anti-epileptics Flashcards
MOA AEDs
1+ of:
- prolonged Na-channel inactivation = delayed depolarization
- T-type Ca channel blocker
- binding GABA-R subtype to inc GABA transmission
- inc GABA release
- inhibit GABA degradation
when to withdraw antiepileptic drug therapy
consider if seizure-free for over 2 years
*reduce over 1-3 months period
carbamazepine use and MOA
partial and secondarily generalized T-C seizures; trigeminal neuralgia, neuropathic pain, bipolar d/o
blocks v-g Na channel
carbamazepine kinetics
CYP1A2 and 3A4
autoinduction = dec T1/2 over 1st month (30->12 h), so must slowly inc dose to keep therapeutic
induces 2C9, 2C19, 3A4
carbamazepine ADR
dose-related: nausea, sedation, diplopia, dizziness, wt gain
severe/ idiosyncratic: rash (*inc risk SJS in Asians HLA-B-1502), leukopenia, SLE, aplastic anemia, SIADH and dilutional hyponatremia
teratogenic
oxcarbazepine use and MOA
partial seizures
carbamazepine analog w similar effects (but less CYP induction)
oxcarbazepine kinetics
liver metab -> active 10-MHD, renally eliminated
no autoinduction = fewer drug interactions
oxcarbazepine ADR
dose-related: HA, somnolence, dizziness, nausea
severe/idio: hyponatremia, rash (may cross-rx w carbamazepine)
phenytoin and fosphenytoin use and MOA
partial and 2’ generalized seizures
blocks neuronal Na and Ca channels
*fos is water soluble injectable pro-drug of phenytoin
phenytoin and fosphenytoin kinetics
highly albumin-bound
zero-order kinetics at high dose d/t saturation of metabolizing enzymes
need loading dose
CYP 2C9 and 2C19 substrate
phenytoin and fosphenytoin ADR
dose-related: nystagmus, diplopia, dizziness, drowsiness
severe/idio: dyskinesia, gingival hyperplasia, facial coarsening, vitamin deficiencies, severe rash
valproate uses and MOA
all types of seizures
also bipolar, migraine prophylaxis, trigeminal neuralgia
blocks Na and Ca channels, inc GABA transmission
valproate ADR
dose-related: n/v, tremor, drowsiness, sedation
severe/idio: alopecia, weight gain, hepatotoxicity, thrombocytopenia
*lower IQ in children exposed in utero
teratogenic
topiramate uses and MOA
partial and generalized T-C seizures
also migraine prophylaxis, neuropathic pain, weight loss (+ phentermine)
Na channel blocker, GABA-R activator
topiramate ADR
dose-related: drowsiness, ataxia, dizziness, paresthesias, poor concentration, weight loss
severe/idio: decreased sweating, hyperthermia, kidney stones, metabolic acidosis
lamotrigine use and MOA
partial and generalized seizures
blocks Na channels
lamotrigine ADR
dose-related: dizziness, HA, diplopia, ataxia, somnolence
severe/idio: severe rash -> SJS; inc risk aseptic meningitis
gabapentin use and MOA
adjunct for partial seizure, also primary agent
also postherpetic neuralgia, neuropathic pain, restless leg syndrome
GABA analog = inc GABA concentration
gabapentin ADR
dose-related: somnolence, fatigue, dizziness, confusion, blurred vision
severe/idio: weight gain
ethosuximide use and MOA
absence seizures
blocks T-type Ca channels
ethosuximide ADR
dose-related: sedation, nausea, HA
severe/idio: irritability, psychosis, leukopenia
pregabalin use and MOA
adjunct for partial seizures
also diabetic neuropathic pain, postherpetic neuralgia, fibromyalgia
MOA - similar to gabapentin
pregabalin ADR
dose-related: somnolence, dizziness, ataxia, peripheral edema, weight gain
zonisamide use and MOA
adjunct in partial seizures, monotherapy in children
blocks T-type Ca channels and prolongs inactivated state of Na channels
zonisamide ADR
similar to topiramate
dose-related: somnolence, fatigue, anorexia, wt loss, paresthesias
severe/idio: SJS, kidney stones
diazepam
BZD
rectal gel for tx of inc seizure activity while on other AEDs
may be used in status epilepticus
clonazepam
BZD for tx resistance absence and myoclonic seizures
tolerance will develop
highly sedating
may be used in status epilepticus
clorazepate
BZD used as adjunct for partial seizures
metabolized to DMDZ (active metabolite of diazepam)
felbamate
rarely used, but used as adjunct-therapy for drug-resistant seizures
low and high suicide risk AEDs
low: conventional AEDs, lamotrigine, gabapentin, pregabalin, oxcarbazepine
high: levetiracetam, tiagabine (rarely used), topiramate
DOC for partial seizures
carbamazepine, oxcarbazepine, levetiracetam, lamotrigine
DOC for generalized T-C seizures
levetiracetam, valproate, lamotrigine
DOC for generalized absence seizures
ethosuximide, valproate
teratogenic effects of AEDs
30%- cleft lip or palate
most serious: neural tube defects
high incidence with polytherapy
greatest risk: valproate, carbamazepine, phenobarbital
AED use during pregnancy
stop 6 mos before pregnancy, but do not stop during pregnancy (monitor through U/S)
AEDs and OCPs
oral contraceptives commonly fail d/t enzyme-inducing AEDs (inc estrogen metabolism)
AEDs and folic acid
repro age women on AEDs should take folic acid prophylaxis
carbamazepine, phenytoin, phenobarbital decreased FA absorption
levetiracetam ADR
SJS, inc suicide risk
