Propofol, Etomidate Flashcards
propofol chemical name
2, 6 di-iso-propophenol
propofol is mixed with:
1.2% egg
10% soybean
2.25% glycerol base
propofol draw up safety
supports bacterial growth, never use same bottle
propofol extended infusion efect
increased glycerides
propofol allergies
egg yolk allergies, anaphylactic
2 ways propofol is supplied
Diprivan EDTA - ok
Propofol Sodium Metabisulfite - bronchospasms
propofol mechanism of action
GABAa, Glycine
decreases rate of dissociation of GABA from GABAa
no spinal cord depression
propofol Vd, clearance, model of distribution, T1/2
3.5-4.5 L/Kg
clearance exceeds hepatic blood flow
2-3 compartment model
T1/2 - 0.5-1.5 hrs
propofol: what affects pharmacokinetics
weight, co-existing disease, age, co-administration with other drugs
propofol CNS effects specifics
chloride channel activation of B subunit of GABA receptor, NMDA inhibition
propofol CNS effects
rapid onset, one arm-brain circulation decreases CMRO2, CBF, ICP, CPP, cerebral protective EEG burst suppression age effects ED95 - highest in toddlers, decreases with age hiccups, muscle twitching hallucinations, opisthotonos decreased IOP antioxidant effects myoclonus
propofol respiratory effects
apnea following induction decreases TV, RR decreased response to CO2 and hypoxia PaCO2 rises, pH decreases bronchodilation in COPD
propofol CV effects
25-40% decrease in BP greater than with STP dose dependent myocardial depression and vasodilation similar decrease in SV, CO, SVR HR UNCHANGED
propofol other effects
does not potentiate muscle relaxants pain on injection antiemetic/antipruritic at 10 mg doeses amnestic at >30 mcg/kg/min crosses placenta, removed from fetal circulation
propofol doses
induction 1-2.5 mg/kg up to 3 mg/kg in toddlers
GA maintenance infusion 100-300 mcg/kg/min
sedation infusion 25-100 mcg/kg/min
propofol metabolism
conjugated in liver by CP 450
liver function does not affect rate of metabolism
metabolites mostly inactive
4-hydroxypropofol is 1/3 as potent
CKD doesn’t affect clearance
highly metabolised, less than 3% excreted unchanged
etomidate derivative name, parent compound, solvent name, pH
carboxylated imidazole derivative
imidazole refers to the parent compound C3H4N2
propylene glycol solvent
pH 6.9 - water soluble in solution
at physiological pH, becomes highly lipid soluble
etomidate mechanism of action
selective GABAa
binds to specific receptor
increases affinity of GABA to GABAa
etomidate onset of action, solubility, Vd, compartment model, T1/2, protein bound %
rapid onset of action highly lipid soluble weak base pH 8.2 Vd 2.5-4.5 L/Kg 3 compartment model T1/2 3-5 hrs high hepatic extraction ratio - changes in hepatic blood flow will prolong effect 75% protein bound
etomidate CNS effects
rapid loss of consciousness no analgesia direct cerebral vasoconstriction, decrease CBF, ICP, CMRO2 reduced IOP increases EEG activity in epileptogenic foci rare association with Grand Mal siezures myoclonic movement anticonvulsant
etomidate respiratory effects
minimal ventilatory response to CO2 drop
decrease in TV, increase in RR
hiccups, coughing
etomidate CV effects
minimal effects on CV, b/c no effect on SNS and baroreceptors
etomidate endocrine effects
dose dependent reversible inhibition of 2 enzymes in biosynthesis of cortisol/aldosterone
etomidate 2 enzymes
11 betahydroxylase
17 alphahydroxylase
prevents conversion of cholesterol to cortisol
results in adrenocortical suppression for 4-8 hrs
reduces mineralcorticoid and corticosteroid production
etomidate and same day surgery
not ideal, too much N/V
etomidate dosage
induction 0.2-0.6 mg/kg (0.3 mg/kg)
maintenance infusion 10 mcg/kg/min w/ N2O and opioids
sedation 5-8 mcg/kg/min for short procedure
rectal 6.5 mg/kg has been used in peds
etomidate and N/V
high incidence of N/V 30-40%
myoclonic movement 30-60%
enhance NMDR activity
etomidate metabolism
liver, ester hydrolysis or N dealkylation to carboxylic acid
biotransformation 5x faster than thiopental
85% renal, 13% biliary excretion
2% excreted unchanged
