IV anesthetics Flashcards
T/F
90% of anesthesia is done with propofol
False
90% of anesthesia can be done with propofol
emulsion
mix of water and oil into continuous form (ie: mayo)
add emulsifying agent (lipid sol end & w. sol end)
Prop emulsion vehicle
soybean oil and egg lecithin
used b/c prop isn’t very water soluble
egg lecithin is also known as
(an emulsifier)
phosphatidyl choline
serine
naturally occurring in cell membrane
Prop
chemical name & structure
2,6-diisopropylphenol
(know how to draw it)
Propofol
class
MoA
Unique class of anesthetics
interacts w/ GABA A receptor
decreases GABA dissociation
~ selective with few perceivable effects at other receptors
EDTA
disodium edenate
preservative in Diprivan (brand)
Generic prop should not be used in pts with…
sulfite allergies
generic contains sodium metabisulfite
Your pt is allergic to wine. Which should you administer?
Diprivan
Generic propofol
Diprivan
generic contains sodium metabisulfite
(wines also have sulfites)
Egg lecithin is found in
the fatty part of the yolk
not a protein (which pts with egg allergies are most likely allergic to)
Prop induces how quickly?
15-30 secs
not as fast as thiopental
How is prop taken up by cells?
(very lipid soluble; put into an emulsion)
remains as micelle in BS
outer layer begins brkdwn
oil droplets taken up via endocytosis or absorb across membrane
T/F
Push propofol fast
False
painful on injxn
T/F
Hand veins are ideal for propofol administration
False
smaller veins a/w more pain on injxn
Mixing propofol w/ liodcaine
not recommended
1) lido cant act fast enough
2) breaks emulsion –> oil droplet –> PE
Awakening time faster than with other IV induction agents
prop
Less occurrence of post-op hang-over, reports of elevated post-op mood
prop
Prop and BZDs have ____ properties
anticonvulsant
Prop metabolism
_____ loses most of the compounds activity.
_____ removes it from the body
hydroxylation (now 1/3 as active)
glucuronide/sulfate conjugation
Prop
termination of actions d/t…
redistribution to fatty tissues and metabolism
Prop metabolism
Hepatic and extrahepatic P-450 oxidative metabolism
secondary: phase II glucuronide & sulfate conjugation
High lung uptake but released ~unchanged
Prop metabolism
first [O] rxn
form 4 hydroxy diisopropyl phenol (hydroxylate 4th C on ring; “ring hydroxylation”)
becomes point of attachment for glucuronide
Lung metab of propofol
not a primary method of metab
but
becomes important for uptake of IAs
Prop
DoE
5-10 minutes
Prop
HL
2-3 hours
Prop
OB
crosses placenta
but
rapidly metabolized by fetus
Pregnancy Category B – no proof of direct risk, however only recommended if benefits outweigh risk
T/F
Liver/renal Dz significantly affects prop elimination
False
d/t extra hepatic metab (hydroxylation by tissues outside the liver)
T/F
Prop & BARBs increase pain sensitivity
False
prop does not
BARBs do
Prop effects on BP
decreased d/t ↓CO & vascular resistance
decreases more than Thiopental
inhibits SNS vasoconstriction
Prop
Increased risk of ___ death, due to ….
brady♡-related
inhibition of cardiac sarcolemmal calcium release (blocks muscle activity)
T/F
Skeletal muscle inhibition is seen with Prop.
True
inhibition of cardiac sarcolemmal calcium release (blocks muscle activity)
Opioids increase ____ respiration & inhibits the ability to …
Cheyne stokes (deep breathing followed by shallow breathing)
sense CO2
caution when using prop with opioids
Prop resp fx
Depresses ventilation
apnea in ~30% of patients.
Which accumulates in fat more?
Prop
BARBs
BARBs
(they both accumulate in fat but prop has a shorter HL; metabolized out of fat faster)
Prop
when continuously administered for more than 24 hours
lactic acidosis
d/t high triglyceride levels
Why does prop cause high TGC?
lipid emulsion vehicle
Prop
SEs
bradycardia
pain (limited to injxn)
hypertriglyceridemia (lipid emulsion vehicle)
allergic reactions
lactic acidosis (long term infusion)
Fospropofol (Lusedra)
propofol prodrug
FDA approve 2008
cleaved to propofol on administration by endothelial alkaline phosphatases
Fospropofol (Lusedra)
current status
Dc’d bc not making enough $, but still FDA approved
Could go back into production if shortage of prop
Fospropofol (Lusedra)
pros and cons
water soluble (~no pain on injection)
more expensive
half-life (to Propofol) = 8 min (slower onset)
other metabolite = formaldehyde (toxicity in large doses)
Propoven
different vehicle formulation
more lipids
no preservative
short vial life
Propofol Pumps
Mechanical syringe presser
Motor pushes on end of plunger
Adjust speed to control rate of infusion
Use with BIS
hold a certain rate of infusion/anesthetic depth
Controversy: Japan company says pump can replace anesthesiologist and use general nursing staff (US protests prevented entry into practice)
BIS monitor
___% of normal brain wave activity is considered anesthetized
40
Etomidate (Amidate)
Structure
unlike any other anesthetics
(he did not say to memorize it)
propylene glycol toxicity
relatively low
avoid very large doses
Why makes etomidates HL so short?
1) rapid lipid redistribution
2) Metabolized rapidly (ester) hydrolysis of side chain ester group by plasma esterases and hepatic P-450 system
Etomidate
MoA
GABA-activity enhancement like BARBs and BZDs
GABA A site but unclear location
Etomidate is more selective for ___ receptors than the barbiturates
GABA A
weak base, that’s 99% unionized at physiological pH
etomidate
Etomidate
protein binding
75%
Etomidate
Vd
large (~300 L) (tissue distribution)
Etomidate
time until peak brain concentration
w/in 1 min
Etomidate
emergence time
5-10 mins
Etomidate
elim HL
2-5 H
T/F
Etomidate does not cause any resp depression
False
Occasional apnea on rapid administration
Less ventilatory depression than with barbiturates or propofol
Etomidate
incidence of myoclonus on rapid IV induction
> 80%
Etomidate depresses….
Depresses steroid (cortisol) synthesis in adrenals
T/F
A single dose of etomidate can increase risk of mortality.
True
Depressed steroid (cortisol) synthesis in adrenals can cause…
Increased risk in sepsis and hemorrhage
Dexmedetomidine (Precedex)
alpha-2 agonist
shuts off norepi release
Alpha 2 receptors in brain are mostly
pre-synaptic inhibitory
on adrenergic neurons
advantage of PREsynaptic inhibition
reduces risk of overstimulation
“fine-tuning”
Goal when developing Precedex
mimic the CNS depressant effects of Clonidine but with better distribution to the brain
Dexmedetomidine (Precedex)
uses
control of stress, anxiety and pain
used alone: sedates + can arouse to communicate
T/F
Placebo can cause sedation
True
T/F
Adjust Precedex dosing based on age.
False
hepatic disease
Pharmacokinetics unaltered by age
Precedex
Vd
HL
protein binding
Vd ~ 118 liters
t1/2 ~ 2 hrs
~95% protein bound
Precedex
Metabolism
mainly via glucuronidation (34%) and P-450 hydroxylation
Why do we usually give Precedex as a drip?
short half-life (~ 2 hrs)
T/F
Precedex is lipid insoluble & doesn’t cross BBB
False
some lipid solubility; gets into brain
Versed
indxn time
DoE
~60 secs
~15 mins
Versed + opioids
for longer durations
greater pain relief than midaz alone
T/F
BZDs tend to be highly protein bound
True
True
“Versed is 95% plasma protein bound (similar to other benzodiazepines)”
T/F
Versed has minimal CV fx
True
Remimazolam (Byfavo)
midazolam analog with an ester linkage (rapid metab)
Remimazolam FDA approval
2020
Remimazolam (Byfavo)
Primary use
induction
conscious/ procedural sedation (< 30 min )
Remimazolam
SEs
hypo/hyperTN
hypoxia (due to hypoTN)
Remimazolam vs Versed
duration
~ ¼ the duration of an equivalent dose of midazolam
T/F
Ketamine can be used IV only
False
IV and IM
T/F
Ketamine has amnesic effects
True
Good analgesic and amnesic
Ketamine
action at opioid receptors
Blocks Mu
agonist @ Kappa
Ketamine
psych instability & hallucinations
d/t kappa antagonism/stimulation
Ketamine
IV duration
15 mins
catalepsy (dissociative anesthesia)
(Ketamine)
eyes wide open, look awake but don’t respond
blockade of specific neural tracts (block consciousness) + stimulate RAS
Ketamine
solubility and protein binding
Highly lipid soluble but minimal protein binding
Ketamine:
fat and free
Recovery phase characterized by CNS stimulation
Ketamine
emerge in quiet & dim (avoid seizures)
Adjust Ketamine dosing in the presence of…
liver Dz
Ketamine MoA
Blocks:
glutamate excitatory NMDA receptors (CNS) neuromuscular nACh receptors
Mu receptors
agonism:
Kappa receptors
Ketamine
metab
N-demethylated (P450) => Norketamine (25% active)
hydroxylation (P450) => hydroxynorketamine (inactive)
Glucuronated & excreted in urine.
T/F
Glucuronidation of ketamine inactivates the compound
False
hydroxylation (P450) => hydroxynorketamine (inactive)
glucuronidation allows excretion
T/F
A pt’s tonic-clonic movements under ketamine can help estimate the depth of anesthesia.
False
Ketamine should be given slowly bc
limit respiratory depression
and
strong vasopressor effects (Possibly life threatening)
Ketamine
emergence reaction occurence
over 10%
Ketamine hallucinations
can be dream-like or delirium
possible long term mental health effect
less often in old ppl
Ketamine can be given with ___ to reduce the risk of seziures
diazepam
PF0713
propofol analog
less injxn pain
slower onset and longer duration
Benefits questionable – possibly better for maintenance
Carboetomidate
etomidate analog
“no” adrenal suppression
slower onset
