Pharmacology - Antiepileptic Drugs

Question 1

What are the molecular targets and actions of antiepileptic drugs?

Answer 1

1. To limit excitability - voltage-gated Na and Ca channels and glutamate receptors
2. To enhance inhibition of GABA system

Question 2

Phenytoin
Carbamazepine
Oxcarbamazepine
Lamotrigine

These drugs all do what?

Answer 2

Antiepileptics and voltage-gated Na channels

Goal to stabilize the inactive state inhibiting recurrent depolarization

Question 3

Blocking what channels decreases neuropathic pain?

Answer 3

Calcium channels

Ie Ethosuximide - T-type in thalamus

Gabapentin, Pregabalin - the high voltage type

Question 4

Give the class: Felbamate

Answer 4

Glutamate receptor blocker

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

Question 5

Give the class: Topiramate

Answer 5

Glutamate receptor blocker

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

Question 6

Phenobarbitol and benzodiazepines activate what system in treating epilepsy?

Answer 6

GABA system

Question 7

Give the class: Carbamazepine

Answer 7

Sodium channel blocker

MOA: Stabilize inactive conformation of Na channel

AEs: Dizzy, drunk, double vision, mild myelosuppression

Question 8

Give the indications for Carbamazepine.

Answer 8

Better for complex partial epilepsy than primary generalized seizures

Question 9

In addition to epilepsy, carbamazepine is also useful in treating:

Answer 9

Bipolar Affective disorder (also neuropathic pain)

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

Question 10

What is the most important thing to remember about carbamazepine?

Answer 10

Autoinduction - it can induce metabolism of itself (requires dose increase after reaching steady state)

Heteroinduction - it can induce metabolism of other drugs
for example: contraceptive pill failure

Question 11

Give the side effects: carbamazepine

Answer 11

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

Question 12

Give the class: Phenytoin

Answer 12

Voltage-gated Na channel stabilizer

Question 13

Give the MOA: Phenytoin

Answer 13

Stabilize inactive conformation of Na channel

Question 14

Give the indications: Phenytoin

Answer 14

Effective for tonic-clonic seizures of primary generalized epilepsy or partial onset and secondary generalized seizures

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

Question 15

Give the side effects: Phenytoin

Long term side effects?

Answer 15

Rash, gingival hyperplasia, hirsutism, lupus-like reaction; can cause contraceptive failure

Long term: Cerebellar degeneration, peripheral neuropathy, osteoporosis

Question 16

IV-Phenytoin is useful to treat what condition?

Answer 16

Status epilepticus

same with IV Valproate

Question 17

How is oxcarbazepine different from carbamazepine?

Answer 17

Oxcarbazepine is less protein-bound, less autoinduction, fewer interactions, less toxic, has a longer half-life than carbamazepine

Question 18

TEST QUESTION:

Lamotrigine is associated with what toxicity?

Answer 18

Dizziness
Sedation
Ataxia
Diplpia

AEs: rash (rarely Stevens-Johnson syndrome), slow initial titration is important

Question 19

Is Lamotrigine indicated for use in children to treat epilepsy?

Answer 19

Yes

Effective for primary generalized epilepsy, partial complex epilepsy and secondary generalization, absence

Question 20

Lamotrigine is NOT effective for what kind of seizures?

Answer 20

Myoclonic seizures

May exacerbate myoclonic seizures; competes with valproic acid for excretion (potential synergy); hepatic enzyme inducer; not very protein bound

Question 21

Give the indications for Lamotrigine.

Answer 21

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

Question 22

Lamotrigine has synergistic action with what drug?

Answer 22

Depakote (valproic acid)

Question 23

T/F: Lamotrigine can cause contraceptive failure.

Answer 23

True

Same with ALL voltage-gated sodium channel blockers - Phenytoin, Carbamazepine, Oxcarbamazepine

Question 24

Give the class: Gabapentin and Pregabalin

Answer 24

GABA analog

Question 25

Give the MOA of Gabapentin and Pregabalin.

Answer 25

Block presynaptic influx of Ca

Question 26

Give the indications for Gabapentin and Pregabalin.

Answer 26

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

Question 27

Ethosuximide is only effective against what kind of seizure?

Answer 27

Absence seizures

Question 28

Give the side effects: Ethosuximide

Answer 28

Nausea (transient) Sedation Irritability

Question 29

What is the half life of ethosuximide?

Answer 29

40-60 hours

Question 30

T/F: Topiramate is active at the postsynaptic membrane.

Answer 30

True Partial AMPA, Kainate Ca receptor blocker; secondary effect at voltage-gated Na channel, GABA system Use: Partial onset seizures, secondary generalized seizures, primary generalized epilepsy; migraine prevention, long-term prevention of cluster headaches Side Effects: Mild metabolic acidosis, kidney stones (due to some carbonic anhydrase activity); modest weight loss; rare acute glaucoma; sedation and **word finding difficulties** -Respiratory compensation from acidosis results in mild alkylosis, calcium ionization, and a sensation of tingling in fingers that can be alleviated with vitamin C

Question 31

What drug is a good choice to treat partial onset and secondarily generalized seizures?

Answer 31

Levetiracetam

Question 32

Give the class: Levetiracetam

Answer 32

Synaptic vesicle binder Binds to vesicle protein 2 resulting in less neurotransmitter release

Question 33

Give the side effects: Levetiracetam

Answer 33

Irritability Aphasia Thrombocytopenia Toxicity: Sedation

Question 34

What is the MOA for Ethosuximide?

Answer 34

Blocks T-type calcium channels in thalamus

Question 35

What is a common cause of temporal lobe epilepsy?

Answer 35

Head trauma

Question 36

What is the difference in molecular targets between Felbamate and Topiramate?

Answer 36

``` Felbamate = NMDA antagonist Topiramate = partial AMPA/Kinate antagonist ```

Question 37

Difference between side effect and toxicity?

Answer 37

Side effect is a drug effect that is not related to drug's intended mechanism of action (e.g. developing a rash from taking a sodium channel blocker - Carbamazepine) whereas toxicity is an undesirable effect that is related to the mechanism of action (e.g. sedation, ataxia, diplopia from sodium channel blocking anti-epileptic - Carbamazepine)

Question 38

What causes carbamazepine toxicity (drunk, dizzy, double vision)?

Answer 38

epoxide metabolite