Unit 5 - NMB Reversals & Anticholinergics

Question 1

what metabolizes succs

Answer 1

pseudocholinesterase

Question 2

acetylcholinesterase inhibitors that antagonize pseudocholinesterase

Answer 2

neostigmine & pyridostigmine (not edrophonium)

Question 3

where is AChE concentrated

Answer 3

around nicotinic receptors at NMJ

Question 4

acetylcholinesterase inhibitors that inhibit AChE

Answer 4

Edrophonium, neostigmine, and pyridostigmine

Question 5

how do acetylcholinesterase inhibitors antagonize block with NDNMB

Answer 5

inc. concentration of ACh at NMJ

more ACh available to antagonize the block

Question 6

2 ways AChE inhibitors increase ACh at nicotinic receptor

Answer 6

1) enzyme inhibition, 2) presynaptic effects

Question 7

Primary mechanism of edrophonium

Answer 7

most likely presynaptic

Question 8

MOA of edrophonium

Answer 8

• forms electrostatic bond at anionic site and a noncovalent H+ bond at the esteratic site (short duration of action, H+ bonds are weak)
• competitive

Question 9

2 possible mechanisms of presynaptic action:

Answer 9

1. Similar to succs, AChE inhibitors stimulate presynaptic receptor = additional ACh release
2. Inhibition of AChE near presynaptic receptor increases ACh concentration in that region

Question 10

is a dose adjustment of AChE inhibitors needed for renal failure

Answer 10

nope - duration of NMBs also prolonged

Question 11

effect of mixing AChE inhibitors

Answer 11

additive effect

Question 12

neostigmine antagonism is faster in children or adults?

Answer 12

infants & children

Question 13

which AChE inhibitor(s) pass the BBB

Answer 13

only Physostigmine (tertiary amine)

Edrophonium, neostigmine, & pyridostigmine are quaternary amines (do not

Question 14

risks of extubating with TOF ratio < 0.9

Answer 14

↑ risk airway obstruction, hypoxemic events, postop pulm. complications

Question 15

effect of giving AChE inhibitor at full recovery

Answer 15

paradoxical muscle weakness

Question 16

dose of intrathecal neostigmine that produces analgesia

Answer 16

50-100 mcg

Question 17

SEs of intrathecal neostigmine

Answer 17

• N/V
• pruritis
• prolonged sensory and motor block

Question 18

AChE inhibitor that can be used for postop shivering

Answer 18

Physostigmine (40 mcg/kg)

Question 19

4 drugs that ↓ shiving in PACU:

Answer 19

physostigmine, meperidine, clonidine, dexmedetomidine

Question 20

cholinergic side effects

r/t ↑ concentration of ACh at muscarinic receptor

Answer 20

DUMBBELLS
* Diarrhea
* Urination
* Miosis
* Bradycardia
* Bronchoconstriction
* Emesis
* Lacrimation
* Laxation (elimination of fecal waste)
* Salivation

Question 21

how do antimuscarinics affect HR

Answer 21

increase
atropine > glyco > scopolamine

Question 22

most to least antisialogogue effects of anticholinergics

Answer 22

scopolamine > glycopyrollate > atropine

Question 23

how do anticholinergics affect gastric H+ secretion

Answer 23

increased

Question 24

Job of M1 receptor

Answer 24

• to reduce ACh release via negative feedback loop
• blockade “turns off” loop and allows continued ACh release/bradycardia

Question 25

can anticholinergics be given to a patient with a transplanted heart

Answer 25

* Do not affect HR in patients with previous heart transplant (denerevated heart) * Can still experience other cholinergic effects from AChE inhibitors - give with AChE inhibitors

Question 26

MOA of sugammadex

Answer 26

* gamma-cyclodextrin made of 8 sugars assembled in a ring * ring encapsulates the NMB & renders it inactive/unable to engage with nicotinic receptor * Encapsulating ↓ free concentration of drug in plasma  augments concentration gradient between NMJ & plasma

Question 27

which NMBs does sugammadex reverse

Answer 27

Roc > vec > pancuronium

Question 28

excretion of sugammadex

Answer 28

Excreted unchanged by kidneys

Question 29

sugammadex dose after roc with TOF 2/4 or better

Answer 29

2 mg/kg

Question 30

sugammadex dose after roc with TOF 0/4 + 1 PTC or better or better

Answer 30

4 mg/kg

Question 31

what NMB should be used if pt needs to be paralyzed after 16 mg/kg sugammadex

Answer 31

Use NMB from outside aminosteroid class (succs, atracurium, cisatracurium…) for 24 hours

Question 32

re-dosing roc after reversed with < 4 mg/kg sugammadex

Answer 32

* Can give 1.2 mg/kg roc if relaxant needed between 5 min-4 hours of admin. * > 4 hours, can give roc at 0.6 mg/kg or vec 0.1 mg/kg

Question 33

AEs of sugammadex

Answer 33

* anaphylaxis * bradycardia * reduces effectiveness of hormonal contraceptives for up to 7 days

Question 34

neostigmine MOA

Answer 34

reversibly binds to AChE at NMJ by forming a carbamyl ester complex at esteratic site, competitively antagonizes acetylcholine hydrolysis

Question 35

why is physostigmine the only AChE inhibitor used to treat anticholinergic crisis

Answer 35

only AChE inhibitor that crosses BBB | 15-60 mcg/kg

Question 36

s/s anticholinergic syndrome

Answer 36

confusion, agitation, hallucinations, somnolence, unconsciousness | Often mistaken as slow emergence from anesthesia

Question 37

job of M1 receptor on vagal nerve endings

Answer 37

to reduce ACh release via negative feedback loop blockade “turns off” loop and allows continued ACh release/bradycardia explains why small doses of atropine can cause paradoxical bradycardia d/t inhibition of presynaptic M1 receptors on vagal nerve endings

Question 38

MOA of organophosphates

Answer 38

Produce non-reversible inhibition of AChE by forming a stable complex with esteratic site