PHENYTOIN

PHARMACOLOGICAL ACTION:
  • Not CNS depressant
  • But muscular rigidity and excitement at toxic doses
  • Abolish tonic phase of GTC seizure
  • No effect on clonic phase
  • Prevents spread of seizure activity
  • Tonic-clonic phase is suppressed but no change in EEG and aura 
  • In CVS – depresses ventricular automaticity, accelerates AV conduction
MOA:
  • Prevents repetitive detonation of normal brain cells during `depolarization shift` 
  • Prolonging the inactivation of voltage sensitive Na+ channel
  • Phenytoin is a potent microsomal enzyme inducer
  • No high frequency discharges 
  • Na+ channel recovers 
  • No interference with kindling – only on high frequency firing
PHARMACOKINETICS:
  • Slow oral absorption 
  • 80-90% bound to plasma protein 
  • Metabolized in liver by hydroxylation and glucoronide conjugation
  • Elimination varies with dose – first order to zero order
  • T1/2 life is 12 to 24 hrs 
  • Cannot metabolize by liver if plasma conc. is above 10 mcg/ml 
  • Monitoring of plasma concentration
ADVERSE EFFECTS:
  • Hirsutism, coarsening of facial features and acne 
  • Gum hypertrophy and Gingival hyperplasia.
  • Hypersensitivity – rashes, lymphadenopathy 
  • Megaloblastic anaemia & Folic acid deficiency
  • Osteomalacia 
  • Hyperglycaemia 
  • Pseudolymphoma 
  • Cognitive impairment 
  • Exacerbates absence seizures 
  • Ataxia
  • Fetal Hydantoin Syndrome:Therefore not indicated in pregnancy
USES:
  • It is the first line antiepileptic for 
  1. GTCS, no effect in absence seizure 
  2. Status epilepticus ( slow IV injection)
  3. Trigeminal neuralgia – 2nd to Carbamazepine 
  4. Available as caps/tabs/inj 25 to 100 mg caps and tabs.
DRUG INTERACTIONS:
  • Phenytoin and carbamazepine increases each others metabolism
  • Induces microsomal enzyme – steroids, digitoxin etc 
  • Phenytoin metabolism inhibition – by warfarin, isoniazide etc. 
  • Sucralfate – decreases phenytoin ebsorption
PRODRUG:
  • Fosphenytoin
  1. It is a water-soluble phenytoin prodrug that is administered intravenously to deliver phenytoin, potentially more safely than intravenous phenytoin.
  2. Highly protein bound 
  • USES:
  1. It is most commonly used in the acute treatment convulsive status epilepticus.
  2. GTC
  3. Endotracheal intubation
  • SIDE EFFECTS:
  1. Hypotension Cardiac arrhythmias, 
  2. CNS adverse events (nystagmus, dizziness, sedation/somnolence, ataxia and stupor),
  3. Local dermatological reactions
  4. Purple glove syndrome probably occurs with fosphenytoin but possibly at lower frequency than with intravenous phenytoin.
  5. Fosphenytoin can cause hyperphosphatemia in end-stage renal failure patients
Exam Question
  • Phenytoin follows zero order kinetics
  • Phenytoin is a potent microsomal enzyme inducer
  • Phenytoin is Highly protein bound
  • Phenytoin with increasing dose, the T 1/2 increases
  • Dilantain (Phenytoin) is known to cause Folic acid deficiency
  • FOS phenytoin is Used for generalised tonic clonic seizures
  • FOS phenytoin is a Produrg
  • FOS phenytoin is Highly protein bound
  • Phenytoin acts on voltage sensitive neuronal Na+ channels
  • Phenytoin Used by slow IV injection in status epilepticus
  • In Phenytoin Kinetics change from 1st order to 0 order over therapeutic range
  • A lady having epileptic seizure with phenytoin therapy and become pregnant, Treatment is Tapering to lowest level of phenytoin and con­tinue pregnancy
  • Adverse effect of phenytoin include Lymphadenopathy, Ataxia & Hirsutism
  • Pseudolymphoma is a manifestation of Phenytoin
  • Fetal hydantoin syndrome is caused by Phenytoin
Don't Forget to Solve all the previous Year Question asked on PHENYTOIN