very rare: eye drops to obtain miosis

15. Direct acting cholinergic agonists
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1. Stimulation of atonic bladder
2. Nonobstructive urinary retention
3. Neurogenic atony
4. Megacolon
Ophthalmology
-glaucoma
-surgery

16. Direct acting cholinergic agonists
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PILOCARPINE - PK
1. Tertiary nitrogen
2. Good adsorbtion
3. Penetrate BBB

17. Direct acting cholinergic agonists
Jaborandi (Pilocarpus pennatifolius)
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PILOCARPINE - Effects
1. Secretagoge (sweat, tears,
saliva)
• Jaborandi - what causes
slobbering
PILOCARPINE – Clinical usage
1. Sjögren’s syndrome
• Dry mouth, lack tears
2. Glaucoma

18. Direct acting cholinergic agonists
PILOCARPINE open-angle vs. closed angle glaucoma
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posterior
synechiae
anterior
synechiae

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Mushroom poisoning
 Miosis
 Hyper salivation
 Excessive sweating, lacrimation
 Cold, wet skin
 Bradycardia
 Polyuria
 Diarrhea
 Convulsions

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Nicotinic receptors
• High affinity to nicotine
• NM- neuro-muscular junction
• NN – ganglion, adrenal gland
CNS, carotid sinus

21. Indirect acting cholinergic agonists
Reversible Irreversible
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Edrophonium
Neostigmine
Physostigmine
Rivastigmine
Galantamine
Echothiophate
Organophosphates

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Mechanism of action

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Mechanism of action

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Mechanism of action

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Reversible
Physostigmine
Calabar Bean
1. Tertiary nitrogen
2. Good adsorbtion
3. Penetrate BBB

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Reversible
Physostigmine
1. Atony of intestine
2. Atony of bladder
3. Glaucoma
4. Overdose of ATROPINE,
ANTIPSYCOTICS, ANTIDEPRESSANTS

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Reversible
Physostigmine
1. Convulsions
2. Bradycardia
3. Paralysis of skeletal muscle

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Reversible
Neostigmine
1. Quatenary nitrogen
2. Poor adsorbtion
3. Not penetrate BBB

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Reversible
Neostigmine
1. Paralyzes
2. Myastenia gravis
3. Antidote of neuro-muscular blocker
TUBOCURARINE

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Reversible
Neostigmine
1. Salivation
2. Flushing
3. Decreased BP
4. Abdominal pain
5. Diarrhea
6. Bronchospasm

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Reversible
Neostigmine
1. Bronchial asthma
2. Intestinal inflammation,
obstruction
3. Bladder obstruction
4. Peritonitis

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Reversible
Edrophonium
1. Quatenary nitrogen
2. Poor adsorbtion
3. Not penetrate BBB
4. Fast elimination
5. Duration 10-20 min

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Reversible
Edrophonium
1. Diagnosis of myasthenia gravis
2. Antidote of neuro-muscular
blocker

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Reversible
Rivastigmine
1. Tertiary nitrogen
2. Good adsorbtion
3. Penetrate BBB

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Reversible
Rivastigmine
Alzheimer disease

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Irreversible
Echothiophate
Glaucoma

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Toxicology
Organophosphates

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Toxicology
Salivation
Lacrimation
Urination
Defecation
Gastrointestinal motility
Emesis
Miosis

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Toxicology
1. Reactivation of acetylcholinesterase
• PRALIDOXIME
 Not enter BBB
2. M-cholinoblocker
• ATROPINE
 Antimuscarinic only
3. Anticonvulsant
• DIAZEPAM

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SUMMARY