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 of non-opioid analgesics|
|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 COX-1 and COX-2 → decreased prostaglandin synthesis
- Aspirin is the exception, because it leads to irreversible COX-1 and COX-2 inhibition. (See for more information.)
- Anti-inflammatory (antirheumatic)
- Minor antiplatelet function (with the exception of aspirin)
- Gastric and duodenal ulcers with the risk of gastrointestinal bleeding and perforation (inhibition of COX disrupts the production of protective gastric mucosal prostaglandins)
- 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. ; 
- Aplastic anemia 
- Pseudoallergic reactions 
- For side effects of aspirin, see .
- Acute and chronic pain (particularly musculoskeletal)
- Indomethacin: closure of a patent ductus arteriosus
- See aspirin. for specific indications of
- 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 
Mechanism of action
- Reversible selective inhibition of COX-2 with almost no inhibition of COX-1
- COX-2 is found in:
- 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.
- Increased risk of thrombosis, MI, and/or stroke
- allergic reaction
- Renal side effects in at-risk patients
- Rheumatoid arthritis, osteoarthritis, acute pain, 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)
Other non-opioid analgesics
Mechanism of action
- Minimal gastric side effects
Hepatotoxicity due to acetaminophen overdose (drug-induced hepatitis)
- 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).
- Clinical features
- 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.
- Activated charcoal; administered < 4 hours after ingestion
- Measure acetaminophen (APAP) levels 4 hours after ingestion (or immediately, if ingestion occurred > 4 hours prior to presentation)
Antidote: PO or IV N-acetylcysteine (NAC)
- Administered 4–24 hours after ingestion
- NAC replenishes glutathione stores in the liver
- Serum acetaminophen level above the treatment line when measured 4 hours after ingestion
- Single ingestion of acetaminophen > 150 mg/kg (7.5 g irrespective of patient weight) if the acetaminophen level cannot be assessed within 8 hours of ingestion
- History of acetaminophen ingestion with signs of liver injury
- High serum acetaminophen level (> 10 mcg/mL) with an unknown time of ingestion
- Treatment of liver failure
- Liver transplant in severe cases
- Fever and pain
- Severe liver impairment
Maximum daily dose of acetaminophen: 4 g (adults).