Antiepileptic pharmacotherapy

Question 1

MOA of Na+ blocking antiepileptics

Answer 1

Binds to inactive form of Na+ channels, resulting in preferential inhibition of epileptic focus

Question 2

MOA of Ca++ blocking antiepileptics

Answer 2

Thanlmic T-type Ca++ channels inhibit absence seizures

Presynaptic HVA Ca++ channels- suppresses Glu signalling

Question 3

Ways of enhancing GABA signalling

Answer 3

Activate GABA-A receptors
inhibit GABA re-uptake GAT-1
Inhibit GABA degredation GABA-T

Question 4

Ways of antagonizing glutamanergic transmission

Answer 4

antagonize receptors

block glu release SV2A

Question 5

MOA of Ca++ blocking antiepileptics

Answer 5

Thanlmic T-type Ca++ channels inhibit absence seizures

Presynaptic HVA Ca++ channels- suppresses EAA release

Question 6

Ways of antagonizing glutamanergic transmission

Answer 6

antagonize receptors

block glu release SV2A

Question 7

Phenytoin MOA

Answer 7

blocks Na+ channels

Question 8

Pharmacokinetics of phenytoin

Answer 8

oral, IV (fosphenytoin)
non-linear elimination- need to monitor in blood
plasma protein binding
hepatic CYP metabolism

Question 9

Therapeutic use of phenytoin

Answer 9

focal and tonic-clonic seizures, SE

not effective against absence seizures

Question 10

Drug interactions with phenytoin

Answer 10

OCPs, warfarin

Question 11

Adverse effects of phenytoin

Answer 11

CNS- nystagmus, ataxia, and sedation
Rash and SJS
hirsutism
blood dyscrasias
teratogenic
gingival hyperplasia

Question 12

MOA of carbamazepine

Answer 12

Na+ channel blockade

Question 13

carbamazepine pharmacokinetics

Answer 13

linear kinetics

autoinduction of CYP3A4

Question 14

Therapeutic use of carbamazepine

Answer 14

generalized tonic-clonic seizures, simple and complex partial seizures
trigeminal neuralgia
bipolar disorder

Question 15

Adverse effects of carbamazepine

Answer 15

CNS- drowsiness, ataxia, vertigo, diplopia, blurred vision; nausea
hyponatremia
Boxed warning- rash and SJS, asian variant more susceptible
teratogenic

Question 16

Valproic acid MOA

Answer 16

blocks Na+ channels
Blocks T-type Ca++ channels
Stimulates GABA synthesis and inhibits degredation

Question 17

Therapeutic use of valproic acid

Answer 17

broad spectrum anti-seizure
absence, focal and tonic-clonic seizures
bipolar disorder and migraine prophylaxis

Question 18

What is divalproex

Answer 18

1:1 acid/salt

Question 19

Adverse effects of valproic acid

Answer 19

GI
CNS
hepatic toxicity and pancreatitis (boxed warning)
Teratogenic (boxed warning)

Question 20

Drug interaction of valproic acid

Answer 20

phenytoin

Question 21

MOA of ethosuximide

Answer 21

Blocks t-type Ca++ channels in thalmic nucleus

Thalmic 3-Hz spike and wave rythms are characteristic of absence seizures

Question 22

Therapeutic use of ethosuximide

Answer 22

drug of choice for uncomplicated absence seizures

not effective for other types

Question 23

Adverse effects of ethosuximide

Answer 23

well-tolerated
GI
Rare SLE, leucopenia, aplastic anemia and SJS

Question 24

MOA of Gabapentin

Answer 24

blocks HVA Ca++ channels, may reduce glu release

Question 25

Pharmacokinetics of gabapentin

Answer 25

not metabolized; excreted unchanged in urine

Question 26

Therapeutic use of gabapentin

Answer 26

add-on for focal and generalized seizures posttherpetic neuralgia off-label pain, migrane, bipolar

Question 27

Adverse effects of gabapentin

Answer 27

some sedation and dizziness but mostly well tolerated

Question 28

Lamotrigine MOA

Answer 28

complex, major is blockade of Na+ channels

Question 29

Pharmacokinetics of lamotrigine

Answer 29

metabolized by glucuronidation, hepatic clearance is increased by enzyme inducers

Question 30

therapeutic use of lamotrigine

Answer 30

Lennox-Gastaut syndrome monotherapy for partial and secondarily generalized tonic-clonic, alternative to ethosuximide for absence biopolar

Question 31

Adverse effects of lamotrigine

Answer 31

dizziness, ataxia, blurred vision, nausea, vomiting Rash/SJS boxed warning teratogen

Question 32

Levetiracetam MOA

Answer 32

unknown, binds to SV2A

Question 33

Pharmacokinetics of levetiracetam

Answer 33

mostly devoid of drug interactions

Question 34

Therapeutic use of levetiracetam

Answer 34

add on for partial or generalized tonic-clonic and myoclonic seizures

Question 35

Adverse effects of levetiracetam

Answer 35

fatigue, dizziness, hypertension | behavioral symptoms

Question 36

MOA of tiagabine

Answer 36

prolongs inhibitory effect of gaba by blocking GAT-1

Question 37

Therapeutic use of tigabine

Answer 37

add on for refractory partial seizures without generalization off-label discouraged-may promote seizures

Question 38

Topiramate MOA

Answer 38

blocks Na+ channels, hyperpolarization, Carbonic anydrase inhibitor

Question 39

Pharmacokinetics of topiramate

Answer 39

excreted unchanged in urine

Question 40

Therapeutic use of topiramate

Answer 40

monotherapy for partial and generalized tonic-clonic seizures, adjunct for lennox-gastaut syndrome migrane prophylaxis

Question 41

Adverse effects of topiramate

Answer 41

well-tolerated renal calculi from CA inhibition cognitive impairment

Question 42

MOA of vigabatrin

Answer 42

irriversible inhibitor of GABA transaminase

Question 43

Therapeutic use of vigabatrin

Answer 43

restricted use for refractory complex partial seizures | monotherapy for infantile spasms

Question 44

Adverse effects of vigabatrin

Answer 44

boxed warning for progressive and permanent bilateral vision loss