Pharmacology of Epilepsy

Question 1

What drugs prolong the fast inactivation state of sodium channels?

Answer 1

• Carbamazepine
• Lamotrigine
• Phenytoin (fosphenytoin)
• Topiramate
• Valproic acid
• Lacosamide

Question 2

What drug enhance the slows inactivation of sodium channels?

Answer 2

• Lacosamide

Question 3

What drugs are AMPA receptor blockers?

Answer 3

• Topiramate

- Perampanel

Question 4

What drug is a NMDA receptor blocker?

Answer 4

• Felbamate

Question 5

What is the use of ethosuximide?

Answer 5

• Absence seizures –> young child who spaces off in class a lot

Question 6

What drugs are calcium T-type channel blockers?

Answer 6

• Ethosuximide

- Zonisamide

Question 7

What drugs are synaptic vesicle 2A protein blockers?

Answer 7

• Levetiracetam

- Brivaracetam

Question 8

What drugs are alpha-2-gamma calcium channel blockers?

Answer 8

• Gabapentin

- Pregabalin

Question 9

What drug is a potassium channel opener?

Answer 9

• Ezogabine

Question 10

What are some drugs that are PRE-synaptic GABA promoting agents?

Answer 10

• Valproic acid
• Gabapentin
• Pregabalin
• Tiagabine
• Vigabatrin

Question 11

What drugs are GAD stimulators?

Answer 11

• Valproic acid
• Gabapentin
• Pregabalin

Question 12

What drug is a GAT-1 inhibitor?

Answer 12

• Tiagabine

Question 13

What drugs are GABA-T inhibitors?

Answer 13

• Vigabatrin

- Valproic acid

Question 14

Where do benzodiazepines bind to enhance GABA transmission?

Answer 14

• Distinct allosteric site which helps Cl- channels open with greater frequency

Question 15

Where do barbiturates bind to enhance GABA transmission?

Answer 15

• Distinct site and increases the duration of the Cl- channel opening

Question 16

What is different about benzodiazepines and barbiturates when enhancing GABA transmission?

Answer 16

• Barbiturates are GABA independent meaning they do not need it
• Benzos are GABA dependent

Question 17

Why are barbiturates dangerous?

Answer 17

• Because they are GABA independent, there is no limiting factor

Question 18

What drugs are POST-synaptic GABA promoting agents?

Answer 18

• Benzodiazepines
• Barbiturates
• Topiramate

Question 19

What is the proposed MOA of cannabidiol?

Answer 19

• Antagonism of GPR55 receptors
• Desensitization of TRPV1 receptors
• Inhibition of adenosine reuptake transport via blockage of ENT-1 receptors

Question 20

What are some indications of cannabidiol?

Answer 20

• Dravet syndrome
• Lennox-Gastaut syndrome
• Tuberous sclerosis complex

Question 21

What are some side effects of cannabidiol?

Answer 21

• Hepatocellular injury –> obtain AST/ALT and albumin levels both pre and post therapy
• Sedation/somnolence

Question 22

What is a broad warning when giving AEDs?

Answer 22

• Abrupt withdrawal may precipitate status epilepticus

- Suicidal behavior and ideation

Question 23

What is a big side effect of phenytoin, carbamazepine, and phenobarbital?

Answer 23

• Well known inducer of CYP450

Question 24

What are some select toxicities of phenytion?

Answer 24

• Gingival hyperplasia
• Hypocalcemia/Vit D def/osteoporosis
• Hypothyroidism

Question 25

What drugs could we see osteopenia/osteoporosis with?

Answer 25

- Carbamazepine - Phenytoin - Phenobarbital - Valproic acid

Question 26

What are some select toxicities of carbamazepine?

Answer 26

- Hematological --> leukopenia/neutropenia/thrombocytopenia (Need to get a baseline CBC) - Hypocalcemia/vit D def/osteoporosis

Question 27

What is special about carbamazepine?

Answer 27

- It induces its own metabolism could make it have less efficacy on seizures

Question 28

What is oxcarbazepine?

Answer 28

- Analogue of carbamazepine but has fewer CNS/hematological SE's due to an alternative metabolism - Less potent CYP450 inducer

Question 29

What is a big toxicity of vigabatrin?

Answer 29

- Permanent, progressive, bilateral, concentric vision loss

Question 30

What is needed in order to prescribe vigabatrin?

Answer 30

- Only via REMS program to evaluate risks

Question 31

What is a big drug-drug interaction with a lot of CYP inducers?

Answer 31

- Oral contraceptive since they make the OCPs less effective --> results in increased unplanned pregnancy - Anticoagulants --> increase the clearance of warfarin leading to increased risk of thrombosis - Antivirals --> increased clearance leading to elevated risk of HIV replication

Question 32

What metabolism do valproic acid and lamotrigine go through?

Answer 32

- NOT CYP450 | - Inhibit conjugation of drugs by UGT causing an accumulation of parent drug

Question 33

What is another metabolism pathway that phenytoin, carbamazepine, and phenobarbital go through?

Answer 33

- Induce conjugation of drugs by UGT causing a reduction of parent drug

Question 34

What drugs are not cleared by the liver but by the kidney?

Answer 34

- Levetiracetam - Topiramate - Oxcarbazepine - Gabapentin - Pregabalin - Vigabatrin

Question 35

What are some causes of status epilepticus?

Answer 35

- Abrupt withdrawal of AEDs, BZD's, opioids, alcohol - Brain mass/tumor - Infection - Fever

Question 36

What is the treatment for status epilepticus?

Answer 36

1. IV benzodiazepine | 2. Fosphenytoin/valproic acid/levetiracetam/phenytoin

Question 37

What are the MOAs of topiramate?

Answer 37

1. Na+ channel blocker 2. AMPA receptor blocker 3. Post synaptic GABA promoting agent

Question 38

What are the MOAs of valproic acid?

Answer 38

1. Na+ channel blocker 2. GAD stimulation 3. GABA-T inhibition