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Aetiopathogenesis of Epilepsy and Classification of Antiepileptic Drugs

Aetiopathogenesis of Epilepsy

Epilepsy is a neurological disorder characterized by recurrent, unprovoked seizures due to abnormal electrical activity in the brain. The aetiopathogenesis of epilepsy can be divided into several factors, which include genetic, structural, metabolic, and environmental causes.

  • Genetic Factors: Specific mutations in genes encoding ion channels may predispose individuals to seizures.
  • Structural Factors: Brain abnormalities, such as cortical malformations, tumors, and head trauma, may lead to epilepsy.
  • Metabolic Factors: Imbalances in electrolytes, glucose, or other metabolic conditions can trigger seizures.
  • Environmental Factors: Exposure to toxins, alcohol withdrawal, or sleep deprivation can precipitate seizures.

The abnormal electrical discharges during a seizure typically originate from a hyperexcitable neuronal network, which can be triggered by the aforementioned factors.

Classification of Antiepileptic Drugs (AEDs)

Sodium Channel Blockers

  • Examples: Phenytoin, Carbamazepine, Lamotrigine, Valproate
  • Mechanism of Action: These drugs inhibit voltage-gated sodium channels, reducing neuronal excitability and preventing seizure propagation.
  • Therapeutic Uses: Effective in focal seizures, generalized tonic-clonic seizures, and partial seizures. Carbamazepine is used for focal seizures, and Lamotrigine is used for both generalized and focal seizures.
  • Adverse Effects:
    • Phenytoin: Gingival hyperplasia, hirsutism, ataxia, osteomalacia.
    • Carbamazepine: Drowsiness, dizziness, hyponatremia, rash.
    • Lamotrigine: Skin rash, dizziness, headache.
  • Contraindications:
    • Phenytoin: Contraindicated in patients with bradycardia or heart block.
    • Carbamazepine: Contraindicated in patients with bone marrow suppression or hypersensitivity.
    • Lamotrigine: Caution in patients with a history of skin reactions or hepatic impairment.

GABAergic Drugs

  • Examples: Benzodiazepines (e.g., Diazepam, Lorazepam), Phenobarbital, Valproate
  • Mechanism of Action: Enhance GABA activity, leading to increased inhibition of neuronal firing.
  • Therapeutic Uses: Benzodiazepines are used in acute seizures, while Phenobarbital and Valproate are used for long-term management of generalized seizures.
  • Adverse Effects:
    • Benzodiazepines: Sedation, memory impairment, tolerance.
    • Phenobarbital: Drowsiness, cognitive impairment, respiratory depression.
    • Valproate: Weight gain, hepatotoxicity, teratogenicity.
  • Contraindications:
    • Benzodiazepines: Caution in elderly patients due to falls and fractures.
    • Phenobarbital: Contraindicated in patients with respiratory failure or drug abuse history.
    • Valproate: Contraindicated in liver disease and pregnancy.

Calcium Channel Blockers

  • Examples: Ethosuximide, Gabapentin
  • Mechanism of Action: These drugs inhibit T-type calcium channels in the thalamus, preventing absence seizures.
  • Therapeutic Uses: Ethosuximide is used for absence seizures, and Gabapentin is used as an adjunct in focal seizures.
  • Adverse Effects:
    • Ethosuximide: Drowsiness, nausea, anorexia.
    • Gabapentin: Dizziness, peripheral edema, weight gain.
  • Contraindications:
    • Ethosuximide: Caution in liver or renal impairment.
    • Gabapentin: Caution in renal impairment.

Glutamate Receptor Inhibitors

  • Examples: Felbamate, Topiramate
  • Mechanism of Action: Inhibit glutamate receptors (NMDA and AMPA), reducing excitatory neurotransmission.
  • Therapeutic Uses: Felbamate is used for refractory seizures, and Topiramate is used for focal and generalized seizures.
  • Adverse Effects:
    • Felbamate: Aplastic anemia, weight loss.
    • Topiramate: Cognitive dysfunction, kidney stones, weight loss.
  • Contraindications:
    • Felbamate: Contraindicated in patients with liver failure or blood dyscrasias.
    • Topiramate: Caution in patients with kidney stones or metabolic acidosis.

Other AEDs

  • Examples: Levetiracetam, Lacosamide
  • Mechanism of Action: Levetiracetam binds to SV2A to prevent neurotransmitter release, and Lacosamide enhances slow sodium channel inactivation.
  • Therapeutic Uses: Levetiracetam is used for focal and generalized seizures, and Lacosamide is used for focal onset seizures.
  • Adverse Effects:
    • Levetiracetam: Irritability, somnolence, dizziness.
    • Lacosamide: Dizziness, headache, nausea.
  • Contraindications:
    • Levetiracetam: Caution in renal impairment.
    • Lacosamide: Caution in patients with cardiac conduction disorders.