• Clinical science

Non-opioid analgesics

Abstract

Non-opioid analgesics include nonsteroidal anti-inflammatory drugs (NSAIDs), selective COX-2 inhibitors, and acetaminophen. NSAIDs inhibit cyclooxygenases (COX-1 and COX-2), thereby disrupting the production of prostaglandin, an important mediator of pain and inflammation. Consequently, NSAIDs possess antipyretic, analgesic, and anti-inflammatory effects, and are particularly effective in the management of musculoskeletal pain (e.g., rheumatic disorders, inflammatory joint pain). Side effects include gastrointestinal ulcers and bleeding, increased risk of heart attacks, and renal function impairment. The severity of these side effects is often underestimated because most non-opioid analgesics are easily available OTC. Selective COX-2 inhibitors have similar effects to NSAIDs, but show a lower risk for gastrointestinal side effects. Acetaminophen possesses antipyretic and analgesic effects and is the most commonly used over-the-counter (OTC) oral analgesic drug. It is generally well tolerated, but overdose can result in significant hepatotoxicity with the risk of acute liver failure.

Overview

Common agents Activity profile Side effects
Nonsteroidal anti-inflammatory drugs (NSAID)
  • Analgesic
  • Antipyretic
  • Anti-inflammatory
  • Antiplatelet effect
COX-2 inhibitors (selective NSAID)
  • Analgesic
  • Anti-inflammatory
  • Increased cardiovascular risk
  • Renal side effects
Other non-opioid analgesics
  • Analgesic
  • Antipyretic

References:[1]

Nonsteroidal anti-inflammatory drugs

Agents

Mechanism of action

  • Reversible inhibition of the enzymes cyclooxygenase 1 and 2 (COX-1 and COX-2) decreased prostaglandin synthesis

Effects

  • Analgesic
  • Antipyretic
  • Anti-inflammatory (antirheumatic)
  • With the exception of aspirin, only minor antiplatelet function

Side effects

The risk of an ulcer is 10–15 times higher if NSAIDS and glucocorticoids are administered simultaneously!

Indications

Contraindications

References:[1][2][3][4][5][6][7][8]

Selective COX-2 Inhibitors

Agent

Effect

  • Analgesic and anti-inflammatory
  • Advantages in comparison to nonselective NSAIDs
    • No antiplatelet effect
    • Minimal gastrointestinal side effects

Side effects

Indications

Contraindications

References:[9][10][11][12][13][14]

Other Non-opioid analgesics

Agent

Effect

  • Reversibly inhibits cyclooxygenase in the CNSantipyretic and analgesic effects
  • Is peripherally inactivated → no anti-inflammatory effect, minimal gastric side effects

Side effects

  • Hepatotoxicity due to acetaminophen overdose
    • Minimum toxic dose: 7.5 g/day in adults
    • Leading cause of acute hepatic failure in the US
    • Pathophysiology
      • Exhaustion of hepatic metabolic pathways causes increased formation of a toxic metabolite of acetaminophen, N-acetyl-p-benzoquinoneimine (NAPQI).
        • Glutathione initially inactivates NAPQI, but its reserves are eventually depleted, leading to NAPQI build-up.
        • NAPQI causes irreversible oxidative hepatocyte injury → liver cell necrosis.
    • Clinical features
    • Management
      • Activated charcoal; (oral 1 g/kg (maximum dose 50 g)) administered < 4 hours after ingestion
      • Antidote; : PO or IV N-acetylcysteine (NAC)
      • Measure acetaminophen (APAP) levels 4 hours after ingestion (or immediately, if ingestion occurred > 4 hours prior to presentation)
      • Treatment of liver failure
      • Liver transplant in severe cases

Indications

Contraindications

  • Severe liver impairment

Maximum daily dose of acetaminophen: 4 g (adults)and 80 mg/kg (children)!;
References:[15][16][17][18]