Unit 5 - NMB Reversals & Anticholinergics Flashcards
what metabolizes succs
pseudocholinesterase
acetylcholinesterase inhibitors that antagonize pseudocholinesterase
neostigmine & pyridostigmine (not edrophonium)
where is AChE concentrated
around nicotinic receptors at NMJ
acetylcholinesterase inhibitors that inhibit AChE
Edrophonium, neostigmine, and pyridostigmine
how do acetylcholinesterase inhibitors antagonize block with NDNMB
inc. concentration of ACh at NMJ
more ACh available to antagonize the block
2 ways AChE inhibitors increase ACh at nicotinic receptor
1) enzyme inhibition, 2) presynaptic effects
Primary mechanism of edrophonium
most likely presynaptic
MOA of edrophonium
- forms electrostatic bond at anionic site and a noncovalent H+ bond at the esteratic site (short duration of action, H+ bonds are weak)
- competitive
2 possible mechanisms of presynaptic action:
- Similar to succs, AChE inhibitors stimulate presynaptic receptor = additional ACh release
- Inhibition of AChE near presynaptic receptor increases ACh concentration in that region
is a dose adjustment of AChE inhibitors needed for renal failure
nope - duration of NMBs also prolonged
effect of mixing AChE inhibitors
additive effect
neostigmine antagonism is faster in children or adults?
infants & children
which AChE inhibitor(s) pass the BBB
only Physostigmine (tertiary amine)
Edrophonium, neostigmine, & pyridostigmine are quaternary amines (do not
risks of extubating with TOF ratio < 0.9
↑ risk airway obstruction, hypoxemic events, postop pulm. complications
effect of giving AChE inhibitor at full recovery
paradoxical muscle weakness
dose of intrathecal neostigmine that produces analgesia
50-100 mcg
SEs of intrathecal neostigmine
- N/V
- pruritis
- prolonged sensory and motor block
AChE inhibitor that can be used for postop shivering
Physostigmine (40 mcg/kg)
4 drugs that ↓ shiving in PACU:
physostigmine, meperidine, clonidine, dexmedetomidine
cholinergic side effects
r/t ↑ concentration of ACh at muscarinic receptor
DUMBBELLS
* Diarrhea
* Urination
* Miosis
* Bradycardia
* Bronchoconstriction
* Emesis
* Lacrimation
* Laxation (elimination of fecal waste)
* Salivation
how do antimuscarinics affect HR
increase
atropine > glyco > scopolamine
most to least antisialogogue effects of anticholinergics
scopolamine > glycopyrollate > atropine
how do anticholinergics affect gastric H+ secretion
increased
Job of M1 receptor
- to reduce ACh release via negative feedback loop
- blockade “turns off” loop and allows continued ACh release/bradycardia
can anticholinergics be given to a patient with a transplanted heart
- 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
MOA of sugammadex
- 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
which NMBs does sugammadex reverse
Roc > vec > pancuronium
excretion of sugammadex
Excreted unchanged by kidneys
sugammadex dose after roc with TOF 2/4 or better
2 mg/kg
sugammadex dose after roc with TOF 0/4 + 1 PTC or better or better
4 mg/kg
what NMB should be used if pt needs to be paralyzed after 16 mg/kg sugammadex
Use NMB from outside aminosteroid class (succs, atracurium, cisatracurium…) for 24 hours
re-dosing roc after reversed with < 4 mg/kg sugammadex
- 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
AEs of sugammadex
- anaphylaxis
- bradycardia
- reduces effectiveness of hormonal contraceptives for up to 7 days
neostigmine MOA
reversibly binds to AChE at NMJ by forming a carbamyl ester complex at esteratic site, competitively antagonizes acetylcholine hydrolysis
why is physostigmine the only AChE inhibitor used to treat anticholinergic crisis
only AChE inhibitor that crosses BBB
15-60 mcg/kg
s/s anticholinergic syndrome
confusion, agitation, hallucinations, somnolence, unconsciousness
Often mistaken as slow emergence from anesthesia
job of M1 receptor on vagal nerve endings
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
MOA of organophosphates
Produce non-reversible inhibition of AChE by forming a stable complex with esteratic site
