Seizures and Antiepileptic Drugs

• Seizure: Sudden, abnormal electrical activity in the brain, which may or may not cause convulsions.
• Convulsion: Characterized by involuntary muscle contractions.
• Epilepsy: A chronic neurologic disorder defined by recurrent, unprovoked seizures.

Types of Seizures

• Focal Onset (Partial): Occurs in a localized area of the brain.
• Generalized Onset: Affects both hemispheres of the brain.
• Tonic-Clonic: Involves stiffening (tonic phase) followed by jerking (clonic phase).
• Status Epilepticus: An emergency situation where seizures last longer than 5 minutes or occur repeatedly without recovery.

Antiepileptic Drug (AED) Therapy

• Goals: Control seizures, minimize side effects, and improve quality of life for patients.
• Therapeutic Monitoring: Serum drug levels are monitored to guide effectiveness and toxicity of AEDs.
• Low levels may indicate nonadherence.
• High levels require holding the dose and notifying the provider.
• Mechanisms of Action: AEDs increase the threshold for excitation in the motor cortex, suppress the spread of impulses, and decrease nerve conduction speed.
• General Principles: Initiate treatment with monotherapy, increasing the dose slowly, and consider polytherapy only if necessary.
• Never stop AEDs abruptly.
• Pregnancy: Use AEDs with caution, requiring a risk-benefit assessment.

Common Antiepileptic Drugs

• Phenytoin (Dilantin): Monitor serum levels due to its narrow therapeutic index.
  • Adverse Effects: Gingival hyperplasia, rash, ataxia, nystagmus, hepatotoxicity, and blood dyscrasias.
  • Enzyme inducer: reduces the effect of other drugs, such as oral contraceptives.
  • Administer IV phenytoin slowly through a large-gauge vein.
• Phenobarbital: Inexpensive AED that causes sedation and is an enzyme inducer.
  • Monitor for CNS depression.
• Carbamazepine (Tegretol) & Oxcarbazepine (Trileptal): First-line treatment for focal/generalized seizures.
  • Autoinduction (especially with Trileptal) increases its own metabolism, requiring level monitoring.
  • Avoid grapefruit juice with Carbamazepine.
  • Vision changes and skin reactions are possible.
• Gabapentin (Neurontin): GABA analog used for partial seizures and neuropathic pain, with sedation and dizziness as common side effects.
• Lamotrigine (Lamictal): Used in Lennox-Gastaut syndrome, bipolar disorder, and generalized seizures.
  • Risk of Stevens-Johnson Syndrome; titrate slowly.
• Levetiracetam (Keppra): Used as adjunctive therapy.
  • May cause behavioral effects such as agitation or hostility.
  • Requires no routine serum level monitoring.
  • Well-tolerated with low interaction risk.
• Valproic Acid (Depakote): Used for generalized and focal seizures, as well as bipolar disorder.
  • Contraindicated in liver disease.
  • Adverse effects: Hepatotoxicity, pancreatitis, GI upset, and weight gain.
• Topiramate (Topamax): Used for seizures, drop attacks, and migraines.
  • Adverse effects: Vision changes, sedation, and cleft palate risk during pregnancy.
  • Titrate slowly.

Emergency AEDs for Status Epilepticus

• Lorazepam (Ativan): first-line IV treatment.
• Diazepam (Valium): Can be administered IV, rectally, or nasally.
  • Adverse effects: Apnea, somnolence, and hypotension.

Parkinson’s Disease Pharmacology

• Parkinson's disease is caused by dopamine deficiency in the substantia nigra.
• Classic symptoms: Tremor, Rigidity, Akinesia (bradykinesia), and Postural instability (TRAP).
• Drug Classes:
  • MAO-B Inhibitors (e.g., Selegiline, Rasagiline): Prevent dopamine breakdown and have fewer food interactions than MAO-A inhibitors.
  • Dopamine Modulator (Amantadine/Symmetrel): Increases dopamine release and is also used as an antiviral.
  • COMT Inhibitor (Entacapone): Prevents levodopa breakdown and extends its effect.
  • Levodopa-Carbidopa: Carbidopa prevents peripheral metabolism of levodopa.
    • Avoid B6 which reduces effectiveness.
    • Avoid in patients with melanoma or glaucoma.
  • Anticholinergics (e.g., Benztropine, Atropine, Oxybutynin, Scopolamine): Reduce acetylcholine to restore dopamine balance.
    • Adverse effects: Dry mouth, blurry vision, urinary retention, and tachycardia.
    • Avoid in elderly patients and those with glaucoma or BPH.