Pharm: AEDs

Question 1

voltage gated Na channel blockers

Answer 1

-zepine
promote inactivated state to limit sustained, repetitive firing of neurons
Tx: partial and secondarily generalized tonic-clonic seizures

Question 2

GABA enhancers

Answer 2

pre- or postsynaptic enhancement of GABA synaptic inhibition

Tx: partial and secondarily generalized tonic-clonic seizures

Question 3

voltage gated Ca channel blockers

Answer 3

inhibition of T-type Ca currents

Tx: absence seizure

Question 4

carbamazepine

Answer 4

Na channel blocker
induces its own metabolism
AE: aplastic anemia; constipation/dry mouth
BBW: AGRANULOCYTOSIS
TERATOGEN: FETAL HYDANTOIN syndrome, SPINA BIFIDA
Tx: partial, including secondarily generalize seizures

Question 5

clonazepam

Answer 5

GABA agonist

NO skin AE

Question 6

ethosuximide

Answer 6

Ca channel blocker

Tx: absence seizure

Question 7

felbamate

Answer 7

NMDA antagonist, GABA agonist

BBW: APLASTIC ANEMIA,bone marrow suppression, HEPATIC

Question 8

gabapentin

Answer 8

inhibit alpha-2 delta-1 subunit of Ca channel

enhancement of presynaptic GABA release

Question 9

lacosamide

Answer 9

PO, IV
Na channel blocker
NO skin AE

Question 10

lamotrigine

Answer 10

Na channel blocker
BBW: SKIN (TEN/SJS)
TERATOGEN: inhibits dihydrofolate reductase; cleft
Tx: partial, including secondarily generalize seizures; primary generalized tonic-conic seizures; atypical absence, myoclonic, atonic seizures

Question 11

levetiracetam

Answer 11

PO, IV
MoA: unknown
Tx: partial, including secondarily generalized seizures; primary generalized tonic-clonic seizures; atypical absence, myoclonic, atonic seizures

Question 12

oxcarbazepine

Answer 12

Na channel blocker
possibly: increase K and decrease Ca effects
Tx: partial, including secondarily generalize seizures

Question 13

phenytoin

Answer 13

PO, IV
Na channel blocker
PROTEIN BINDING
CYP induction: lots of drug interactions
highly variable metabolism
elimination: stool; ZERO order (T1/2 varies with dose)
AE: GINGIVAL HYPERPLASIA; HYPERTRICHOSIS; BLOOD DYSCRASIA
TERATOGEN: FETAL HYDANTOIN syndrome, cardiac, cleft, growth deficiency

Question 14

pregabalin

Answer 14

inhibit alpha-2 delta-1 subunit of Ca channel

Question 15

topiramate

Answer 15

Na channel blocker
decrease glutamate activity
increase K current and GABA

carbonic anhydrase inhibitor: renal bicarb loss
AE: renal stones
TERATOGEN: cleft lip/palate

Question 16

valproate

Answer 16

PO, IV
Na channel blocker
inhibit GABA metabolism
(Ca channel blocker)
binds protein
AE: THROMBOCYTOPENIA, PROLONGED BLEEDING; HEPATIC, nausea, diarrhea
TERATOGEN: greatest risk; NEURAL TUBE, cleft, skeletal, developmental
Tx: primary generalized tonic-clonic seizures; absence seizures; atypical absence, myoclonic, atonic seizures

Question 17

zonisamide

Answer 17

Na/Ca channel blocker
accumulates in RBCs

carbonic anhydrase inhibitor: renal bicarb loss
AE: renal stones

Question 18

benzodiazepines

Answer 18

postsynaptic
GABA(A) receptor agonist: enhances Cl- influx
increase FREQUENCY (shift dose-response curve)
AE: dependence, withdrawal, sedation, tolerance
can give RAPID IV for seizure

Question 19

barbiturates

Answer 19

postsynaptic
GABA(A) receptor agonist: enhances Cl- influx
increase DURATION
AE: dependence, withdrawal, sedation, tolerance
can give RAPID IV for seizure

Question 20

AED’s in general

Answer 20

oral (slow release available)
limited protein binding
long T1/2
CYPs and UGT
hepatic metabolism
elimination: urine
AE: suicidal ideation, CNS effects, RASH (SJS/DRESS/TEN)
renal dysfunction can cause drug accumulation
need to routine monitoring: if levels high, ok if no AE
TAPER: prevent status epilepticus

Question 21

fosphenytoin

Answer 21

phenytoin pro-drug

Question 22

HLA-B 1502

Answer 22

Asians
increase chance of Steven Johnson’s and toxic epidermal necrolysis
CARBAMAZEPINE
also avoid: (fos)phenytoin, lamotrigine, oxcarbazepine

Question 23

phenobarbital

Answer 23

CYP induction

teratogen: cleft, cardiac, urinary tract

Question 24

Type of teratogenicity

1. valproate
2. phenytoin
3. carbamazepine
4. phenobarbital
5. lamotrigine
6. topirmate

Answer 24

1. neural tube, cleft, skeletal, developmental delay
2. FHS, cardiac, cleft
3. FHS, spina bifida
4. cleft, cardiac, urinary tract
5. low folate; cleft
6. cleft lip/palate

Question 25

fetal hydantoin syndrome

Answer 25

upturned nose, mid facial hypoplasia, long upper lip with vermilion border
digital/ fingernail hypoplasia
CARBAMAZEPINE, PHENYTOIN

Question 26

Tx of partial, including secondarily generalized seizures

Answer 26

lamotrigine
carbamazepine
levetiracetam
oxcarbazepine

Question 27

Tx of primary generalized tonic-clonic seizures

Answer 27

valproate
lamotrigine
levetiracetam

Question 28

Tx of absence seizures

Answer 28

ethosuximide

valproate

Question 29

Tx of atypical absence, myoclonic, atonic seizures

Answer 29

valproate
lamotrigine
levatiracetam

Question 30

status epilepticus

Answer 30

EMERGENCY
prolonged seizure or cluster of seizures without return to baseline lasting longer than 30 min
Tx: BENZODIAZEPINE followed by other IV AED

Question 31

1. benzodiazepines for status epilepticus

2. option for following IV AED

Answer 31

1. IV LORAZEPAM, IM midazolam, rectal diazepam

2. valproate, phenytoin, midazolam, levetiracetam, phenobarbital (can’t be given rapid IV so use benzodiazepines first)