Concise NSAIDs Summary

NSAIDs Overview

  • Nonsteroidal Anti-inflammatory Drugs (NSAIDs) have analgesic, antipyretic, and anti-inflammatory actions.
  • They don't depress the CNS and primarily act on peripheral pain mechanisms.

Mechanism of Action

  • NSAIDs inhibit prostaglandin (PG) synthesis by blocking cyclooxygenase (COX) enzymes.
  • COX exists as constitutive (COX-1) and inducible (COX-2) isoforms.
  • COX-1 serves physiological functions, while COX-2 is induced by cytokines at inflammation sites.

Classification of NSAIDs

  • Nonselective COX inhibitors (e.g., Aspirin, Ibuprofen).
  • Partially COX-2 selective inhibitors (e.g., Nimesulide, Diclofenac).
  • Selective COX-2 inhibitors (e.g., Celecoxib, Etoricoxib).
  • Analgesic-antipyretics with poor anti-inflammatory action (e.g., Paracetamol).

Beneficial Actions

  • Analgesia: Prevention of pain nerve ending sensitization.
  • Antipyresis: Reduction of body temperature in hyperthermia.
  • Anti-inflammatory action: Suppression of inflammation signs.
  • Antithrombotic action: Inhibition of platelet aggregation.

Shared Toxicities

  • Gastric mucosal damage.
  • Bleeding: Inhibition of platelet function.
  • Limitation of renal blood flow.
  • Asthma and anaphylactoid reactions.

Salicylates - Aspirin

  • Actions: Analgesic, antipyretic, and anti-inflammatory.
  • High doses (3-6 g/day) are needed for anti-inflammatory action.
  • Irreversibly inhibits TXA2 synthesis by platelets.
  • Adverse effects: Gastric damage, hypersensitivity, salicylism, Reye’s syndrome.
  • Contraindications: Peptic ulcer, bleeding tendencies, children with viral infections.
  • Interactions: Displaces other drugs from binding sites.

Propionic Acid Derivatives

  • Examples: Ibuprofen, Naproxen.
  • Inhibit PG synthesis. Ibuprofen is considered the safest traditional NSAID.

Fenamates

  • Example: Mephenamic acid.
  • Weak anti-inflammatory drug, effective in dysmenorrhea.

Enolic Acid Derivatives

  • Example: Piroxicam.
  • Long-acting NSAID used in RA and OA.

Acetic Acid Derivatives

  • Ketorolac: Effective for postoperative pain; limited use due to toxicity.
  • Indomethacin: Potent anti-inflammatory with high GI and CNS side effects.

Partially COX-2 Selective Inhibitors

  • Nimesulide: Used for painful inflammatory conditions.
  • Diclofenac: Similar efficacy to naproxen, used in various inflammatory conditions.

Selective COX-2 Inhibitors (Coxibs)

  • Examples: Celecoxib, Etoricoxib.
  • Anti-inflammatory, analgesic, and antipyretic actions.
  • Better tolerability than traditional NSAIDs but contraindicated in patients with IHD.

Para-amino Phenol Derivatives

  • Paracetamol (Acetaminophen): Central analgesic action, weak anti-inflammatory.
  • Safe antipyretic and analgesic, can be used in all age groups.
  • Overdose can cause hepatic necrosis.
  • Treatment for overdose: N-acetylcysteine.

Topical NSAIDs

  • Used for local pain relief with minimized systemic effects.

Choice of NSAIDs - Guidelines

  • Mild-to-moderate pain: Paracetamol or low-dose ibuprofen.
  • Postoperative pain: Injectable ketorolac, diclofenac, or oral propionic acid derivative.

Analgesic Combinations

  • Aspirin and paracetamol: Additive effect up to 1000mg.
  • Codeine/tramadol with paracetamol: Additional analgesia beyond paracetamol's ceiling effect.