• Important drug – know PK and PD well.
  1. Diphenyl substituted hydantoin
  1. Affects Na, K and Ca2+ conductance.
    • Preferentially binds to the inactivated state of Na+ channels, therefore prolonging the inactivated states.
    • Has a use dependent effect.
    • Overall inhibits the generation of rapidly repetitive action potentials.
  2. Thought to also reduce glutamate synthesis
  3. Thought to enhance GABA release
  1. PO or IV
  1. Very highly bound to plasma proteins. Drugs that are highly protein bound (e.g. sulfonamides/warfarin) will displace it.
  1. To inactive metabolites.
    • Phenytoin demonstrates dose-dependent metabolism and excretion.
    • It follows first order kinetics at low blood levels.
    • At higher blood levels (even within the therapeutic range) the metabolism then begins to follow zero order kinetics.
    • A small increase in dosage may represent a large increase in plasma levels.
  2. T ½ of 12-36 hours, taking 5-7 days to reach steady state.
  1. Renal
  1. Status epilepticus
  2. Partial/generalized TCS
  3. Digitalis induced arrhythmias
Special precautions
  1. Drugs that are highly protein bound will displace phenytoin and reduce its effect (e.g. warfarin, sulfasalazine)
  2. Enzyme inducers will reduce its level (carbamazepine, rifampicin)
  3. Enzyme inhibitors will increase its level (amiodarone, metronidazole)
  4. Phenytoin itself is an enzyme inducer and therefore it may reduce effects of corticosteroids or doxycycline. There is no auto-induction.
Adverse events
  1. Mainly CVS, CNS and skin complications
    • CNS: ataxia, nystagmus and diplopia
    • CVS: arrhythmia, hypotension especially at fast infusion rates.
    • Skin: rare. However, may get SJS/idiosyncratic rash.
  1. In status epilepticus, the adult dose is 15-20mg/kg.
    • Deliver as an IV infusion of no more than 50mg/minute. This avoids the complication of hypotension and possible cardiovascular collapse.
Withdrawal syndrome
Special notes