Pharmacology I: Anti-Seizure Medications

Seizures, Epilepsy, and Convulsions

• Seizures result from excessive, hypersynchronous cortical neuron activity.
• Epilepsy is a chronic disorder marked by unpredictable seizure occurrences.
• Symptomatic epilepsy arises from identifiable causes like brain injury or tumors.
• Idiopathic epilepsy has no structural abnormalities and is often genetic.
• Convulsions are involuntary muscle contractions; seizures can occur without them (e.g., petit mal).

Classification of Seizures

• Focal Onset Seizures affect localized cortical areas:

  • Focal aware (simple partial): consciousness remains intact.
  • Focal impaired (complex partial): consciousness impaired.
  • Focal-to-Bilateral Tonic-Clonic: starts focal, progresses to generalized tonic-clonic.

• Generalized Onset Seizures affect both brain hemispheres:

  • Generalized Tonic-Clonic (Grand mal): involves both hemispheres, often idiopathic.
  • Generalized Absence (Petit mal): brief consciousness loss common in children.
  • Myoclonic: sudden brief muscle contractions, seen in juvenile seizures.
  • Atonic (drop seizure): sudden loss of muscle tone, common in Lennox-Gastaut syndrome.
  • Epileptic spasms: infantile spasms with grimacing and head nodding.

Treatment of Epilepsy

• Oral anti-seizure medications are tailored to the patient’s seizure type.
• Single medication is preferred; adults may require multiple for hard-to-control seizures.
• Pharmacoresistant epilepsy is when seizures are inadequately controlled.
• Epilepsy surgery can resect affected brain areas, used for focal and generalized seizures and status epilepticus.
• Side effects include CNS effects (nystagmus, ataxia, diplopia) and others like gingival hyperplasia, hirsutism, osteopenia, and anemia.

Phenobarbital

• Increases GABAergic inhibition, enhancing Cl-channel opening duration.
• Metabolized in the liver and mainly excreted in urine; can induce liver enzyme changes impacting other drugs.
• Clinical use includes focal unaware, generalized tonic-clonic, and febrile seizures.
• Toxicity signs include respiratory depression; can lead to dependence and tolerance.

Antipsychotic Agents

• Schizophrenia affects 1% of the population and is marked by thinking and perceptual disturbances.
• Three main hypotheses of schizophrenia:
  • Serotonin hypothesis: abnormal 5-HT2A and 5-HT2C transmission leads to hallucinations.
  • Dopamine hypothesis: hyperactivity in mesolimbic dopamine affects positive symptoms.
  • Glutamate hypothesis: NMDA receptor hypoactivity results in cognitive impairment.

Symptoms of Schizophrenia

• Positive Symptoms: Observable traits like delusions, hallucinations, and combativeness.
• Negative Symptoms: Unobservable traits like affective flattening, alogia, avolition, anhedonia, and attention issues.

Clinical Use of Antipsychotic Agents

• Used for acute bipolar depression, agitation in bipolar disorder, Tourette syndrome, and autism spectrum disorder.
• First-generation antipsychotics (except Thioridazine) have strong anti-emetic effects and produce sedation.

Adverse Effects of Antipsychotic Agents

• Behavioral effects: EPS (extrapyramidal symptoms), pseudodepression, tardive dyskinesia, seizures (from Chlorpromazine).
• ANS and cardiovascular effects: sedation, orthostatic hypotension, dry mouth, constipation.
• Metabolic effects: weight gain, hyperglycemia, and hyperlipidemia.
• Neuroleptic Malignant Syndrome is a serious adverse reaction to high-potency antipsychotics.