Autonomics: Cholinomimetic agents

Question 1

Bethanechol

Answer 1

direct cholinomimetic agonist

MOA: Activates bladder smooth muscle; resistant to
AChE. No nicotinic activity. “Bethany, call
me to activate your bladder.”

Clinical use: urinary retention

Question 2

carbachol

Answer 2

direct cholinomimetic agonist

MOA: Carbon copy of acetylcholine (but resistant to
AChE).

Clinical use: Constricts pupil and relieves intraocular
pressure in open-angle glaucoma.

Question 3

methacholine

Answer 3

direct cholinomimetic agonist

MOA: Stimulates muscarinic receptors in airway when
inhaled.

Clinical use: Challenge test for diagnosis of asthma.

Question 4

pilocarpine

Answer 4

direct cholinomimetic agonist

MOA: Contracts ciliary muscle of eye (open-angle
glaucoma), pupillary sphincter (closed-angle
glaucoma); resistant to AChE, can cross bloodbrain
barrier (tertiary amine). “You cry, drool,
and sweat on your ‘pilow.’ ”

Clinical use: Potent stimulator of sweat, tears, and saliva
Open-angle and closed-angle glaucoma,
xerostomia (Sjögren syndrome).

Question 5

donepezil, rivastigmine, galantamine

Answer 5

indirect cholinomimetic agonist (anticholinesterases)

MOA: ↑ ACh

Clinical use: 1st line for Alzheimer disease (Dona Riva
dances at the gala).

Question 6

edrophonium

Answer 6

indirect cholinomimetic agonist (anticholinesterases)

MOA: ↑ ACh

Clinical use: Historically used to diagnose myasthenia gravis;
replaced by anti-AChR Ab (anti-acetylcholine
receptor antibody) test.

Question 7

neostigmine

Answer 7

indirect cholinomimetic agonist (anticholinesterases)

MOA: ↑ ACh
Neo CNS = No CNS penetration (quaternary
amine).

Clinical use: Postoperative and neurogenic ileus and
urinary retention, myasthenia gravis,
reversal of neuromuscular junction blockade
(postoperative).

Question 8

physostigmine

Answer 8

indirect cholinomimetic agonist (anticholinesterases)

MOA: ↑ ACh
Phreely (freely) crosses blood-brain
barrier –> CNS (tertiary amine).

Clinical use: Antidote for anticholinergic toxicity;
physostigmine “phyxes” atropine overdose.

Question 9

pyridostigmine

Answer 9

indirect cholinomimetic agonist (anticholinesterases)

MOA: ↑ ACh; ↑ muscle strength. Used with
glycopyrrolate, hyoscyamine, or propantheline
to control pyridostigmine side effects.
Pyridostigmine gets rid of myasthenia gravis.

Clinical use: Myasthenia gravis (long acting); does not
penetrate CNS (quaternary amine).

Question 10

anticholinesterase poisoning

Answer 10

Often due to organophosphates (eg, parathion) that irreversibly inhibit AChE. Organophosphates
commonly used as insecticides; poisoning usually seen in farmers.

Muscarinic effects: Diarrhea, Urination, Miosis, Bronchospasm,
Bradycardia, Emesis, Lacrimation, Sweating,
Salivation. (DUMBBELSS)
–Reversed by atropine, a competitive inhibitor.
Atropine can cross BBB to relieve CNS
symptoms.

Nicotinic effects: Neuromuscular blockade (mechanism similar to
succinylcholine).
–Reversed by pralidoxime, regenerates AChE if
given early.
Pralidoxime (quaternary amine) does not readily
cross BBB.

CNS effects: Respiratory depression, lethargy, seizures, coma