Lecture 46: Antiepileptics

Question 1

Narrow-spectrum medications are useful for what kind of seizure? What two kinds are they not useful for?

Answer 1

Focal seizures; generalized tonic-clonic seizures and myoclonic seizures

Question 2

Broad-spectrum medications are effective for…

Answer 2

Focal and generalized seizures

Question 3

Name the narrow spectrum drugs (2)

Answer 3

Gabapentin, tiagabine

Question 4

Name the broad spectrum drugs (6)

Answer 4

Phenytoin, carbamazepine, valproate, topiramate, levetiracetam, lamotrigine*

Question 5

What drug treats absence epilepsy?

Answer 5

Ethosuximide**

Question 6

What drug treats status epilepticus?

Answer 6

Lorazepam*

Question 7

Three most common mechanisms of antiepileptics

Answer 7

Inhibit VG-Na+, inhibit VG-Ca2+, enhance GABA

Question 8

Why is the hippocampus predisposed to seizures? (2)

Answer 8

Excitatory positive feedback to CA3 neurons; densely packed neurons

Question 9

An epilepsy linked to a genetic defect might have a defect where?

Answer 9

Channels (i.e. increased excitatory/reduced inhibitory currents through VG-channels)

Question 10

How do AEDs inhibit Na* channels? Name them (5)

Answer 10

Stabilize inactive state of channel; Carbamazepine, valproate, topiramate, phenytoin, lamotrigine

Question 11

How do AEDs enhance GABA signaling? Name them (3)

Answer 11

Allosterically at GABAa; Benzos, phenobarbital (barbituate), topiramate

Question 12

Which AED increases synaptic levels of GABA? How?

Answer 12

Tigabine; blocks GABA reuptake

Question 13

What channel underlies absence epilepsy? Where? Usually associated with?

Answer 13

Ca2+ channels in thalamocrotical neurons; sleep spindles

Question 14

Which two drugs inhibit T-type Ca2+ channels, making them good at treating…

Answer 14

Ethosuximide and Valproate; absence seizures

Question 15

What other drug can be used to treat absence seizures?

Answer 15

Clonazepam

Question 16

Two drugs inhibit another type of Ca2+ channel. What are these drugs?

Answer 16

Lamotrigine and levetiracetam

Question 17

Topiramate inhibits Na+ channels. What is another mechanism of its action?

Answer 17

Modulates AMPA receptors

Question 18

According to LC, the mechanism of this drug is unknown. According to lecture, it increases K+ conductance. Drug?

Answer 18

Levetiracetam

Question 19

Key note about Phenytoin and relevant SEs (acute: 3, chronic: 1)

Answer 19

Non-linear pharacokinetics in therapeutic window make window narrow; nystagmus, ataxia, hypersensitivity (Stevens-Johnson); gingival hyperplasia

Question 20

Is phenobarital commonly prescribed? SE?

Answer 20

No! Was once widely prescribed AED; sedation

Question 21

Carbamazepine comes with what important 3 warnings. Which are rare?

Answer 21

Rare: blood dyscrasias, Stevens-Johnson; hyponatremia

Question 22

Tigabine has what common side effect?

Answer 22

Dizziness

Question 23

What is the most widely used AED, worldwide? Describe its clinical use

Answer 23

Valproate; Can be used for general, partial, absence AND myoclonic

Question 24

Topiramate’s other uses and some SEs

Answer 24

Headache, alcoholism, tremor, obesity…paresthesias in 30%

Question 25

While the mechanism fr this drug is unknown, it has some advantages…what are those?

Answer 25

Levetiracetam; does not induced liver enzymes and is well-tolerated

Question 26

When you see Ethosuximide, think about this seizure type. How is it tolerated?

Answer 26

Absence; well

Question 27

Four specific adverse events in AEDs

Answer 27

Serious hypersensitivity reactions, cognitive slowing, sedation, seizure induction

Question 28

Which two drugs are associated with malformations in pregnancy?

Answer 28

Valproate and phenobarbital

Question 29

What warning do all AEDs bear?

Answer 29

Increased suicide risk

Question 30

Describe status epilepticus treatment (5 steps)

Answer 30

1. Start ASAP to protect neurons; 2. Begin w/ benzos; 3. Give phenytoin to prevent recurrence; 4. If not controlled, give phenobarbital or valproate; 5. If still not, induce general ansethesia

Question 31

Induction

Answer 31

Drug A increases enzyme for Drug B –> Drug B eliminated faster

Question 32

Competition

Answer 32

Drug A and Drug B are substrates for same enzyme –> Drug B eliminated slower

Question 33

Inhibition

Answer 33

Drug A inhibits enzyme for Drug B –> Drug B eliminate slower

Question 34

Which pharmacokinetic interaction is important for AEDs? Which enzymes? Which drugs?

Answer 34

Induction; CYP450; phenytoin, carbamazepine, phenobarbital