Phenytoin

(Dilantin)

DOC:

Partial seizures

Generalized tonic-clonic

Status epilepticus –IV (fosphenytoin for longer DoA)

Cardiac Arrhythmias – IV

E.g. Vtach and digitalis-induced arrhythmia

Phenytoin

(Dilantin)

Conjugated à inactive metabolites à excreted in urine

Oral à complete but slow and variable b/c poorly soluble unlike fosphenytoin

IM à unpredictable & not recommended – use fosphen. instead

IV à status epilepticus only

Highly plasma protein bound (90%) à widely distributed

Dose dependent rate of metabolism

[Low] à 1^st order, (t1/2=24h)

[High] à saturation of liver enzymes à small ↑ cause toxicity = zero-order

Phenytoin

(Dilantin)

Ataxia, diplopia, nystagmus (interfere w/cerebellar fxns), confusion, drowsiness, sedation, gingival hyperplasia (pediatric), hirsutism, NV, megaloblastic anemia (interfere w/folate abs in GIT), hypersensitivity rxns: rash, fever, Stevens-Johnson syndrome (SJS) – severe erythmatous skin eruption/exfoliative dermatitis, blood dyscrasias, lymphadenopathy, heptatitis

Phenytoin

(Dilantin)

Contraindications:

Hypersensitivity

Cardiac, hepatic or renal impairment

Pregnancy à Teratogenic à Fetal Phenytoin Syndrome: congenital HD, ear/lips/palate malformation, MR

Drug interactions:

Dicumarol, cimetadine, valproic acid à inhibit metabolism

Barbiturates, PB, carbamazepine à ↑ metabolism

Phenytoin à ↑ metabolism of carbamazepine, dicumarol, oral contraceptives, cyclosporine

Carbamazepine

(Tegretol

DOC:

Partial seizures Generalized tonic-clonic (DoC) Severe cases à w/ phenytoin

Trigeminal neuralgia

Manic episodes in bipolar disorder

Carbamazepine

(Tegretol)

Plasma bound (70%) & slowly distributed but well absorbed

By liver microsomal enzymes à produce microsomal enzyme induction (dec its own metabolism -- ↓ t1/2 w/ chronic use – adjust dose prn) à excreted in urine

Carbamazepine

(Tegretol)

Dose-related: diplopia and ataxia, NV, drowsiness

but < phenytoin

Idiosyncratic rxns: erythematous skin rash, SJS, agranulocytosis, aplastic anemia( rare but serious – BBW!!)

-          Genetic test for CBZ-induced SJS: 10x higher in Asians than Caucasians. HLA B1502 allele only in Asians

Carbamazepine

(Tegretol)

Contraindications & cautions:

Hypersensitivity, bone marrow depression

Cardiac, hepatic or renal impairment

Pregnancy à Teratogenic

Check CBC initially & periodically à liver function

Drug interactions:

Phenytoin, ethosuximide, valproic acid, clonazepam, oral anticoagulants, doxycycline, haloperidol à ↓ [carbamazepine] by enzyme induction (incl its own metabolism)

Erythromycin, cimetidine à ↓↓ metabolism

Phenobarbital, phenytoinà ↑ metabolism

Lamotrigine

(Lamictal)

Broad spectrum:

Partial seizures

Generalized tonic-clonic

Absence & Myoclonic

Lamotrigine

(Lamictal)

Well absorbed orally (t1/2 = 24h)

Glucuronidation à 2-N glucuronide à excreted in urine

NO ENZYME INDUCTION

Lamotrigine

(Lamictal)

Dose related: somnolence, diplopia, life threatening dermatitis, e.g. SJS (pediatric) – not for pts < 16yo! Also dizziness, HA, NV

Drug interactions:

Carbamazepine, PB, Phenytoinà ↑ metabolism

Valproic acids à ↓↓ metabolism