Unit 3-Antiepileptics

Question 1

Phenytoin

Drug class

Answer 1

Voltage-gated Na channel stabilizer

Question 2

Phenytoin

Mechanism

Answer 2

Stabilize inactive conformation of Na channel

Question 3

Phenytoin

Uses

Answer 3

Less effective for absence (particular pediatric), myoclonic, atonic seizures

IV route useful for status epilepticus

Question 4

Phenytoin

Side effects

Answer 4

• Rash, gingival hyperplasia, hirsutism, lupus-like reaction;
• can cause contraceptive failure
• Mild myelosuppression, increased LFT;
• long-term: cerebellar degeneration, peripheral neuropathy, osteoporosis
• IV infusion limited by hypotension;
• hepatic enzyme inducer (both auto- and hetero-inducer), highly protein bound

Question 5

Carbamazepine

Drug class

Answer 5

Voltage-gated Na channel stabilizer

Question 6

Carbamazepine

Mechanism

Answer 6

Stabilize inactive conformation of Na channel

Question 7

Carbamazepine

Uses

Answer 7

• More effective for complex partial seizure than primary generalized;
• bipolar disorder;
• neuropathic pain

Question 8

Carbamazepine

Side effects

Answer 8

• Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs;
• can cause contraceptive failure
• 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 9

Oxcarbamazepine

Drug class

Answer 9

Voltage-gated Na channel stabilizer

Question 10

Oxcarbamazepine

Mechanism

Answer 10

Stabilize inactive conformation of Na channel

Question 11

Oxcarbamazepine

Uses

Answer 11

• More effective for complex partial seizure than primary generalized;
• bipolar disorder;
• neuropathic pain

Question 12

Oxcarbamazepine

Side effects

Answer 12

• Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs;
• can cause contraceptive failure
• Designed to bypass carbamazepine epoxide;
• less protein-bound, less autoinduction, fewer interactions, less toxic, longer half-life than carbamazepine

Question 13

Lamotrigine

Drug class

Answer 13

Voltage-gated Na channel stabilizer

Question 14

Lamotrigine

Mechanism

Answer 14

Stabilize inactive conformation of Na channel

Question 15

Lamotrigine

Uses

Answer 15

• Primary generalized epilepsies, absence seizures;
• indicated in children;
• bipolar disorder;
• neuropathic pain

Question 16

Lamotrigine

Side effects

Answer 16

• Rash, (rarely, Stevens-Johnson):
• slow initial titration important;
• may lead to contraceptive failure
• May exacerbate myoclonic seizures;
• competes with valproic acid for excretion (potential synergy);
• hepatic enzyme inducer;
• not very protein bound

Question 17

Valproate

Mechanism

Answer 17

Unknown; likely affects Na-gated channels and GABA system

Question 18

Valproate

Uses

Answer 18

• 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

Question 19

Valproate

Side effects

Answer 19

Weight gain, hair turnover, hyperammonemia (which can be mitigated with oral carnitine), teratogenicity, blood dyscrasias

Pancreatitis

Question 20

Vigabatrin

Drug class

Answer 20

GABAergic anti-epileptic

Question 21

Vigabatrin

Mechanism

Answer 21

GABA transaminase binder (slows down intracellular breakdown of GABA)

Works on GABA-A

Question 22

Vigabatrin

Uses

Answer 22

Anti-epileptic

Question 23

Tigabine

Drug class

Answer 23

GABAergic anti-epileptic

Question 24

Tigabine

Mechanism

Answer 24

GABA reuptake inhibitor

Works on GABA-A

Question 25

Tigabine Uses

Answer 25

Anti-epileptic

Question 26

Benzodiazapines Uses

Answer 26

GABAergic anti-epileptic

Question 27

Benzodiazapines Mechanism

Answer 27

Bind GABA-A

Question 28

Benzodiazapines Uses

Answer 28

Status epilepticus (refractory); anesthesia

Question 29

Benzodiazapines Side effects

Answer 29

Sedation Long-term usefulness limited by tolerance

Question 30

Gabapentin Drug class

Answer 30

GABA analog

Question 31

Gabapentin Mechanism

Answer 31

Block presynaptic influx of Ca

Question 32

Gabapentin Uses

Answer 32

* Adjunct for partial complex epilepsy; * more commonly used for neuropathic pain

Question 33

Gabapentin Side effects

Answer 33

Sedation 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 34

Pregabalin Drug class

Answer 34

GABA analog

Question 35

Pregabalin Mechanism

Answer 35

Block presynaptic influx of Ca

Question 36

Pregabalin Uses

Answer 36

* Adjunct for partial complex epilepsy; * more commonly used for neuropathic pain

Question 37

Topiramate Drug class

Answer 37

Glutamate Receptor Blockers

Question 38

Topiramate Mechanism

Answer 38

* Partial AMPA, Kainate Ca receptor blocker * secondary effect at voltage-gated Na channel, GABA system

Question 39

Topiramate Uses

Answer 39

* Partial onset seizures, secondary generalized seizures, primary generalized epilepsy; * migraine prevention, long-term prevention of cluster headaches

Question 40

Topiramate Side effects

Answer 40

Mild metabolic acidosis, kidney stones (due to some carbonic anhydrase activity); modest weight loss; rare acute glaucoma; sedation Word-finding problems 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 41

Felbamate Drug class

Answer 41

Glutamate Receptor Blockers

Question 42

Felbamate Mechanism

Answer 42

NMDA receptor blocker; secondary effect at voltage-gated Na and Ca channels, GABA system

Question 43

Felbamate Uses

Answer 43

Partial onset seizures with or without secondary generalization; medically refractory epilepsy

Question 44

Felbamate Side effects

Answer 44

Uncommon but potentially fatal. Aplastic anemia, acute hepatic failure. Requires monitoring.

Question 45

Levetiracetem Drug class

Answer 45

Synaptic vesicle binder

Question 46

Levetiracetem Mechanism

Answer 46

Binds synaptic vesicle protein 2, leading to less NT release

Question 47

Levetiracetem Uses

Answer 47

Partial onset seizures, secondary generalized seizures; maybe primary generalized epilepsy

Question 48

Levetiracetem Side effects

Answer 48

Well tolerated; sedation, mostly; rarely, irritability, aphasia, thrombocytopenia

Question 49

Ethosuximide Drug class

Answer 49

Voltage-gated Ca channel blocker

Question 50

Ethosuximide Mechanism

Answer 50

Blocks T-type Ca-channels in thalamo-cortical circuits Readily absorbed, minimal first pass metabolism; not protein bound

Question 51

Ethosuximide Uses

Answer 51

Absence seizures only (and neuropathic pain)

Question 52

Ethosuximide Side effects

Answer 52

Nausea (transient), sedation, irritability