Nondepolarizing Muscle Relaxants

Metabolism/Excretion
- Liver metabolizes pancuro/vec. Biliary excretes vec/roc. Liver failure potentiates pancuro/roc> vec>>pipecuronium. Miva is metabolized by pseudocholinesterases, atra/cis metabolized by hoffman
- Kidney excretes pancuro/vec/pipe/doxa but not roc

Potentiation/Resistance
Potentiation:
- calcium channel blockers, beta blockers, magnesium, lithium, aminoglycosides, volatiles, local anesthetics
- Volatiles decrease nondepolarizer requirements by 15%. Des>Sevo>Iso>NO2 and pancuro>vec/atra
- Combining nondepolarizers of different classes (aminosteroid vs benzylisoquinoliniums) provide synergistic effects (greater than additive)
- Neuro disease potentiates N-NMBs except burn, CP, denervation, sepsis which causes resistance
- Newborns are more sensitive to NMB because of immature receptors but they also have greater extracellular space so no net effect in dosage. N-NMB have faster onset though. Vec is longer lasting.

Resistance:
- anticonvulsants (only aminosteroids?)
- Neuro disease potentiates N-NMBs except burn, CP, denervation, sepsis which causes resistance

Onset/Duration
- ED95 for NMB is the dose when 95% twitch suppression occurs in 50% of patients. Intubation dose is usually twice the ED95. Increasing the dose means faster relaxation but more side effects and prolonged block.
- Onset is 2.5 to 3 minutes except roc which works in 1.5 to 2 minutes
- Duration is 40-70 minutes except pancuronium which is 60-90 minutes
- histamine release by vec/atra can cause hypotension, vagolysis by pancuronium can cause tachycardia, older tubocurium and metocurium block sympathetics causing brady and hypotension
 -Dosage by Adjusted BW = 0.4(ABW - IBW)+ IBW. IBW = 50kg + 2.3kg*(each inch after 60)

Atracurium - histamine release (hypotension, tachycardia), bronchospasm (avoid in asthmatics, 2/2 histamine), laudanosine metabolite is degraded by liver (raises seizure threshold), hoffmann slowed by hypothermia and acidosis, anaphylaxis. Cisatracurium is 4x more potent and makes up 15% of atracurium but produces no histamine release and less laudanosine 2/2 potency.

Pancuronium - metabolized by liver with active metabolites, excreted by kidney and bile. Vagolytic and sympathetic effect. Vecuronium is similar. Prolonged infusion in ICU causes prolonged block for days.

Rocuronium - mainly excreted in liver/bile some in kidney.