Topic 8: Cholinergic Agonists

Question 1

Acetylcholine Sites of Action

Answer 1

Preganglionic fibers
Postganglionic fibers
Skeletal muscles of somatic system

Question 2

Cholinergic transmission: step 1

Answer 2

Choline active transport from ECF into neuron
Choline + acetyl coenzyme A in cytosine = ACh
Rate limiting step: choline uptake

Question 3

Cholinergic neurotransmission: step 2

Answer 3

Packing + storage into presynaptic vesicles
Active transport coupled to proton efflux
Vesicle = ACh + cotransmitters (ATP+proteoglycan)

Question 4

Cholinergic neurotransmission: step 3

Answer 4

Voltage-gated Ca++ channels open
Ca++ fuses vesicle & cell membrane
ACh released

Question 5

Cholinergic neurotransmission: step 4

Answer 5

ACh –> synaptic cleft –> receptors

Biological response

Question 6

Cholinergic neurotransmission: step 5

Answer 6

AChE cleaves ACh to choline and acetate in cleft

Question 7

Cholinergic neurotransmission: step 6

Answer 7

Na+ cotransports choline back into neuron (recycled)

Question 8

Cholinergic receptors

Answer 8

Muscarinic

Nicotinic

Question 9

Carbachol (Miostat)

Answer 9

Nonselective N/M agonist
Miosis (constriction) during surgery
Topically: reduce intraocular P in glaucoma or post surgery

Question 10

Bethanechol (Urecholine)

Answer 10

Direct acting muscarinic agonist
Affects smooth muscle of bladder & GI tract
Produces urination
Short duration of action (approx 1hr)

Question 11

Pilocarpine (Salagen)

Answer 11

Direct acting muscarinic agonist
CNS at ED
Topical to eye for miosis & intraocular P reduction
Potent stimulator of secretions: sweat, tears, saliva

Question 12

Edrophonium (Elon)

Answer 12

Indirect acting reversible cholinergic
Short acting AChE inhibitor (10-20mins)
Diagnosis of myasthenia gravis (Edrophonium Test)

Question 13

Myasthenia gravis

Answer 13

Chronic autoimmune neuromuscular disease
Antibodies to nicotinic receptor in NMJ
Fewer available receptors
Skeletal muscle weakness

Question 14

Physostimine

Answer 14

Indirect acting reversible cholinergic agonist
Intermediate duration (30min-2hr)
CNS cholinergic
Treats anticholinergic overdose & glaucoma

Question 15

Neostigmine

Answer 15

Indirect acting reversible cholinergic agonist
Similar Physostigmine, more polar, cannot enter CNS
Skeletal muscle
Stimulate bladder & GI tract
Antidote for neuromuscular blocking agent
Management of Myasthenia gravis
0.5-4hrs

Question 16

Pyridostigmine

Answer 16

Indirect acting reversible cholinergic agonist
Chronic management of myasthenia gravis
Duration 4-6hrs

Question 17

Organophosphate

Answer 17

Indirect acting irreversible cholinergic agonist
Permanently binds to/inactivates AChE
General cholinergic stimulation, paralysis, breathing difficulties, convulsions
Glaucoma (Echothiophate)

Question 18

Organophosphate poisoning therapy

Answer 18

Pralidoxime (2-PAM): reactive AChE, cannot penetrate CNS

Atropine: competitively binds to M receptor