Neuromodulators

Neuromodulators

Gabapentinoids, a class of drugs that are derivatives of the inhibitory neurotransmitter gamma-aminobutyric acid, play an important role in multi-modal analgesia. The most commonly encountered drugs in this class are gabapentin and pregabalin. They are structural analogues of GABA but no activity at the GABA receptor. Patients age, comorbidities and renal function should be considered when deciding the starting dose.

Their precise mechanism of action is unknown – Primary effects are likely via the inhibition of voltage-gated calcium channels – Stimulate descending noradrenergic pain inhibiting pathways – Inhibit descending serotonergic facilitation pathways – Inhibit inflammatory mediators – Alter the emotional component of pain

Uses:

• Neuropathic pain
• Anticonvulsant
• Reduce opioid consumption in the perioperative period
• Reduce anxiety (pregabalin)

Benefits

• Reduce the incidence of chronic postoperative pain
• Reduce perioperative opioid consumption
• Anxiolysis (pregabalin)

Gabapentin

• Suggested dosing
  • 300-600mg preoperatively
  • 300-600mg up to 3 times a day for up to 2 weeks
  • Maximum daily dose 1800mg
• Absorption is saturatable therefore bioavailability is dose dependent (LAT1 transporter)
  • 900mg/day ~ 60%
  • 3600mg/day ~ 33%
• Anracids can significantly impair absorbtion
• Peak plasma level ~ 2 hours
• Elimiation half life ~ 5-7 hours markedly increased in renal impairment
• Low protein binding <3%
• No significant metabolisim
• Renally excreted

Pregablin

• Suggested dosing
  • 50-150mg preoperatively
  • 50-150mg up to three times a day for up to 2 weeks
  • Maximum daily dose 600mg
• Bioavailability >90% dose-independent
• Peak plasma level ~ 1.5 hours (fasted), 3 hours (unfasted)
• Elimination half-life ~ 6 hours markedly increased in renal impairment
• Not protein-bound
• No significant metabolisim
• Really excreted

Caution:

• Neurological side effects: sedation, dizziness, headache and visual disturbance
• Early mobilisation
• Renal dysfunction (decrease dose)
• Peripheral oedema (gabapentin)

These drugs have sedative effects and are best administered at night. Significant delay in wake-up from TIVA can be seen if too high a dose is given preoperatively.