Pancuronium
pancuronium (pavulon) chemical classification
bisquaternary aminosteroid --> vagolytic properities
vecuronium (norcuron) & rocuronium (zemuron) chemical classification
aminosteroid
cisatracurium (nimbex) chemical classification
benzlisoquinolone
chemical classification of mivacurium (mivacron)
benzlisoquinolone
CV effects of vecuronium
essentially none
no histamine release
pancuronium (pavulon)
dose
onset
duration
intubating dose 0.1mg/kg
onset 3-5 min
duration 60-90 minutes
*most common long-acting NMBD
vecuronium (norcuron)
dose
onset
duration
0.1 mg/kg
onset 3-5 minutes
duration 20-35 min
cisatracurium (nimbex)
dose
onset
duration
0.1 mg/kg
onset 3-5 min
duration 20-35 min
mivacurium (Mivacron)
dose
onset
duration
0.15 mg/kg
2-3 min onset with conditions less desirable
12-20 duration *only short-acting non-depolarizer
rocuronium (zemuron)
dose
onset
duration
0.6 mg/kg or 1.2 mg/kg
*larger doses parallel onset of SCh but offset of pancuronium
onset= 3-5 min, 1-2 min
duration = 20-35 min
pancuronium (pavulon) metabolism
80% eliminated unchanged in urine
vecuronium (norcuron) metabolism
hepatic metabolism *principle organ of elimination
3-desacetlvecuronium 50-80% potent but rapidly converted to metabolite with 1/10 the effects
renal excretion
30% unchanged (70% metabolized in liver)
renal dysfunction - E1/2 time prolonged
repeated doses or infusion = cumulative effects
cisatracurium (nimbex) metabolism
Cis-isomer
recovery from infusion is not affected by time
**Degradation
Hoffman elimination
doesnt use specific plasma cholinesterases as much as atracurium
mivaron metabolism
3 stereoisomers
(Cis-Cis, *Cis-Trans, *Trans-Trans) *NM blocking ability
cleared by plasma cholinesterase
not currently on market
rocuronium (zemuron) metabolism
excreted unchanged in bile
*longer duration of action in liver failure and elderly due to decreased clearance and increased Vd
10-30% renal excretion, only marginally affected in renal failure
pancuronium (pavulon) CV effects
increase HR, MAP, CO due to vagal blockade
*mostly at SA Node, BP increase due to HR
direct SNS activation
*release of NE presynaptically, blockade of NE reuptake
No change in SVR or inotropy
No Histamine Release
acid base changes with vecuronium (norcuron)
prior to NMBD - no prolonged blockade
Respiratory acidosis - following NMBD - prolongs blockade
*actively inversely proportional to bound drug... acidosis decreases the bound amount
*change in ionization at receptor increases attachment time
*concern with postop hypoventilation
cisatracurium (nimbex) in elderly and obese
elderly - slight delay (1 min) due to cardiac output
obese - duration of action prolonged if dosed at actual body weight due to volume of distribution
CV effects with mivacron
minimal effects
histamine release
*>3 * ED95... transient MAP drop
*more common with rapid, large doses
*MAP drop more in HTN patients than non HTN patients
CV effects of rocuronium (zemuron)
no cardiac effects - slight vagolytic effect??
alterations in metabolism with pancuronium
Renal failure: 30-50% decreased plasma clearance, 10-40% deasacetylpancuronium metabolite 1/2 active (by liver)
In liver disease: increased Vd, larger initial dose need, prolonged Elimination 1/2 time
in aging: decreased plasma clearance due to renal function
vecuronium (norcuron) in the elderly and pregnant patient
elderly - decreased VD (less muscle mass), decreased plasma clearance (less hepatic flow)
*single dose mechanics unchanged, delayed recovery with infusions
obstetrics
*insignificant effects to fetus, increased clearance in 3rd trimester, prolonged during during early postpartum (dose IBW)
cisatracurium (nimbex) CV effects
CV stable
Compared with LA NMBDs
similar onset of maximum blockade (except high dose roc)
approximately 1/3 duration of action
minimal/absent CV effects
antagonized by anticholinesterase drugs approx 20 min
Long Acting NMBDs
Intermediate Acting NMBDs
Short Acting NMBDs
Intermediate - cisatracurium, atracurium, vecuronium, rocuronium
Short - mivacurium