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PhenytoinAka: Dilantin, Diphenylhydantoin, DPH, Hydantoin, Mephenytoin, Ethotoin, Phenacemide

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  1. Classification: Hydantoin
    1. Phenytoin (Dilantin)
    2. Phenytoin congeners (limited use)
      1. Mephenytoin
      2. Ethotoin
      3. Phenacemide
  2. History
    1. Oldest non-sedative antiepileptic drug (1938)
    2. Based on research into phenobarbital antiseizure effect
  3. Indications
    1. Partial Seizures
    2. Generalized tonic-clonic Seizures
  4. Contraindications
    1. Pregnancy (See Fetal Hydantoin Syndrome)
  5. Pharmacokinetics
    1. Hepatic metabolism
    2. Highly protein bound
    3. Half-life: 12 to 36 hours
      1. Average half life for moderate dosages: 24 hours
      2. Very long half-life at toxic concentrations
    4. Therapeutic level: 10-20 ug/ml
  6. Dosing: Adults
    1. Loading dose
      1. Oral loading regimen
        1. Dose 1: 400 mg PO
        2. Dose 2: 300 mg PO at 2 hours after dose 1
        3. Dose 3: 300 mg PO at 4 hours after dose 1
      2. Parenteral loading regimen
        1. Dose: 10-20 mg/kg (average 1 gram) IV
        2. Do not administer faster than 50 mg/min
    2. Maintenance dose
      1. Initial: 5 mg/kg to 300 mg/day divided qd to tid
    3. Titrating dose
      1. Avoid increasing dose by >25-30 mg per trial
      2. Wait for steady state (7 days) before level recheck
  7. Drug Interactions
    1. Drugs that increase plasma phenytoin levels
      1. Amiodarone
      2. Clobazam
      3. Fluconazole
      4. Ranitidine
      5. Phenylbutazone
      6. Sulfonamides
      7. Benzodiazepines
      8. Anticoagulants
      9. Isoniazid
    2. Drugs that decrease phenytoin level or free fraction
      1. Influenza Vaccine
      2. Tolbutamide
      3. Carboplatin
      4. Rifampicin
      5. Theophylline
      6. Phenobarbital
      7. Carbamazepine
    3. Phenytoin decreases plasma level of other drug
      1. Doxorubicin
  8. Adverse Effects
    1. See Dilantin Toxicity
    2. Fetal Hydantoin Syndrome
    3. Drug hypersensitivity
      1. Fever
      2. Lymphadenopathy
      3. Drug-Induced Agranulocytosis
    4. Common chronic changes associated with phenytoin
      1. Gingival Hyperplasia
      2. Hirsutism
      3. Coarse facial features
      4. Peripheral Neuropathy (decreased Deep Tendon Reflex)
    5. Other effects
      1. Hepatotoxicity
      2. Stevens-Johnson Syndrome
      3. Pancreatitis
      4. Osteoporosis
      5. Folic Acid deficiency

Ethotoin (C0015046)

Definition (NCI)A hydantoin anticonvulsant with anti-epileptic activity. The mechanism of action is not completely known, but is thought to be fairly similar to phenytoin. Ethotoin influences synaptic transmission by altering sodium and calcium ion influx across neuronal membranes in the repolarization, depolarization, and membrane stability phase and interferes with the calcium uptake in presynaptic terminals. This inhibits neuronal firing and results in the stabilization of neuronal membranes, thereby preventing the spread of seizure activity at the motor cortex.
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishEthotoin, ETHOTOIN PREPARATION, Ethotoin product, Ethylphenylhydantoin
Spanishetilfenilhidantoína, etilfenilhidantoina, etotoína, etotoina
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Hydantoins (C0020209)

Definition (MSH)Compounds based on imidazolidine dione. Some derivatives are ANTICONVULSANTS.
Definition (CSP)group of anticonvulsants containing an allantoin heterocyclic base.
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishHydantoin, Hydantoin antiepileptic, Hydantoins
Spanishhidantoína, hidantoina
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Mephenytoin (C0025381)

Definition (MSH)An anticonvulsant effective in tonic-clonic epilepsy (EPILEPSY, TONIC-CLONIC). It may cause blood dyscrasias.
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
English5 Ethyl 3 Methyl 5 Phenylhydantoin, Mefenetoin, Mephenytoin, MEPHENYTOIN PREPARATION, Methoin, Methyl Phenetoin, Methylphenylethylhydantoin
Spanishmefenitoína, mefenitoina, metilfeniletilhidantoína, metilfeniletilhidantoina, metoína, metoina
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Phenytoin (C0031507)

Definition (MSH)An anticonvulsant that is used in a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.
Definition (CSP)anticonvulsant used in a wide variety of seizures; also an anti-arrhythmic and a muscle relaxant.
Definition (NCI)A hydantoin derivative and a non-sedative antiepileptic agent with anticonvulsant activity. Phenytoin potentially acts by promoting sodium efflux from neurons located in the motor cortex reducing post-tetanic potentiation at synapses. The reduction of potentiation prevents cortical seizure foci spreading to adjacent areas, stabilizing the threshold against hyperexcitability. In addition, this agent appears to reduce sensitivity of muscle spindles to stretch causing muscle relaxation.
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishDiphenylhydantoin, DPH, Fenitoin, Phenylhydantoin, Phenytoin, PHENYTOIN PREPARATION, Phenytoin product
Spanishdifenilhidantoína, difenilhidantoina, fenitoína, fenitoina
CreditsDerived from the NIH UMLS (Unified Medical Language System)


phenacemide (C0070525)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
Englishphenacemide, PHENACEMIDE PREPARATION, phenuron, Phenylacetylcarbamide, Phenylacetylurea
Spanishfenacemida, fenilacetilcarbamida, fenilacetilurea
CreditsDerived from the NIH UMLS (Unified Medical Language System)


Dilantin (C0699512)

ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishDilantin
CreditsDerived from the NIH UMLS (Unified Medical Language System)



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