Pharmacology of Epilepsy (Segars)

Question 1

Membrane depolarization leads to?

Answer 1

1) Enhanced excitatory (glutamate) actions

2) Reduced inhibitor (GABA) function

Question 2

Where do the anti-epileptic drugs (AED) that block the voltage-gated Na channels bind?

Answer 2

Interior side of voltage Na channel pore

Question 3

When can AEDs access the pore in voltage-gated Na channels?

When can they not?

Answer 3

1) Activation gate is open

2) Activation gate is closed

Question 4

What are examples of an AED Na channel blocker?

Answer 4

1) Lamotrigine
2) Carbamazepine (also other -azepine drugs)
3) Phenytoin
4) Topiramate
5) Valproic acid
6) Lacosamide (also other -amide drugs)

Question 5

The probability of a Na channel blockade is proportional to?

Answer 5

Frequency of voltage Na channel opening and the dose

Question 6

Lamotrigine, Carbamazepine, Phenytoin, Topiramate, Valproic acid, and Lacosamide have what effect on the state of Na ion channels?

Lacosamide can also have what effect on the state of voltage Na channels?

Answer 6

1) Prolong fast inactivation state of voltage Na channel

2) Enhance slow inactivation of the channel

Question 7

What is the overall goal of blocking voltage gated Na channels?

Answer 7

Suppress excitatory (glutamate) actions

Question 8

What are the AMPA receptor antagonists?

Answer 8

1) Topiramate (also a Na channel blocker)

2) Perampanel (has AMPA is name)

Question 9

What is the overall goal of blocking AMPA receptors?

Answer 9

Suppress glutamate

Question 10

What is the NMDA receptor antagonist?

Answer 10

Felbamate

Question 11

What is the overall goal of blocking NMDA receptors?

Answer 11

Suppress glutamate

Question 12

What channels mediate 3-Hz spike and wave activity in the thalamus?

This is a hallmark of what type of seizure?

Answer 12

1) T-type Ca2+ channels

2) Absence (petit mal) seizures

Question 13

Antagonists of T-type Ca2+ channels target?

Answer 13

Cortex-thalamus oscillation

Question 14

What drug is only used for absence seizures?

Answer 14

Ethosuximide

Question 15

What are the antagonists of T-type Ca2+ channels?

Answer 15

1) Ethosuximide

2) Zonisamide (also a Na channel blocker)

Question 16

What is the overall goal of blocking T-type Ca2+ channels?

Answer 16

Suppress glutamate

Question 17

What drugs inhibit Synaptic Vesicle 2A (SV2A) protein?

Answer 17

1) Levetiracetam

2) Brivaracetam

Question 18

What is the overall goal of blocking Synaptic Vesicle 2A (SV2A) protein?

Answer 18

Suppress glutamate

Question 19

What drugs block the α2δ subunit of T-type Ca2+ channels?

Answer 19

1) Gabapentin

2) Pregabalin

Question 20

What is the overall goal of blocking the α2δ subunit of T-type Ca2+ channels?

Answer 20

Suppress glutamate

Question 21

What drug opens KCNQ K+ channels (pre-/post-synaptic)?

Answer 21

Ezogabine

Question 22

What is the overall goal of opening the KCNQ K+ channels?

Answer 22

Suppress glutamate

Question 23

What is the MOA of Topiramate and Perampanel?

Answer 23

AMPA receptor blockers

Question 24

What is the MOA of Ethosuximide and Zonisamide?

Answer 24

Ca2+ T-type Channel Blockers

Question 25

What is the MOA of Gabapentin and Pregabalin?

Answer 25

α2δ subunit Ca2+ Channel Blocker

Question 26

What is the MOA of Carbamazepine, Oxcarbazepine, Eslicarbazepine, Lamotrigine, Phenytoin, Rufinamide, Topiramate, Valproic acid, Lacosamide, and Zonisamide?

Answer 26

Na+ Channel Blockers

Question 27

What is the MOA of Felbamate?

Answer 27

NMDA Receptor Blockers

Question 28

What is the MOA of Levetiracetam and Brivaracetam?

Answer 28

Synaptic Vesicle 2A Protein Blockers

Question 29

What is the MOA of Ezogabine?

Answer 29

K+ Channel Openers

Question 30

When GABA(A) receptor is unoccupied what happens to the Cl- channel? When it is occupied?

Answer 30

1) Closed | 2) Opened

Question 31

What drug blocks the reuptake of GABA by blocking GAT-1 (GABA transproter-1)?

Answer 31

Tiagabine

Question 32

What drugs block the metabolism of GABA by blocking GABA-T (GABA Transaminase)?

Answer 32

1) Vigabatrin (Has GABA-T in name) | 2) Valproic acid (also a Na channel blocker)

Question 33

What drugs increase GABA levels by stimulating GAD (glutamic acid decarboxylase)?

Answer 33

1) Valproic acid 2) Gabapentin (also blocks the α2δ subunit of T-type Ca2+ channels) 3) Pregabalin (also blocks the α2δ subunit of T-type Ca2+ channels)

Question 34

Tiagabine, Vigabatrin, Valproic acid, Gabapentin, and Pregabalin all act on what side of GABA-ergic Transmission?

Answer 34

Pre-Synaptic

Question 35

What is the MOA of Vigabatrin and Valproic acid?

Answer 35

GABA promoting agents by GABA-T inhibition

Question 36

What is the MOA of Tiagabine?

Answer 36

GABA promoting agent by GAT-1 inhibition

Question 37

What is the MOA of Valproic acid, Gabapentin, and Pregabalin?

Answer 37

GABA promoting agents by GAD stimulation

Question 38

Barbiturates, Benzodiazepines, and Topiramate all act on what side of GABA-ergic Transmission?

Answer 38

Post-Synaptic

Question 39

What happens when benzodiazepines bind to a distinct allosteric site?

Answer 39

Potentiate GABA binding causing Cl- channels to open with greater frequency

Question 40

What happens when barbiturates bind to a distinct allosteric site?

Answer 40

Increases the duration of Cl- channel opening

Question 41

Between barbiturates and benzodiazepines, which are GABA independent? This has what effect at high doses?

Answer 41

1) Barbiturates | 2) Barbiturates are more lethal

Question 42

What is a GABA agonist?

Answer 42

Topiramate

Question 43

What are the GABA promoting agents that work on the post-synaptic side?

Answer 43

1) Barbiturates (Phenobarbital, Primidone) 2) Benzodiazepines (Clonazepam, Clobazam, Lorazepam, Diazepam) 3) Topiramate

Question 44

What are the multiple MOA of topiramate?

Answer 44

1) Na+ channel blocker 2) AMPA receptor blocker 3) GABA agonist

Question 45

What are the multiple MOA of Valproic acid?

Answer 45

1) Na+ channel blocker 2) GABA promoting agent by GAD stimulation 3) GABA promoting agent by GABA-T inhibition

Question 46

What are the broad warning/risk of all AEDs?

Answer 46

1) Abrupt withdrawal of AED may cause status epilepticus | 2) Suicidal behavior

Question 47

Why does phenytoin have many drug-drug interactions?

Answer 47

It is an inducer of CYP-450 enzymes

Question 48

What is an unique toxicity that can be caused by phenytoin?

Answer 48

Gingival hyperplasia

Question 49

Chronic administration of carbamazepine, phenytoin, phenobarbital and valproic acid can cause? Why?

Answer 49

1) Osteoporosis | 2) They induce CYP450-dependent vitamin D catabolism

Question 50

What are unique toxicities that can be caused by Carbamazepine?

Answer 50

1) Leukopenia 2) Neutropenia 3) Thrombocytopenia

Question 51

Oxcarbazepine which is an analogue of carbamazepine has fewer CNS/Hematological symptoms due to?

Answer 51

Formation of an alternative active metabolite

Question 52

What is an unique toxicity that can be caused by vigabatrin?

Answer 52

Permanent vision loss

Question 53

What interaction do the AED inducers have with contraceptives?

Answer 53

Increase clearance of oral hormonal contraceptives which increases risk of unplanned pregnancy

Question 54

What interaction do the AED inducers have with anticoagulants?

Answer 54

Increase clearance of warfarin which increases risk for thrombosis

Question 55

What interaction do the AED inducers have with antivirals?

Answer 55

Increase clearance of HIV medications which increases the risk for HIV replication

Question 56

How do Valproic acid and Lamotrigine increase the accumulation of other drugs? How do Phenytoin, Carbamazepine & Phenobarbital cause reduction of parent drug?

Answer 56

1) Inhibit UGT | 2) Induce UGT

Question 57

In the treatment of convulsive status epilepticus in adults what is given in the first IV? What is given in the second IV?

Answer 57

1) Lorazepam | 2) Levetiracetam