Block 2 Lecture 5 -- ASDs Flashcards
Indications for phenytoin:
1) focal seizures
2) generalized tonic-clonic
3) emergency status epilepticus
Indications for carbamazepine:
1) temporal lobe epilepsy
2) all others except absence
Indications for oxcarbazepine:
1) temporal lobe epilepsy
2) all others except absence
Indications for valproic acid:
1) absence
2) most others
Indications for lamotrigine:
all seizure types
– including generalized w/ absence attacks in children
Indications for topiramate:
1) focal seizures
2) generalized tonic-clonic
Indications for zonisamide:
1) focal seizures
Indications for lacosamide:
adjunct for focal-onset
Indications for gabapentin
focal seizures
Indications for pregabalin:
same as gabapentin
– focal seizures
Indications for ethosuximide:
absence seizures
Indications for retigabine:
adjunct for focal seizures
Indications for levetiracetam:
1) focal
2) generalized tonic-clonic
Indications for perampanel:
focal seizures
Indications for felbamate:
lennox-gastaut syndrome
retractable epilepsy with uncontrollable seizures
MoA of phenytoin
use-dependent Na+ channel blockade
MoA of carbamazepine
use-dependent Na+ channel blockade
MoA of oxcarbazepine
use-dependent Na+ channel blockade
MoA of lamotrigine
use-dependent Na+ channel blockade
MoA of lacosamide
use-dependent Na+ channel blockade
MoA of valproic acid
1) use-dependent Na+ channel blockade
2) stimulate GABA synthesis
3) inhibit GABA TA
MoA of topiramate
1) use-dependent Na+ channel blockade
2) augment GABA at GABAa
3) blockade of GluR (kainate and AMPA)
MoA of zonisamide
1) use-dependent Na+ channel blockade
2) t-type Ca channel blockade
MoA of Gabapentin
1) Ca channel blocker
2) GABAergic
MoA of pregabalin
Ca channel blocker
MoA of ethosuximide
Ca channel blocker
MoA of retigabine
K channel stabilizer
MoA of levetiracetam
SV2A binder
MoA of perampanel
AMPAr blocker (non-competitive)
MoA of felbamate
NMDAr blocker
Which ASDs exhibit PPB?
1) phenytoin (95%)
2) perampanel (95%)
3) valproic acid (90%)
4) levetiracetam (10%)
Which ASDs are non-sedating?
1) phenytoin
2) lamotrigine
3) valproic acid
4) ethosuximide
5) felbamate
What is the black box warning on felbamate?
1) aplastic anemia
2) acute hepatic failure
Which ASDs are secreted as a glucuronide?
1) oxcarbazepine
2) lamotrigine
3) valproic acid
Describe the metabolism of phenytoin.
1) non-linear (induces and saturates)
2) CYP2C9 + CYP2C19
3) t1/2 = 15-20h
Describe the metabolism of carbamazepine.
1) CYP2C9, C19, 3A4
2) t1/2 = 12-30h
3) long-term t1/2 = 15hr
Describe the metabolism of oxcarbazepine.
1) t1/2 = 1-2h
2) t1/2 (active mets) = 8-12h
Describe the metabolism of lamotrigine.
t1/2 = 25h
Describe the metabolism of lacosamide.
1) cyp2c19
2) t1/2 = 12-16h
Describe the metabolism of valproic acid.
1) cyp2c19
2) t1/2 = 8-17h
Describe the metabolism of topiramate?
t1/2 = 20-30h
Describe the metabolism of zonisamide.
cyp3a4
t1/2 = 60+ hr
Describe the metabolism of gabapentin.
hardly metabolized
t1/2 = 6h
Describe the metabolism of pregabalin.
hardly metabolized
t1/2 = 6h
Describe the metabolism of ethosuximide.
t1/2 = 60h
Describe the metabolism of retigabine.
t1/2= 8-11h
Describe the metabolism of levetiracetam.
hardly metabolized
t1/2 = 6-8h
Describe the metabolism of perampanel.
1) cyp3a4
2) t1/2= 70 - 105h
Describe the metabolism of felbamate
1) t1/2 = 20h
Which ASDs are affected by CYP3A4 inducer and inhibitors?
1) perampanel
2) zonisamide
3) oxcarbazepine (less)
4) carbamazepine (more)
5) phenytoin
Which ASDs are metabolized by CYP2C19?
phenytoin
lacosamide
What are DDIs for lamotrigine?
hepatic inducers that increase glucuronidation and clearance
What are DDIs of valproic acid?
1) PPB displacers
2) inhibits metabolism of phenobarb, phenytoin, carbamazepine
What are DDIs for topiramate?
carbamazepine and phenytoin increase metabolism
Which ASDs don’t have DDIs according to PK?
1) Ca channel blockers
2) K channel blockers (retigabine)
3) SV2a (keppra)
4) lacosamide
What drugs are metabolized by CYP3A4?
1) ASDs
2) OCC
3) warfarin
4) corticosteroids
What are CYP3A4 inhibitors?
1) valproic acid
2) cimetidine
3) erythromycin
What are CYP3A4 inducers?
1) phenytoin
2) primidone
3) phenobarbitol
What drugs displace PPB’ers?
1) valproate
2) phenytoin
3) salicylate
What ASD has a serine residue?
lacosamide
What drugs is cross-reactive to sulfonamide allergy?
zonisamide
What drug is a monosaccharide derivative?
topiramate (fructopyranose)
What drug has a triazine group?
lamotrigine
What is phenytoin’s prodrug?
fosphenytoin
How does retigabine work?
increases relative refractory period by binding to retigabine binding site on K+ channel
What is the effect of SV2a modulation?
altered Glu and GABA release
What drugs affect the AMPAr?
1) primary = perampanel
2) also: phenobarb, topiramate, lamotrigine
What ASDs carry black box warnings?
1) perampanel: aggression, anger, homocidal
2) felbamate: aplastic anemia, acute hepatic failure
3) retigabine: retinal abnormalities and skin discoloration
What is the intermediate in phenytoin metabolism?
reactive ARENE OXIDE
– probably causes the ADRs
What ASDs act on CRMP2?
lacosamide has secondary activity
