Anti-Inflammatory Pharmacology: NSAIDs, COX-2 Inhibitors and Paracetamol

3rd Year MBBS • Infection and Inflammation

A rapid connection of drug targets, therapeutic effects, adverse effects and major toxicity pathways.

1. THE TOPIC IN ONE CONNECTED FLOW

The central relationship in this topic is simple: altering cyclooxygenase activity changes prostaglandin and thromboxane formation. This produces useful analgesic, antipyretic, anti-inflammatory or antiplatelet effects, but the same pathway also explains important gastric, renal, cardiovascular and toxic effects.

Drug Selection
NSAID, aspirin, COX-2 inhibitor or paracetamol

→

Main Target
COX inhibition or central prostaglandin suppression

→

Mediator Change
↓ prostaglandins ± ↓ thromboxane A₂

→

Therapeutic Effect
Analgesic, antipyretic, anti-inflammatory or antiplatelet

→

Physiological Cost
Loss of protective gastric, renal or vascular prostanoids

→

Clinical Outcome
GI injury, renal effects, thrombosis or toxicity

Two important branches:

Aspirin: irreversible platelet COX-1 inhibition → ↓ thromboxane A₂ → prolonged antiplatelet action.

Paracetamol: predominantly central reduction of prostaglandin synthesis → analgesia + antipyresis → weak peripheral anti-inflammatory effect.

2. KEY CLINICAL CONNECTIONS

Aspirin: benefit and bleeding

Platelet COX-1 inhibition → ↓ thromboxane A₂ → ↓ aggregation → useful antiplatelet effect.

The same irreversible action → prolonged platelet dysfunction → increased bleeding tendency.

COX selectivity and adverse effects

Non-selective COX inhibition → ↓ gastric protective prostaglandins → ulceration or GI bleeding.

Selective COX-2 inhibition → less gastric injury → but renal effects and thrombotic cardiovascular risk remain.

Toxicology link

Salicylate toxicity → acid-base disturbance → bicarbonate alkalinization increases renal salicylate elimination.

Paracetamol overdose → excess NAPQI + glutathione depletion → hepatic necrosis → N-acetylcysteine restores detoxification capacity.

3. AIM HIGH-YIELD INTEGRATION REVIEW

⭐ Aspirin → irreversible COX-1 inhibition → ↓ platelet thromboxane A₂ → prolonged antiplatelet effect, which explains why low-dose aspirin differs from ordinary reversible NSAIDs.

Non-selective NSAIDs → ↓ inflammatory prostaglandins → analgesic and anti-inflammatory benefit, but ↓ protective prostaglandins → gastric and renal adverse effects.

Short-acting drugs such as ibuprofen suit brief symptom control, whereas long-acting piroxicam provides prolonged effect but also prolongs drug exposure.

⭐ Selective COX-2 inhibition → less interference with gastric COX-1 → reduced GI injury, but preservation of platelet thromboxane with reduced vascular prostacyclin can favor thrombosis.

Salicylate accumulation becomes more important at higher doses because metabolic elimination pathways become saturated → plasma concentration may rise disproportionately.

Salicylate poisoning → hyperventilation and acid-base disturbance → sodium bicarbonate promotes ion trapping in urine; severe toxicity may require hemodialysis.

⭐ Paracetamol → predominantly central prostaglandin suppression → strong analgesic and antipyretic effects but weak peripheral anti-inflammatory action.

⭐ Paracetamol overdose → excessive NAPQI + depleted glutathione → hepatocellular necrosis; N-acetylcysteine restores glutathione-dependent detoxification.

AIM Exam Trap: COX-2 selectivity reduces gastrointestinal toxicity but does not provide aspirin-like platelet inhibition and does not remove renal or cardiovascular risk.

Anti-Inflammatory Pharmacology: NSAIDs, COX-2 Inhibitors and Paracetamol

1. THE TOPIC IN ONE CONNECTED FLOW

2. KEY CLINICAL CONNECTIONS

3. AIM HIGH-YIELD INTEGRATION REVIEW

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