Adjuvant analgesics

Adjuvant Analgesics - The Pain Sidekicks

• Drugs with primary indications other than pain, but effective in managing pain, especially neuropathic pain.
• Key Classes & Agents:
  • Antidepressants:
    • TCAs: Amitriptyline, Nortriptyline
    • SNRIs: Duloxetine, Venlafaxine
  • Anticonvulsants:
    • Gabapentinoids: Gabapentin, Pregabalin (for diabetic neuropathy, postherpetic neuralgia)
    • Carbamazepine (for trigeminal neuralgia)
  • Topical Agents: Lidocaine patch, Capsaicin
  • Corticosteroids: Dexamethasone (for cancer-related pain)

⭐ Carbamazepine is the first-line treatment for trigeminal neuralgia.

Antidepressants - More Than Mood

• TCAs (Amitriptyline, Nortriptyline):

  • Inhibit norepinephrine (NE) & serotonin (5-HT) reuptake.
  • Effective for neuropathic pain (diabetic neuropathy, postherpetic neuralgia).
  • ⚠️ Caution: Strong anticholinergic/antihistaminic effects (sedation, dry mouth), cardiotoxicity in overdose. 📌 Overdose "Tri-C's": Coma, Convulsions, Cardiotoxicity.

• SNRIs (Duloxetine, Venlafaxine):

  • Also inhibit NE & 5-HT reuptake, but with fewer side effects than TCAs.
  • Broad application for neuropathic pain, fibromyalgia, and chronic musculoskeletal pain.

⭐ Duloxetine is FDA-approved for both depression and multiple pain syndromes, a key choice for comorbid conditions.

Anticonvulsants - Calming Nerve Storms

Primarily for neuropathic pain, these drugs reduce neuronal hyperexcitability.

• Gabapentinoids (Gabapentin, Pregabalin)

  • MOA: Bind to the α2δ-1 subunit of voltage-gated Ca²⁺ channels, decreasing neurotransmitter release.
  • Uses: First/second-line for diabetic neuropathy, postherpetic neuralgia, and fibromyalgia (Pregabalin).

• Carbamazepine & Oxcarbazepine

  • MOA: Block voltage-gated Na⁺ channels.
  • Uses: First-line therapy for trigeminal neuralgia.

⭐ High-Yield: Carbamazepine is notorious for inducing agranulocytosis and Stevens-Johnson syndrome (SJS), especially in patients with the HLA-B*1502 allele. Genetic screening is often recommended before initiation.

Other Agents - Specialists & Topicals

• Ketamine

  • Mech: NMDA receptor antagonist; blocks excitatory glutamate transmission.
  • Use: Anesthetic, procedural sedation, treatment-resistant depression, acute pain.
  • SEs: Dissociative state, hallucinations, emergence delirium, ↑BP, ↑HR.

• Topical Agents

  • Lidocaine 5% Patch:
    • Mech: Blocks voltage-gated Na+ channels, inhibiting nerve impulse initiation.
    • Use: Postherpetic neuralgia (PHN), localized neuropathic pain.
  • Capsaicin Patch/Cream:
    • Mech: TRPV1 agonist. Causes initial release then depletion of substance P in nociceptive fibers.
    • Use: PHN, diabetic neuropathy, osteoarthritis.

⭐ Ketamine has emerged as a rapid-acting antidepressant for treatment-resistant depression, with effects seen within hours of a single infusion.

• Gabapentin and pregabalin are first-line agents for neuropathic pain (e.g., diabetic neuropathy, postherpetic neuralgia) by blocking presynaptic voltage-gated Ca²⁺ channels.
• TCAs (amitriptyline) and SNRIs (duloxetine) are also first-line for neuropathic pain, inhibiting norepinephrine and serotonin reuptake.
• Carbamazepine is the drug of choice for trigeminal neuralgia.
• Corticosteroids (e.g., dexamethasone) reduce pain from inflammation and nerve compression, especially in cancer patients.
• Ketamine, an NMDA receptor antagonist, is used for complex, refractory pain syndromes.