NSAIDs Overview

Overview of NSAIDs

• Nonsteroidal Anti-inflammatory Drugs (NSAIDs) vary chemically and in their therapeutic effects—antipyretic, analgesic, and anti-inflammatory.
• Common NSAID classes include:
  • Salicylic acid: aspirin, diflunisal, salsalate
  • Propionic acid: ibuprofen, naproxen, flurbiprofen
  • Acetic acid: diclofenac, indomethacin, sulindac
  • Enolic acid: meloxicam, piroxicam
  • Fenamates: mefenamic acid, meclofenamate
  • Selective COX-2 inhibitor: celecoxib

Mechanism of Action

• NSAIDs primarily inhibit cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis.
• COX-2 inhibition leads to anti-inflammatory and analgesic effects, while COX-1 inhibition is linked to cardiovascular protection and adverse events.
• Aspirin uniquely irreversibly inhibits cyclooxygenase, affecting platelet function.

Therapeutic Effects

• Major actions include:
  • Anti-inflammatory: Reduces inflammation but does not halt disease progression.
  • Analgesic: Effective for mild to moderate pain by decreasing pain sensitization (primarily via COX-2 inhibition).
  • Antipyretic: Decreases fever by inhibiting PGE2 synthesis, resetting the hypothalamic set-point.

Clinical Applications

• Used for conditions such as osteoarthritis, rheumatoid arthritis, gout, headaches, and dysmenorrhea.
• Aspirin prevents cardiovascular events; low doses are commonly used for prophylaxis.
• Topical preparations like diclofenac gel and salicylic acid for acne and warts are available.

Risks and Adverse Effects

• NSAIDs can lead to gastrointestinal issues (ulcers), renal impairment, and cardiovascular events, especially with prolonged use or in patients with existing conditions.
• Possible allergic reactions include urticaria and bronchoconstriction.
• Use caution with asthma patients due to potential leukotriene production increasing hyper-responsiveness.

Drug Interactions and Toxicity

• NSAIDs, particularly salicylates, can displace other drugs from protein binding, leading to increased effects or toxicity.
• Mild salicylism can cause nausea and tinnitus; severe toxicity can lead to respiratory failure and is particularly dangerous in children.

Special Considerations

• NSAIDs should generally be avoided in pregnancy, especially during the third trimester due to the risk of ductus arteriosus closure.
• Celecoxib has similar therapeutic effects as traditional NSAIDs but selectively inhibits COX-2, offering an alternative in certain cases.

Note on Safety in High-Risk Patients

• Patients at high risk for gastrointestinal events should use proton pump inhibitors or misoprostol concurrently when using NSAIDs.
• Aspirin has a longer-lasting antiplatelet effect, which complicates its use with other NSAIDs; recommended to take aspirin at least 30 minutes before other NSAIDs to mitigate this risk.