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,
they increase the actions of endogenous Ach
What is the effect of Indirect Cholinergic Agonists on vascular smooth muscle (and blood pressure)?
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?"
What are the important Indirect Cholinergic Agonists we need to know?
Name the durations of actions of:
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?
What do the key indirect cholinomimetics treat?
Neostigmine: Myasthenia Gravis, Paralytic Ileus
Physostigmine: Glaucoma (miotic)
What Anticholinesterase would you prescribe to treat Alzheimer's
What anticholinersterase would you prescribe for a patient with glaucoma
What Indirect Cholinomimetic would you prescribe to treat Myasthenia Gravis or Paralysic Ileus?
is used to diagnose Myasthenia Gravis?
Why is this the best anticholinesterase for this purpose?
Because its Duration of action is 5-15 minutes
Which reversible anticholinesterase
can cross the blood brain barrier?
(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")
Your patient just got out of abdominal surgery
and now has a paralytic ileus.
How do you treat this?
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)
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
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?
What is the antidote to nerve gas/Sarin gas?
Atropine to block excess muscarinic activation
Pralidoxime to reactivate acetylcholinesterase.
What is the only available ganglionic blocker and what is it used to treat and why?
Used to treat acute dissecting aortic aneurysm
Used to allow physician to completely control BP
by blocking physiologic reflexes
Does Trymethaphan control the
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?
Used to paralyze skeletal muscles for 1-1.5 hrs during surgury.
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?
increases Ach levels
and overcomes the competitive blockade
at the nicotinic receptors.
Atropine often added as well.
a depolarizing or nondepolarizing muscle blocker?
What is it used for?
Used in preparation for endrotracheal intubation
because it has rapid onset and is short acting.