Carbamazepine & Valproic Acid Flashcards
Carb
MOA
inducation
TCA used in the tx of tonic-clonic (grand mal) seizures, partial or secondary generalized seizures
Na channel blocker that binds voltage gated Na channels in the inactive conformation to prevent repetitive and sustained firing of an action potential
Carb dosage forms
IV po IR tabs po susp ER tabs ER caps Rectal enema
Carb PK
F = 1 for all dosage forms, no first pass metabolism
absorption of IR forms is erratic and unpredictable
CArb evening dose is absorbed more _____ than morning dose
slowly
Carb conc time profile has two peaks, why
absorbed in the upper and then lower intestine
carb has _____ absorption so doses >20mg/kg may have _____ bioavailability
saturable
reduced
moisture may decrease carb potency T or F
true
carb has what order of kinetics
First and zero-order simultaneiusly
can we use CSF as surrogate for brain tissues carb [ ]
yes, distributes rapidly and uniformly
carb Vd the same for everyone?
no, varies by age
carb elimination
hepatic via CYP3A4
autoinduction
carbamazepine
when drug reaches steady state, autoinduction increases own metabolism and [ ] will then decrease w time
on a graph of dose (x-axis) vs ratio of Css metabolite:Css parent drug, why dose the curve increase and then plateau
metabolite elimination/clearance is independent of anything else going on
as tiem goes on, more metabolite is produced and feeds back to induce the metabolism of parent drug to metabolite
parent drug (denominator) concentrations will decrease while metabolite increases then plateaus
carbamazepine induces _____
and increases concentrations of _______ and ________
CYP2C19
selegiline and clomipramide
child pugh score >____ warrants a ____ decrease in the initial daily dose of carbamazepine
> 8 –> 25-50%
what allele can increase risk of SJS with carb
HLA-B15:02 causes >100 fold increase
carbamazepine therapeutic range
4-12 mg/L
carbamazepine loading dose
no loading doses, short dosing interval, start with 1/4 to 1/3 of desired MD and titrate
valproic acid uses, MOA
tx generalized, partial and absence (petit mal) seizures
widest spectrum of activity
increases GABA concentrations or effects cellular membranes
VPA dosage forms
valproic acid po caps
divalproex sod po caps and tabs
valproate sodium inj, po soln
VPA absorption
almost completely absorbed
rate (not extent) decreased by food
nighttime concentrations are ____% of daytime
~40%
VPA conc in CSF tend to be _____than unbound Cp
lower
fu for VPA
VERY high, fu = 0.5-1, unbound is very affected by diseases affecting albumin
how is VPA eliminated
primarily eliminated by liver
LOW extraction drug (CL independent of BF)
VPA has _____ clearance at _____ concentrations
higher, higher
VPA _____ enzymes
inhibits
