Antidepressants and Antiepileptic Medications

Antidepressants

Tricyclic Antidepressants (TCAs) have a core of condensed 3-rings, a side chain, and amine ends. The introduction of oxygen and nitrogen in the core and the branched side chain are associated with antidepressant action, and the introduction of halogens increases this action. These drugs are well absorbed orally but have low bioavailability. They can also be administered intramuscularly. They tend to bind to plasma proteins and are easily metabolized. TCAs are typically administered twice a day.

Adverse Reactions:

• Cardiovascular: Hypotension, palpitations, tachycardia.
• Anticholinergic: Dry mouth, constipation, urinary retention, nasal congestion, blurred vision (glaucoma).
• Neurological: Confusion, hallucinations, tremors of the hand and head.
• Other: Weight gain, excessive sweating, skin rash.

Poisoning: May present with arrhythmias, convulsions, and coma.

Uses:

• Depressive syndromes
• Anxiety
• Pain (particularly chronic cancer pain and headaches)
• Nocturnal enuresis (urinary incontinence)

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs were initially used to irreversibly inhibit monoamine oxidase (MAO). They were largely replaced by TCAs, but recently, they are being re-evaluated for patients who respond poorly to TCAs. There are two MAO isoenzymes (type A and type B), and therefore two types of inhibitors:

• Nonselective inhibitors of type A and B: Iproniazid (a hydrazine derivative) and Pargyline (a non-hydrazine derivative).
• Selective inhibitors: Clorgyline (MAO-A), Deprenyl (MAO-B), Moclobemide, Brofaromine, and Toloxatone. The last three have a non-irreversible inhibition.

Antiepileptic Drugs

Epilepsy is a chronic disease characterized by synchronous, paroxysmal, uncontrolled discharges of a neuron or neuronal group. It can be classified into:

• Focal or partial epilepsy: Discharge is localized.
• Generalized epilepsy: Discharge involves the rest of the neighboring structures, and there is always a loss of consciousness.

Antiepileptic drugs work by blocking sodium (Na) channels, blocking calcium (Ca) channels, and/or affecting GABA involvement.

Generations of Antiepileptic Drugs

• Classic First-Generation Antiepileptic Drugs:
  • Phenobarbital (increases the action of GABA, causing CNS depression)
  • Phenytoin (blocks Na channels)
  • Ethosuximide (affects Ca channels)
  • Primidone (CNS depression similar to GABA)
• Classic Second-Generation Antiepileptics: These are typically used first. If the treatment is ineffective, first-generation drugs may be considered.
  • Carbamazepine (blocks Na channels)
  • Valproate (affects all mechanisms of action: Na and Ca channels, and GABA)
  • Benzodiazepines
• New Antiepileptics:
  • Felbamate (restricted use due to severe hepatotoxicity and bone marrow suppression)
  • Gabapentin (similar to GABA)
  • Lamotrigine (blocks Na channels)
  • Vigabatrin (increases the activity of GABA)