Test 2 Cholinergics Flashcards
Nicotine
Stimulates Nn receptors. Used for smoking cessation
Succinylcholine
Muscle relaxant during intubation/convulsive shock therapy.
Remains on Nm receptors, causing depolarization block. The constant stimulation of the receptors prevents repolarization of the neuron.
Contra: Familial hyperthermia, skeletal muscle myopathies
Acetylcholine
Muscarinic and nicotinic agonist
Binds nicotinic and muscarinic receptors. Rapidly hydrolyzed by AchE and plasma cholinesterase, so it is not useful therapeutically.
Methacholine
Stimulates muscarinic receptors. Resists hydrolysis by AchE.
Use: Diagnose bronchial hyperactivity in cases of suspected asthma.
Tox: Bronchiolar constriction
Contra: β-blockers (overdose antidote is β-agonist treatment)
Carbachol
Muscarinic and nicotinic agonist, resist hydrolysis by AchE.
Use: Topical miotic (constriction of pupil) agent for ocular surgery and glaucoma.
Tox: Excessive muscarinic activity (eg. bronchoconstriction, decreased cardiac conduction)
Bethanechol
Selective muscarinic agonist (and low M2 affinity, so decreased cardiac effect). Resists hydrolysis by AchE.
Use: Treatment of post-op urinary retention and neurogenic bladder atony (esp targets receptors in GI and on urinary bladder)
Tox: Bradycardia and bronchoconstriction
Contra: Asthma, peptic ulcer (don’t want to stimulate secretions), bradycardia
Muscarine
Muscarinic agonist. No medicinal use; gives profound parasympathetic stimulation. Treat w/ atropine (muscarinic antagonist) if ingested.
From Clitocybe dealbata (a mushroom).
Pilocarpine
Non-selective muscarinic agonist, crosses BBB.
Use: Dry mouth due to head and neck radiotherapy or Sjogren’s syndrome (Ab destruction of salivary glands). Treatment of open-angle glaucoma.
Tox: Excessive muscarinic activation (slowed AV nodal conduction), hypotension, excessive salivation, and bronchoconstriction.
Neostigmine
Reversible inhibitor of Acetylcholinesterase, and has direct stimulation of nicotinic receptors at skeletal muscle endplate (NMJ).
Use: Myasthenia gravis (Ab attack of skeletal muscle nicotinic receptors), and reversal of neurotransmitter blockade.
Tox: Muscarinic and nicotinic excess.
Contra: Intestinal obstruction (don’t want to stimulate motility if the intestine is blocked).
Edrophonium
Inhibits cholinesterases and stimulates nicotinic receptors at NMJ. Very rapid and short duration of action, readily crosses BBB.
Use: To establish diagnosis of myasthenia gravis, or as a differential between progression of myasthenic weakness and cholinergic crisis (due to excess Ach) resulting from cholinesterase toxicity (neuromuscular block mimicking M.G. because of excess stimulation of Ach receptors).
Tox: Bradycardia, cardiac standstill
Contra: intestinal blockage, urinary obs.
Physostigmine
Inhibits cholinesterases. Long duration of action (t1/2 = 2hours). Readily crosses BBB.
Use: To counteract delirium secondary to excess anticholinergic activation (atropine poisoning).
Tox: Convulsions, respiratory and CV depression.
Contra: Asthma, CV disease, intestinal obstruction
Donepezil
Reversible CNS acetylcholinesterase (specifically) inhibitor.
Use: Treatment of Alzheimer’s disease.
Long half-life allows for once a day oral dosing.
Organophosphates
Irreversible cholinesterase inhibitor.
DUMBBELS (diarrhea, urination, miosis, bradycardia, bronchorrhea, emesis, lacrimation, salivation)
Treat with ventilation, suction of tracheal secretion, atropine (anti-muscarinic agent), 2-PAM (pralidoxamine chloride) to reactivate AchE.
Echothiophate
Irreversible AchE inhibitor used clinically.
Use: Long term miosis in the treatment of open-angle glaucoma (topically administered).
The goal is to stretch the trabecular network, but this leads to blurry vision. So this drug is usually only given to the elderly.
Atropine
Muscarinic antagonist
Use: 1) Allaying urgency and frequency of micturition (urination) associated with UTI.
2) Relieve hypermotility of colon and hypertonicity of SI.
3) Cholinesterase inhibitor induced poisoning (organophosphates)
4) Induce mydriasis (dilation) and cycloplegia (paralysis of ciliary muscle of eye)
5) Reverse bradycardia of vagal origin