Antiepileptic Drugs

Question 1

general goal of antiepilpetics

Answer 1

*reduce the ability of neurons to fire action potentials at a high rate and reduce neuronal synchronization

Question 2

4 main mechanisms of action of antiepilpetics

Answer 2

1. modulate voltage-gated sodium, calcium, or potassium channels
2. enhance fast GABA-mediated synaptic inhibition (MORE inhibition)
3. reduce fast glutamate-mediated excitation (LESS excitation)
4. modify synaptic release process

Question 3

antiepileptics that target voltage-gated SODIUM channels

Answer 3

-carbamezepine
-phenytoin
-lamotrigine
-lacosamide

Question 4

antiepileptics that target voltage-gated CALCIUM channels

Answer 4

ethosuximide

Question 5

antiepileptics that enhance GABA inhibition by targeting GABA receptors

Answer 5

-phenobarbital
-benzodiazepines

Question 6

antiepileptics that enhance GABA inhibition by targeting GAT-1 GABA transporter

Answer 6

tiagabine

Question 7

antiepileptics that enhance GABA inhibition by targeting GABA transaminase

Answer 7

vigabatrin

Question 8

antiepileptics that target SV2A to inhibit glutamate release

Answer 8

levetiracetam

Question 9

antiepileptics that target alpha-2-delta to inhibit glutamate release

Answer 9

-gabapentin
-pregabalin

Question 10

narrow-spectrum antiepileptic agents

Answer 10

*specific for a given seizure type (usually focal)
*these can exacerbate certain generalized onset seizures

Question 11

broad-spectrum antiepileptics

Answer 11

effective in focal and generalized seizures

Question 12

carbamazepine - target & seizure type

Answer 12

*target: blocks voltage-gated sodium channels
*SZ type: narrow (focal)

Question 13

phenytoin - target & seizure type

Answer 13

*target: blocks voltage-gated sodium channels
*SZ type: narrow (focal; gen. tonic-clonic)

Question 14

lamotrigine - target & seizure type

Answer 14

*target: blocks voltage-gated sodium channels
*SZ type: broad

Question 15

lacosamide - target & seizure type

Answer 15

*target: blocks voltage-gated sodium channels
*SZ type: narrow (focal)

Question 16

ethosuximide - target & seizure type

Answer 16

*target: blocks voltage-gated CALCIUM channels (T-type calcium channels)
*SZ type: narrow (ABSENCE)

Question 17

phenobarbital - target & seizure type

Answer 17

*target: GABA receptors (enhancing GABA inhibition)
*SZ type: narrow (focal)

Question 18

benzodiazepines - target & seizure type

Answer 18

*target: GABA receptors (enhancing GABA inhibition)
*SZ type: broad (for status epilepticus)

Question 19

tiagabine - target & seizure type

Answer 19

*target: GAT-1 GABA transporter (enhancing GABA inhibition)
*SZ type: narrow (focal)

Question 20

levetiracetam - target & seizure type

Answer 20

*target: SV2A (inhibits glutamate release)
*SZ type: broad

Question 21

gabapentin & pregabalin - target & seizure type

Answer 21

*target: alpha-2-delta (inhibits glutamate release)
*SZ type: narrow; used more for other things (neuropathic pain, restless leg syndrome, anxiety)

Question 22

valproate - uses

Answer 22

*SZ type: broad (generalized tonic-clonic)
*used for many other things, like mood stabilization in bipolar disease and to prevent migraines

Question 23

topiramate - seizure type

Answer 23

*SZ type: broad

Question 24

phenytoin - testable pearls

Answer 24

*zero-order metabolism
*highly bound to albumin
*ADEs: hirsutism, nystagmus, gingival hyperplasia
*tons of drug interactions

Question 25

carbamazepine - testable pearls

Answer 25

*induces its own metabolism *ADEs: agranulocytosis (leukopenia), teratogenic, SIADH *tons of drug interactions

Question 26

lacosamide - testable pearls

Answer 26

*minimal drug interactions

Question 27

gabapentin and pregabalin - testable pearls

Answer 27

*do NOT act via GABA *instead, act via alpha-2-delta to **inhibit glutamate release**

Question 28

levetiracetam - testable pearls

Answer 28

*NO LIVER METABOLISM *few drug interactions

Question 29

valproate - testable pearls

Answer 29

*teratogenic *causes hepatotoxicity

Question 30

topiramate & zonisamide - testable pearls

Answer 30

*cause cognitive impairment & weight loss *metabolic acidosis via CA inhibition

Question 31

antiepileptic drugs associated with Stephens-Johnson Syndrome

Answer 31

*lamotrigine *carbamazepine

Question 32

which antiepileptics INDUCE CYP450 enzymes

Answer 32

*carbamazepine *phenytoin *phenobarbital

Question 33

which antiepileptics INHIBIT CYP450 enzymes

Answer 33

*valproate

Question 34

which 2 antiepileptics have minimal drug interactions

Answer 34

*levetiracetam *lacosamide

Question 35

treatment of status epilepticus

Answer 35

1. give **benzodiazepine (usually IV lorazepam)** 2. follow immediately with IV loading dose of either: -fosphenytoin -valproate -levetiracetam

Question 36

what symptoms do all antiepileptic drugs cause

Answer 36

*dizziness *fatigue *ataxia *diplopia

Question 37

phenytoin - adverse drug effects

Answer 37

**1. hirsutism:** (excess hair, often around mouth and chin) **2. nystagmus 3. gingival hyperplasia**

Question 38

carbamazepine - adverse drug effects

Answer 38

*agranulocytosis (leukopenia) *Stephens-Johnson syndrome *teratogenic in first trimester *SIADH (too much ADH secretion)

Question 39

which antiepileptic med is used for absence seizures

Answer 39

ethosuximide

Question 40

elimination of levetiracetam (Keppra)

Answer 40

NO liver metabolism: *two-thirds excreted unchanged in urine *one-third metabolized in the blood

Question 41

phenobarbital - adverse drug effects

Answer 41

*severe sedation *cardiac depression and hypotension in high doses *drug interactions