Cholinergic Receptor

Question 0

Methacholine

Answer 0

Drug class: M3 agonist
Indication: Dx of diagnosis by challenging bronchial hyperreactivity
Kinetics: methylated ACh, has quarternary ammonium so poorly absorbed.

Question 1

Acetylcholine (Miochol)

Answer 1

Drug class: cholinergic agonist
Indication: Glaucoma (Topical)
Special considerations: unequal access of ACh to various sites (epithelial cells > para/sympathetic effector organs > NMJ, Ganglia, CNS), rapidly cleared from the blood by plasma pseudocholinesterase, access further limited in less perfused sites.

Question 2

Bethanechol

Answer 2

Drug class: muscarinic receptor agonist
Indication: formerly used to relieve GI dysmotility syndromes such as postsurgical ileus
Consideration: largely replaced by metoclopramide, stimulates presynaptic D2 receptors to trigger ACh release

Question 3

Nicotine

Answer 3

Drug class: nicotinic receptor agonist
Dynamics: initial activation of Na/K channel leads to subsequent deactivation, i.e. Depolarization-desensitization blockade, receptor phosphorylation.
Kinetics: rapidly absorbed orally or through skin, rapid onset
Concern: nicotine poisoning, marked by tachycardia, HTN, cold sweat, nausea, vomiting, diarrhea, salivation, urinary incontinence (PS stimulation), paradoxical flaccid paralysis of diaphragm.
Addiction: stimulation of receptors in CNS elevates mesolimbic dopamine–leads to craving.
Indication: smoking cessation, Nicotine patch, gum.

Question 4

Varenicline (Chantix)

Answer 4

Drug class: very selective and potent competitive partial agonist of a2-b4 nicotinic receptors, for smoking cessation
Dynamics: CNS mesolimbic dopamine, partial stimulation prevents low dopamine and cravings, also prevents nicotine from creating dopamine surges, chemical reward
Kinetics: well absorbed, peak 4h, half-life 24h, excreted primarily in urine as unchanged drug
Special considerations: reports of suicidal thoughts and aggressive and erratic behavior. Use for psychiatric cautions with extreme caution
Contraindication: pregnancy/lactation, causes drowsiness, caution operating machinery
Monitor: neuropsychiatric Sx

Question 5

Edrophonium

Answer 5

Drug class: short-acting AChE inhibitor
Mechanism: do not form ester bond, highly charged, do not cross BBB, short-acting 5-10min IV, 5-30min IM, fast onset
Indication: Dx of Myasthenia Gravis
Special consideration: muscarinic poisoning–with possible effects of respiratory inundation

Question 6

Physostigmine

Answer 6

Drug class: intermediate-acting AChE inhibitor
Dynamic: lipid soluble, can cross BBB, not useful for Mysthenia Gravis
Indication: occasionally used to treat CNS signs of muscarinic blockers

Question 7

Neostigmine

Answer 7

Drug class: intermediate-acting AChE inhibitor
Dynamic: designed with quaternary ammonium group to keep it out of CNS
Indication: just peripheral effects, useful for mysthenia gravis
Special indication: too little can lead to MG crisis, too much can lead to cholinergic crisis

Question 8

Organophosphate (Echothiophate, Sarin)

Answer 8

Drug class: long-acting phosphorlayting inhibitor of AchE
Special considerations: insecticide, nerve gas
Treatment: manage DUMBBELSS/SLUDGE Sx with atropine, aggressive resp support
Antidote: Pralidoxime (2-PAM), can reactivate phosphorylated enzymes if given soon enough within a few hr, rescues muscular function, contraindicated in poisoning by carbamate AChE inhibitors

Question 9

Atropine

Answer 9

Drug class: muscarinic antagonist, inverse agonist, works via reversible blockade
Dynamic: parasympatholytic, unopposed sympathetic flow
Toxicity: delirium, hallucinations (unclear CNS effects), mydriasis (dilation of pupils), blurred vision, exacerbates closed angle glaucoma, dry mouth, hyperthermia, urinary retention

Question 10

Scopolamine

Answer 10

Drug class: muscarinic blocker
Indication: motion sickness, reduces vertigo, post-surgical nausea, also indicated in anesthetic adjuvant (induces amnesia)
Side effects: similar to Atropine, CNS excitation/depression

Question 11

Dicyclomine

Answer 11

Drug class: M3 specific muscarinic competitive antagonist
Indication: irritable bowel, minor diarrhea
Kinetics: IM, PO
Dynamics: short half life but long duration 6hr

Question 12

Methscopolamine, Pirenzepine, Propantheline

Answer 12

Drug class: muscarinic blocker

Indication: peptic ulcer, inhibits acid secretion

Question 13

Oxybutynin, Glycopyrrolate

Answer 13

Drug class: muscarinic blocker

Indication: urgency and bladder problems, decrease detrusor muscle tone

Question 14

Ipratropium

Answer 14

Drug class: non selective muscarinic antagonist
Delivery: aersol, tid, qid
Kinetics: quaternary amine, low CNS penetration, low systemic absorption
Indication: persistent COPD, asthma (first line therapy), inhibits bronchoconstriction
Special consideration: sometimes packaged with b2 agonist for asthma
Treat side effects of cholinergic poisoning with Atropine

Question 15

Succinylcholine

Answer 15

Drug class: depolarizing nicotinic antagonist
Drug mechanism: depolarization-desensitization blockade
Kinetics: dimers of Ach, acts like Ach, rapidly cleared by AchE
Indication: used for short surgical procedures, intubation
Contraindication: FMx of malignant hyperthermia, heart failure, hyperkalemia, burns, trauma, tissue injury
Side effects: big efflux of K, hyperkalemia, muscle fasiculation, histamine release, rarely malignant hyperthermia
Special: do NOT reverse paralysis with neostygmine (can cause muscarinic syndrome), allow plasma AChE to clear.

Question 16

D-tubocurarine

Answer 16

Drug class: non-depolarizing Nm blocker
Drug mechanism: reversible competitive inhibition
Kinetics: quaternary amine, so minimal CNS effects
Special consideration: produces paralysis in fully conscious pts, never give such a drug to unanesthetized pts, never let a pt emerge from anesthesia before reversing the paralysis, reverse with neostygmine (AchE inhibitor)

Question 17

Trimethaphan

Answer 17

Drug class: non-depolarizing ganglionic nicotinic (Nn) blocker
Mechanism: blocks all ganglia, but used for its effects on sympathetic ganglia
Kinetics: given IV, rapid onset, rapidly cleared by liver, minimal CNS effect
Indication: extremely potent effects on lowering BP, only used in hypertensive crisis, dissecting aortic aneurysm
Side effects: orthostatic hypotension, urinary retention, constipation, impaired accommodation of lens

Question 18

Botox

Answer 18

Drug class: indirect anticholinergic
Details: produced from Clostridium botulinis, most toxic molecule known, toxin A binds receptors and is endocytosed, light chain of toxin cleaves SNARE, blocks docking
Kinetic: Local delivery
Dynamic: at NMJ, flaccid paralytic effect, at Muscarinic recptors, atropinic effect
Indication: cosmetic, axillary hypehyrdrosis, strabismus (unaligned eyes)

Question 19

Tropicamide

Answer 19

Drug class: muscarinic blocker

Causes mydriasis for retinal exam

Question 20

Homatropine

Answer 20

Drug class: muscarinic receptor

Indication: prevention of scarring post eye-surgery