ANALGESICS - Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Drug Class: antipyretics, analgesics, anti-inflammatory, anti-platelets

Drugs:

• ASA
• Non-selective NSAIDs—diclofenac [Voltaren], ibuprofen [Advil, Motrin], indomethacin [Indocin], naproxen [Anaprox, Naprosyn]
• COX-2 selective NSAIDs—celecoxib [Celebrex]

Mechanism of Action & Indications

• All act by inhibition of prostaglandin formation by cyclooxygenase (COX), which converts the substrate arachidonic acid. COX-1 is present in gastric mucosa and platelets, while COX-2 is present in inflamed tissue and the afferent arteriole of the kidney.
• For the treatment of mild to moderate pain and fever. Also for inflammation associated with non-infectious causes, usually of MSK origin, but also of pericarditis or pleuritis. Other specific indications include the use of low dose ASA for platelet inhibition.

Common Dosages

• Celecoxib 100-200mg PO BID
• Diclofenac 50mg PO BID-TID
• Diclofenac topical 1.5, 2, or 5% apply BID over affected area
• Ibuprofen 300-800mg PO TID-QID
• Indomethacin 25-50mg PO BID-TID

Adverse Effects & Contraindications

• Gastric ulcer, gastritis, or GI discomfort. The degree of GI side effects variesdepending on which class of NSAID drug is used (i.e. indomethacin>ASA>ibuprofen).
• Hypertension, fluid retention, renal dysfunction, interstitial nephritis.
• Impaired platelet function.
• Hypersensitivity with angioedema, hives, and bronchospasm.
• Less commonly causes abnormal liver function tests.
• Recent reports of COX-2 selective inhibitors and other NSAIDs increasing cardiovascular risk. Use with caution in patients at risk of cardiovascular diseases. Benefits of these agents should to be weighed against the potential adverse effects.

      Contra-indications include:

• Hypersensitivity (ASA sensitivity): severe reactions to one are frequentlyassociated with cross reaction to all NSAIDs, particularly in asthmatics.
• Significant renal impairment, hypertension, or CHF. All may lead to an increase in creatinine, increase in blood pressure, fluid and salt retention, and hyperkalemia, particularly at higher doses.
• Active acid peptic disease.

Practical Tips

• ASA is the prototype. It has unique, irreversible effects at low doses on platelets. Other non-specific NSAIDs (diclofenac, naproxen, and indomethacin) have reversible platelet effects. COX-2 selective inhibitors (celecoxib, valdecoxib) do not cause platelet inhibition, and less risk for gastric ulceration.

• Topical diclofenac is safer than oral as only a small quantity is systemically absorbed.

Interactions:

• May reverse the therapeutic effect of some anti-hypertensive medications (thiazide, β-blockers, ACE inhibitors, ARBs). With concurrent ACE inhibitor use,there is also a risk of hyperkalemia and acute renal failure.
• Increased risk of bleeding with anti-coagulants.
• Increased risk of lithium toxicity

Written by Stephen Aaron; reviewed by Raj Padwal and Jeff Whissell