DRUGS FOR SEIZURE DISORDERS

Seizure

abnormal firing of neurons leading to excitability

Valproic Acid

All anticonvulsants are enzyme inducers EXCEPT ‘blank’ – extensive enzyme inhibitor

TYPES OF SEIZURE

✓ Partial / Focal Seizure

✓ Generalized Seizure

✓ Status Epilepticus

PARTIAL / FOCAL SEIZURE

• Only affects one hemisphere of the brain

• Simple: Jacksonian Epilepsy, repetitive jerking, no loss of consciousness

• Complex: Psychomotor Epilepsy, ↓ level of consciousness, automatism behavioral changes, hallucinations

• Drugs (1st Line): Carbamazepine, Phenytoin

• Alt: Lamotrigine, Oxcarbazepine, Valproic Acid

GENERALIZED SEIZURE

• Involves both hemispheres

• Loss of consciousness

• Tonic-Clonic Seizure (Grand Mal)
o Full body convulsion, urination and defecation (uncontrolled)

o DOC: Valproic Acid

Absence Seizure (Petit Mal)

o Sudden onset and abrupt cessation

o Involves a brief, abrupt, and self limiting loss of consciousness

o Blank stares, lip smacking, rapid eye blinking

o Common in children

o DOC: Ethosuximide

o Alt: Valproic Acid

Atonic Seizure (Drop Seizure)

o Loss of muscle tone

o DOC: Clonazepam

o Alt: Valproic Acid, Topiramate, Lamotrigine

Myoclonic Seizure

o Muscle jerking

o DOC: Valproic Acid

Febrile Seizure

o Consists of GTC convulsions of short duration

o Develops in children (3 mos – 5 years)

o Accompanied by high fever

o DOC: Phenobarbital

o Alt: Primidone

STATUS EPILEPTICUS

• Recurrent seizure episodes without regaining consciousness

• New DOC: Clonazepam

• Old DOC: Diazepam → Lorazepam

CARBAMAZEPINE

• MOA: Na channel blocker

• Enzyme inducer and capable of autoinduction (induces metabolism)

CARBAMAZEPINE: uses

✓ DOC for trigeminal neuralgia

✓ 1st line in partial / focal seizure

Carbamazepine: S/E: (Dose Related)

o Diplopia – double vision; 1st sign of toxicity; requires dose adjustment

o Ataxia – loss of control of voluntary movement

o Teratogenic: Neural tube defect / spina bifida – use Folic Acid / Vit B9 for prevention

PHENYTOIN (DIPHENYLHYDANTOIN)

• MOA: Block conductance of Na, K, and Ca

• Enzyme inducer

• S/E:
o Nystagmus – horizontal eye movement ▪ Most common S/E ▪ Doesn’t require dose adjustment; not dose related

o Dose Related: Diplopia, Ataxia – requires dose adjustment

o Cosmetic Changes: Gingival hyperplasia, hirsutism

o Teratogenic: Fetal hydantoin syndrome – abnormalities

• Idiosyncratic Reactions: SJS-TEN, Hemolytic anemia

Fosphenytoin

phenytoin derivative; can be given IV/IM

Phenytoin (IV)

if given IM, erratic absorption and tissue necrosis

VALPROIC ACID AND VALPROATE

Mechanism of Action:

✓ Increases GABA concentration by stimulating glutamic acid decarboxylase (enzyme for GABA synthesis)

✓ Blocks Na and Ca conductance

VALPROIC ACID AND VALPROATE: side effects

o Hepatotoxicity – should not be given to < 2 years old

o Teratogenic: Neural tube defect / spina bifida – use Folic Acid / Vit B9 for prevention

LAMOTRIGINE (Lametal®)

• MOA: Na channel blocker

• Safest in pregnancy

• Black Box Warning: ↑ Suicidal ideation

Ethosuximide

• MOA: T-type Ca channel blocker

• NOTE: L-type is for periphery ANS

Topiramate

MOA: Na and Ca channel blocker

Vigabatrin

Irreversible inhibitor of GABA-T / GABA Aminotransferase = ↑ GABA

Felbamate

NMDA (Excitatory) receptor blocker = ↑ GABA

Gabapentin

analog of GABA but does not act on GABA receptors; unknown mechanism

Pregabalin

analog of Gabapentin; unknown MOA

Tiagabine

inhibits GABA uptake = ↑ GABA

Lamotrigine

Na and Ca channel blocker; ↓ Glutamate conc = inhibitory effect

Neonatal seizure

Phenobarbital

Infantile spasm

Vigabatrin

Status epilepticus (very severe seizure)

Diazepam, lorazepam, midazolam

DOC for trigeminal neuralgia

Carbamazepine

Lamotrigine

Migraine HA prophylaxis

Topiramale

Valproic acid
gabapentin
pregabalin

Diabetic neuropathy

Lamotrigine

Gabapentin