Cholinergic Agonists & Receptors Flashcards
Cholinergic receptors are divided into
Muscarinic receptors & nicotinic receptors
Muscarinic receptors & nicotinic receptors can be further divided to
Muscarinic receptors M1 M2 M3 M4 M5
Nicotinic receptors Nm Nn
Muscarinic / metabotropic receptors act on
M1 +: CNS, parietal cells in gastric gland
M2 -: heart, postsynaptic membrane
M3 +: exocrine glands (lacrimal gland, salivary, parotid, sweat, pancreatic, gastric gland), GIT, urination & defecation, ciliary muscle & constrictor pupillae
M4 -
M5 +
ALL GPCR
+ Gq
- Gi
Nicotinic receptors produce effects at ?
Nn- nerves ,autonomic ganglia, CNS
Nm- skeletal muscle contraction (NMJ)
Cholinergic agonists produce
parasympathetic effects
There are two categories under cholinergic agonists
Direct agonists
Indirect agonists
List all direct and indirect cholinergic agonists
Direct agonists
muscarinic & nicotinic : Ach
muscarinic: pilocarpine, methacholine
nicotinic: nicotine, succinylcholine
Indirect agonists (inhibit AchE)
reversible effect
Short acting: edrophonium
Medium-duration: neostigmine/proserine, physostigmine/eserine
Long acting: pyridostigmine
irreversible effect
Organophosphate: soman (nerve gas), malathion (insecticides)
Clinical indications & adverse effects
Decrease motility in GIT & bladder due to postop ileus, postpartum urinary retention, gastroparesis in diabetes mellitus
drug to give?
Neostigmine
Pyridostigmine
Clinical indications & adverse effects
Bronchial provacalation test due to asthma, COPD
drug to give?
Methacholine (increase bronchospasm) :acts on airway smooth muscles
Clinical indications & adverse effects
Alzheimer disease due to drastic decrease in Ach
drug to give?
Tacrine (increase Ach, slow the progression of disease, but cannot cure)
Clinical indications & adverse effects
Glaucoma - to relieve:dilation of pupil, cilliaris contraction
drug to give?
Pilocarpine (to drain): act on glands to increase lacrimation (Sjogren syndrome), increase salivation (radiation induced necrosis)
Physostigmine
What is myasthenia gravis?
An autoimmune disease which the antibodies attack nicotinic receptors and block the binding of Ach to receptors, causing weakness in muscle
Treatment for myasthenia gravis
When treated, antibodies get hit by Ach, increased in Ach binding will reduce weakness in muscle
drugs to give
1. Edrophonium (TENSILON TEST)
-help diagnose MG
-short acting drug, will see improvement in weakness within short period of time
2. Neostigmine
-treat MG
-duration of action is shorter than pyridostigmine
3. Pyridostigmine
-treat MG (chronic/ long term management)
-longer duration
Why physostigmine is not used in the treatment of MG?
CNS toxicity
Will cause seizures and convulsions
How to differentiate myasthenic crisis from cholinergic crisis?
MC: severe muscle weakness and pyridostigmine is unable to displace the antibodies
CC: excessive stimulation of muscle (increase in Ach binding)
Give edrophonium
-inhibit AchE, Ach increases, antibodies are knocked out, causing contraction, weakness decreases, then it is MC: treat with higher dose of pyridostigmine
-inhibit AchE, Ach increases, increase in weakness+ presents cholinergic signs, then it is CC: treat with decrease does of pyridostigmine
