drugs for epilepsy Flashcards
what are the 3 general mechanisms of action for anti-epilepsy drugs?
- promote the inactivated state of voltage gated Na+ channels
- Pre or post synaptic enhancement of GABA medicated inhibition
- inhibition of T-type voltage-activated Ca2+ channels (absence seizures)
FDA has issued a warning of what adverse effect with the use of anticonvulsants?
suicidal ideation
- 2 fold increase
- monitor all pts for emerging depression/suicidal thoughts
- educate pts about risks
- use minimum drug levels for epilepsy
current drugs control seizures only in what percentage of pts?
50%
the adverse effects of anti epileptic drugs can have what effect on pts?
responsible for limited pt adherence
instead of adding a drug to an exisint anticonvulsant monotherapy regimen, what should you do?
substitute rather than additive treatment
MOA of carbamazepine
blocks voltage gated Na channels and decreases glutamate release
MOA of clonazepam
enhance GABA-A receptor responses
MOA ethosuximide
decreases T-Type Ca2+ currents (used for absence seizures)
MOA felbamate
blocks NMDA receptors; increase GABA
MOA gabapentin
blocks alpha-2 delta-1 subunit of Ca2+ channels
MOA of lacosamide
blocks Na+ channels
MOA lamotrigene
blocks Na+ channels
MOA oxcarbazepine
blocks Na+ channels, possibly increases K+ & decreases Ca2+ effects
MOA Phenytoin
blocks voltage gated Na+ channels
MOA pregablin
blocks alpha-2 delta-1 subunit of Ca2+ channel
MOA Topiramate
blocks Na+ channels; increases K+ current, increases GABA; decreases glutamate activity
MOA valproate
increases GABA activity; also decreases Na+ channnels
MOA zonisamide
blocks Na+ channels, & decreases T-type Ca2+ actions
the anti-epileptic drug have limited protein binding except which two drugs?
phenytoin & valproate
which antiepileptic drug accumulates in erythrocytes?
zonisamide
which type of formulation for anti-epileptic drugs promotes adherence?
slow release products (fewer doses / day)
what happens to the half-life of carbamazepine as treatment progresses?
the half life decreases due to an increased rate of hepatic metabolism
which two anti-epileptic drugs are not metabolized?
gabapentin & pregabalin
which antiepileptic drug has no CYP activity and is metabolized by uridine glucuronosyl transferasewith subsequent induction of UGT (hint its metabolites are eliminated in urine)?
lamotrigine
which antiepileptic drug is metabolically conjugated, decreases CYP2C19& increases CYP3A4/5?
OXCARBAZEPINE
what is the only antiepileptic drug that is eliminated in the stool?
phenytoin
Phenytoin is metabolized by what CYP Enzymes?
CYP2C9»CYP2C19
Routine monitoring of serum drug levels is required with what 3 drugs?
carbamazepine
Phenytoin
Valproate
what should the physician do for a pt experiencing good seizure control and no signs or symptoms of significant drug toxicity, despite serum drug levels being high?
physician doesn’t have to reduce drug dose, but rather use clinical presentation to guide treatment
which two drugs are weak carbonic anhydrase inhibitors?
topiramate/zonisamide
what is the adverse effect you may predict with the weak carbonic anhydrase activity of topiramate/zonisamide therapy?
promotes stone formation by reducing urinary citrate excretion & by increasing urinary pH (monitor serum bicarbonate levels)
discontinuation of antiepileptic drugs can precipitate what adverse effects?
status epilepticus, increased frequency of seizures & various neurologic issues, like anxiety (remember to taper the dose rather than stop it abruptly)
what is the name of the phytoin prodrug?
fosphenytoin (remember dose adjustment is important when transitioning b/w the two)
which antiepileptic drugs has zero order elimination?
phenytoin
what are some of the ADME problems with phenytoin?
issues of protein binding displacement and CYP mediated drug-drug interactions
- –highly variable induction of CYPs
- –Age, cigarette smoking & hepatic status confounding factors
what is the most common CNS adverse effect of phenytoin therapy?
nystagmus
which antiepileptic drug can cause gingival hyperplasia?
phenytoin
what are some of the dermatologic adverse effects of phenytoin therapy?
usually benign-measles-like rash, SJS, TEN, & DRES
Hypertrichosis or hirsutism (generally confined to extremities but can affect the trunk and face, may be irreversible)
what are some of the CNS adverse effects of carbamazepine?
esp. during initial treatment phase dizziness drowsiness ataxia blurred vision
which antiepileptic drug has a BBW for agranulocytosis?
carbamazepine
the incidence of SJS while using antiepileptic drugs is higher in Asian pts because they carry which allele?
SNP change for HLAB-1502 (good idea for these pts to also avoid other structurally related anticonvulsants like phenytoin, oxcarbazepine, lamotrigene)
the incidende of hepatotoxicity with valproic acid is more common in what pt population?
children
what are some of the CNS adverse effects of valproic acid?
somnolence, dizziness
what are the two main hematologic adverse effects of valproic acid?
thrombocytopenia
prolonged bleeding time
what are the adverse effects of clonazepam?
somnolence, ataxia, dizziness, fatigue
what are the AEs of ethosuximide?
somnolence, dizziness, headache, N/V, Diarrhea
what are the BBWs for felbamate?
aplastic anemia, bone marrow suppression, hepatic disease
what are 3 common adverse effects of antiepileptic drugs?
sedation, dizziness, ataxia
what are some of the AEs of gabapentin?
somnolence, dizziness, fatigue
what are some of the AEs of lacosamide?
diplopia, dizziness, headache
what is the BBW for lamotrigine?
serious rash (TEN/SJS) other AEs are : dizziness, diplopia, ataxia, blurred vision, rhinitis
which antiepileptic drug has an adverse effect of causing URTIs?
levetiracetam
name the antiepileptic drug: AEs including-dizziness/diplopia, headache, N/V, nystagmus/somnolence/ataxia
oxcarbazepine
which antiepileptic drug has AEs that include ataxia/parasethesias/abnormal vision/psychomotor slowing?
topiramate
which antiepileptic drug has these AEs: somnolence, anorexia, dizziness?
zonisamide
which AED has the greatest risk of adverse outcomes in pregnancy?
valproate (cat. X)
which two AEDs can cause fetal hydantoin syndrome?
carbamazepine & phenytoin
what are the fetal abnormalities for valproate?
neural tube defects, clefts, skeletal abnormalities, developmental delay
name the AED with these Adverse effects: cleft lip, cleft palate
topiramte
name the AED with these adverse effects: inhibits dihydrofolate reductase lowering fetal folate levels. Registry data suggest increased risk for clefts
lamotrigine
what are the fetal abnormalities seen with phenobarbital?
clefts, cardiac anomalies, urinary tract malformations
what are some of the fetal abnormalities seen with phenytoin?
fetal hydantoin syndrome: craniofacial anomalies, fingernail hypoplasia, growth deficiency, developmental delay, cardiac defects, clefts
what are the four drugs of choice for partial, including secondarily generalized seizures?
lamotrigine
carbamazepine
levetiracetam
oxycarbazepine
what are the 3 drugs of choice for primary generalized tonic-clonic seizures?
valproate
lamotrigine
levetiraetam
what are the 2 drugs of choice for absence seizures?
ethosuximide
valproate
what are the 3 drugs of choice for atypical absence, myoclonic, atonic seizures?
valproate
lamotrigine
levatiracetam
what are some of the predictors of mortaility for status epilepticus?
generalized seizure, increased pt age, anoxic brain injury, stroke, CNS infection or tumor, and lon duration of SE
what is the treatment of choice for status epilepticus?
benzodiazepines
what are the 3 benzodiazepines that are treatments of choice for status epilepticus?
IV lorazepam (first line for SE)
IM midazolam
Rectal dizepam
Followed by an IV AED: (valproate, phenytoin, midazolam, levetiracetam, phenobarbital)
why is a benzodiazepine first line treatment for SE?
reinforcement of inhibitory effects of GABA and these drugs can be given rapidly IV
only ___________ will induce CYP2B6 & CYP3A4 compared to benzodizepines
phenobarbital
what do phenobarbital and benzodiazepines have in common?
both work on GABA receptor but at different sites
BOTH have issues of dependence & withdrawal
BOTH have tolerance development
BOTH produce dose-related sedation
how are phenobarbital and benzodiazepines different?
barbiturates prolong opening time of Cl- channel (increased efficacy)
Benzodiazepines shift dose-response curve for GABA (potency)
-work at different sites of GABA receptor
which 3 AEDs have blood toxicities?
carbamazepine, felbamate, & valproate
name 5 AEDs that are big time teratogens?
lamotrigine, carbamazepine, phenytoin, topiramate, phenobarbital & valproate (worst one of all)
which drug is first line for status epilepticus?
lorazepam IV
