- Clinical science
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.
|Common agents||Activity profile||Side effects|
|Nonsteroidal anti-inflammatory drugs (NSAID)|
|COX-2 inhibitors (selective NSAID)|| || || |
|Other non-opioid analgesics|| |
Mechanism of action
- Reversible inhibition of the enzymes cyclooxygenase 1 and 2 (COX-1 and COX-2) → decreased prostaglandin synthesis
- Anti-inflammatory (antirheumatic)
- With the exception of aspirin, only minor antiplatelet function
Gastric and duodenal ulcers with the risk of gastrointestinal bleeding and perforation
- Risk increases with duration and dose of treatment
- Prophylaxis: simultaneous administration of proton pump inhibitors
- Increased risk of heart attack and stroke (with the exception of aspirin and naproxen)
- Renal function impairment: prostaglandins normally maintain renal blood flow by inducing vasodilation of the afferent arterioles. NSAIDS inhibit prostaglandin production, which leads to harmful hypoperfusion of the kidneys and reduced GFR.
- Pseudoallergic reactions
- For side effects of aspirin, see .
The risk of an ulcer is 10–15 times higher if NSAIDS and glucocorticoids are administered simultaneously!
- Acute and chronic pain (particularly musculoskeletal)
- Gastroduodenal ulcers
- Acute hemorrhage (especially )
- Renal failure
- Recent myocardial infarction, unstable angina, heart failure
- Surgery: discontinue NSAIDs 1–3 days prior to surgery
- Avoid NSAIDs during pregnancy!
- Celecoxib (Celebrex®)
- Analgesic and anti-inflammatory
Advantages in comparison to nonselective NSAIDs
- No antiplatelet effect
- Minimal gastrointestinal side effects
- Increased risk of heart attack and stroke
- Renal side effects in at-risk patients
- Acute pain, rheumatoid arthritis, nonrheumatoid joint pain
- Especially as an alternative to nonselective NSAIDs for patients with a history of peptic ulcer disease and platelet disorders (e.g., Glanzmann thrombasthenia)
- Reversibly inhibits cyclooxygenase in the CNS → antipyretic and analgesic effects
- Is peripherally inactivated → no anti-inflammatory effect, minimal gastric 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
- Exhaustion of hepatic metabolic pathways causes increased formation of a toxic metabolite of acetaminophen, N-acetyl-p-benzoquinoneimine (NAPQI).
- Nonspecific symptoms (nausea, vomiting, pallor lethargy) or asymptomatic in the first 24 hours after ingestion
- Progressive liver impairment (RUQ pain; , liver enlargement and tenderness, abnormal liver function tests)
- If acute liver failure does not develop, patients typically begin to recover within 2 weeks after ingestion.
- Acute kidney failure occurs in approx. 50% of patients with acute hepatic failure.
- Severe liver impairment
Maximum daily dose of acetaminophen: 4 g (adults)!