12.1 Epilepsy and Anticonvulsant Drugs

Epilepsy is a neurological disorder characterized by recurrent seizures resulting from abnormal electrical activity in the brain. At its core, there's an imbalance between excitatory and inhibitory neurotransmitters that causes neurons to fire excessively.

Anticonvulsant drugs are the primary treatment. They work by reducing neuronal excitability and raising the seizure threshold through several different mechanisms. Understanding which drug classes target which mechanisms is essential for safe administration and effective patient education.

Pathophysiology and Diagnosis of Epilepsy

Mechanisms and manifestations of epilepsy

Seizures occur when neurons fire excessively and synchronously. This happens because of an imbalance between glutamate (the main excitatory neurotransmitter) and GABA (the main inhibitory neurotransmitter). Too much glutamate activity or too little GABA activity tips the balance toward uncontrolled electrical discharge.

Seizures are classified into two broad categories:

• Generalized seizures involve both hemispheres of the brain from the start. Types include tonic-clonic (convulsive, formerly "grand mal"), absence (brief staring spells, formerly "petit mal"), myoclonic (sudden brief jerks), and atonic (sudden loss of muscle tone, "drop attacks").
• Focal seizures are localized to one brain area. Simple focal seizures preserve consciousness, while complex focal seizures involve altered awareness.

Beyond the seizure itself, patients may experience an aura beforehand (sensory, motor, or psychological warning symptoms) and a postictal state afterward (confusion, fatigue, headache) that can last minutes to hours.

Causes and diagnosis of epilepsy

Epilepsy has many possible causes:

• Genetic factors (family history, inherited channelopathies)
• Structural brain abnormalities (traumatic brain injury, stroke, brain tumors, congenital malformations)
• Metabolic disorders (electrolyte imbalances, inborn errors of metabolism)
• Infections (meningitis, encephalitis)

Diagnosis typically involves:

1. A thorough neurological examination and patient history
2. Electroencephalogram (EEG) to record brain electrical activity and identify abnormal patterns (spike-and-wave discharges, for example)
3. Neuroimaging (MRI or CT scan) to detect structural causes
4. Blood tests to rule out metabolic causes like hypoglycemia or electrolyte disturbances

Neuronal excitability and seizure threshold

Neuronal excitability refers to how easily neurons generate action potentials. The more excitable the neurons, the less stimulation it takes to trigger abnormal firing.

Seizure threshold is the level of stimulation required to trigger a seizure. Genetics, brain injury, sleep deprivation, and medications all influence this threshold. Anticonvulsant drugs work by reducing neuronal excitability and raising the seizure threshold, making it harder for abnormal electrical activity to spread.

Anticonvulsant Drugs and Treatment Strategies

Classes of anticonvulsant drugs

Each drug class targets a different mechanism to reduce seizure activity:

• Sodium channel blockers (phenytoin, carbamazepine, lamotrigine) stabilize neuronal membranes by blocking voltage-gated sodium channels, preventing the rapid repetitive firing that drives seizures.
• GABA enhancers (benzodiazepines like diazepam and lorazepam, barbiturates, valproic acid) boost inhibitory GABA activity. Benzodiazepines and barbiturates increase the effect of GABA at its receptor, while valproic acid also inhibits GABA degradation.
• Calcium channel blockers (ethosuximide, gabapentin) reduce calcium influx into neurons, decreasing neurotransmitter release. Ethosuximide specifically blocks T-type calcium channels in thalamic neurons, which is why it's particularly effective for absence seizures.
• Glutamate antagonists (topiramate, perampanel) block excitatory glutamate receptors, reducing excitatory neurotransmission.
• Other mechanisms: Levetiracetam binds to synaptic vesicle protein SV2A, modulating neurotransmitter release through a unique mechanism. Zonisamide works through multiple pathways (sodium and calcium channel blockade plus GABA enhancement).

Effects and interactions of anticonvulsants

The therapeutic goal is seizure control with minimal side effects. Common side effects across the class include:

• CNS effects: drowsiness, dizziness, ataxia, cognitive impairment (difficulty with memory and concentration)
• GI effects: nausea, vomiting
• Weight changes: valproic acid tends to cause weight gain; topiramate tends to cause weight loss
• Serious dermatologic reactions: Stevens-Johnson syndrome (SJS) is a potentially life-threatening skin reaction, particularly associated with lamotrigine, carbamazepine, and phenytoin. Patients of certain genetic backgrounds (HLA-B*1502 allele, more common in people of Asian descent) are at higher risk with carbamazepine.

Drug interactions are a major concern with anticonvulsants:

• Enzyme inducers (phenytoin, carbamazepine, phenobarbital) speed up hepatic metabolism via cytochrome P450, decreasing levels of other drugs.
• Enzyme inhibitors (valproic acid) slow hepatic metabolism, increasing levels of other drugs.
• Oral contraceptives become less effective with enzyme-inducing anticonvulsants. Patients need to be counseled about alternative or additional contraception methods.

Nursing considerations for anticonvulsants

• Before administration: Assess for allergies, contraindications, and current medications (watch for interactions). Check baseline liver and renal function.
• Therapeutic drug monitoring: Phenytoin, carbamazepine, and valproic acid all require regular serum level monitoring to maintain therapeutic ranges and avoid toxicity.
• Signs of toxicity to watch for: nystagmus (involuntary eye movements), ataxia (unsteady gait), slurred speech, and excessive sedation. These often appear before levels become dangerously high, so catching them early matters.
• Administration tips: Give with food if GI upset occurs. Phenytoin should not be mixed with dextrose solutions (it precipitates); use normal saline for IV administration.
• Never stop abruptly: Sudden discontinuation of anticonvulsants can trigger rebound seizures or even status epilepticus. Doses must be tapered gradually under provider supervision.
• Ongoing monitoring: Assess for side effects at each visit and ensure dosage adjustments are made based on drug levels and clinical response.

Patient education for epilepsy medications

• Take medications exactly as prescribed, at the same time each day. Missed doses increase seizure risk.
• Know the side effects of your specific medication and when to seek medical attention (rash, unusual bleeding, severe fatigue, mood changes).
• Keep a seizure diary to track seizure frequency, potential triggers, and medication effectiveness. This information helps providers make treatment decisions.
• Maintain a consistent sleep schedule, since sleep deprivation is a common seizure trigger.
• Discuss the impact of epilepsy on daily activities with your provider. Many states have driving restrictions that require a seizure-free period before driving is permitted. Swimming and bathing should involve supervision.
• Connect with epilepsy support groups and resources (the Epilepsy Foundation is a good starting point).
• Keep all follow-up appointments for drug level monitoring and medication adjustments.

Treatment approaches for seizure types

Choosing the right anticonvulsant depends on the seizure type. Using the wrong drug can actually worsen certain seizures.

Generalized tonic-clonic seizures:

• First-line: valproic acid, lamotrigine, levetiracetam
• Second-line: phenytoin, carbamazepine, topiramate

Absence seizures:

• First-line: ethosuximide, valproic acid, lamotrigine
• Avoid carbamazepine and gabapentin, which can worsen absence seizures

Focal seizures:

• First-line: carbamazepine, lamotrigine, levetiracetam
• Second-line: phenytoin, zonisamide, topiramate

Status epilepticus (a seizure lasting >5 minutes or repeated seizures without recovery between them) is a medical emergency:

1. Secure the airway, ensure safety, and call for help
2. Administer a benzodiazepine first (IV lorazepam or rectal/IV diazepam)
3. If seizures continue, give phenytoin (or fosphenytoin) IV
4. If still refractory, phenobarbital IV
5. Persistent refractory cases may require general anesthesia (propofol, midazolam) in an ICU setting

Non-pharmacological treatments for drug-resistant epilepsy include:

• Ketogenic diet (high-fat, low-carbohydrate), used primarily in children with refractory epilepsy
• Vagus nerve stimulation (VNS), a surgically implanted device that delivers electrical impulses to reduce focal seizure frequency
• Surgical resection of the seizure focus, considered when seizures originate from a single identifiable brain area that can be safely removed

For patients with drug-resistant epilepsy, combination therapy with two or more anticonvulsants or referral to a comprehensive epilepsy center should be considered.