Cholinergics II and Muscle Blockers Flashcards
What is the mechanism of action
of Indirect Cholinergic Agonists?
Block acetylcholinesterase thereby increasing the amount of Ach in the synapse
Why are anticholinesterases called “Indirect” Cholinergic Agonists?
They do not directly activate the Cholinergic receptors,
but rather,
they increase the actions of endogenous Ach
What is the effect of Indirect Cholinergic Agonists on vascular smooth muscle (and blood pressure)?
No effect
because they increase the amount of
endogenous Ach in the synapse
and there is no endogenous Ach
at smooth muscles because there is no innervation!
How much do Indirect Cholinergic Agonists
affect muscarinic and nicotinic receptors?
At low-moderate doses they affect muscarinic.
At high concentration they activate nicotinic receptors
and thus muscle contractions, fasciulations and convulsions
What are other names for “Indirect Cholinergic Agonists?”
Indirect Cholinomimetics
Anticholinesterases
What are the important Indirect Cholinergic Agonists we need to know?
Neostigmine
Physostigmine
Donepesil
Sarin
Name the durations of actions of:
Physostigmine
Neostigmine
Donepezil
Sarin
Physostigmine: .5 - 2 hours
Neostigmine: .5 - 2 hours
Donepezil: 24 hours
Sarin: > 4 days
If you needed to prescribe a short-acting anticholinesterase, what would your choices be?
Neostigmine
Physostigmine
What do the key indirect cholinomimetics treat?
Neostigmine
Physostigmine
Donepezil
Neostigmine: Myasthenia Gravis, Paralytic Ileus
Physostigmine: Glaucoma (miotic)
Donepezil: Alzheimers
What Anticholinesterase would you prescribe to treat Alzheimer’s
Donepezil
What anticholinersterase would you prescribe for a patient with glaucoma
Physostigmine
What Indirect Cholinomimetic would you prescribe to treat Myasthenia Gravis or Paralysic Ileus?
Neostigmine
What Anticholinesterase
is used to diagnose Myasthenia Gravis?
Why is this the best anticholinesterase for this purpose?
Edrophonium
Because its Duration of action is 5-15 minutes
Which reversible anticholinesterase
can cross the blood brain barrier?
Physostigmine
Donepezil
(Neostigmine cannot cross BBB)
If you are prescirbing Neostigmine to treat Myasthenis Gravis, what do you do about
unwanted muscarinic receptor activiation?
Give Atropine to control these side effects
What anticholineresterase can reverse the paralytic effects of Vecuronium?
(What is the “antidote”)
Neostigmine
Your patient just got out of abdominal surgery
and now has a paralytic ileus.
How do you treat this?
Neostigmine
How does Donepezil treat Alzheimer’s Disease?
Alzheimer’s patients have decreased cholinergic function
due to cholinergic neuron damage and death,
leading to problems with memory and cognition.
Donepezil crosses the BBB
decreases aceylcholinesterase by 40%
and thereby increases ACh at CNS synapses.
HOWEVER: does not prevent progression!
How do Sarin
and other organophosphates like Parathion
get into the body?
They are very volatile liquids and
are lipid soluble and enter through any exposure to skin
What are the initial symptoms
of organophosphate poisoning?
(like Sarin or Parathion)
SLUDGE:
Salivation
Lacrimation
Urination
Defecation
GI Distress
Emesis
Basically if you have a patient who has stuff pouring out of every orifice, think organophosphate poisoning!
What are late symptoms of organophosphate poisoning?
bronchodilation, bradycardia, hypotension, pulmonary edema
twitching
respiratory paralysis (skeletal muscles: diaphragm, etc)
Ataxia, confusion, convulsions, coma, death
A 25 year old landscaper is brought in on an ambulance.
He loos very sick, vomiting, drooling, with watery eyes.
He smells terrible and the EMT says that he urinated and defecated in his pants and was moaning about his stomach hurting.
What are you thinking?
Organophosphate poisoning
What is the antidote to nerve gas/Sarin gas?
Atropine to block excess muscarinic activation
plus
Pralidoxime to reactivate acetylcholinesterase.
What is the only available ganglionic blocker and what is it used to treat and why?
Trimethaphan
Used to treat acute dissecting aortic aneurysm
Used to allow physician to completely control BP
by blocking physiologic reflexes
Does Trymethaphan control the
sympathetic or
parasympathetic systems?
Both
because it blocks gangionic nicotinic receptors.
But it has no effect on skeletal muscles.
What are skeletal muscle blockers and how are they used?
Skeletal Muscle Nicotinic Antagonists
used to temporarily paralyze muscles for surgery
What are the two types
of skeletal muscle blockers and how to they work?
Depolarizing: agonist that opens channel gate,
but then blocks the channel
Nondepolarizing: Prevents the channel gate from opening, thus a competitive antagonist.
Is vecuronium a nondepolarizing or depolarizing skeletal muscle blocker?
What is it used for?
Nondepolarizing
Used to paralyze skeletal muscles for 1-1.5 hrs during surgury.
Highly charged.
Does not cross BBB.
NOT an anesthetic!!!!
Your patient is out of surgery
and you want to reverse the effect of Vercuronium.
What can you use?
Neostigmine
increases Ach levels
and overcomes the competitive blockade
at the nicotinic receptors.
Atropine often added as well.
Is succinylcholine
a depolarizing or nondepolarizing muscle blocker?
What is it used for?
Depolarizing
Used in preparation for endrotracheal intubation
because it has rapid onset and is short acting.
You have given your patient succinylcholine
to paralyze the muscles to trach him,
but it has been over 30 minutes
and the effect has not worn off.
What is happening and what do you do?
Some patients (rare) have atypical cholinesterase.
Usually succinylcholine is metabolized by acetylcholinesterase, but this this case, it is not readily metabolized.
You cannot use neostigmine as an antidote.
(Presumable you would just wait it out.)
What is a major contraindication
for use of succinylcholine?
It increases K+ from the muscle
causing hyperkalemia and cardiac arrhythmia.
Contraindicated if patient has renal failure, is a burn patient, or multiple trauma, or has large areas of denervated muscle.
Alternative: rocuronium (duration of activity: 20-40 mins)
“Succ sucks, roc rocks”
What is the mechanism of action
of Botulinum Toxin?
It is a neurotoxin found in Botulinus anaerobic bacteria
that blocks ACh release by cleaving SNAP-25
thereby paralyzing muscles.
What are the therapeutic uses of Botulinum Toxin
Botox is used for:
Cosmetic surgery
Chronic Migraine
Local IM injection for blepharospasm, hemifacial spasm
and spasms in muscular diseases.
What neurotransmitters do Botulinum toxin target?
It is specific for the presynaptic terminals
of cholinergic neurons.
Your 55 year old female patient
suffers from migraines about 7 days each month
and asks you to prescribe Botox shots.
Should you?
FDA says Botox shots are for patients with a migraine
most days of the month.
Shot is administered every 12 weeks
in areas around the head and neck.
Adverse effects: neck pain and headache.
