Pharmacotherapy: Antiseizure Medications

Pharmacotherapy for Seizure Disorders

Introduction to Seizures and Epilepsy

• Terminology:

  • Pharmacotherapy: Refers to drug treatment.

  • Anticonvulsants/Anti-seizure medicines/Anti-epileptics: Terms used for these medications. The most appropriate are anti-seizure medicine or anti-epileptic.

  • Seizure: A symptom, not a disease itself. It represents hyperexcitability of neurons in the brain, lowering the seizure threshold.

    • Goal: Identify and eliminate the underlying cause to terminate seizure activity.

  • Convulsions: A type of seizure activity, but not all seizures involve convulsions. This term is less appropriate for all seizures than anti-seizure or anti-epileptic.

  • Epilepsy: A disorder characterized by recurrent seizures for which no underlying cause can be identified (idiopathic) or treated.

  • Idiopathic: A seizure disorder categorized as such when no underlying cause can be identified.

Types of Seizure Activity

• Nurses must know how to describe different seizure types and their manifestations to:

  • Determine the kind of seizure a patient is experiencing or is likely to experience.

  • Identify necessary protective mechanisms.

• Clinical signs depend on the seizure type, which can be convulsive or non-convulsive.

Triggers and Causes of Seizures

• Triggers: Factors that can provoke a seizure in susceptible individuals.

  • Fatigue

  • Flashing lights

  • Other unidentified factors.

• Causes: Underlying physiological conditions.

  • If an underlying cause is identified and can be treated, ongoing seizure medication may not be needed.

  • If a cause is identified but cannot be treated, or if no cause is identified (idiopathic), ongoing medication is likely required.

  • Specific Causes (potentially reversible/treatable):

    • Febrile seizures: Caused by a rapid, usually high, increase in body temperature. Risk decreases when temperature lowers. (Does NOT indicate increased risk of seizures later in life).

    • Infection: E.g., Meningitis or Encephalitis. Can cause inflammation and irritation in brain tissue/neurons. Treating the infection removes the inflammation and irritation.

    • Metabolic disorders: E.g., Fluid and electrolyte imbalances, hypoglycemia, hyponatremia. Correcting these can resolve seizure activity.

    • Neoplastic disease (tumors): Can be benign or malignant. If surgically removable, it may be the only treatment needed. If not safely removable, anti-seizure medication may be required.

    • Vascular disease: Changes in oxygenation and perfusion can lead to seizures. Correcting vascular issues can reduce or eliminate risk.

    • Trauma: Can similarly lead to seizures.

  • Idiopathic: Over 50 ext{ %} of cases have no specific etiology identified. These typically require ongoing seizure medication.

Special Seizure Conditions

• GABA (Gamma-Aminobutyric Acid): The primary inhibitory neurotransmitter in the brain. It suppresses neuron firing. Drugs that mimic GABA's effects prevent seizure activity.

• Eclampsia: A severe hypertensive disorder of pregnancy, characterized by uncontrolled hypertension leading to seizure activity.

  • Preeclampsia: Hypertension identified during pregnancy, managed to prevent eclampsia.

  • If preeclampsia is untreated and leads to seizures, it becomes eclampsia.

  • Treatment: Magnesium sulfate.

  • This is covered in more detail in perinatal/OB-GYN courses.

• Status Epilepticus: A medical emergency characterized by either:

  • A series of repeated seizures.

  • One prolonged seizure lasting more than 30 ext{ minutes}.

  • Consequences: Can lead to coma and death due to extreme physical fatigue, poor oxygenation, and underlying brain hyperexcitability.

  • Requires immediate treatment.

General Principles of Anti-Seizure Pharmacotherapy

• Drug Choice: Depends on patient's symptoms, medical history, EEG data, and associated pathologies/comorbidities.

• Dosing Strategy:

  • Start with a low dose of a single drug to manage or minimize seizure activity.

  • Serum Drug Levels: Frequently monitored to ensure the drug is within the therapeutic range. Success is indicated by reduced/eliminated seizure activity and tolerable side effects.

  • If successful, current serum level is noted, and intermittent draws continue to maintain consistency despite other factors (e.g., diet, other medications).

  • Adjunctive Therapy: If a second medication is needed, it's added at a small, low dose. The goal is the lowest effective dose for both drugs. Serum levels are monitored for both.

  • Therapeutic Goal: Ideally, completely stop seizure activity. Minimally, significantly reduce it without intolerable side effects.

• Discontinuation:

  • NEVER discontinue abruptly. Abrupt cessation can rapidly decrease the seizure threshold and lead to a marked increase in seizure activity, including status epilepticus.

  • Medications must be tapered off slowly.

  • If a patient is seizure-free for a substantial period, tapering off medication may be considered in conjunction with a healthcare provider. However, many remain on medication indefinitely.

  • Patients with continued, even rare, seizures will remain on medication.

• Adherence: Crucial to prescribed regimens. Non-adherence can cause seizure recurrence, including status epilepticus.

Mechanisms of Action for Anti-Seizure Drugs

Drugs work by raising the seizure threshold through three main mechanisms:

1. Drugs that Potentiate GABA Action

• Mechanism: Enhance the effects of GABA, the primary inhibitory neurotransmitter. This increases GABA's inhibitory action, decreasing neuronal firing.

  • Bind to GABA receptors.

  • Make more GABA available in the synapse.

  • Enhance GABA release.

  • Block GABA reuptake.

  • Prevent GABA breakdown.

• Neuronal Firing: Neurons fire when ions (e.g., sodium, calcium) cross cell membranes through ion channels, generating an action potential. Preventing this influx delays depolarization, thus delaying neuron firing.

• Examples:

  • Barbiturates (e.g., Phenobarbital - prototype):

    • Effective for all major seizure types except absence seizures.

    • High potential for abuse, dependence, and tolerance.

    • Decreased safety margin.

  • Benzodiazepines (e.g., Diazepam/Valium - prototype, Lorazepam/Ativan):

    • Also have a high potential for abuse, dependence, and tolerance.

    • Decreased safety margin.

    • Diazepam and Lorazepam can be used for status epilepticus.

  • Other drugs: Some used for neuropathic pain (e.g., Gabapentin), depression, or migraines also potentiate GABA action.

2. Drugs that Suppress Sodium Influx

• Mechanism: Delay depolarization of neurons by preventing sodium ions from crossing the cell membrane, thus delaying action potential generation.

• Characteristics:

  • Effective against most types of seizures except absence seizures.

  • No abuse potential.

  • Do not cause CNS depression (less drowsiness compared to GABA potentiators).

• Examples:

  • Hydantoins (e.g., Phenytoin/Dilantin - prototype):

    • Older drug with a very narrow therapeutic range.

    • Requires careful dose monitoring with frequent serum drug level draws.

  • Valproic acid (Depakene, Depakote - prototype):

    • Has a larger therapeutic range than phenytoin, but still requires careful and frequent dose monitoring to ensure it stays in range despite other medications or diet.

    • Lower abuse potential and fewer CNS side effects compared to GABA potentiators, but needs more lab monitoring.

3. Drugs that Suppress Calcium Influx

• Mechanism: Raise the seizure threshold by keeping neurons from firing too quickly (preventing calcium ions from crossing the cell membrane).

• Characteristics:

  • Drugs of choice for treating absence seizures.

• Examples:

  • Succinimides (e.g., Ethosuximide/Zarontin - prototype):

    • Prototype drug for this class.

Nursing Considerations and Patient Education

• Patient Identification and Safety:

  • Identify patients at risk for seizures.

  • Document seizure patterns (frequency, length, prodromal phase, post-ictal period).

  • Implement safety precautions.

  • Encourage patients to maintain a seizure diary to track activity and triggers.

• Medication Management and Interactions:

  • Avoid CNS Depressants: Patients should avoid alcohol and other CNS depressants, as they can increase adverse effects and potentially lower the seizure threshold, especially when combined with anti-seizure medications.

  • Report All Medications: Notify the primary care provider of all medications, including over-the-counter drugs, as many can lower the seizure threshold or interfere with anti-seizure drugs.

  • Driving and Alertness: Many anti-seizure medications cause drowsiness, dizziness, and can impair mental and physical abilities. Patients should avoid driving and activities requiring mental alertness until drug effects are known. This may be a permanent restriction depending on seizure frequency.

  • Compliance/Adherence: Crucial for effectiveness. Side effects can be unpleasant, leading to non-adherence. The care team should monitor for this and consider regimen adjustments to support adherence.

• Monitoring Drug Levels:

  • Periodic monitoring of serum drug levels is necessary, particularly for drugs with narrow therapeutic indexes (e.g., Phenytoin, Valproic acid).

  • While essential for safety and efficacy, this can be frustrating for patients due to frequent lab draws and potential dose changes.

• Prevent Abrupt Discontinuation: Reiterate that abrupt discontinuation can rapidly decrease the seizure threshold and cause status epilepticus.

• Specific Side Effects and Management:

  • Oral Health (Hydantoins/Phenytoin-like drugs): Can increase the risk of oral infections and cause gingival hyperplasia (gum overgrowth).

    • Patient Education: Maintain meticulous oral hygiene and have regular dental visits. (This is a classic standardized test question: "Dilantin should be monitored for what oral condition?" Answer: Gingival hyperplasia).

  • Stimulants (Caffeine and Nicotine): Can decrease the effectiveness of benzodiazepines (CNS depressants). Patients using benzodiazepines should limit caffeine and limit or avoid smoking.

• Holistic Patient Care:

  • Ensure treatment is effective without intolerable adverse effects.

  • Monitor for side effects and adjust regimens if they lead to non-compliance.

  • Treat the whole patient, addressing psychological and emotional needs, especially given the unpredictable nature of seizure disorders.

Impact on Quality of Life and Livelihood

• Stigma and Embarrassment:

  • Seizures can occur randomly and at inopportune times, causing discomfort for friends/family.

  • Patients may experience embarrassment, amplified by loss of bladder control or injuries sustained during a seizure.

  • Increased risk of injury, especially if engaging in risky activities during a seizure.

• Limitations on Daily Life:

  • Driving: Many states require a seizure-free period (e.g., 6 ext{ months to } 1 ext{ year}) before obtaining a driver's license.

  • Occupations: Certain occupations (e.g., piloting an airplane) may be prohibited due to the substantial risk if a seizure occurs during the activity.

• Psychological Impact: These limitations can negatively impact self-esteem and lead to symptoms of depression. Emotional support is vital.