APEX NMB Reversal Agents

What type of bond is fromed when edrophoium binds to anionic site on acetycholinesterase

A. Electrostatic

B. Hydrogen

C. Covalent

D. Ester

A. Electrostatic

AchE terminates effect of Ach by?

Hydrolyzing into choline & acetate.

Where is the AchE enzyme located

Located around the nicotinic receptors at the NMJ

How does reversing NMB work

By giving an AChE-I at the NMJ. Since more ACH becomes available, its better able to compete for alpha binding site on nicotinic receptor and antagnoize the block.

Important to note: even though Ach concentration is inrease, NMB still needs to be eliiminated from the body

Ache-I reverses what NMBs

Edrophium,neostigmine, and pyridostigmine.

AchE-I reverse effects of NMB in what 2 ways

Enzyme inhibition

Presynaptic effects

Where does pseudocholinesterase reside

in the plasma

What does pseudocholinesterase do

metabolized succs.

inhibited by neostigmine and pyridiostime but NOT EDROPHONIUM.

Therefore if succs is given after neo or pyrdo—> DOA of succs will be prolonged

ACHE interacts with sites in 1 of three ways

electrostatic attachment, formation of caramly esters, and phosphorylation

How is ACh inhibited;type of inhibition; Examples:

Electrostatic attachment

Electrostatic attachment= competitive

Ex. Edrophonium

How is ACh inhibited;type of inhibition; Examples:

Formationation of carbamyl Esters

Formationation of carbamyl Esters= competitive

Ex. Neostigmine, pyridostigmine; physostigmine

How is ACh inhibited;type of inhibition; Examples:

Phosphorylation

Phosphorylation= noncompetitive

Ex. organophosphates & echothiophate

Presynaptic site of action effects 2 mechanisms

1. similar to succs, AChe-I stimulate presynatpic receptors anc release more ACh

2. ACHE-1 near presynaptic receptor increases ACH concentration so it’s actually ACH that stimulate the receptor

— therefore MOA of edrophonium is likely presynaptic

Which statement regarding ache drugs are true 2

A. 50% of neostigmine is metabolized by the liver

B. Edro + neo has synergistic effects

C. Renal failure necessities second dose

D. Neostigmine is more portent than pyridostigmine

A. 50% of neostigmine is metabolized by the liver

D. Neostigmine is more portent than pyridostigmine

How do you reduce the cholinergic SE

Give anticholinergic drug with ACHE-I

Atropine is best paired with

Edrophonium

Glycopyrrolate is best paired with

Neostigmine or pyridostigmine

Do you need to renal dose NMB or ACH-I

No, renal failure prolongs DoA for both NMB and ACH-I. No need to adjust dose or re-dose it

The deeper the NMB, the

longer the onset time of the ACHE-I

ACHE-I & celiing effect

NO ceiling effect —> additional doses DO NOT produce better recovery

Which only makes SE worse

Does mixing Ach-I give synergistic effect

No

Who has a faster antagonsium with neostimgme

Faster in infants/children compared to adults

What group crosses BB

Tertiary amines (physostigmine) cross BBB

quaternary amines= Edrophonium, neostigmine, and pyridostigmine DO NOT cross BBB

What does TOF <0.9 indicate 3

Increase risk of airway obstruction, hypoxemic effects, and postop pulmonary complications

What can happen if you give excessive dose of ACH-I

can cause paradoxical weakness

Other uses of neostigmine & physiolgstimine

Intrathecal neostigmine (50-100mcg) produces analgesia. SE N/V, pruitrisits, and prolong sensory & motor block

Physostigmine (40mcg/kg) reduces post op shivery. Efficacy= meperidine and clonidine (Dex also reduces shivering)

What SE is LEAST likely to occur after neostigmine admin

A. bronchospasm

B. mydriasis

C. Nausea

D. prolong QT interval

B. mydriasis

Neostigmine causes miosis not mydriasis

Why do Cholinergic SE occur

increasing ACH concetnratin at musarinc recepor—> causes parasympathetic SE

What are the cholinergic SEs & pneumonic

DUMBBELLS
Diarrhea, Urination, Miosis, Muscle Weakness, Bradycardia, Bronchoconstriction, Emesis, Lacrimation, Salivation.

Compared to atropine, glyco is MORE likely to cause

A. Tachycardia

B. Xerostomia

C. Sedation
D. Mydriasis

B. Xerostomia

Atropine & scopalamine

naturally occurring tertiary amines

They are lipophilic (nonionized) can easily cross lipid membranes (I.e placenta, GIT, BBB—> so think CNS SE)

Glyco

quaternary ammonium derivative

Ionized

Does not cross cell membrane (placenta)

NO CNS activity

Small doses of atropine can cause

paradoxical bradycardia

due to inhibition of presynaptic M1 receptor on vagal nerve endings. M1’s jb is to reduce ACH release via negative feedback loop. Blocking Presynaptic M1 receptor turns off feedback loop and allows for continued ACH release and l/t bradycardia

Previous heart transplant vs muscarinic effects

muscarinic antagonists do not effect s/p heart transplant plts so HR is not affected.

HOWVER, they can still experience other cholinergic effects from ACHE-I so you still have to give muscarinic antagonists with ACHE-I

Atropine vs Scopolamine vs glycopyrrolate

Which one increases the HR the most

Atropine> glyco> Scop

Atropine vs Scopolamine vs glycopyrrolate

Which one has the most smooth muscle relaxation

Atropine & glyco> scop

Atropine vs Scopolamine vs glycopyrrolate

Which one causes the most sedative effect

Scopalamine> atropine

Glyco has not sedative effect

Atropine vs Scopolamine vs glycopyrrolate

Which has the most antisialoguse

Scop>glyco> atropine

Atropine vs Scopolamine vs glycopyrrolate

Which has the most mydriasis (pupil dilation) & cycloplegia ( temporary paralysis of the ciliary muscle in the eye, which prevents the lens from adjusting for near vision)

Scop> atropine

Glyco has no affect

Atropine vs Scopolamine vs glycopyrrolate

What prevents the most motion induced nasuea

Scop> Atropine

Glyco has no effect

Atropine vs Scopolamine vs glycopyrrolate

What decreases Gastric H secretion the most

Trick question= they all have slight effect

Which NMB is MOST effectively antagonized by sugammadex

A. Mivacurium

B. Rocuronium

C. Cisatracurium

D. Succs

B. Rocuronium

How does sugammadex work

Selectively binds to aminosteroid ND NMB (Roc>Vec> Panc)

No effect on succs of any benzylisoquinolines (atracurium, cisatracurium, mivacurium)

Suggamadex MOA

Gamma cyclodextrin made of 8 sugars in assembled in a ring. Ring encapsulates NMB, making it inactive and unable to engage with nicotinic receptors.

Analogy= febreze for aminosteroid NMB

• Encapsulating Roc reduces concentration in plasma which augments concentration gradient between NMJ and plasma therefore increasing rate of transfer of Roc to NMB toward plasma. Affinity for roc is strong but can be reversed

How is roc and sugammadex excreted

Roc= primarily excreted by biliary system

Sugammadex- roc complex excreted unchanged by the kidneys

How does sugammadex improve safety 3

1. Can be used for difficult intubation without drawbacks of succs

2. Cna reverse DENSE NMB quickly reducing risk of residula arlaysis

3. ALlows for dnese blockated until end of sx without delaying extubation

Dosing for sugammadex for Roc and Vec

ACTUAL BODY WEIGHT

if Roc or Vec with TOF 2 or better—> 2 mg/kg

If Roc or Vec with TOF 0 + 2 PTC or better—> 4 mg/kg

If ROC > 3min after admin at 1.2 mg/kg or less —> 16mg/kg

What if the patient needs to be paralyzed after suggamadex

Use a non-aminosteriod NMB or redose roc or vec (sometimes works)

1. Use non-aminosteroid NMB (Succs, atracurium, cisatracurium, mivacurium)

   1. Can be given regardless of when sugammadex was administered

   2. This is the only option if 16 mg/kg of sugammadex was given within 24 hours of the need for addition MR

2. If <4 mg/kg of sugammadex was administered→ can redose roc or vec

   1. The patient received suggammed 5 min-4 hrs→ give Roc 1.2mg/kg

   2. If patient receiving sugammadex> 4 hrs ago—> give rock 0.6 mg/kg or Vec 0.1mg/kg

Risks of sugammadex 3

analphyalsiz (0.3%)

bradycardia and cardiac arrest— anticholinergics useful in this context

Reduces hormonal contraception up to 7 days. so use backup method

After administering 50mg of roc to an 80 kg patient, CRNA encounters can’t intubate and can’t ventilation situation. How much sugammadex should be administered at this time

16 mg/kg x 80kg= 1280

What type of bond is formed when neostigmine binds to ache

A. covalent

B. electrostatic

C. Ester

D. Hydrogen

C. Ester

What SE is LEAST likely to occur after neostigmine administration

A. prolong QT interval

B. Miosis

C. Bronchodilation

D. Nausea

C. Bronchodilation

Compared to scopolamine, atropine is more likely to cause

A. tachycardia

B. cycloplegia

C. Xerostomia

D. sedation

A. tachycardia

What statements regarding ache drugs are true 2

A. Pyridostigmine is less potent than neostigmine

B. 90% of neostigmine is metabolized by the liver

C. Edrophonium + neostigmine have additive effect

D. Renal failure necessitates larger dose

A. Pyridostigmine is less potent than neostigmine

C. Edrophonium + neostigmine have additive effect

Rank the following drugs acording to tendency to cause cycloplegia

Scop, glyco, atropine

Scop +++

Atropine ++
Glyco 0

The following are well absorbed from GIT EXCEPT

A. Scop

B. Glyco

C. Physostigmine

D. Atropine

B. Glyco

Atropine & scop are naturally occuring; Phys is lipid soluble; Glyco does not cross any membranes

Match ache-I to dose

Pyridostigmine

Neostigmine

Edrophonium

Pyridostigmine= 0.3 mg/kg

Neostigmine= 0.05 mg/kg

Edrophonium= 1 mg/kg

What ache-I prolong duration of succs 2

A. phys

B. Edrop

C. Pyridio

D. Neo

C. Pyridio

D. Neo

Match the drug to onset of action. Assume steady state of NDNMB in plasma

Neostigmine

Edrophonium

Pyridostigmine

Edrophonium= 1 min

Neostigmine= 10 min

Pyridostigmine= 15 min

Select the best statement regarding anticholinergic agent and edrophonium when used as NMB

A. Glyco should be mixed in the same syringe as edrophonium

B. Atropine pairs better than glyco

C. Atropine is given after edrophonium

D. Atropine should be avoided due to CNS SE

B. Atropine pairs better than glyco

In PACU, 85 female received scopolamine is now confused and agitated. What is the best intervention at this time.

A. Physostigmine

B. Pyridostigmine

C. Reduce environmental stimuli

D. Midazolam

A. Physostigmine

Phys crosses BBB

Sugammadex antagonized NDMR by encapsulating

A. Roc only

B. Benzyliquinoones and aminosteroids

C. Benzylisoquinolines

D. Aminosteroids

D. Aminosteroids

Select the best ACHe-I to antagonize 90% twitch suppression

A. Pyridostigmine

B. Physostigmine

C. Edrophonium

D. Neostigmine

D. Neostigmine

Phys has prolonged onset

Edro is effective in reversing mild to mod NMB but cannot reverse profound relaxation (90% twitch depression or one twitch)

Neostigmine antagonized Roc by

A. potentiating ache activity

B. reversibly binding to butyrylcholinesterase

C. Decreases ach hydrolysis

D. competing with roc at nicotinic receptor

C. Decreases ach hydrolysis

Click on the box that represents neostigmine

navy blue