PHENYTOIN
PHARMACOLOGICAL ACTION:
- Not CNS depressant
- Abolishes tonic phase of GTC seizure
- Prevents spread of seizure activity
- In CVS – depresses ventricular automaticity accelerating AV conduction
MOA:
- Prevents repetitive detonation of normal brain cells during `depolarization shift`
- Prolonged inactivation of voltage-sensitive Na+ channel
- Potent microsomal enzyme inducer
PHARMACOKINETICS:
- Slow oral absorption
- 80-90% bound to plasma protein.
- Metabolized in liver by hydroxylation & glucuronide conjugation
- t1/2 – 12 to 24 Hrs.
- Cannot metabolize by liver if plasma conc. is above 10 mcg/ml
- Monitoring of plasma concentration essential.
- Elimination varies with dose – first order to zero order.
USES:
- First line antiepileptic for
- GTCS – Tonic-clonic phase is suppressed but no change in EEG and aura
- Status epilepticus ( slow IV injection).
- No effect in clonic phase & absence seizure.
- Trigeminal neuralgia – 2nd to Carbamazepine
- Available as caps/tabs/in 25 to 100 mg caps and tabs.
ADVERSE EFFECTS:
- Hirsutism – Coarsening of facial features and acne.
- Gum hypertrophy & Gingival Hyperplasia.
- Hypersensitivity – Rashes & lymphadenopathy.
- Megaloblastic anemia.
- Folic acid deficiency
- Osteomalacia
- Hyperglycaemia
- Pseudolymphoma
- Cognitive impairment
- Toxic epidermal necrolysis
- Exacerbates absence seizures
- Ataxia
- Fetal Hydantoin Syndrome: Not indicated in pregnancy.
PRODRUG:
Fosphenytoin
- Water-soluble phenytoin prodrug.
- Administered IV to deliver phenytoin.
- Potentially more safely than intravenous phenytoin.
- Highly protein bound
- Fosphenytoin different from phenytoin as – Can be mixed with saline
USES:
- Used in acute treatment of convulsive status epilepticus.
- GTC
- Endotracheal intubation
SIDE EFFECTS:
- Hypotension
- Cardiac arrhythmias
- CNS adverse events (nystagmus, dizziness, sedation/somnolence, ataxia & stupor)
- Local dermatological reactions
Purple glove syndrome:
- At lower frequency than with intravenous phenytoin.
- Cause hyperphosphatemia in end-stage renal failure patients.
DRUG INTERACTIONS:
- Phenytoin and carbamazepine increases each others metabolism
- Steroids & digitoxin – Induces microsomal enzyme.
- Warfarin & isoniazid – Phenytoin metabolism inhibition.
- Sucralfate – Decreases phenytoin absorption.
Exam Important
- 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
- Dilantin (Phenytoin) is known to cause folic acid deficiency
- FOS phenytoin is Used for generalized tonic-clonic seizures
- FOS phenytoin is a Prodrug
- 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 gingival hyperplasia, Lymphadenopathy, Ataxia & Hirsutism
- Pseudolymphoma is a manifestation of Phenytoin
- Fetal hydantoin syndrome is caused by Phenytoin
- Phenytoin toxicity shows Gum hypertrophy
- Toxic epidermonercrolysis is caused by Phenytoin
- Fosphenytoin route of administration Intravenous
- Exanthema is caused by Phenytoin
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