9 - ANTI-SEIZURE DRUGS

b. Valproic Acid

b. Valproic Acid

1. This anti-seizure drug is linked to spina bifida and hepatotoxicity

   a. Carbamazepine

   b. Valproic Acid

   c. Gabapentin

   d. Pregbalin

b. Tiagabine

2. A GABA-transporter 1 blocker

   a. Gabapentin

   b. Tiagabine

   c. Vigabatrin

   d. Diazepam

b. Phenobarbital

3. Primidone is converted to

   a. diazepam

   b. Phenobarbital

   c. Carbamazepine

   d. Phenytoin

a. Ethosuximide

4. DOC for absence seizure

   a. Ethosuximide

   b. felbamate

   c. gabapentin

   d. perampanel

a. Carbamazepine

5. DOC for trigeminal neuralgia

   a. Carbamazepine

   b. Phenytoin

   c. Valproic acid

   d. Gabapentin

SEIZURE

Abnormal discharge of neuron in the brain

EPILEPSY

Recurrent, unprovoked seizure

Focal Seizures

• Aka Partial seizures

• Affect 1 hemisphere

Generalized Seizures

affect both hemisphere

Partial seizures

Focal Seizures is also known as

• Simple Partial

• Complex Partial

Subtypes of Partial seizures

Simple Partial

• Subtype of Partial seizures

• NO LOC

• tingling or twitching (Jacksonian March)

Complex Partial

• Subtype of Partial seizures

• LOC

• behavioral changes (hallucinations, chewing)

• Tonic-Clonic / Grand mal

• Absence / Petit mal

• Atonic

• Myoclonic

Subtypes of Generalized Seizures

Tonic-Clonic / Grand mal

• most dramatic

• LOC

• tonic (10s) – stiffening

• clonic (1-2mins)

• muscle contractions alternating with relaxation

Grand mal

Tonic Clonic is also known as

Absence / Petit mal

• primarily affect children

• blank stare, blinking,

• LOC (lasting 10- 30 secs)

Petit mal

Absence Seizure is also known as

Atonic

• sudden loss of postural tone

• LOC

Myoclonic

• involuntary jerking of the facial, limb, or trunk muscles

• NO LOC

• Excessive neuronal depolarization (Na influx/Calcium = ↑ Glutamate = SEIZURE

• suppression GABA neurotransmission

• increase in calcium influx via Ttype calcium channels in thalamic neurons

Seizures problems:

• Block Na+ CH

• Block Ca+2 CH

• Block Glutamate

Goals of therapy for excessive neuronal depolarization (Na influx/Calcium

↑ GABA

Goals of therapy for suppression of GABA neurotransmission

Block T-type

Goals of therapy for increase in calcium influx via T-type calcium channels in thalamic neurons

Non NMDA

• aka AMPA, Kainate

• High permeability: Na, K

• low Ca2+ permeability

NMDA

• permits the influx of relatively large amounts of Ca+2 along with Na+

• influx of Ca+2

• coactivated by Glycine

L-type & SV2A

They are responsible for the release of glutamate

TRUE

TRUE or FALSE

NMDA and AMPA should be blocked if the px has seizures

• Carbamazepine and Oxcarbazepine

• Phenytoin and Fosphenytoin

• Valproate

1st line drugs for partial seizures and generalized seizures

Oxcarbazepine

Carbamazepine prodrug:

Carbamazepine

DOC for Tic Douloureux (Trigeminal Neuralgia)

• depression, aplastic anemia (rare),

• Stevens-Johnson syndrome (SJS)

Carbamazepine S/E:

Phenytoin

• more dangerous than Carbamazepine because of the S/E

poor water solubility

Problem w/ Phenytoin

Diphenylhydantoin

Phenytoin is formerly known as

PEG and Alcohol

To increase the water solubility: Add & _

Hypotension & Cardiotoxicity

The problem with PEG and Alcohol is that they can cause __ & _

Fosphenytoin

Phenytoin’s Prodrug that has a better water solubility

• megaloblastic anemia, birth defects

• osteomalasia

• Gingival hyperplasia, hirsutism

• SJS

Phenytoin’s A/E

Valproate

• broad spectrum AED

• free acid form (valproic acid)

• sodium salt of valproic acid (valproate sodium)

• divalproex sodium (mixture of valproic acid and valproate sodium)

valproic acid

Valproate has a free acid form called

valproate sodium

Valproate has a sodium salt of valproic acid called

divalproex sodium

Valproate has a mixture of valproic acid and valproate sodium)

• little sedation,

• GI complaints,

• weight gain,

• Hepatotoxicity (< 2 y/o),

• Spina bifida (birth defects)

S/E for valproate

Phenobarbital and Primidone

2nd line drug for partial and generalized tonic clonic seizures

Na channel blocker

MOA of Primidone acts as a __ bloccke

• Lamotrigine

• Topiramate

• Clobazam

• Felbamate

• Levetiracetam and Brivaracetam

• Perampanel

• Clorazepate

• Gabapentin

• Pregabalin

• Ezogabine

• Vigabatrin

• Tiagabine

ADJUNCT DRUGS FOR PARTIAL SEIZURES

Lamotrigine

• Effective in adults and children

• Tx: of Lennox-Gastaut Syndrome, child onset epilepsy w/ mental retardation and other neurologic abnormalities

Lennox-Gastaut Syndrome

a child onset epilepsy w/ mental retardation and other neurologic abnormalities

• cerebellar dysfunction, drowsiness, and rash

• SJS (Lamotrigine + Valproic acid)

• Aseptic meningitis (rare)

Lamotrigine S/E:

Valproic acid

There’s a greater chance of SJS if __ is added w/ Lamotrigine

Topiramate

• NO for baby

• Teratogenic: cleft palate in children born

Clobazam

• Orphan Drug

• adjunct treatment of seizures in children and adults with LGS

Felbamate

• Problem: fatal aplastic anemia and acute hepatic failure

• Use: treatment of Partial seizures refractory to other drugs

Levetiracetam and Brivaracetam

bind to a synaptic vesicle protein (SV2A), reducing vesicular packaging of GABA and impeding neurotransmission across synapses

AMPA blocker

Perampanel a __ blocker

Diazepam

Clorazepate turns into __ in the liver

Gabapentin

Tx for Post-Herpetic Neuralgia

Gabapentin enacarbil

Prodrug of Gabapentin that is tx for Restless Leg Syndrome

Pregabalin

• Treatment of neuropathic pain

• 1st Line: treatment of Fibromyalgia

Ezogabine

Aka Ritigabine

Tiagabine

GAT-1 inhibitor (GABA reuptake inhibition = increase GABA levels in the synapse)

• Ethosuximide

• Valproic Acid

DRUG FOR GENERALIZED ABSENCE, MYCLONIC, OR ATONIC SEIZURES

T-Type blocker

Ethosuximide is a __ blocker

Ethosuximide

DOC for absence seizure (children) (If adult: less effective)

Valproic Acid

DOC for absence seizure (adult)

• Carbamazepine

• Phenytoin

• Gabapentin or Tiagabine

In absence seizure, DO NOT USE the ff drugs:

• LORAZEPAM,

• DIAZEPAM

DRUGS FOR STATUS EPILEPTICUS

STATUS EPILEPTICUS

• life-threatening emergency

• recurrent episodes of tonic-clonic seizures without regaining consciousness or normal muscle movement between episodes

BARBITURATES

For status epilepticus, if If uncontrolled by benzo or phenytoin, use

GENERAL ANESTHESIA

In highly resistant cases of status epilepticus, use

• Carbamazepine

• Valproic Acid

• Lamotgrine

• Lacosamide

• Topiramate

Sodium Channel Blockers:

• Pregabalin

• Gabapentin

L-Type blockers:

• Topiramate

• Perampanel

• Valproate Acid

AMPA blockers:

Felbamate

NMDA blocker

• Brivaracetam

• Brivaracetam

SV2A Blocker

Vigabatrin

A drug that blocks GABA-T

GABA-T

GABA is degraded by an enzyme called

GAT1

Transfer GABA Neurotransmitter to the vesicle

Ezogabine

An agent that opens K channel and Cl channel

• Ezogabine

• Benzodiazipines

• Barbiturates

• Topiramate

agents that open Cl channel by potentiation activation of GABA-A receptor