Cholinergic Inhibitors Flashcards
Name the two naturally occurring muscarinic antagonists.
atropine and scopolamine; found in plants
Name the three (semi)synthetic muscarinic antagonists. They’re all tertiary amines and used for peripheral applications.
dicyclomine, tropicamide, and tolterodine
Name the three (semi)synthetic muscarinic antagonists that are quaternary amines used in asthma.
ipratropium, tiotropium, and benztropine
What’s the main difference caused by quaternary vs tertiary amine?
Tertiary amines are generally better absorbed and penetrate the CNS better; they therefore typically have more central effects than quaternary.
Are the muscarinic antagonists selective?
No; they’re essentially non-selective and don’t discriminate well between the five receptor sub-types
Effects and MOA of muscarinic antagonists in the CNS.
receptor sub-type unknown; sedation, anti-motion sickness, antiparkinson, amnesia, delirium
Effects and MOA of muscarinic antagonists in the eye.
M3; cycloplegia, mydriasis (paralysis of ciliary muscle and dilation)
Effects and MOA of muscarinic antagonists in the bronchi.
M3; bronchodilation (especially if constricted)
Effects and MOA of muscarinic antagonists in the GI tract.
M1, M3; relaxation, slowed peristalsis
Effects and MOA of muscarinic antagonists in the GU tract.
M3; relaxation of bladder wall, urinary retention
Effects and MOA of muscarinic antagonists in the heart.
initial bradycardia (esp low doses) from block of inhibitory presynaptic receptors; tachycardia from block of M2 in SA node
Effects and MOA of muscarinic antagonists in the blood vessels.
M3 on endothelial cells; block of muscarinic vasodilation (only manifests if a muscarinic agonist is present)
Effects and MOA of muscarinic antagonists in the glands.
M1, M3; marked reduction of salivation, moderate reduction of lacrimation and sweating, less reduction of gastric secretion
Effects and MOA of muscarinic antagonists in the skeletal muscle.
none!
Use of benzotropine.
CNS; treat manifestations of Parkinsons
Use of scopolamine.
CNS; prevent or reduce motion sickness
Use of atropine.
eye; produce mydriasis and cycloplegia
Use of tropic amide.
eye; produce mydriasis and cycloplegia
Use of ipratropium and tiotropium.
bronchodilation in asthma, COPD
Use of dicyclomine
GI tract; reduce transient hypermotility
Use of tolterodine.
GU tract; treat transient cystitis, postop bladder spasms, incontinence
What’s the pneumonic for the toxicity/overdose of atropine?
dry as a bone, blind as a bat, red as a beet, mad as a hatter
Explain dry as a bone.
reduced sweating, lacrimation, salivation
Explain blind as a bat.
blockade of accommodation and excessive pupillary dilation
Explain red as a beet.
dilation of cutaneous vessels in upper body (atropine flush)
Explain mad as a hatter.
inhibitions of CNS receptors - series of complex consequences
What’s the most important atropine side effect that’s potentially lethal in children?
atropine fever, hyperthermia; results from blockade of thermoregulatory sweating`
Name and mechanism of a ganglion-blocking drug.
hexamethonium; non-depolarizing; competitively inhibits Nn receptors in both sympathetic and parasympathetic ganglia (non-selective); very rarely used
What’s the largest effect of hexamethonium and what’s the only clinical use?
blood pressure effect is marked (large reduction in vascular tone); used in hypertensive emergencies and to produce hypotension for ‘bloodless field’ surgery
Contrast depolarizing and non-depolarizing NMJ blockers.
non-depolarizing - prevent the opening of the channel
depolarizing - super agonists; persistently occupy receptor and cause persistent depolarization
Name three NMJ blockers and whether they’re depolarizing or non-depolarizing.
succinylcholine - depolarizing
tubocurarine, mivacurium - non-depolarizing
Use of tubocurarine and mivacurium. Which lasts longer?
cause flaccid paralysis of skeletal muscle necessary for surgery without depressant effects of deep anesthesia; tubocurarine lasts 30-60 min; mivacurium is shorter acting because it’s hydrolyzed more rapidly
Use and duration of action of succinylcholine.
causes flaccid paralysis quickly and is effective only for a few minutes; used for brief procedures such as tracheal intubation
Toxic effects of NMJ blockers?
respiratory paralysis and disturbance of autonomic function (interact with Nn to a lesser extent)
(pancuronium, non-depolarizing, is a component in lethal injections for capital punishment)
Effects of cholinesterase inhibitors on NMJ blockers.
effective at blocking effects of non-depolarizing blockers; depolarization blockers unaffected or increased effect
MOA of botulinum toxin A
degrades SNAP-25, which mediates fusion of synaptic vesicles with presynaptic terminal membrane (blocks release of Ach)
Use of botulinum toxin A
treatment of diseases associated with increased muscle tone:
reduce frown lines and wrinkles
achalasia (abnormal esophageal contractions)
strabismus (misalignment of eyes)
oromandibular dystonia (continuous spasms of face, jaw, neck, etc)
