Anti-inflammatory action of steroids is due to

Increased activity of lipoprotein lipase

Which of the following is a false statement?

Gastric irritation is more severe with NSAIDs compared to aspirin

Acetaminophen does not have anti-inflammatory action

Non-selective COX inhibitors are contraindicated in postoperative patients

NSAID with least cardiovascular risk is Naproxen

Pegloticase is used for the treatment of:

Refractory Rheumatoid Arthritis

A 50-year-old man presents with complaints of bilateral morning stiffness in his wrists and knees and painful joints on exercise. On physical examination, the joints are slightly swollen. The rest of the examination is unremarkable. His laboratory findings are also negative except for slight anemia, elevated erythrocyte sedimentation rate, and positive rheumatoid factor. The patient was started on weekly methotrexate to control the inflammation. What is the principle mechanism of action here?

Increased extracellular levels of adenosine

Inhibition of assembly of microtubules in neutrophils impairing chemotaxis

Inhibition of cyclooxygenase enzyme

Inhibition of Dihydrofolate reductase enzyme

NSAIDs: Classification and Mechanism for INI-CET: High-Yield Pharmacology Lessons

NSAIDs: The Basics - Pain & Fire Fighters

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Combat pain, inflammation, fever.
Core Therapeutic Actions: 📌 "The 3 A's"
- Analgesic: Relieve mild-moderate pain (somatic > visceral).
- Anti-inflammatory: Reduce inflammation (redness, swelling, pain, heat).
- Antipyretic: Reduce fever (antipyresis).
General Pharmacokinetics:
- Most are weak organic acids.
- Good oral absorption.
- High plasma protein binding (e.g., to albumin).
- Hepatic metabolism, renal excretion.
Key Features:
- Mechanism: All inhibit cyclooxygenase (COX) enzymes.
- Common ADRs: GI irritation, peptic ulcers, renal adverse effects.

⭐ Aspirin is the prototype NSAID, unique for its irreversible COX inhibition and significant antiplatelet effect at low doses (e.g., 75-150 mg daily).

Mechanism of Action - Prostaglandin Power Down

Core Action: NSAIDs inhibit Cyclooxygenase (COX) enzymes (COX-1 & COX-2).
- This blocks conversion of Arachidonic Acid (AA) to Prostaglandin H2 (PGH2).
- PGH2 is a precursor to Prostaglandins (PGs), Prostacyclin (PGI2), & Thromboxane A2 (TXA2).
AA Source: Released from cell membrane phospholipids by Phospholipase A2 (PLA2).
- 📌 Corticosteroids inhibit PLA2, a step before NSAID action.

Arachidonic Acid Pathway and NSAID Inhibition

Simplified Arachidonic Acid Pathway & NSAID Action:

Consequences of COX Inhibition:
- Therapeutic Effects:
  - ↓ PGs → Analgesia (↓ pain), Antipyresis (↓ fever), Anti-inflammatory action.
- Adverse Effects (mainly via COX-1 inhibition):
  - ↓ Gastric PGs (PGE2, PGI2) → Gastropathy, ulcers.
  - ↓ Renal PGs → Na+/water retention, ↓ GFR, hypertension.
  - ↓ Platelet TXA2 (COX-1) → Impaired hemostasis, ↑ bleeding time (esp. Aspirin - irreversible).

⭐ The primary mechanism of NSAIDs involves the inhibition of cyclooxygenase (COX) enzymes (COX-1 and COX-2), leading to decreased synthesis of prostaglandins and thromboxanes from arachidonic acid.

NSAID Classification - Selective Strategies

Selectivity	Chemical Class	Examples	Key Points / Clinical Pearls
Non-selective (Inhibit COX-1 & COX-2)	Salicylates	Aspirin	Irreversible COX inhibitor. Low dose ($75-150$ mg) for antiplatelet effect. Main risk: GI toxicity, Reye's syndrome in children.
	Propionic Acids	Ibuprofen, Naproxen	Reversible inhibitors. Good analgesic, antipyretic, anti-inflammatory. Moderate GI risk. Naproxen: longer half-life, considered CV safer by some.
	Acetic Acids	Diclofenac, Indomethacin, Ketorolac	Potent. Diclofenac: some COX-2 preference, ↑ liver enzyme risk. Indomethacin: potent, for gout, PDA closure; ↑ GI/CNS SE. Ketorolac: strong analgesic, short-term use (≤5 days).
Preferential COX-2 (Higher affinity for COX-2)	Various (e.g., Sulfonanilides, Oxicams)	Nimesulide, Meloxicam, Etodolac	Better GI tolerance than non-selective. Nimesulide: hepatotoxicity risk ⚠️, banned in some countries. Meloxicam: for osteoarthritis, long t½. Etodolac: well-tolerated.
Selective COX-2 (Coxibs) (Specifically inhibit COX-2)	Coxibs	Celecoxib, Etoricoxib, Parecoxib (IV)	Significantly ↓ GI toxicity vs non-selective. Increased CV thrombotic risk (MI, stroke) due to unopposed TXA2. Sulfa allergy (Celecoxib). 📌 Mnemonic: "Celebrex Eats Pain" (for Celecoxib, Etoricoxib, Parecoxib).

High‑Yield Points - ⚡ Biggest Takeaways

NSAIDs inhibit COX enzymes, reducing prostaglandin synthesis to decrease pain and inflammation.

COX-1 is constitutive (e.g., gastric cytoprotection); COX-2 is inducible by inflammatory stimuli.

Aspirin is a unique irreversible COX inhibitor.

Selective COX-2 inhibitors (e.g., Celecoxib) have ↓ GI toxicity but ↑ cardiovascular risk.

Non-selective NSAIDs inhibit both COX-1 and COX-2 isoforms.

Paracetamol: weak peripheral anti-inflammatory, primarily central analgesic/antipyretic effects.

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