Cholinergics II and Muscle Blockers Flashcards by Deana Cairo

What is the mechanism of action

of Indirect Cholinergic Agonists?

Block acetylcholinesterase thereby increasing the amount of Ach in the synapse

How well did you know this?

Not at all

Perfectly

Why are anticholinesterases called “Indirect” Cholinergic Agonists?

They do not directly activate the Cholinergic receptors,

but rather,

they increase the actions of endogenous Ach

How well did you know this?

Not at all

Perfectly

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 well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What are other names for “Indirect Cholinergic Agonists?”

Indirect Cholinomimetics

Anticholinesterases

How well did you know this?

Not at all

Perfectly

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

Neostigmine

Physostigmine

Donepesil

Sarin

How well did you know this?

Not at all

Perfectly

Name the durations of actions of:

Physostigmine

Neostigmine

Donepezil

Sarin

Physostigmine: .5 - 2 hours

Neostigmine: .5 - 2 hours

Donepezil: 24 hours

Sarin: > 4 days

How well did you know this?

Not at all

Perfectly

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

Neostigmine

Physostigmine

How well did you know this?

Not at all

Perfectly

What do the key indirect cholinomimetics treat?

Neostigmine

Physostigmine

Donepezil

Neostigmine: Myasthenia Gravis, Paralytic Ileus

Physostigmine: Glaucoma (miotic)

Donepezil: Alzheimers

How well did you know this?

Not at all

Perfectly

What Anticholinesterase would you prescribe to treat Alzheimer’s

Donepezil

How well did you know this?

Not at all

Perfectly

What anticholinersterase would you prescribe for a patient with glaucoma

Physostigmine

How well did you know this?

Not at all

Perfectly

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

Neostigmine

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Which reversible anticholinesterase

can cross the blood brain barrier?

Physostigmine

Donepezil

(Neostigmine cannot cross BBB)

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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.