How do you diagnose Dilantin (phenytoin) toxicity?

Diagnosing Dilantin (Phenytoin) Toxicity

Dilantin toxicity should be diagnosed through a combination of serum drug level monitoring and clinical assessment of characteristic neurological symptoms, with therapeutic levels typically between 10-20 mcg/mL and toxic effects commonly appearing at levels above 20 mcg/mL.

Clinical Manifestations of Phenytoin Toxicity

Phenytoin toxicity presents with a characteristic progression of symptoms that correlate with increasing serum levels:

Early Signs (20-30 mcg/mL)

• Nystagmus (most commonly horizontal, but can be downbeat in severe cases) 1
• Dizziness
• Blurred vision
• Diplopia

Moderate Toxicity (30-40 mcg/mL)

• Ataxia (unsteady gait)
• Slurred speech (dysarthria)
• Tremor
• Hyperreflexia

Severe Toxicity (>40 mcg/mL)

• Lethargy and confusion
• Delirium
• Psychosis or encephalopathy
• Hallucinations
• Coma in extreme cases

Additional Manifestations

• Gastrointestinal symptoms: nausea, vomiting
• Vegetative depression (changes in mood, sleep, and appetite) 2
• Cardiac complications (rare with oral administration, more common with IV administration)

Laboratory Assessment

• Serum phenytoin level measurement is essential

  • Therapeutic range: 10-20 mcg/mL
  • Toxic effects typically appear at >20 mcg/mL 3
  • Severe toxicity often occurs at >40 mcg/mL

• Timing of blood draws:

  • Trough levels (just before next scheduled dose) are most useful for monitoring compliance
  • Peak levels (4-12 hours after administration) help assess threshold for side effects 3
  • In suspected toxicity, immediate level measurement regardless of timing

• Additional laboratory tests to consider:

  • Liver function tests (phenytoin is metabolized by the liver)
  • Complete blood count
  • Electrolytes
  • Renal function tests

Risk Factors for Phenytoin Toxicity

Several factors can increase risk of toxicity:

• Pharmacokinetic considerations:

  • Non-linear (zero-order) metabolism at higher doses 4
  • Small incremental dose increases can cause disproportionate rises in serum levels 3

• Drug interactions that increase phenytoin levels 3:

  • Acute alcohol intake
  • Amiodarone, chloramphenicol
  • Cimetidine, omeprazole (H2-antagonists)
  • Fluoxetine, fluvoxamine, sertraline
  • Isoniazid
  • Salicylates, sulfonamides

• Patient factors:

  • Hepatic impairment
  • Elderly patients
  • Severely ill patients
  • Genetic slow metabolizers
  • Hypoalbuminemia (affects interpretation of total levels)

Diagnostic Algorithm

1. Suspect phenytoin toxicity when:

   • Patient is on phenytoin therapy
   • Presents with characteristic neurological symptoms (especially nystagmus, ataxia, confusion)
   • Recent dosage adjustment, addition of interacting medications, or change in health status

2. Obtain serum phenytoin level immediately

3. Correlate clinical symptoms with serum level:

   • If level >20 mcg/mL with corresponding symptoms → phenytoin toxicity likely
   • If level in therapeutic range but symptoms present → consider:
     • Free phenytoin level (in hypoalbuminemia)
     • Other causes of neurological symptoms

4. Assess for contributing factors:

   • Medication review for drug interactions
   • Evaluation of liver function
   • Assessment of compliance (intentional or unintentional overdose) 5

Management of Phenytoin Toxicity

1. Discontinue or reduce phenytoin dose based on severity of toxicity

2. Supportive care:

   • Attention to vital functions
   • Management of nausea/vomiting
   • Prevention of injuries due to ataxia/confusion
   • No specific antidote exists 4

3. Consider activated charcoal for recent ingestion/overdose

4. Monitor serum levels until return to therapeutic range

5. Observe for symptom resolution - symptoms typically resolve as serum levels decrease 6

Important Caveats

• Phenytoin toxicity can mimic other neurological conditions, including stroke, intoxication, or metabolic encephalopathy
• Symptoms may persist for extended periods due to prolonged half-life in overdose
• Depression and mood changes can be manifestations of toxicity and should prompt level checking before starting antidepressants 2
• Cardiac complications (arrhythmias, hypotension) are rare with oral phenytoin but more common with IV administration 4

By systematically evaluating clinical symptoms and obtaining serum phenytoin levels, clinicians can accurately diagnose phenytoin toxicity and initiate appropriate management to prevent complications.