Cholinergics II and Muscle Blockers

Question 1

What is the mechanism of action

of Indirect Cholinergic Agonists?

Answer 1

Block acetylcholinesterase thereby increasing the amount of Ach in the synapse

Question 2

Why are anticholinesterases called “Indirect” Cholinergic Agonists?

Answer 2

They do not directly activate the Cholinergic receptors,

but rather,

they increase the actions of endogenous Ach

Question 3

What is the effect of Indirect Cholinergic Agonists on vascular smooth muscle (and blood pressure)?

Answer 3

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!

Question 4

How much do Indirect Cholinergic Agonists

affect muscarinic and nicotinic receptors?

Answer 4

At low-moderate doses they affect muscarinic.

At high concentration they activate nicotinic receptors

and thus muscle contractions, fasciulations and convulsions

Question 5

What are other names for “Indirect Cholinergic Agonists?”

Answer 5

Indirect Cholinomimetics

Anticholinesterases

Question 6

What are the important Indirect Cholinergic Agonists we need to know?

Answer 6

Neostigmine

Physostigmine

Donepesil

Sarin

Question 7

Name the durations of actions of:

Physostigmine

Neostigmine

Donepezil

Sarin

Answer 7

Physostigmine: .5 - 2 hours

Neostigmine: .5 - 2 hours

Donepezil: 24 hours

Sarin: > 4 days

Question 8

If you needed to prescribe a short-acting anticholinesterase, what would your choices be?

Answer 8

Neostigmine

Physostigmine

Question 9

What do the key indirect cholinomimetics treat?

Neostigmine

Physostigmine

Donepezil

Answer 9

Neostigmine: Myasthenia Gravis, Paralytic Ileus

Physostigmine: Glaucoma (miotic)

Donepezil: Alzheimers

Question 10

What Anticholinesterase would you prescribe to treat Alzheimer’s

Answer 10

Donepezil

Question 11

What anticholinersterase would you prescribe for a patient with glaucoma

Answer 11

Physostigmine

Question 12

What Indirect Cholinomimetic would you prescribe to treat Myasthenia Gravis or Paralysic Ileus?

Answer 12

Neostigmine

Question 13

What Anticholinesterase

is used to diagnose Myasthenia Gravis?

Why is this the best anticholinesterase for this purpose?

Answer 13

Edrophonium

Because its Duration of action is 5-15 minutes

Question 14

Which reversible anticholinesterase

can cross the blood brain barrier?

Answer 14

Physostigmine

Donepezil

(Neostigmine cannot cross BBB)

Question 15

If you are prescirbing Neostigmine to treat Myasthenis Gravis, what do you do about

unwanted muscarinic receptor activiation?

Answer 15

Give Atropine to control these side effects

Question 16

What anticholineresterase can reverse the paralytic effects of Vecuronium?

(What is the “antidote”)

Answer 16

Neostigmine

Question 17

Your patient just got out of abdominal surgery

and now has a paralytic ileus.

How do you treat this?

Answer 17

Neostigmine

Question 18

How does Donepezil treat Alzheimer’s Disease?

Answer 18

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!

Question 19

How do Sarin

and other organophosphates like Parathion

get into the body?

Answer 19

They are very volatile liquids and

are lipid soluble and enter through any exposure to skin

Question 20

What are the initial symptoms

of organophosphate poisoning?

(like Sarin or Parathion)

Answer 20

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!

Question 21

What are late symptoms of organophosphate poisoning?

Answer 21

bronchodilation, bradycardia, hypotension, pulmonary edema

twitching

respiratory paralysis (skeletal muscles: diaphragm, etc)

Ataxia, confusion, convulsions, coma, death

Question 22

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?

Answer 22

Organophosphate poisoning

Question 23

What is the antidote to nerve gas/Sarin gas?

Answer 23

Atropine to block excess muscarinic activation

plus

Pralidoxime to reactivate acetylcholinesterase.

Question 24

What is the only available ganglionic blocker and what is it used to treat and why?

Answer 24

Trimethaphan

Used to treat acute dissecting aortic aneurysm

Used to allow physician to completely control BP

by blocking physiologic reflexes

Question 25

Does Trymethaphan control the

sympathetic or

parasympathetic systems?

Answer 25

Both

because it blocks gangionic nicotinic receptors.

But it has no effect on skeletal muscles.

Question 26

What are skeletal muscle blockers and how are they used?

Answer 26

Skeletal Muscle Nicotinic Antagonists

used to temporarily paralyze muscles for surgery

Question 27

What are the two types

of skeletal muscle blockers and how to they work?

Answer 27

Depolarizing: agonist that opens channel gate,

but then blocks the channel

Nondepolarizing: Prevents the channel gate from opening, thus a competitive antagonist.

Question 28

Is vecuronium a nondepolarizing or depolarizing skeletal muscle blocker?

What is it used for?

Answer 28

Nondepolarizing

Used to paralyze skeletal muscles for 1-1.5 hrs during surgury.

Highly charged.

Does not cross BBB.

NOT an anesthetic!!!!

Question 29

Your patient is out of surgery

and you want to reverse the effect of Vercuronium.

What can you use?

Answer 29

Neostigmine

increases Ach levels

and overcomes the competitive blockade

at the nicotinic receptors.

Atropine often added as well.

Question 30

Is succinylcholine

a depolarizing or nondepolarizing muscle blocker?

What is it used for?

Answer 30

Depolarizing

Used in preparation for endrotracheal intubation

because it has rapid onset and is short acting.

Question 31

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?

Answer 31

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.)

Question 32

What is a major contraindication

for use of succinylcholine?

Answer 32

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”

Question 33

What is the mechanism of action

of Botulinum Toxin?

Answer 33

It is a neurotoxin found in Botulinus anaerobic bacteria

that blocks ACh release by cleaving SNAP-25

thereby paralyzing muscles.

Question 34

What are the therapeutic uses of Botulinum Toxin

Answer 34

Botox is used for:

Cosmetic surgery

Chronic Migraine

Local IM injection for blepharospasm, hemifacial spasm

and spasms in muscular diseases.

Question 35

What neurotransmitters do Botulinum toxin target?

Answer 35

It is specific for the presynaptic terminals

of cholinergic neurons.

Question 36

Your 55 year old female patient

suffers from migraines about 7 days each month

and asks you to prescribe Botox shots.

Should you?

Answer 36

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.