Anti-Epileptic Drugs

Question 1

MOA of Phenytoin

Answer 1

Antagonist to voltage gated Na+ channel and is also secondary Ca2+ channel blocker. This delays the onset of neuron firing.

Question 2

MOA for Oxcarbazepine

Answer 2

Antagonist to voltage gated Na+ channel

Question 3

What Na+ voltage gated channel antagonist is preferred for children?

Answer 3

Oxcarbazepine

Question 4

Phenytoin is used to treat what type of seizures?

Answer 4

All generalized partial and tonic-clonic seizures.

Question 5

What is phenytoin a BIG NO for?

Answer 5

Treating juvenile myoclonic seizure because PHT aggravates JM seizures

Question 6

Adverse effects for phenytoin

Answer 6

Gingival hyperplasia and Hirsutism

Question 7

Phenytoin increases the conversion of of primidone to what compound?

Answer 7

phenobarbital

Question 8

Concurrent administration of Phenytoin and carbamazepine does what?

Answer 8

Enhances metabolism of each other due to hepatic cytochrome P450 enzymes

Question 9

Felbamate MOA:

Answer 9

Glutamatergic receptor antagonist

Question 10

Felbamate is used only in…

Answer 10

1) Lennox-Gastaut Syndrome or

2) in patients highly refractory to other drugs.

Question 11

Why is febamate rarely used?

Answer 11

Causes hepatic failure

Question 12

What is the action of felbamate (FBM) on NMDA receptor?

Answer 12

1) FBM inhibits NMDA channel in a use-dependent manner.
2) FBM binds to NR2B and NR1 subunits in a voltage-independent manner.
3) FBM delays the recovery of desensitized NMDA channels. FBM is a weak positive modulator of GABA-AR Cl- current.

Question 13

List 3 GABA regulating drugs:

Answer 13

Gabapentin, Tiagabine, Vigabatrin

Question 14

MOA of Gabapentin

Answer 14

Releases GABA from glial cells. New drug, lipophilic, crosses BBB. Does NOT bind to GABA analog GAABA-AR.

Question 15

MOA for Tiagabine

Answer 15

Inhibits reuptake of GABA by GABA transporter (GAT-1).

Question 16

MOA for Vigabatrin:

Answer 16

inhibits the metabolism of GABA by GABA transaminase.

Question 17

Therapeutic uses for Gabapentin:

Answer 17

used for neuropathic pain and migraine, but not effective for controlling seizures.

Question 18

Therapeutic uses for Tiagabine

Answer 18

Controls tonic clonic seizures for children below 12 years old.

Question 19

Therapeutic uses for Vigabatrin

Answer 19

First oral drug approved recently for treatment of INFANTILE SPASM and REFRACTORY COMPLEX partial seizures that are not controlled by usual treatments.

Question 20

Adverse effects of Vigabatrin

Answer 20

VGB causes liver failure, psychotic disorder, suicidal thoughts, and visual field defect.

Question 21

What are 3 drugs that can be used to treat myoclonic seizures?

Answer 21

Valproic acid, Zonisamide, Lamotrigine

Question 22

Describe Myoclonic seizures:

Answer 22

1) Common in juvenile, but rare in childhood.
2) Single multiple clonic jerks in the face, neck, upper arms.
3) Most myoclonic seizures originate from the brainstem in the CNS.

Question 23

What drugs aggravate juvenile myoclonic seizures?

Answer 23

Phenytoin and Carbamazepine

Question 24

Valproic acid is used for treatment of juvenile myoclonic seizures. What is the mechanism of action?

Answer 24

Blocker of NA+ channel and Ca2+ channel, also decreases GABA metabolism. It prolongs the recovery of voltage-activated Na+ channel from inactivation.

Question 25

Adverse effects of Valproic acid (VPA)

Answer 25

Hepatotoxic, during pregnancy can cause spina bifida (folic acid deficiency). If pregnant and need to control seizures, give VPA with folate.

Question 26

What is Zonisamide used to treat and what is the MOA?

Answer 26

Myoclonic seizures: an antagonist to NA+ and Ca2+ channels. It can cause renal stone formation.

Question 27

What type of seizure can lamotrigine treat and what is the MOA?

Answer 27

A Na+ channel blocker also effective against myoclonic seizure in children with mild side effects of dizziness, rash and headache.

Question 28

What type of seizure is this? Onset 4-12 years old and continues to adolescnece. Brief and abrupt unconsciousness (5-10sec). High voltage bilaterally synchronous spike-wave discharge is typically 2.5-3.5 Hz.

Answer 28

Absence seizure (Petit Mal)

Question 29

Drug of choice to treat Absence seizures

Answer 29

Ethosuximide (ESX)

Question 30

MOA of Ethosuximide

Answer 30

Blocks T-Type Ca+ channel. Known to inhibit GABA-T.

Question 31

Other drugs for treatment of Absent Seizures

Answer 31

Valporate and Lamotrigine (a Na+ channel blocker)

Question 32

Current Definition of Status Epilepticus

Answer 32

Seizure activity lasts for 10 min w/o recovery, or two or more seizures within 30 min.

Question 33

What was once used to treat Status Epilepticus seizures?

Answer 33

Phenobarbital- sedative and hypnotic schedule

Question 34

What has largely replaced phenobarbital for Status Epilepticus seizures?

Answer 34

Safer benzodiazepines: Lorazepam and Diazepam

Question 35

Diazepam vs Lorazepam: Which drug has a high lipid solubility?

Answer 35

Diazepam. Lorazepam has low lipid solubility.

Question 36

Diazepam vs Lorazepam: Which drug has a rapid action onset?

Answer 36

Diazepam. Lorazepam is delayed 2 min

Question 37

Diazepam vs Lorazepam: Which drug has a longer Anti-epileptic effect?

Answer 37

Lorazepam (6-12 hr). Diazepam last 15-30 min.

Question 38

Diazepam vs Lorazepam: Which drug has a longer half-life?

Answer 38

Diazepam (20-100 hr-can cause toxicity). Lorazepam (10-20 hrs).

Question 39

Diazepam vs Lorazepam: WHich drug has less respiratory depression?

Answer 39

Lorazepam. Diazepam has Resp. depression and hypotension.

Question 40

MOA for Lorazepam and Diazepam?

Answer 40

Binding of benzodiazepine to GABA receptor forms a positive allosteric effector. This stabilizes the receptor conformation to keep Cl- channel open. This increase Cl- ion influx to cause hyperpolarization, which prevents repetitive neuron firing.

Question 41

Preferred drugs for partial and generalized seizures?

Answer 41

Phenytoin, Oxcarbazepine (child), Gabapentin

Question 42

Preferred drug for myoclonic seizures?

Answer 42

Valproic Acid (Never Carbamazepine/Phenytoin)

Question 43

Preferred drug for Absence Seizures?

Answer 43

Ethosuximide (Children, adult)

Question 44

Preferred drug for Status Epilepticus?

Answer 44

Lorazepam and Diazepam

Question 45

Preferred drug for infantile spasms?

Answer 45

Vigabatrin