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NSAIDs

In this article, we will discuss the role of NSAIDs in preventive analgesia

NSAIDs

NSAIDs play a central role in preventive analgesia regimens. They reduce both inflammation and analgesia requirements. NSAIDs inhibit COX enzymes. COX-1 is a constitutive enzyme (always present) whilst COX-2 an inducible enzyme (in response to tissue injury). Inhibition of COX-1 and COX-2 results in decreased prostaglandin production. Prostaglandins are involved in the processes that result in signs and symptoms of acute inflammation. They are typically very well tolerated but we should proceed with caution in certain cohorts.

Uses:

  • Mild to moderate pain
  • Reduce opioid consumption in the perioperative period

Benefits

  • Analgesia
  • Reduce perioperative opioid consumption
  • Anti-inflammatory

Ibuprofen

  • Non-selective propionic acid derivative
  • No IV formulation available
  • Oral dosing
    • Adults: 400mg TDS
    • Paediatric: 10mg/kg TDS
  • Bioavailabilty ~ 100%
  • Onset of action 30 minutes
  • Peak plasma level ~2 hours
  • Elimination half life ~2-4 hours
  • Relative weak anti-inflammatory effects

Ketorlac

  • Non-selective acetic acid derivative
  • PO, IM, IV
  • Perioperative dosing
    • Adults: 15-30mg
    • Paediatric: 0.6mg/kg
  • PO/IM bioavailability 80-100%
  • Onset of action ~ 30 minutes
  • Peak plasma level: PO ~ 20-60 minutes, IM ~ 30-50 minutes, IV ~ 3-5 minutes
  • Elimination half-life 5 hours
  • Potent analgesic and anti-pyretic but weak anti-inflammatory action

Diclofenac

  • Non-selective pheylacetic acid derivative
  • PO, PR, IV
  • Dosinsg
    • Adult: 150mg daily in divided doses
    • Paediatric: 1mg/kg TDS
  • PO/PR bioavailability 50-60% (routes subject to 1st pass metabolism)
  • Onset of action ~ 30 minutes
  • Peak plasma level: PO ~ 60 minutes, IM~ 20-30 minutes, IV determined by rate of infusion
  • Elimination half-life 1-2 hours

Caution diclofenac is a venous irritant that may cause thrombophlebitis

Celecoxib

  • Selective COX-2 derivative
  • PO
  • Dosinsg
    • Adult: 200mg daily (can give 400mg preoperatively)
    • Paediatric: 4mg/kg daily
  • PO bioavailability 40%
  • Onset of action ~ 40 minutes
  • Peak plasma level: PO ~ 2-3 hours
  • Elimination half-life 8-12 hours

Parecoxib

  • Selective COX-2 derivative
  • IM/IV
  • Dosinsg
    • Adult: 40mg stat then 20-40mg BD
    • The safety and efficacy of parecoxib in children under 18 years old have not been established.
  • Prodrug of valdecoxib
  • Onset of action ~ 15-30 minutes
  • Peak plasma level: valdecoxib ~ 1.5 hours
  • Elimination half-life: parecoxib ~ 20 minutes , valdecoxib ~ 8 hours

Kinetics:

  • NSAIDs in general are well absorbed from the gut
  • Some are subject to first pass metabolism
  • Half-life 4 hours increases in renal impairment
  • Highly protein binding 99%: may displace other highly protein-bound drugs potentiating their effects
  • Hepatic metabolism
  • Excreted in an inactive form in the urine and bile

Caution:

  • Gastric: ulcers, GI bleeding
  • Myocardial infarction
  • NSAID induced asthma
  • Renal impairment
  • Bleeding

COX-1 is also involved in the control of renal blood flow and the formation of gastric mucosa protective barrier. Therefore, selective inhibition of COX-2 should result in fewer unwanted side effects but the intricate thromboxane/prostacyclin balance may be altered favouring platelet aggregation and thromboembolism.

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