non-depolarizing muscle relaxants

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