anti-epileptics

Question 1

MOA AEDs

Answer 1

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

Question 2

when to withdraw antiepileptic drug therapy

Answer 2

consider if seizure-free for over 2 years

*reduce over 1-3 months period

Question 3

carbamazepine use and MOA

Answer 3

partial and secondarily generalized T-C seizures; trigeminal neuralgia, neuropathic pain, bipolar d/o
blocks v-g Na channel

Question 4

carbamazepine kinetics

Answer 4

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

Question 5

carbamazepine ADR

Answer 5

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

Question 6

oxcarbazepine use and MOA

Answer 6

partial seizures

carbamazepine analog w similar effects (but less CYP induction)

Question 7

oxcarbazepine kinetics

Answer 7

liver metab -> active 10-MHD, renally eliminated

no autoinduction = fewer drug interactions

Question 8

oxcarbazepine ADR

Answer 8

dose-related: HA, somnolence, dizziness, nausea

severe/idio: hyponatremia, rash (may cross-rx w carbamazepine)

Question 9

phenytoin and fosphenytoin use and MOA

Answer 9

partial and 2’ generalized seizures
blocks neuronal Na and Ca channels
*fos is water soluble injectable pro-drug of phenytoin

Question 10

phenytoin and fosphenytoin kinetics

Answer 10

highly albumin-bound
zero-order kinetics at high dose d/t saturation of metabolizing enzymes
need loading dose
CYP 2C9 and 2C19 substrate

Question 11

phenytoin and fosphenytoin ADR

Answer 11

dose-related: nystagmus, diplopia, dizziness, drowsiness

severe/idio: dyskinesia, gingival hyperplasia, facial coarsening, vitamin deficiencies, severe rash

Question 12

valproate uses and MOA

Answer 12

all types of seizures
also bipolar, migraine prophylaxis, trigeminal neuralgia
blocks Na and Ca channels, inc GABA transmission

Question 13

valproate ADR

Answer 13

dose-related: n/v, tremor, drowsiness, sedation
severe/idio: alopecia, weight gain, hepatotoxicity, thrombocytopenia
*lower IQ in children exposed in utero
teratogenic

Question 14

topiramate uses and MOA

Answer 14

partial and generalized T-C seizures
also migraine prophylaxis, neuropathic pain, weight loss (+ phentermine)
Na channel blocker, GABA-R activator

Question 15

topiramate ADR

Answer 15

dose-related: drowsiness, ataxia, dizziness, paresthesias, poor concentration, weight loss
severe/idio: decreased sweating, hyperthermia, kidney stones, metabolic acidosis

Question 16

lamotrigine use and MOA

Answer 16

partial and generalized seizures

blocks Na channels

Question 17

lamotrigine ADR

Answer 17

dose-related: dizziness, HA, diplopia, ataxia, somnolence

severe/idio: severe rash -> SJS; inc risk aseptic meningitis

Question 18

gabapentin use and MOA

Answer 18

adjunct for partial seizure, also primary agent
also postherpetic neuralgia, neuropathic pain, restless leg syndrome
GABA analog = inc GABA concentration

Question 19

gabapentin ADR

Answer 19

dose-related: somnolence, fatigue, dizziness, confusion, blurred vision
severe/idio: weight gain

Question 20

ethosuximide use and MOA

Answer 20

absence seizures

blocks T-type Ca channels

Question 21

ethosuximide ADR

Answer 21

dose-related: sedation, nausea, HA

severe/idio: irritability, psychosis, leukopenia

Question 22

pregabalin use and MOA

Answer 22

adjunct for partial seizures
also diabetic neuropathic pain, postherpetic neuralgia, fibromyalgia
MOA - similar to gabapentin

Question 23

pregabalin ADR

Answer 23

dose-related: somnolence, dizziness, ataxia, peripheral edema, weight gain

Question 24

zonisamide use and MOA

Answer 24

adjunct in partial seizures, monotherapy in children

blocks T-type Ca channels and prolongs inactivated state of Na channels

Question 25

zonisamide ADR

Answer 25

similar to topiramate dose-related: somnolence, fatigue, anorexia, wt loss, paresthesias severe/idio: SJS, kidney stones

Question 26

diazepam

Answer 26

BZD rectal gel for tx of inc seizure activity while on other AEDs may be used in status epilepticus

Question 27

clonazepam

Answer 27

BZD for tx resistance absence and myoclonic seizures tolerance will develop highly sedating may be used in status epilepticus

Question 28

clorazepate

Answer 28

BZD used as adjunct for partial seizures | metabolized to DMDZ (active metabolite of diazepam)

Question 29

felbamate

Answer 29

rarely used, but used as adjunct-therapy for drug-resistant seizures

Question 30

low and high suicide risk AEDs

Answer 30

low: conventional AEDs, lamotrigine, gabapentin, pregabalin, oxcarbazepine high: levetiracetam, tiagabine (rarely used), topiramate

Question 31

DOC for partial seizures

Answer 31

carbamazepine, oxcarbazepine, levetiracetam, lamotrigine

Question 32

DOC for generalized T-C seizures

Answer 32

levetiracetam, valproate, lamotrigine

Question 33

DOC for generalized absence seizures

Answer 33

ethosuximide, valproate

Question 34

teratogenic effects of AEDs

Answer 34

30%- cleft lip or palate most serious: neural tube defects high incidence with polytherapy greatest risk: valproate, carbamazepine, phenobarbital

Question 35

AED use during pregnancy

Answer 35

stop 6 mos before pregnancy, but do not stop during pregnancy (monitor through U/S)

Question 36

AEDs and OCPs

Answer 36

oral contraceptives commonly fail d/t enzyme-inducing AEDs (inc estrogen metabolism)

Question 37

AEDs and folic acid

Answer 37

repro age women on AEDs should take folic acid prophylaxis | carbamazepine, phenytoin, phenobarbital decreased FA absorption

Question 38

levetiracetam ADR

Answer 38

SJS, inc suicide risk