Cholinoceptor-blocking drugs

Question 1

Scopolamine

Answer 1

• MOA
• unknown in CNS
• Effects
• reduces vertigo, postoperative nausea
• Clinical
• prevention of motion sickness and postoperative nausea and vomiting
• Kinetics, tox, int.
• transdermal patch for motion sickness
• IM injection for postop use
• tox: tachycardia, blurred vision, xerostomia, delirium
• int: with other antimuscarinics

Question 2

Dicyclomine

(hyoscyamine, glycopyrrolate)

Answer 2

• MOA
• competitive antagonism at M₃ receptors
• Effects
• reduces smooth muscle and secretory activity of gut
• Clinical
• IBS, minor diarrhea
• Kinetics, tox, int.
• oral/parenteral
• short t_1/2 but action lasts up to 6h
• tox: tachycardia, confusion, urinary retention, increased intraocular pressure
• int: with other antimuscarinics

Question 3

Atropine (in ophthamology)

(homatropine, cyclopentolate, tropicamide)

Answer 3

• MOA
• competitive antagonism at all M receptors
• Effects
• mydriasis, cycloplegia
• Clinical
• retinal examination, prevention of synechiae after surgery
• Kinetics, tox, int.
• drops, long (5-6 days) action
• tox: increased intraocular pressure in closed-angle glaucoma
• int: with other antimuscarinics

Question 4

Ipratropium

(tiotropium, aclidinium)

Answer 4

• MOA
• competitive nonselective antagonist at M receptors
• Effects
• reduces or prevents bronchospasm
• Clinical
• prevention and relief of acute episodes of bronchospasm
• Kinetics, tox, int:
• aerosol canister, up to qid
• tox: xerostomia, cough
• int: with other antimuscarinics

Question 5

Oxybutynin

(darifenacin, solifenacin, tolterodine), (trospium)

Answer 5

• MOA
• slightly M₃-selective muscarinic antagonist
• Effect
• reduces detrusor smooth muscle tone, spasms
• Clinical
• urge incontinence, postoperative spasms
• Kinetics, tox, int.
• oral, IV, patch
• tox: tachycardia, constipation, increased intraocular pressure, xerostomia, patch-pruritus
• int: with other antimuscarinics

Question 6

Atropine (cholinergic poisoning)

Answer 6

• MOA
• nonselective competitive antagonist at all muscarinic receptors in CNS and periphery
• Effects
• blocks muscarinic excess at exocrine glands, heart, smooth muscle
• Clinical
• mandatory antidote for severe cholinesterase inhibitor poisoning
• Kinetics, tox, int.
• IV for as long as necessary until antimuscarinic signs appear
• tox: insignificant as long as AChE inhibition continues

Question 7

Pralidoxime

Answer 7

• MOA
• very high affinity for phosphorus atom but does not enter CNS
• Effects
• regenerates active AChE
• can relieve skeletal muscle end plate block
• Clinical
• usual antidote for early-stage (48h) cholinesterase inhibitor poisoning
• Kinetics, tox.
• IV every 4-6h
• tox: muscle weakness in overdose