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.

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Overview
Common agents Activity Side effects
profile
Nonsteroidal anti- Ibuprofen Analgesic Gastric and intestinal ulcers,
inflammatory drugs Diclofenac Antipyretic bleeding, and perforation
(NSAID) Indomethacin Anti- Renal function impairment
Naproxen inflammatory Acute renal failure
Ketorolac Antiplatelet Deterioration of chronic renal
Aspirin effect failure
Chronic analgesic nephropathy
Increased risk of heart attack
and stroke (with the exception
of aspirin and naproxen)
COX-2 inhibitors Analgesic Increased cardiovascular risk
Celebrex (celecoxib)
(selective NSAID) Anti- Renal side effects
Deterioration of chronic renal
inflammatory
failure
Increase in blood pressure
Minimal gastrointestinal
toxicity
Other non- Acetaminophen Analgesic Hepatotoxicity
opioid analgesics Antipyretic Acute liver failure in cases of
intoxication
Limited nephrotoxicity
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Nonsteroidal anti-inflammatory drugs

Agents
Ibuprofen, diclofenac, indomethacin, naproxen, aspirin

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
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
Electrolyte and fluid abnormalities (edema, hyperkalemia, hyponatremia)
Worsening of hypertension
In rare cases, acute renal failure
Analgesic nephropathy: prolonged NSAID use results in tubulointerstitial
nephritis and papillary necrosis ( crea/BUN ratio, slight K+)
Pseudoallergic reactions
Urticaria and angioedema
Asthma
Aspirin-exacerbated respiratory disease (AERD)
For side effects of aspirin, see aspirin.

The risk of an ulcer is 1015 times higher if NSAIDS and glucocorticoids are administered
simultaneously!
Indications
Acute and chronic pain (particularly musculoskeletal)
Rheumatoid arthritis
Inflammatory arthritis
Kawasaki disease
Acute gout attack
Post-operative pain
Dysmenorrhoea
Headache, migraine
Fever

Contraindications
Gastroduodenal ulcers
Acute hemorrhage (especially aspirin)
Renal failure
Recent myocardial infarction, unstable angina, heart failure
Surgery: discontinue NSAIDs 13 days prior to surgery
Avoid NSAIDs during pregnancy!

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

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Selective COX-2 Inhibitors

Agent
Celecoxib (Celebrex)

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

Side effects
Increased risk of heart attack and stroke
 Renal side effects in at-risk patients
Deterioration of chronic renal failure
Worsening of hypertension

Indications
Acute pain, rheumatoid arthritis, nonrheumatoid joint pain

Contraindications
Severe heart failure, recent myocardial infarction, gastrointestinal bleeding

References: [7][8][9][10]

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Other Non-opioid analgesics

Agent
Acetaminophen

Effect
Antipyretic and analgesic

Side effects
Gastrointestinal: nausea, vomiting
Hepatotoxicity with acetaminophen overdose
Minimum toxic dose: 7.5 g/day in adults
Leading cause of acute hepatic failure in the US
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
Management
 Activated charcoal administered < 4 hours after ingestion
Antidote: PO or IV N-acetylcysteine (NAC)
Treatment of liver failure
Liver transplant in severe cases

Indications
Fever and pain
Good tolerability
Preferred analgesic/antipyretic drug during pregnancy

Contraindications
Severe liver impairment

Maximum daily dose of acetaminophen: 4 g (adults)!