Autonomic Drugs: Acetylcholine B&B Flashcards
name 5 places where acetylcholine receptors are found in the body
- muscarinic parasympathetic receptors in cardiac and smooth muscle, glands
- muscarinic sympathetic receptors in sweat glands
- nicotinic somatic receptors in skeletal muscle
- nicotinic receptors in 1st synapse of SNS and PNS
- nicotinic receptors at adrenal medulla
explain why flushing occurs with muscarinic antagonists
muscarinic receptors are found in parasympathetic system + SWEAT GLANDS of SNS
block muscarinic receptors —> no sweat —> increased body temp —> skin flushing
how do muscarinic agonists affect endothelial cells?
no direct effect on vascular smooth muscle
indirectly stimulate NO release —> activates guanylate cyclase —> less intracellular calcium —> vasodilation and lowered BP
what is the clinical use of the following acetylcholine agonists?
a. bethanechol
b. carbachol
c. pilocarpine
d. methacholine
a. Bethanechol: activates Bowel and Bladder to treat urinary retention
b. carbachol: lowers intraocular pressure to treat glaucoma or pupillary constriction
c. pilocarpine: lowers intraocular pressure to treat glaucoma
d. methacholine: bronchoconstrictor used to diagnosis asthma
name 2 acetylcholine agonists which lower intraocular pressure to treat glaucoma
- carbachol
- pilocarpine
what kind of drug is bethanechol?
Bethanechol: acetylcholine agonist, activates Bowel and Bladder to treat urinary retention (ex, after surgery)
what kind of drug are carbachol and pilocarpine?
acetylcholine agonists
carbachol: lowers intraocular pressure to treat glaucoma or pupillary constriction
pilocarpine: lowers intraocular pressure to treat glaucoma + treats Sjögren’s syndrome (increases salivation)
what kind of drug is neostigmine, and for what is it used?
acetylcholine esterase inhibitor (non-competitive, covalent but reversible) —> increases activity of ACh
used to treat urinary retention and myasthenia gravis
what kind of drugs are pyridostigmine and edrophonium, and what do they treat?
acetylcholine esterase inhibitor —> increases activity of ACh
edrophonium (competitive, reversible) - used for diagnosis of myasthenia gravis
pyridostigmine (non-competitive, covalent but reversible) - used to treat myasthenia gravis
what is physostigmine used for?
acetylcholine esterase inhibitor (non-competitive, covalent but reversible) —> increases activity of ACh
used to treat anti-cholinergic toxicity (such as by atropine) and glaucoma
a pt in the ED is accidentally given an overdose of atropine - what should you prescribe to reverse the effects?
atropine = anti-cholinergic drug
give physostigmine (ACh esterase inhibitor) to reverse the toxicity
what kind of drug is donepezil, and what does it treat?
acetylcholine esterase inhibitor —> increases activity of ACh
used to treat Alzheimer’s (in which there is decreased ACh activity)
what is the clinical use of the following acetylcholine esterase inhibitors?
a. neostigmine
b. pyridostigmine
c. edrophonium
d. physostigmine
e. donepezil
a. neostigmine - urinary retention, myasthenia gravis
b. pyridostigmine - myasthenia gravis (tx)
c. edrophonium - myasthenia gravis (dx)
d. physostigmine - anti-cholinergic toxicity (ex, atropine), glaucoma
e. donepezil - Alzheimer’s
which receptors are affected by myasthenia gravis? how does it present?
autoantibodies against ACh receptors, primarily nicotinic receptors in skeletal muscle
—> presents with problems of eye/chewing/talking/swallowing
—> classic finding is fatiguability due to decreasing ACh levels with more movement
COPD and peptic ulcers are similar in that they can both be worsened by what type of medication? explain
cholinergic (ACh agonist or ACh-esterase inhibitor) medication
bronchoconstriction —> COPD flare
increased gastric acid —> ulcers
Who is at risk for organophosphate poisoning and how does it present?
Exposure to insecticides often through skin (farmers) —> irreversible (covalent) blocker of acetylcholine esterase —> all ACh synapses in overdrive
- increased muscarinic activity —> diarrhea, urination, bronchospasm, bradycardia, salivation, lacrimation
- increased nicotinic activity —> muscle fasciculations
- increased CNS activity —> confusion, lethargy, seizures
Pt is 44yo farmer presenting to the ER with difficulty breathing. There is audible wheezing. Pt reports diarrhea, and unintentional loss of urine. Pt appears agitated. PE reveals pinpoint pupils. Pt is sweaty, drooling, and eyes are watery. Pulse is 30.
What is likely going on?
organophosphate poisoning: exposure to insecticides often through skin (farmers) —> irreversible blocker of acetylcholine esterase —> all ACh synapses in overdrive
- increased muscarinic activity —> diarrhea, urination, bronchospasm, bradycardia, salivation, lacrimation
- increased nicotinic activity —> muscle fasciculations
- increased CNS activity —> confusion, lethargy, seizures
How is organophosphate poisoning treated? Name 2 drugs used to treat.
exposure to insecticides often through skin (farmers) —> irreversible blocker of acetylcholine esterase —> all ACh synapses in overdrive
treat with:
1. atropine: muscarinic antagonist
2. pralidoxine: regenerates AChE (oxime group has high affinity for phosphate group in organophosphates, breaks interaction with cholinesterase)
what kind of drugs are homatropine and tropicamide, and what are they used to treat?
acetylcholine antagonists - muscarinic blockers
used to dilate eyes (mydriasis), applied topically
name 2 muscarinic blockers used to dilate eyes (mydriasis)
- homatropine
- tropicamide
what kind of drugs are benztropine and trihexyphenidyl, and what are they used to treat?
acetylcholine antagonists - muscarinic blockers
used to treat Parkinson’s
what kind of drugs are ipratropium and triotropium, and what are they used to treat?
acetylcholine antagonists - muscarinic blockers
used in inhalers to treat COPD
name 2 muscarinic blockers used in inhalers to treat COPD
- ipratropium
- tiotropium
what kind of drug is oxybutynin, and what is it used to treat?
acetylcholine antagonist - muscarinic blocker
used to treat urinary incontinence by reducing bladder spasms
what kind of drug is glycopyrrolate, and when is it used?
acetylcholine antagonist - muscarinic blocker
used pre-operatively to reduce airway secretions
what kind of drug is scopolamine, and what is it used to treat?
acetylcholine antagonist - muscarinic blocker
used to treat motion sickness (via patch)
what occurs in motion sickness, and considering this, how can it be treated? name 2 specific drugs from 2 different drug classes
motion sickness = overstimulation of M1 and H1 receptors
- scopolamine patch: muscarinic blocker (M1)
- meclizine or dimenhydrinate (Dramamine): antihistamines (H1)
what would be the side effects of a scopolamine patch for motion sickness? why does this make sense?
motion sickness = overstimulation of M1 and H1 receptors
scopolamine patch: muscarinic blocker (M1)
blocking acetylcholine at M1 receptors would also cause other symptoms related to parasympathetic nervous system such as: dry mouth, urinary retention, constipation
What kind of drug is atropine? And when is it used? What are the potential side effects?
atropine = muscarinic antagonist used to treat bradycardia and to cause pupil dilation, also sometimes used in cardiac arrest to speed the heart up
toxicity would cause dampening of the parasympathetic system + loss of sweating (M1 used in sympathetic system for sweating)
for what condition is atropine contraindicated and why?
atropine = muscarinic antagonist used to treat bradycardia and to cause pupil dilation, also sometimes used in cardiac arrest to speed the heart up
contraindicated in glaucoma!! decreases outflow of fluid and can cause sudden eye pain + halos
what occurs in Gardner’s Mydriasis?
due to Jimson weed toxin, which acts similarly to atropine (muscarinic blocker)
—> dilated pupils, tachycardia, HTN, dry mouth
tx: physostigmine (AChE inhibitor)
mechanism of botulism vs atropine overdose vs organophosphate poisoning
botulism = nicotinic + muscarinic blockage —> descending paralysis + GI symptoms
atropine overdose = muscarinic blockage —> lack of sweating + parasympathetic activity, no muscle effects
organophosphate poisoning = nicotinic + muscarinic activation —> fasciculations, miosis, bradycardia, tears, sweat
what is the shared mechanism of bethanechol, pilocarpine, and muscarine?
direct acting muscarinic agonists: activates muscarinic (M) acetylcholine receptors leading to increased production of IP3 and diacylglycerol, or inhibition of adenylyl cyclase (depending on receptor subtype coupling)
what would be the expected adverse effects of bethanechol, pilocarpine, and muscarine, and why does this make sense?
all direct-acting muscarinic agonists
side effects include parasympathomimetic effects: (cyclospasm, diarrhea, urinary urgency); vasodilation, reflex tachycardia, sweating
bethanechol - treats bladder/bowel retention
pilocarpine - treats Sjögren’s syndrome (to increase salivation)
muscarine - no clinical use, alkaloid found in mushrooms
what is the mechanism of nicotine acting on nicotinic receptors?
opens Na-K channels in ganglia and neuromuscular end plates
action is tissue dependent, e.g. vasoconstriction due to sympathetic innervation of blood vessels; increase motility and secretions due to parasympathetic postganglionic neuron discharge in the gut; muscle fasciculations and spasm due to neuromuscular end plate activation
what kind of drug is rivastigmine, and what is it used to treat?
cholinesterase inhibitor (non-competitive, covalent but reversible)
used to treat mild/moderate Alzheimer’s disease
