Reversal Agents Flashcards
Neostigmine
Neostigmine
class: Reversal agent, acetylcholinesterase inhibitor, also a quartenary ammonium compound.
MOA:
Neostigmine covalently binds to acetylcholinesterase and inhibits its action, thereby preventing the degradation of acetylcholine at the NMJ and allow the concentration of acetylcholine to accumulate and outcompete any remaining NMB agent.
Neostigmine is also a quartenary ammonium compound so it does not cross the BBB.
Used:
Used to antagonize the effects of NMB agents
Works best with deep blocks compared to other agents, still is not reliable with PROFOUND blocks.
Pk:
Onset: 3 minutes
Peak: 7-10 minutes
DOA: 1 hour
E1/2T: 1 hour
Metabolized by plasma and liver esterases, 50% is excreted unchanged in urine.
Dose:
0.05 to 0.07 mg/kg neostigmine, given with 0.01 mg/kg glycopyrolate.
SE:
- Increase salivation
- Increase gastric secretions - N/V/adominal pain
- Increase peristalsis
- Decrease HR/BP
- Bronchoconstriction
- SIEZURES
C/I:
Asthma!
caution in CAD
GI/GU obstruction
RENAL FAILURE will prolong clerance
Edrophonium
Edrophonium
Class: Reversal agent, acetylcholinesterase inhibitor, also a quartenary ammonium compound so it does not cross the BBB.
MOA:
Edrophonium reversibly binds to acetylcholinesterase, and inhibits the acetylcholinesterase, this prevents the breakdown of acetylcholine at the NMJ, acetycholine accumulates and can outcompete the NMB.
Uses:
Reverse NMB agents, edrophonium is NOT AS EFFECTIVE AS NEOSTIGMINE in reversing deep blocks.
Pk:
Onset: immediate
Peak action reached between 1-3 minutes
DOA: 1 hour
Vd: 1L/kg
Metabolized by liver (25%) and excreted 75% unchanged in urine.
Dose:
0.05 to 0.1 mg/kg with atropine (0.01 mg/kg) IV
SE:
SE are less severe than with neostigmine because edrophonium is less potent.
Increase salivation
bronchoconstriction
increase gastric secretion -> n/v/abd pain
increase peristalsis
Decrease HR/BP
Seizures!!
C/I:
Asthma
caution in CAD
GI/GU obstruction
RENAL FAILURE -> will prolong clearance
Pyridostigmine
Pyridostigmine
Class:
acetylcholinesterase inhibitor, also a quartenary ammonium compound, does not cross BBB.
MOA:
Reversibly binds to acetylcholinesterase, inhibits its action, preventing the degradation of acetylcholine. so you have more acetylcholine at the NMJ to bind to acetycholine receptors.
Uses:
not routinely used in reversal because it only has 1/5th the potency of neostigmine and has the longest onset, but is given in myasthenia gravis
Pk:
onset: 10 minutes
peak: 12 minutes
DOA: 1.5 to 2 hours
E1/2T: 2 hours, inc in renal failure
Metabloized by liver, excreted 80% unchanged in urine.
Dose:
0.2mg/kg , given with glycopyrolate 0.01 mg/kg IV
SE:
Increase in salivation
bronchoconstriction
increase in gastric secretions, n/v/abdominal pain
increase in GI peristalsis
Decrease in HR/BP
Seizures!!
C/I:
asthma
GI/GU obstruction
CAD
renal failure!!!
Physostigmine
Physostigmine
class: acetylchloinesterase inhibitor, also a TERTIARY amine so it DOES cross the BBB
MOA:
binds to acetylcholinesterase and inhibits it, therefore preventing the breakdown of acetylcholine and increasing the amount of acetylcholine available.
Uses:
not used as a reversal agent.
Used more for central anti-cholinergic syndrome which can be seen with atropine or scopalamine.
Also to tx glaucoma
Also to tx myasthenia gravis.
Pk:
Onset: 5 minutes
DOA: 1-5 hours
e1/2T: 30 minutes
vD: 1L/KG
hydrolyzed at ester linkage by cholinesterase, renal excretion is minimal
dose:
15-60 mcg/kg. Usually given alone for central anti-cholinergic syndrome.
SE:
Increase salivations
bronchoconstriction
increase GI secretions - n/v/abd. pain
increase Gi peristalsis
decrease HR/BP
INHIBITS SOLMONENT EFFECTS OF OPIOIDS, KETAMINE, IA, AND BENZOS.
C/I
asthma
caution in CAD
gi/gu obstruction
renal failure!! will prolong clearance.
