GANDAKI MEDICAL COLLEGE LEKHNATH -2 KASKI ; NEPAL

Correlation Seminar Gastrointestinal System

Peptic Ulcer OBJECTIVE: NSAIDs as inducer of Peptic Ulcer.

Bibek Adhikary Surendra Poudel

NSAIDs: Non- steriodal Anti-inflammatory drugs along with antipyretic and analgesic action. These drugs act primarily on peripheral pain mechanisms to raise pain threshold.

Peptic Ulcer: The erosion of musosal lining which is exposed to the gastric juice and pepsin , especially stomach and duodenum.

Mucus that coats the stomach lining and shields it from stomach acid,

The chemical bicarbonate that neutralizes stomach acid.

Blood circulation to the stomach lining that aids in cell renewal and repair.

Defense mechanisms of stomach:

1. Prostaglandins synthesis inhibition:

Inhibits the formation of Prostaglandins by inhibiting cyclooxygenase pathway.

How do NSAIDs induce Peptic Ulcer?

Membrane phospholipid phospholipase

Arachidonic acid cyclooxygenase NSAIDs(-)

Prostaglandin G2(PGG2) Lipooxygenase pathway

Prostaglandins H2(PGH2)

Prostacyclin(PGI2) PGE2 Thromboxane A2

PGD2

MOA of NSAIDs

Promotes mucus synthesis Enhances bicarbonate secretion. Reduces acid secretion in stomach by decreasing

volume of gastric juice and pepsin Inhibits fasting as well as stimulated secretion (by

feeding , histamine and gastrin) Increases vascular perfusion. So PG’s are anti-ulcerogenic. (Note: That’s why, PG analogues like

“Misoprostal” are used in peptic ulcer treatment)

Role of Prostaglandins in gastro duodenal defense mechanism;

Most of the commonly used NSAIDs( Indomethacin, Aspirin ,diclofenac , etc) irritate gastric mucosa.

Long term use of these drugs may cause prolonged irritation leading to mucosal damage.

2. Gastric mucosal irritation:

NSAIDs(particularly Aspirin) remains unionized and diffusible in the acid gastric juice but on entering the mucosal cell it ionizes and becomes indiffusible. This is known as ion trapping.

This ‘ion trapping’ in gastric mucosal cell enhances gastric toxicity focal necrosis of mucosal cells and capillaries acute ulcers , erosive gastritis.

3.Ion trapping

Therapeutic doses of most NSAIDs inhibit platelet aggregation so bleeding time is prolonged.

If there is any prior mucosal damage it delays healing , thus making the wound prone to develop ulcer.

4.Anti-Platelet Action

Age > 60 years. Past history of peptic ulcer. Past history of adverse events with NSAIDs. Concomitant corticosteroid use. High dose of multiple NSAIDs.

Risk factors for NSAIDs induced ulcer

NSAIDs induce peptic ulcer by:

1.Inhibition of prostaglandins synthesis.

2.Gastric mucosal irritation.3.Ion trapping.4.Antiplatelet action.

SUMMARY:

Davidson’s Principles & Practice of Medicine 20th edition

Goldman Ausiello,Cesil Medicine 23rd edition Robbins & Cotran, Pathologic Basis of Disease 8th

edition K.D Tripathi,Essential of Medical Pharmacology. Wikipedia.

References:

THANK YOU!

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