• Clinical science

Non-opioid analgesics

Summary

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)
COX-2 inhibitors (selective NSAID)
  • Increased cardiovascular risk
  • Renal side effects
Other non-opioid analgesics

Nonsteroidal anti-inflammatory drugs

Agents

Mechanism of action

Effects

Side effects

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

Indications

Contraindications

NSAIDs are contraindicated in the second and third trimester as they may cause premature closure of the ductus arteriosus. Furthermore, they can inhibit uterine contractility.

References:[1][9][2][4][6][10][11][5][12]

Selective COX-2 Inhibitors

Agent

Mechanism of action

Effects

  • Analgesic and anti-inflammatory
  • Advantages in comparison to nonselective NSAIDs
    • No antiplatelet effect: platelets only possess COX-1 and are therefore not targeted by selective COX-2 inhibitors. This means that the activity of thromboxane A2 (TXA2) is not interrupted (TXA2 normally promotes platelet aggregation).
    • Gastric mucosal cells express mostly COX-1, which is involved in maintaining a healthy gastric mucosa, so there are minimal gastrointestinal side effects and a lower risk of gastric ulcers.

Side effects

Indications

Contraindications

To remember the effect of celecoxib, think: “seleCOXib = selective COX-2 inhibition”.

References:[14][13][15][16][17][18]

Other non-opioid analgesics

Agent

Mechanism of action

Effects

Side effects

Indications

Contraindications

  • Severe liver impairment

Maximum daily dose of acetaminophen: 4 g (adults)!
References:[19][20][21][17]