Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are a cornerstone in pain management and are widely used for their:
- Analgesic (pain relief)
- Antipyretic (fever reduction)
- Anti-inflammatory effects
They are considered non-opioid analgesics, often referred to as aspirin-like drugs, and are used extensively for minor to moderate pain, fever, and inflammatory conditions.
🔍 Classification of Analgesics
- Opioid Analgesics – act on CNS opioid receptors (e.g., morphine)
- Non-Opioid Analgesics – include NSAIDs and acetaminophen (paracetamol)
🧪 Classification of NSAIDs
- Salicylates – e.g., Aspirin
- Para-aminophenol derivatives – e.g., Paracetamol (Acetaminophen)
- Non-selective COX inhibitors – e.g., Ibuprofen, Diclofenac, Naproxen
- Selective COX-2 inhibitors – e.g., Celecoxib, Etoricoxib
🧬 Mechanism of Action
NSAIDs inhibit the cyclooxygenase (COX) enzymes involved in prostaglandin synthesis:
- COX-1: Constitutive; protects gastric mucosa, supports platelets & renal function
- COX-2: Inducible; mediates inflammation, pain, and fever
Most NSAIDs inhibit both COX-1 and COX-2 → ↓ Prostaglandins → ↓ pain, inflammation, fever
➡️ Side effect: Gastric ulceration due to COX-1 inhibition
➡️ Solution: Selective COX-2 inhibitors reduce GI toxicity
💊 Detailed Drug Profiles
🧴 1. Salicylates (Aspirin / Acetylsalicylic Acid)
Pharmacokinetics:
- Administered orally, absorbed in stomach/small intestine
- Converted to active salicylate in the liver (prodrug)
- Plasma protein binding increases with dose
Mechanism:
- Irreversible inhibition of COX-1 & COX-2
- Antipyretic: Acts on hypothalamus to reset thermoregulation
- Analgesic & anti-inflammatory: Reduces prostaglandin-mediated inflammation
Therapeutic Uses:
- Mild pain & inflammation (e.g. arthritis)
- Fever control
- Cardioprotection: Low-dose aspirin inhibits platelet aggregation by blocking thromboxane A2 (TXA2)
Adverse Effects:
- GI: Nausea, epigastric pain, ulceration
- Salicylism (toxicity): tinnitus, vertigo, hyperventilation, confusion
- Reye’s Syndrome: Avoid in children with viral infections
- Hypersensitivity: Asthma, rash
- Bleeding risk
- Acute overdose: Metabolic acidosis, convulsions, coma
Treatment of Overdose:
- Supportive care: IV fluids, temperature control
- Gastric lavage, activated charcoal
- Alkaline diuresis to enhance salicylate elimination
- Vitamin K if bleeding
- Hemodialysis in severe cases
Contraindications:
- Peptic ulcer disease, bleeding disorders, asthma, liver disease, pregnancy (especially 3rd trimester)
🧴 2. Paracetamol (Acetaminophen)
Mechanism:
- Weak COX inhibitor, mainly in CNS
- No significant anti-inflammatory action
- Does not affect platelet function
Therapeutic Uses:
- Antipyretic and mild analgesic
- Preferred for children, elderly, and gastric-sensitive patients
Advantages:
- No gastric irritation
- No effect on clotting or uric acid levels
- No risk of Reye’s syndrome
Adverse Effects:
- Generally safe at therapeutic doses
- Overdose risk: Hepatotoxicity due to formation of toxic metabolite (NAPQI) that depletes glutathione
Treatment of Overdose:
- Activated charcoal (within 1–2 hours)
- N-acetylcysteine (NAC): Replenishes glutathione, prevents liver damage
💊 3. Common NSAID Combinations
Often, aspirin or paracetamol is combined with weak opioids (e.g., codeine) to manage moderate pain without significant addiction risk:
- Paracetamol + Codeine
- Aspirin + Codeine
🩺 NSAIDs and Uterine Contraction
- Prostaglandins promote uterine contractions during menstruation and labor
- NSAIDs (especially mefenamic acid, ibuprofen) are used for dysmenorrhea and to delay preterm labor (e.g., indomethacin)
🧴 Older NSAIDs
Indomethacin
- Powerful NSAID used in rheumatic diseases and gout
- Can cause CNS and GI side effects
- Also used to close patent ductus arteriosus in neonates
Phenylbutazone
- Potent anti-inflammatory but now rarely used due to serious side effects: agranulocytosis, gastric ulcers
🧴 Commonly Used Non-Selective NSAIDs
| Drug | Notes |
|---|---|
| Ibuprofen | Good safety profile, OTC |
| Diclofenac | Used in arthritis, available as suppository/injection |
| Naproxen | Long half-life |
| Ketoprofen | Rapid onset |
| Aceclofenac | Better GI tolerance |
| Piroxicam | Long-acting, once daily dosing |
| Meloxicam | Preferential COX-2 inhibitor, better GI safety |
➡️ Use lowest effective dose for shortest duration
➡️ Rotate if ineffective after 2–3 weeks
🧴 Selective COX-2 Inhibitors (Coxibs)
| Drug | Notes |
|---|---|
| Celecoxib | Effective for arthritis, lower GI toxicity |
| Etoricoxib | Long-acting, used in osteoarthritis & gout |
May increase cardiovascular risk (MI, stroke)
⚠️ General Side Effects of NSAIDs
- Gastrointestinal: Ulcers, bleeding, nausea
- Renal: ↓ renal perfusion → fluid retention, hypertension, acute kidney injury
- Cardiovascular: Risk of MI and stroke (especially with COX-2 inhibitors)
- Hematologic: Platelet inhibition (esp. aspirin)
- Hypersensitivity: Asthma, rash, anaphylaxis
📌 High-Yield Clinical Pearls
- Aspirin is irreversible COX inhibitor → unique antiplatelet effect
- Avoid aspirin in children with viral illness → Reye’s syndrome risk
- Paracetamol overdose → hepatotoxicity due to NAPQI, treat with N-acetylcysteine
- NSAIDs may mask infection symptoms (fever and pain)
- Use proton pump inhibitors (PPIs) with chronic NSAID therapy in GI-risk patients
- Ibuprofen is safest among OTC NSAIDs for mild-moderate pain
📚 Suggested Exam Questions Focus
- Mechanism of action of NSAIDs and COX inhibition
- Aspirin vs. acetaminophen (clinical use & toxicity)
- Management of overdose (salicylate & paracetamol)
- NSAIDs effect on kidney and GI tract
- COX-2 inhibitors and cardiovascular risks
