Pharm of Epilepsy

Question 1

What are the excitatory neurotransmitters?

Answer 1

Glutamate and Aspartate

Question 2

What neurotransmitter is inhibitory on neurons?

Answer 2

GABA

Question 3

Explain the different states of the Voltage Na Channel

Answer 3

1. Resting state- Activation gate closed; inactivation gate open
2. Open state- both open and Na depolarizes cell
3. Fast-Inactivation state- Inactivation gate closes but activation gate is open (refractory period)
4. Inactivated Closed state- both closed

Question 4

Which Na blockers prolong the fast inactivation state?

Answer 4

Carbamazepine
Lamotrigine
Phenytoin
Topiramate
Valproic Acid 
Lacosamide

Question 5

Which Na blocker additionally can bind to the Na gate even in the closed state?

Answer 5

Lacosamide

Question 6

AMPA receptor antagonists

Answer 6

Topiramate

Perampanel

Question 7

Explain why blocking the AMPA receptor works to treat status epilepticus

Answer 7

Prevents glutamate from binding AMPA and allowing influx of Na (and Ca) into post synaptic neuron

Question 8

NMDA receptor antagonist

Answer 8

Felbamate

Same MOA as AMPA antagonists

Question 9

What type of seizure is treated with T-Type Ca2+ channel blocker?

Answer 9

Absence (petit mal) seizures

Question 10

T-Type Ca2+ channel blockers

Answer 10

Ethosuximide

Zonisamide (additionally is a Na blocker)

Question 11

SV2A Protein inhibitors

Answer 11

Levetiracetam

Brivaracetam

Question 12

T-type Ca2+ channel a2d subunit blockers

Answer 12

Gabapentin

Pregabalin

Question 13

Why does blocking the T-type Ca2+ channel work to suppress glutamate excitatory actions?

Answer 13

Once a neuronal signal reaches the pre-synaptic knob, depolarization allows Ca2+ into the knob which directs vesicles of glutamate to be released into the synaptic junction.

Question 14

KCNQ Channel activator and MOA

Answer 14

Ezogabine

Hyperpolarizes presynaptic and post synaptic neuron to prevent release of Glutamate

Question 15

Explain how GABA works to inhibit a neuronal signal

Answer 15

GABA is released from the presynaptic neuron.

It binds the B-subunit of the GABA receptor and allow efflux of Cl- which hyperpolarizes the post-synaptic neuron.

Question 16

How is GABA made?

Answer 16

L-glutamate is converted to GABA via Glutamic Acid decarboxylase

Question 17

What stimulates GAD (glutamic acid decarboxylase) and enhances inhibitory effects of GABA?

Answer 17

Valproic Acid
Gabapentin
Pregabalin

Question 18

2 enzymes that breakdown GABA

Answer 18

GABA-T

SSD

Question 19

GABA-T antagonists

Answer 19

Valproic Acid

Vigabatrin

Question 20

SSD antagonist

Answer 20

Valproic Acid

Question 21

What drug blocks the reuptake of GABA by GAT-1 in order to potentiate its effects?

Answer 21

Tiagabine

Question 22

2 classes of drugs that enhance post-synaptic GABA-ergic transmission

Answer 22

1. Barbiturates

2. Benzodiazepines

Question 23

What is the most important difference between Benzo’s and Barbiturates?

Answer 23

Barbiturates are GABA-independent and therefore more lethal in toxicity

Question 24

Common Benzos

Answer 24

1. Lorazepam
2. Diazepam
3. Clonazepam
4. Clobazam

Question 25

Benzo MOA

Answer 25

Binds to allosteric site on GABA receptor and potentiates the Cl- efflux by allowing quicker recovery of the channel so it can open more frequently.

Question 26

Barbiturate MOA

Answer 26

Binds allosteric site on GABA receptor WITHOUT GABA present and holds Cl- channel open

Question 27

Name the 3 MOA of Topiramate

Answer 27

1. Na blocker 2. AMPA antagonist 3. GABA receptor agonist

Question 28

Name the 3 MOA of Valproic Acid

Answer 28

1. Na blocker 2. GAD stimulation (more GABA) 3. GABA-T blocker (block reuptake)

Question 29

Name the 2 MOA of Gabapentin and Pregabalin

Answer 29

1 a2d Ca channel blocker | 2. GAD stimulator

Question 30

2 syndromes associated with Cannabidiol

Answer 30

1. Dravet Syndrome | 2. lennox-gastaut syndrome

Question 31

Black box warnings for all AEDs

Answer 31

1. Abrupt withdrawal can cause seizures | 2. Suicidal Ideation

Question 32

Side effect of Phenytoin

Answer 32

``` Follow zero-order kinetics so can easily OD CYP inducer Gingival Hyperplasia Hypothyroidism Hypocalcemia ```

Question 33

AED's associated with osteopenia/osteoporosis

Answer 33

Carbamazepine Phenytoin Phenobarbital Valproic acid

Question 34

Carbamazepine side effects

Answer 34

CYP inducer | Bone Marrow suppression (get baseline CBC)

Question 35

Vigabatrin Side effects

Answer 35

Loss of Vision

Question 36

3 categories of drug-drug interactions to watch for with CYP inducing AED's

Answer 36

1. OCP 2. Anticoags 3. Antivirals (HIV meds)

Question 37

Valproic acid and Lamotrigine inhibit what enzyme leading to increased concentration of other drugs?

Answer 37

UGT

Question 38

What AED's cause increased UGT activity and therefore increased clearance of drugs?

Answer 38

Phenobarbital Phenytoin CBZ

Question 39

Standard of Care for a status epilepticus

Answer 39

1. Benzo (Lorazepam) | 2. SV2a blocker (Levetiracetam)