Barbiturates Flashcards
barbs in bottle vs body
alkaline in bottle
acidic in body
barbs preparation, pH, storage, potent isomer
sodium salt preparation
highly alkaline, bacteriostatic in bottle
stable/sterile for 6 days
levo isomer is potent
barbs are derived from:
urea + malonic acid = barbituric acid
barbs substitutions
carbon 2 & 5 substitutions have sedative, hypnotic properties
barbs branched chain @ 5
increased hypnotic activity
barbs phenyl group @ 5
increased anticonvulsant activity
barbs methyl radical group
increased convulsants (methohexital)
barb sulfuration
fat soluble, short duration, rapid onset, increased potency
barb chain length and potency
long branched chain is more potent than straight
barb isomer comparisons
levo is 2x more potent than dextro isomer
barb mixture availability
only available as racemic mixture
barb w/ oxygen @ #2 name
oxybarbiturate
barb with sulfur @ #2 name
thiobarbiturate
barbiturate relative potency
thiopental = 1
thiamylal (surital) = 1.1
methohexital (brevital) = 2.5
barb mechanism of action
enhance GABAa activity
decrease transmission of sympathetic ganglia = hypotension
mimics GABA at receptor
decreases post synapse membrane sensitivity to aCh - some muscle relaxation, not surgical depth
depresses reticular activating system = sleep
barbs pharmacokinetics
rapid onset rapid redistribution - will wake up in 5-7 minutes extensive metabolism 70-85% protein bound blood fat partition = 11 pK = 7.6
barb metabolism
oxybarbiturates = hepatic only
thiobarbiturates = hepatic and extra hepatic
side chain oxydation at carbon 5 to carboxylic acid
desulfuration, hydrolysis opens ring
renal excretion
heavy hepatic enzyme inducers!
Barb elimination T1/2
thiopental - 11.6 hrs
prolonged in pregnancy due to increased protein binding
methohexital - 3.9 hrs
barb CNS effects on LOC
decrease LOC, CMRO2, CBF, ICP
can produce isoelectric eeg
barb CNS excitatory effects
paradoxical excitement
methohexital - myoclonus and hiccups
barb CNS protection
very good cerebral protection
barb SSEP monitoring
barbs do not affect sensory output from spinal cord
barb and pain threshold
small doses can cause anti-analgesia
barb skeletal muscle relaxation/IOP
no skeletal muscle relaxation
decreased IOP
barb CV effects
decrease SNS, so decrease PVR, preload
decrease SBP, increase HR
minimal myocardial depression
barb and trauma
DO NOT GIVE
if SNS is not intact, hypovolemic, will see significant decrease in BP and contractility
histamine release with rapid IV push, further decreases SBP
minimal effect with PO barbs
barb resp effects
dose dependent depression of medullary and pontine ventilatory centers (CNS)
decreased ventilatory response to hypoxia, hypercarbia
apnea
incomplete depression of laryngeal and cough reflex
stage 2 of induction**
excitatory stage with laryngospasm, bronchospasm when dose is not large enough
Which barb has most potent hepatic enzyme inducer
phenobarbital
barb increases metabolism of what?
oral anticoagulants phenytoin TCAs corticosteroids Vit k
barb and heme
accelerates production of heme by stimulation of D aminolevulinic acid synthetase
barbs and thrombosis, placenta
increases venous thrombosis
readily crosses placenta
barbs and pts with siezures
metabolize drug 2x faster, (especially muscle relaxants)
barbs and tolerance
enhances own metabolism, increases tolerance
barb allergies
1:30,000, high anaphylaxis mortality
barb dosing
Thiopental 3-5 mg/kg IV, decrease with age/pregancy, increase with infant, peds
Methohexital 1-2 mg/kg IV; 20-30 mg/kg peds
duration of single IV induction: 5-8 minutes due to rapid redistribution
what not to mix with barbs
opioids, catechols, NMBs, midazolam pancuronium vecuronium atracurium alfentanil sufentanil midazolam LR (too acidic)
barbs and arterial injection
immediate vasoconstriction, pain dilute w/ NS phenoxybenzamine heparin brachial plexus block papaverine 40-80mg in 10-20ml NS or 5-10ml lido
barbs and prophyria
DO NOT GIVE BARBS TO PATIENTS WITH PROPHYRIA
