ROLE OF NSAIDS ON THE

DEVELOPMENT OF PUD
DANIEL GHOSSEIN
INTRODUCTION

• Nonsteroidal anti-inflammatory drugs (NSAIDs), cause considerable morbidity and mortality

related to gastric and duodenal ulcer disease.
• In rheumatoid arthritis patients alone, it has been estimated that gastrointestinal (GI) toxicity
related to NSAID use accounts for at least 2600 deaths in the United States annually.
• Thus, prevention of NSAID-induced GI damage is an important clinical issue.
RISK FACTORS WHEN USING NSAIDS

• According to 2008 American College of Cardiology Foundation/American College of

Gastroenterology (ACG)/American Heart Association guidelines, patients are considered to be
at high risk for GI toxicity from NSAIDs if they have a history of ulcer disease or complication,
are on dual antiplatelet therapy, are on concomitant anticoagulant therapy, or have more
than one of the following risk factors:
- Age ≥60 years
- Glucocorticoid use
- Dyspepsia or gastroesophageal reflux disease (GERD) symptoms
HOWEVER, IN 2009 GUIDELINES FROM THE ACG, PATIENTS
TAKING NSAIDS WERE INSTEAD CLASSIFIED AS BEING AT
HIGH, MODERATE, OR LOW RISK:
• High risk:
- History of complicated peptic ulcer disease
- Multiple (>2) risk factors (below)
• Moderate risk:
- Age >65 years
- High dose NSAID therapy
- A history of an uncomplicated ulcer
- Concurrent use of aspirin (including low dose), glucocorticoids, or anticoagulants
• Low risk:
- No risk factors
MECHANISM
• The deleterious effect of NSAIDs on the gastrointestinal tract is mainly due to the suppression
of gastric prostaglandin production from the concomitant inhibition of cyclooxygenase (COX)–
1.

• Decreased COX-1 activity results in a corresponding decline in gastric homeostatic function.

• Less mucus and bicarbonate are produced, making the gastric epithelial cells more vulnerable
to damage by hydrochloric acid and pepsin.
SOME OF THE CYTOPROTECTIVE MECHANISMS OF
PGS INCLUDE:

• Stimulation of glycoprotein (mucin) secretion by epithelial cells

• Stimulation of bicarbonate secretion by epithelial cells
• Stimulation of phospholipid secretion by epithelial cells
• Enhancement of mucosal blood flow and oxygen delivery to epithelial cells via local vasodilation
• Increased epithelial cell migration towards the luminal surface (restitution)
• Enhanced epithelial cell proliferation
MUCOSAL INJURY ALSO CAN RESULT FROM THE LOCAL
EFFECTS OF NSAIDS ON GASTRIC EPITHELIAL CELLS.

• NSAIDs are weak acids and, thus, are nonionized in the acidic environment, allowing them to diffuse
readily into the gastric mucosal cells and leading to subepithelial hemorrhage and cell necrosis.

• Concomitant administration of NSAIDs with glucocorticoids or bisphosphonates has been associated

with an increased incidence of PUD. Glucocorticoids and bisphosphonates, as well as anticoagulants,
aspirin, clopidogrel, and serotonin reuptake inhibitors, also have been associated with an increased risk
of complications from ulcers when administered in conjunction with NSAIDS.