🩹 NSAID-Induced Ulcer Mechanism Simulator

NSAIDs Block the COX-1 Active Site

Placeholder: NSAIDs competitively inhibit cyclooxygenase-1 in gastric mucosa.

• COX-1: Target enzyme (Constitutive isoform)
• Competitive: Binding mode (Active-site channel)
• Minutes: Onset (After absorption)
• Varies: Reversibility (Aspirin is irreversible)

How NSAIDs inhibit COX-1

Placeholder: drug occupies the cyclooxygenase channel, blocking arachidonic acid access.

Placeholder: irreversible acetylation (aspirin) differs from reversible NSAID binding.

Prostaglandin Output Falls Sharply

Placeholder: less PGE2 and PGI2 are made once COX-1 is inhibited.

• PGE2: Key mediator (Mucosal defense)
• Arachidonic acid: Pathway step (→ PGH2 blocked)
• Hours: Effect onset (Cumulative with dose)
• Dose-dependent: Dose relation (Higher dose, less PG)

Why prostaglandins matter here

Placeholder: PGE2 normally stimulates mucus, bicarbonate, and mucosal blood flow.

Placeholder: loss of prostaglandins removes the stomach's main defense signal.

The Protective Mucus-Bicarbonate Barrier Thins

Placeholder: reduced prostaglandin signaling thins the gel mucus layer.

• Mucus-HCO3: Barrier type (Gel layer)
• ~200 µm: Normal thickness (Unstimulated stomach)
• Thinning: Change (Reduced turnover)
• Barrier loss: Consequence (Acid can diffuse in)

Mucus barrier breakdown

Placeholder: mucus and bicarbonate secretion slow without prostaglandin stimulation.

Placeholder: a thinner barrier lets hydrogen ions reach epithelial cells.

Gastric Acid Reaches the Epithelium

Placeholder: hydrochloric acid now contacts unprotected epithelial cells.

• ~1–2: Luminal pH (Highly acidic)
• Epithelium: Exposed tissue (Surface mucosal cells)
• Back-diffusion: Cell effect (H+ ions enter cells)
• Erosion: Damage type (Superficial injury first)

Acid back-diffusion injury

Placeholder: hydrogen ions back-diffuse into cells, disrupting normal function.

Placeholder: repeated acid exposure converts erosions into deeper lesions.

Epithelial Erosion Becomes an Open Ulcer

Placeholder: sustained injury erodes through the mucosa into a crater.

• Full-thickness: Lesion depth (Through muscularis mucosae)
• Antrum/duodenum: Common site (NSAID-associated)
• PPI co-therapy: Prevention (Reduces acid burden)
• Dose & duration: Risk factor (Higher dose, higher risk)

From erosion to ulcer crater

Placeholder: unresolved erosion progresses to a defined ulcer crater with raised edges.

Placeholder: PPI co-therapy substantially lowers NSAID ulcer risk.