NSAIDs and Enzyme Inhibition Quiz

NSAIDs Overview

• NSAIDs cause reversible inhibition of cyclooxygenase (COX) enzymes which synthesize prostaglandins (PGs) from arachidonic acid.
• COX-1 is found in most tissues (kidney, platelets, blood vessels, stomach) and regulates normal physiology while COX-2 is inducible during inflammation.

COX Functions

• COX-1:
  • Responsible for biosynthesis of most PGs (e.g., PGI2, PGE2, TXA2).
  • Affects vasodilation, gastric protection, and platelet aggregation.
• COX-2:
  • Induced by inflammatory mediators in brain and kidney.
  • Mediates pain, inflammation, and fever through PGs production.

Pharmacological Actions of NSAIDs

• Analgesic: Primarily through peripheral inhibition of PG production.
• Antipyretic: Causes vasodilation and sweating.
• Anti-inflammatory: High doses provide symptomatic relief; do not alter disease progression.
• Antiplatelet: Aspirin irreversibly inhibits platelet aggregation; high doses lose this effect.
• Gastric irritation and other gastrointestinal side effects common with aspirin use.

Pharmacokinetics

• Salicylates are rapidly absorbed from the gastrointestinal tract, highly bound to plasma proteins, and metabolized in the liver.

Dosage Regimens

• Analgesic dose: 2-3g/day in divided doses.
• Anti-inflammatory dose: 4-6g/day in divided doses.
• Antiplatelet: 50-325mg/day (low dose aspirin).

Adverse Effects

• Gastrointestinal: Nausea, vomiting, dyspepsia, gastritis, ulceration, bleeding; minimized by taking after food or using proton pump inhibitors.
• Hypersensitivity: Rash, urticaria, bronchospasm, especially with aspirin.
• Reye's syndrome: Risk in children receiving salicylates during viral infections.
• Pregnancy: Inhibit PG synthesis and delay labor onset.
• Analgesic nephropathy: Reversible with drug withdrawal; linked to chronic high-dose use.

Clinical Uses of NSAIDs

• Analgesic: Headache, toothache, body pain, dysmenorrhea.
• Antipyretic: Paracetamol preferred due to lower gastrointestinal side effects.
• Osteoarthritis and rheumatoid arthritis: Manage pain and inflammation without altering disease progression.
• Acute rheumatic fever: Aspirin reduces fever and joint pain.
• Thromboembolic disorders: Low-dose aspirin reduces risk of stroke and myocardial infarction.
• Patent ductus arteriosus (PDA): Indomethacin preferred for closure.

Acute Salicylate Poisoning

• Common in children; symptoms include vomiting, dehydration, acid-base imbalance, hyperpnoea, confusion, and possible cardiovascular collapse.

Treatment of Salicylate Poisoning

• No specific antidote; symptomatic treatment includes hospitalization and gastric lavage.
• IV NaHCO3 corrects metabolic acidosis and alkalinizes urine for enhanced renal excretion.
• Haemodialysis may be necessary in severe cases.

Paracetamol

• Effective orally and parenterally; metabolized by liver via conjugation.
• Uses: Analgesic and antipyretic; safe for patients with peptic ulcers and asthma.
• Adverse effects: Hepatotoxicity in overdose; nephrotoxicity with chronic use.

Paracetamol vs. Aspirin

• Aspirin: Antipyretic, analgesic, anti-inflammatory; can cause gastric irritation and is contraindicated in certain conditions.
• Paracetamol: Analogous effects without gastric irritation; has a specific antidote (N-acetyl cysteine).

Migraine

• Initiated by prodromal symptoms and auras, triggered by stress, hormonal changes, sleep disturbances, and alcohol.
• Treatment:
  • Mild analgesics: NSAIDs and acetaminophen.
  • Triptans: Targeted therapy for moderate to severe attacks, acting on selective serotonin receptors.

Ergots

• Similar action as triptans; act as 5HT agonists for migraine treatment.

This quiz explores the mechanisms of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and their reversible inhibition of enzymes such as phospholipase A2 and cyclooxygenase. Test your understanding of arachidonic acid pathways and the roles of lipoxygenase in inflammation. Ideal for students of pharmacology and biochemistry.