NMBD Reversal Agents. Flashcards
Suggamadex
steroidal NMBD Antagonist
cyclodextrin molecule
Uses;
-Reverses the paralytic effect of Steroidal NMBD Rocuronium, Vecuronium and Pancuronium
-Facilitates the use of Roc
@ 1.2mg/kg for RSI
MOA;
cyclodextrin molecule that forms extremely tight water-soluble bone at a 1:1 ratio with NMBD that have steroidal nuclei (Roc, Ver and Pan) to antagonize effect at the NMJ by creating concentration gradient away from the NMJ
*greatest affinity for Roc
Dose;
dependent on twitch response
- 2mg/kg for 2 twitches present in TOF
- 4mg/kg for 1-2 POSTtetanic twitches with NO TOF response
-8-16mg/kg for profound block; after RSI dose of Roc (1.2mg/kg)
Pharmacokinetics;
Kinetics are dose dependent
Half -life is about 2 hours
-Vd; 20L
Metabolism; very limited
Excretion 75% unchanged by the Kidney
Side Effects;
- hypersensitivity
- delayed onset residual neuromuscular block with insufficient doses
- cases go marked bradycardia followed by cardiac arrest have been observed with in minutes of administration
- N/V
- hypotension
- headache
Contraindicated;
- hypersensitivity
- Renal failure; creatine clearance <30mL/min
-Caution in kids under 17 safety and FDA approval not established
Will not reverse benzylisoquinolones or Succinylcholine
Neostigmine
Anti-cholinesterase
Acetylcholinesterase inhibitor
Quaternary ammonium; does NOT cross BBB
Use;
- antagonism of NMBD
- tx of myasthenia gravis and urinary retention
MOA;
- irreversibly binds to and inhibits acetylcholinesterase; increasing the concentration of Acetylcholine in the synaptic cleft; by inhibiting the hydrolyzation of acetylcholine by acetylcholinesterase
- acetycholine is normally hydrolyzed quickly by acetycholineterase; but after administration of neostigmine more Ach is available to bind to the nicotinic acetylcholine receptors and occupy the binding sites
Dose; 0.04 - 0.07mg/kg
always give with Glycopyrrolate 10 - 20 mcg/kg to prevent side effects from increased Ach
Pharmacokinetics; -onset; 5 - 15 min -peak; 7 min -E1/2t; 70 - 80 min (up to 180min internal failure) -DOA; 45 - 90 min -Vd; 0.7 - 0.9 L/kg (increased in renal failure) Pb; minimal
metabolism; 50% hydrolyzed by plasma esterase and hepatic metabolism
3 hydroxyphenyltrimethyammonium
(1/10th the potency)
excretion; 50% unchanged by the kidney
Side Effects;
- seizures
- bronchospam
- salivation
- bradycardia
- ab cramping
- N/V
- loss of bladder and rectal control
- pair with glyco to decrease side effects
Contraindications;
- Bowel obstruction
- Renal obstruction
- Previous AChE inhibitor administration
Physostigmine
Anti-cholinesterase
Acetylcholinesterase inhibitor
medium- duration; central acting
Tertiary amine; Crosses BBB
Uses;
- NOT used to reverse NMBD bc dose is required is too high and causes undesirable CNS effects
- used to tx atropine and scopolamine toxicity (crosses BBB)
- can be used to tx post- op shiver (MOA is unknown)
- tx myasthenia gravis
- eye drops to tx glaucoma
- improves alzheimers/ dementia
MOA;
-reversible competitive inhibitor of acetylcholinesterase; decreases acetylcholine metabolism and increases acetylcholine level; prolongs peripheral and CNS effects of acetylcholine
Dose; 15 - 60 mcg/kg
for central anticholinergic syndrome (can repeat q 1 - 2 hrs)
Pharmacokinetics;
- onset; 5 min
- E1/2t; 15 - 40 min
- DOA; 30 min - 5 hours
- Vd; 0.7 - 1.4 L/kg
metabolism; cholinesterase hydrolyze it at ester linkage by
excretion; minimal renal excretion
Side Effects;
- bradycardia
- hypotension
- pupillary constriction
- bronchoconstriction
- salivation
- N/V
- cholinergic crisis
- EEG arousal
Contraindications;
-CV disease
Pyridostigmine
Anti-cholinesterase; cholinesterase inhibitor Quaternary ammonium (does NOT cross the BBB)
Uses;
- in combo with anticholinergic to reverse NMBD
- tx urinary retention
- tx glaucoma
- tx myasthenia gravis
MOA;
-binds to acetylcholinesterase enzyme and blocks the break down of acetylcholine and increases acetylcholine concentration at the NMJ
Dose; 100 - 300mcg/kg
w/ atropine; 20 mcg/kg or
w/ glyco 10 - 20 mcg/kg
Pharmacokinetics;
- onset; 10 - 20 min (LONG)
- E1/2t; 112 min (380 min in renal failure)
- DOA; 60 - 120 min
- Vd; 1L/kg
metabolized 25% by the liver
20 - 90% excreted by kidney
Side Effects;
- bradycardia
- hypotension
- bronchospasm
- salivation
- diarrhea
- urinary frequency
Contraindicated;
- GI/GU obstruction
- renal failure
- hypersensitivity
Caution;
asthmatics
Edrophonium
- Anticholinesterase; Acetylcholinesterase inhibitor
- Quaternary Amine
- Less effective than neostigmine, but less severe muscarinic effects.
Uses;
- in combo with anticholinergics to reverse NMBD; NOT effective for deep block
- tx glaucoma
- tx urinary retention
- tx glaucoma
MOA;
-binds to acetylcholinesterase enzyme and prevents it from breaking down acetylcholine; increasing acetylcholine concentration at the NMJ
Dose; 0.5 - 1 mg/kg with 0.01mcg/kg of atropine
Pharmacokinetics; Onset; Rapid Peak; 1 - 2 minutes DOA: 1 hour Vd; 1 L/kg
metabolized 25% by liver
excreted 75% unchanged
Side Effects; Less severe than neostigmine -bradycardia -hypotension -salivation -diarrhea -urinary frequency -NV
Contraindicated;
- GI/GU obstruction
- renal failure
- hypersensitivity
Caution;
- asthmatics r/t bronchoconstriction)
- CAD (r/t decreased HR)
