Which of the following is not an anti-seizure medication: phenytoin, digoxin, phenobarb (phenobarbital), or valproic acid?

Anti-seizure Medications: Identifying the Non-Antiepileptic Drug

Digoxin is the only medication listed that is not an anti-seizure medication. 1

Evidence-Based Explanation

The question asks to identify which of the following is NOT an anti-seizure medication:

• Phenytoin
• Digoxin
• Phenobarbital (Phenobarb)
• Valproic acid

Confirmed Anti-seizure Medications

1. Phenytoin:

   • FDA-approved anti-seizure medication 2
   • Commonly used for treatment of convulsive epilepsy and status epilepticus 1
   • Considered weight-neutral in terms of side effects 1
   • Used as a second-line agent for status epilepticus at doses of 18-20 mg/kg 1

2. Phenobarbital (Phenobarb):

   • Well-established anti-seizure medication 3
   • Has selective anticonvulsant activity independent of sedation 3
   • Limits seizure spread and raises seizure threshold in generalized tonic-clonic epilepsy 3
   • Used in status epilepticus with 58.2% efficacy in terminating seizures 1
   • Recommended in guidelines for epilepsy management 1

3. Valproic acid:

   • FDA-approved anti-epileptic drug 4
   • Used for treatment of seizures and status epilepticus 1
   • Recommended for epilepsy management in multiple guidelines 1
   • Can be administered at 20-30 mg/kg for status epilepticus with 88% success rate 1
   • Has a place in seizure management but may cause weight gain as a side effect 1

The Non-Anti-seizure Medication

Digoxin:

• Not mentioned in any of the guidelines or drug information as an anti-seizure medication
• Not included in any of the epilepsy treatment protocols or guidelines 1, 5
• Primarily used as a cardiac medication for heart failure and certain arrhythmias
• Not listed among anti-epileptic drugs in any of the evidence provided

Clinical Relevance

Understanding which medications have anti-seizure properties is critical for proper management of epilepsy and status epilepticus. The three true anti-seizure medications listed have different mechanisms of action and side effect profiles:

• Phenytoin: Sodium channel blocker with potential for cardiac side effects and purple glove syndrome 1, 2
• Phenobarbital: GABA potentiator with sedative properties and risk of respiratory depression 1, 3
• Valproic acid: Multiple mechanisms including GABA enhancement with risks of hepatotoxicity and teratogenicity 1, 4

Digoxin, by contrast, is a cardiac glycoside that inhibits the sodium-potassium ATPase pump and is used primarily for heart conditions, not seizures 6.

Common Pitfalls

• Some medications may have multiple uses across different medical specialties, but digoxin is not recognized for anti-seizure properties
• Anti-seizure medications often have drug interactions with each other (e.g., phenytoin and valproic acid can interact, affecting free drug levels) 7, 8
• Enzyme-inducing anti-seizure drugs like phenytoin and phenobarbital can affect metabolism of other medications and increase vascular risk 9

The evidence clearly identifies digoxin as the only medication in the list that is not used for seizure management.