Antiepileptic Drugs: Nursing Pharmacology Study Guide

Antiepileptic drugs (AEDs) are central to seizure management, and safe use depends on matching the right drug to the seizure type, monitoring for serious adverse effects, and recognizing high-risk drug interactions. This guide summarizes drug selection, mechanisms, side effects, pregnancy considerations, and essential nursing safety rules.

First-Line Drugs by Seizure Type

• Focal onset seizures: lamotrigine, levetiracetam, carbamazepine
• Generalized tonic-clonic seizures: valproate, lamotrigine, levetiracetam
• Absence seizures: ethosuximide (first-line); valproate (alternative)
• Myoclonic seizures: valproate, levetiracetam
• Status epilepticus: benzodiazepines first, then phenytoin

Mechanisms of Action

• Sodium channel blockers: phenytoin, carbamazepine, lamotrigine
• GABA enhancers: valproate, phenobarbital, benzodiazepines
• T-type calcium channel blockers: ethosuximide, valproate
• Valproate is unique — works through multiple mechanisms (GABA enhancement, sodium channel blockade, and calcium channel blockade)

Drug Class Overview

First-Generation Agents

• Include phenytoin, carbamazepine, valproate, phenobarbital
• More side effects and drug interactions than newer agents
• Phenytoin follows zero-order kinetics — small dose increases can produce large jumps in blood levels and toxicity
• Carbamazepine undergoes autoinduction — increases its own metabolism over time, often requiring dose adjustments

Second-Generation Agents

• Include levetiracetam, lamotrigine, oxcarbazepine
• Generally fewer side effects and interactions
• Levetiracetam is renally eliminated without liver metabolism — safest option in liver disease

Side Effects

Common Effects

• Gingival hyperplasia — phenytoin
• Hyponatremia — carbamazepine
• Weight gain and alopecia — valproate
• Behavioral changes — levetiracetam
• Black box warning: all AEDs carry a warning for suicidal thoughts and behaviors — monitor mood

Serious Adverse Effects

• Stevens-Johnson syndrome — lamotrigine, carbamazepine, phenytoin, phenobarbital → any rash, stop the drug immediately
• Agranulocytosis — carbamazepine, valproate → fever or sore throat: hold drug and check CBC
• Hepatotoxicity — valproate → monitor LFTs and ammonia
• Pancreatitis — valproate → severe abdominal pain: hold drug and check lipase
• Purple glove syndrome — IV phenytoin infiltration causes ischemia; use a central line when possible

Mnemonic — "VALPROATE Causes These"

• V — Vomiting (GI upset)
• A — Alopecia (reversible)
• L — Liver damage
• P — Pancreatitis
• R — Reinforce monitoring (LFTs, ammonia)
• O — Obesity (weight gain)
• A — Avoid in pregnancy
• T — Tremor
• E — Enzyme inhibitor (raises other drug levels)

Contraindications

• Phenytoin IV — contraindicated in heart disease
• Carbamazepine — contraindicated in bone marrow depression
• Valproate — contraindicated in hepatic impairment
• Pregnancy — avoid valproate when alternatives exist (highest teratogenic risk)
• Renal impairment — dose reduction needed for levetiracetam, gabapentin, pregabalin
• Elderly — start low to reduce fall risk

Pregnancy Safety

• Valproate: highest risk — neural tube defects, cognitive impairment. Avoid in pregnancy; if unavoidable, high-dose folate.
• Phenytoin: high risk — fetal hydantoin syndrome, folate deficiency. Give folate 4 mg daily.
• Carbamazepine: high risk — neural tube defects, folate deficiency. Give folate 4 mg daily.
• Lamotrigine: relatively safer, but drug levels drop in pregnancy — monitor closely and adjust dose.
• Levetiracetam: relatively safe; preferred alternative after lamotrigine; renal elimination keeps levels stable.
• Never stop AEDs abruptly in pregnancy — uncontrolled seizures cause fetal hypoxia and trauma.
• Folate 4 mg daily for all women on AEDs.
• Vitamin K 10 mg daily in the last month of pregnancy for mothers on enzyme-inducing AEDs.

Nursing Safety Rules

• Phenytoin IV: never mix in D5W — use normal saline only; max push rate 50 mg/min; flush line before and after.
• Fosphenytoin: prodrug; can be given IM, infused faster IV, and causes less tissue damage on infiltration.
• Lamotrigine: titrate very slowly starting at 25 mg daily; if ≥3 doses are missed, restart titration from the beginning.
• Valproate + lamotrigine: cut the lamotrigine dose in half due to interaction.
• Enzyme-inducing AEDs (phenytoin, carbamazepine, phenobarbital) decrease effectiveness of oral contraceptives, warfarin, and steroids — use backup contraception.
• Phenytoin + tube feeding: absorption is decreased — hold tube feeds 1–2 hours before and after the dose.
• Early phenytoin toxicity: nystagmus, progressing to ataxia and coma. Therapeutic level 10–20 mcg/mL.
• Never stop AEDs abruptly — withdrawal can trigger seizures or status epilepticus.
• Report rash, fever, bruising, or severe abdominal pain immediately.

Key Takeaways

• Ethosuximide is the only first-line drug for absence seizures; benzodiazepines are first-line for status epilepticus.
• Any rash on lamotrigine, carbamazepine, or phenytoin = stop the drug — risk of Stevens-Johnson syndrome.
• Valproate causes hepatotoxicity, pancreatitis, and birth defects — avoid in pregnancy and liver disease.
• Phenytoin: therapeutic level 10–20; toxicity starts with nystagmus; IV only in NS at ≤50 mg/min; hold tube feeds around dosing.
• Lamotrigine requires slow titration and dose reduction when combined with valproate.
• Never stop AEDs abruptly — risk of status epilepticus; all AEDs carry a suicidality black box warning.