Antiepileptics

Question 1

Phenytoin (Dilantin)

Answer 1

C: Voltage-gated Na channel stabilizer
M: Stabilize inactive conformation of Na channel
T: Less effective for absence (particular pediatric), myoclonic, atonic seizures
SE: Rash, gingival hyperplasia, hirsutism, lupus-like reaction; can cause contraceptive failure** Mild myelosuppression, increased LFT; long-term: cerebellar degeneration, peripheral neuropathy, osteoporosis
MISC: IV infusion limited by hypotension; hepatic enzyme inducer (both auto- and hetero-inducer), highly protein bound

Question 2

Carbamazepine (Tegretol)

Answer 2

C: Voltage-gated Na channel stabilizer
M: Stabilize inactive conformation of Na channel
T: More effective for complex partial seizure than primary generalized; bipolar disorder; neuropathic pain
SE: Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs; can cause contraceptive failure
MISC: Hepatic enzyme inducer (both auto- and hetero-inducer); highly protein bound; must increase dose in 1-2 wks due to autoinduction; side effects likely due to epoxide metabolite

Question 3

Oxcarbamazepine (Trileptal)

Answer 3

C: Voltage-gated Na channel stabilizer
M: Stabilize inactive conformation of Na channel
T: More effective for complex partial seizure than primary generalized; bipolar disorder; neuropathic pain
SE: Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs; can cause contraceptive failure
MISC: Designed to bypass carbamazepine epoxide; less protein-bound, less autoinduction, fewer interactions, less toxic, longer half-life than carbamazepine

Question 4

Lamotrigine (Lamictal)

Answer 4

C: Voltage-gated Na channel stabilizer
M: Stabilize inactive conformation of Na channel
T: Primary generalized epilepsies, absence seizures; indicated in children; bipolar disorder; neuropathic pain
SE: Rash, (rarely, Stevens-Johnson): slow initial titration important; may lead to contraceptive failure
MISC: May exacerbate myoclonic seizures; competes with valproic acid for excretion (potential synergy); hepatic enzyme inducer; not very protein bound

Question 5

Valproate (Depakote)

Answer 5

C: –
M: Unknown; likely affects Na-gated channels and GABA system
T: Broad spectrum: absence, myoclonic, tonic-clonic, primary generalized, partial onset, and secondary generalized seizures (but not absence seizures); IV for status epilepticus; bipolar treatment, migraine and long-term cluster headache prophylaxis
SE: Weight gain, hair turnover, hyperammonemia (which can be mitigated with oral carnitine), teratogenicity, blood dyscrasias** Pancreatitus
MISC: –

Question 6

Vigabatrin (Sabril)

Answer 6

C: GABAergic anti-epileptic
M: GABA transaminase binder (slows down intracellular breakdown of GABA)
T: Anti-epileptic
SE: --
MISC: Works on GABA-A

Question 7

Tigabine (Gabitril)

Answer 7

C: GABAergic anti-epileptic
M: GABA reuptake inhibitor
T: Anti-epileptic
SE: --
MISC: Works on GABA-A

Question 8

Benzodiazapines

Answer 8

C: GABAergic anti-epileptic
M: Bind GABA-A
T: Status epilepticus (refractory); anesthesia
SE: Sedation
MISC: Long-term usefulness limited by tolerance

Question 9

Gabapentin (Neurontin)

Answer 9

C: GABA analog
M: Block presynaptic influx of Ca
T: Adjunct for partial complex epilepsy; more commonly used for neuropathic pain
SE: Sedation
MISC: Absorption limited by intestinal AA transporter (there is a Tm); limited protein binding; no metabolism or drug interaction in humans (so few side effects)

Question 10

Pregabalin (Lyrica)

Answer 10

C: GABA analog
M: Block presynaptic influx of Ca
T: Adjunct for partial complex epilepsy; more commonly used for neuropathic pain
SE: --
MISC: --

Question 11

Topiramate (Topamax)

Answer 11

C: Glutamate Receptor Blockers
M: Partial AMPA, Kainate Ca receptor blocker; secondary effect at voltage-gated Na channel, GABA system
T: Partial onset seizures, secondary generalized seizures, primary generalized epilepsy; migraine prevention, long-term prevention of cluster headaches
SE: Mild metabolic acidosis, kidney stones (due to some carbonic anhydrase activity); modest weight loss; rare acute glaucoma; sedation** Word-finding problems
MISC: Carbonic anhydrase activity leads to mild metabolic acidosis, which leads to respiratory compensation, which leads to mild alkalosis, which leads to calcium ionization, which leads to tingling; treat with vitamin C (acidify urine)

Question 12

Felbamate (Felbatol)

Answer 12

C: Glutamate Receptor Blockers
M: NMDA receptor blocker; secondary effect at voltage-gated Na and Ca channels, GABA system
T: Partial onset seizures with or without secondary generalization; medically refractory epilepsy
SE: Uncommon but potentially fatal. Aplastic anemia, acute hepatic failure. Requires monitoring.
MISC: –

Question 13

Levetiracetam (Keppra)

Answer 13

C: Synaptic vesicle binder
M: Binds synaptic vesicle protein 2, leading to less NT release
T: Partial onset seizures, secondary generalized seizures; maybe primary generalized epilepsy
SE: Well tolerated; sedation, mostly; rarely, irritability, aphasia, thrombocytopenia
MISC: –

Question 14

Ethosuximide (Zarontin)

Answer 14

C: Voltage-gated Ca channel blocker
M: Blocks T-type Ca-channels in thalamo-cortical circuits
T: Absence seizures only (and neuropathic pain)
SE: Nausea (transient), sedation, irritability
MISC: Readily absorbed, minimal first pass metabolism; not protein bound