Barbs Flashcards
Barbiturates are
weak acids
Barbiturates come prepared as
alkaline solutions
barbiturates with substitutions at carbon #2 and#5 have
sedative, hypnotic, properties
phenyl group at carbon#5 =
phenobarbital, increased anticonvulsant effect i.e. phenobarbitals
methyl group imparts
convulsant activity, i.e. methohexital
Sulfuration of barbiturates =
more fat soluble, lipid soluble,
so: shorter duration, more rapid onset, increase potency
sulfar at carbon #2 of barbiturate =
thiobarbibutrate
Barbiturates: MOA
MOA: Decreases the rate at which GABA dissociates from its receptors.
Increases duration of GABA activated Cl- channel opening
Overall: enhances GABA activity
- Decreases transmission in the sympathetic ganglia : direct acting HYPOTENSION
- Decreases post synaptic membrane sensitivity to Ach -> some muscle relaxation [[not surgical depth!]]
Depresses RAS -> induces sleep
onset of barbiturates
“one arm to brain” so rapid
Redistribution of barbiturates:
rapid termination of effect is from redistribution
metabolism of oxybarbiturates:
hepatic only CYP450
metabolism of thiobarbiturates:
hepatic and some ‘extra hepatic’
action of barbiturates is terminated by
side chain OXIDATION at C#5 to carboxylic acid.
HYDROLYSIS
DESULFRATION
renal excretion of barbiturates
<1% excreted unchanged
enzyme induction / inhibition and barbiturates
does not alter metabolism BUT will increase dose requirements
more potent isomer of barbiturates
s (-) levo isomer
alkinazation of urine favors
barb excretion
e 1/2 t of methohexital and thiopental
methohexital = 3.9 hours thiopental = 11.6 hours
cerebral protective effects of barbs
cerebrovasoconstriction, reduces CBF, decreases ICP, and CMRO2
EEG + barbs
isoelectric, potent enough to accomplish this
methohexital excitatory movements:
myoclonus and hiccups
Barbs + pain
these are anti-analgesic
barbs + IOP
Decrease IOP
CV effects of barbs
Decreases SNS outflow leads to decrease SVR, SBP subsequent increase in HR from peripheral activation of SNS
Myocardial depression: minimal
SIGNIFICANT myocardial depression and BP with: large doses or pre-existing hypovolemia
ONLY IV.
PO barbs = minimal CV effects.
CNS Is not intact in
tiny babies, elderly.
histamine release?
with rapid IV admin of barbs
respiratory effects of barbs
dose dependent depression of medullary and pontine ventilatory centers
decreased ventilatory RESPONSE to hypoxia / hypercapnia
Barbs + laryngeal/cough reflexes
depression of both is incomplete . If dose is not large enough, we can see a “stage 2” repose to a/w manipulation - increased risk of laryngospasm, bronchospasm etc.
most potent enzyme inducer =
phenobarbitals
hepatic enzyme induction with barbs may lead to
increased metabolism of oral anti-coagulants, phenytoin, TCAs, corticosteroids, vit k.
barbs can lead to accelerated production of
heme
patients treated with barbs for sz disorders
metabolize drugs about 2x as fast, especially evident in muscle relaxants.
venous thrombosis
effect of barbs
tolerance of barbs develops
rapidly, more rapidly than can be described by enzyme induction.
allergies with barbs
rare: 1:30,000 but high mortality.
allergy most common in atopic patient, those with multiple allergies, prior TPL exposure.
things that cant be mixed with barbs
opioids, catechols, NMBs, midazolam, LR,
pancuronium, vecuronium, atracurium, alfentanil, sufentanil, midazolam, LR***
to reconstitute barb
must use sterile H2O or NSS
Intra-arterial injection of barb
would cause intense vasoconstriction, pain, crystals may form, possible loss of limb
to treat intra-arterial injection of barb
dilute with NSS
phenoxybenzamine - noncompetitive antagonist.
prevent thrombosis, brachial plexus block of stellate ganglion block.
papaverine 40-80 mg to vasodilator.
drugs to avoid with porphyrias
thiopental thiamylal methohexital etomidate keterolac phenacetin pentazocine
methohexital is used
for ECT because we dont want an isoelectric EEG
histamine release can cause
bronchoconstriction
phenobarbital is excreted
unchanged in the urine, all others are metabolized by CYP450
branched chain on the number 5 carbon atom usually has
greater hypnotic activity than the corresponding drug with a straight chain