NDMR mechanism of action
competitive antagonism at the alpha-subunit of the post-junctional nAChR
how do volatile agents cause altered response to NMB?
-dose dependent enhancement in magnitude and duration of the NDMR
-can induce skeletal muscle relaxation at the level of the spinal cord via nAChR
how do ahminoglycosides affect NDMR?
can stimulate pre-synaptic receptors, causing a decrease of ACh release, prolonging the NDMR effects
how do local anesthetics affect NDMR?
-interfere with pre-junctional release of ACh
-directly depress skeletal muscle fibers
-esters compete for plasma cholinesterase
how does quinidine affect NDMR?
depresses pre-junctional release of ACh
how do diuretics affect NDMR?
furosemide depresses release of ACh
how does magnesium affect NDMR?
stabilizes post-junctional membranes
how do anti-convulsants cause altered responses of NDMR?
-increased hepatic clearance of NDMR
-increased protein-binding of NDMR
-increased enzyme induction
what is an example of an anti-convulsant that alters the responses of NDMR?
phenytoin/dilantin
how do cyclosporines cause altered responses to NDMR?
depress the release of ACh
how does hypothermia cause an altered response to NDMR?
-decreased clearance
-slowed rate of effect site equilibrium
how do burn injuries >30% cause an altered response to NDMR?
alters the affinity of the receptor ACh
trade name for pancuronium
pavulon
what type of NDMR is pancuronium?
aminosteroid
pavulon onset:
3-5 min
pavulon DoA:
70-90 min
pancuronium metabolism:
10-20% hepatic
pancuronium excretion:
60-80% renal, 10% biliary
how does pavulon effect the CV system?
stimulation via blocking mAChR, increasing the HR
commercial prep of pavulon:
2 mg/mL pancuronium bromide
pancuronium dosing:
IV 0.1-0.2 mg/kg
trade name for vecuronium
norcuron
what type of NDMR is norcuron?
aminosteroid
vecuronium onset:
3-4 min
norcuron DoA:
30-50 min
vecuronium metabolism:
30-40% hepatic
norcuron excretion:
40% renal, 10-20% biliary
commercial prep of vecuronium:
10 mg lyophilized powder vecuronium bromide; must be diluted to 1 mg/mL
norcuron dosing:
0.08-0.12 mg/kg
trade name for cisatracurium:
nimbex
what type of NDMR is nimbex?
benzylisoquinolinium compound
cisatracurium onset:
3-5 min
nimbex DoA:
30-50 min
cisatracurium metabolism:
Hoffman elimination dependent on pH and temperature
nimbex elimination:
renal clearance 10-30%
commercial prep of cisatracurium:
2 mg/mL cisatracurium besylate
nimbex dosing:
0.08-0.12 mg/kg
trade name for rocuronium:
zemuron
what type of NDMR is zemuron?
aminosteroid
rocuronium onset:
1-2 min
zemuron DoA:
20-35 min
rocuronium metabolism:
minimal hepatic
zemuron excretion:
30-40% renal, 60% biliary
commercial prep of rocuronium:
10 mg/mL rocuronium bromide
zemuron dosing:
0.6-1.3 mg/kg, max of 50 mg for induction
what causes up-regulation of ACh receptors?
loss of neuronal influences on muscle cells lead to up regulation of the receptors and spread them into peri- and extra-junctional areas
what results from up-regulation of AChR?
-new receptors are immature and have altered sensitivity and affinity
-agonists will depolarize the new AChRs more easily and lead to exaggerated cation fluxes
-increases requirements of NDMR
down-regulation of AChR:
-increase in sensitivity can also be seen
-lower doses of NDMR required
examples of conditions causing down-regulation of AChR:
-myasthenia gravis
-organophosphate poisoning
-chronic cholinesterase inhibition
which muscle relaxants cause a release of histamine?
histamine is released from MAST cells:
-Mivacurium
-Atracurium
-Succinylcholine
-d-Tubocurarine