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Pharmacotherapy of Peptic Ulcer Disease (PUD) - Coggle Diagram
Pharmacotherapy of
Peptic Ulcer Disease (PUD)
Introduction
acid-related disease
3 common forms of peptic ulcers:
Helicobacter pylori positive ulcer
Non-steroidal anti-inflammatory drug (NSAID)
induced ulcer.
Stress ulcers induced ulcer
• Stress ulcer ranges from superficial gastritis and
erosions to deep ulcers.
Chronic PUD is characterized by frequent ulcer
recurrence
important factors
influence ulcer recurrence: H.pylori infection & NSAID use
other factors: cigarette smoking, alcohol use, ulcer-related complications, gastric acid hypersecretion & patient compliance
Peptic ulcers are also associated with ZollingerEllison syndrome (ZES), radiation, chemotherapy,
vascular insufficiency, and other chronic diseases
Etiology and risk factors
H.pylori
H. pylori infection causes chronic gastritis in infected
individuals and is causally linked to PUD.
The prevalence of H. pylori varies by geographic
location, socioeconomic conditions, ethnicity, and age.
most common route of H.pylori transmission is person to person by either gastro-oral (vomitus) or fecal-oral (diarrhea) contact that occurs primarily during childhood
also be transmitted by the
use of inadequately sterilized endoscopes
NSAIDs
cause superficial (topical) mucosal damage within minutes of ingestion, and progress to erosions with continued use.
These lesions typically heal within a few days and rarely cause
ulcers or acute upper GI bleeding.
Gastroduodenal ulcers develop in about 25% of chronic
NSAID users with continued use.
Cigarette smoking
impairs ulcer healing, promotes ulcer
recurrence, and increases ulcer risk
possible mechanisms : mucosal ischemia, inhibition of pancreatic bicarbonate secretion & increase in gastric acid secretion
Psychological stress
Pathophysiology
A physiologic imbalance between aggressive (gastric acid
and pepsin) and protective (mucosal defense and repair) causing gastric and duodenal ulcers
Acid (as well as H.pylori infection & NSAID use) contributes to the disruption of mucosal integrity
Mucosal defense and repair mechanisms (mucus and bicarbonate secretion, intrinsic epithelial cell defense, and mucosal blood flow) protect the gastroduodenal mucosa from noxious endogenous and exogenous substances
maintenance of mucosal integrity and repair is mediated by the production of endogenous prostaglandins (PGs)
Alterations in mucosal defense that are induced by H. pylori or NSAIDs are the most important cofactors in the formation of peptic ulcers
H.pylori
spiral-shaped, pH-sensitive, gram negative, microaerophilic bacterium.
resides between the mucus layer and surface
epithelial cells in the stomach
produces large amounts of urease, which hydrolyzes urea in the gastric juice and converts it to ammonia and CO2 - increase pH in stomach
local buffering effect of ammonia creates a neutral microenvironment protecting it from the lethal effect of gastric acid.
Mucosal injury is produced by
• Elaborating bacterial enzymes (urease, lipases, and proteases)
• Adherence
• H. pylori virulence factors
NSAIDs
(including aspirin)
cause gastric mucosal damage by
two
important mechanisms:
Direct or topical irritation of the gastric epithelium
Systemic inhibition of endogenous mucosal PG synthesis.
Cyclooxygenase (COX) is the rate-limiting enzyme in the conversion of arachidonic acid to PGs and is inhibited by NSAIDs
COX-1 is found in most body tissue, including the
stomach, kidney, intestine, and platelets.
COX-2 is undetectable in most tissues under normal physiologic conditions, but its expression can be induced during acute inflammation and arthritis
COX-1 produces protective PGs that regulate physiologic processes such as GI mucosal integrity, platelet homeostasis, and renal function.
COX-2 is induced (unregulated) by inflammatory stimuli such as cytokines and produces PGs involved with inflammation, fever, and pain.
Nonselective NSAIDs, including aspirin, inhibit both COX-1 and COX-2 to varying degrees and are associated with an increased propensity to cause gastric ulcers.
In contrast, the selective COX-2 inhibitors are associated with a reduction in ulcers and related GI complications
Complications
• Upper GI bleeding, perforation, and obstruction
use of NSAIDs (especially in older adults) - risk factor for upper GI bleeding
Ulcer-related perforation into the peritoneal cavity is
generally considered a surgical emergency.
Gastric outlet obstruction is related to mechanical obstruction caused by scarring, muscular spasm, or edema of the duodenal bulb usually resulting from chronic ulceration.
Clinical presentation
varies depending on the severity of epigastric pain and the presence of complications.
Ulcer-related pain in duodenal ulcer often occurs 1 to 3 hours after meals and is usually relieved by food.
In gastric ulcer, food may precipitate or accentuate
ulcer pain.
Diagnosis
tests for H.pylori
using
endoscopic
or
non
endoscopic
tests
Endoscopic tests are invasive, more expensive, and usually require a mucosal biopsy for histology, culture, or detection of urease activity.
Eg: Rapid urease test, histology examination
Certain medications such as
PPI, antibiotics and bismuth
salts
decrease
the sensitivity of rapid urease test.
They should be withheld for 4 weeks and proton pump inhibitors (PPIs) for 1 to 2 weeks prior to endoscopic testing. Otherwise a gastric biopsy for histology should be
performed
Two types of
non endoscopic
tests are available
tests that identify active infection
tests that detect antibodies
Antibody tests do not differentiate between active infection and previously eradicated H. pylori.
The non endoscopic tests include the urea breath test (UBT), serologic antibody detection tests, and the fecal antigen test.
less invasive, more convenient, and
less expensive than the endoscopic tests
The
UBT
is the most accurate non invasive test and is
based on H. pylori urease activity.
The 13Carbon (nonradioactive isotope) and 14Carbon (radioactive isotope) tests require that the patient ingest radiolabeled urea, which is then hydrolyzed by H. pylori (if present in the stomach) to ammonia and radiolabeled bicarbonate.
The radiolabeled bicarbonate is absorbed in the blood
and excreted in the breath.
A mass spectrometer is used to detect 13Carbon, whereas
14Carbon is measured using a scintillation counter.
The fecal antigen test is less expensive and easier to
perform than the UBT, and may be useful in children.
Serologic tests are a cost-effective alternative for the initial
diagnosis of H. pylori infection in the untreated patient
Antibodies to H. pylori usually develop about 3 weeks after infection and remain present after successful eradication. Therefore, serology should not be used to confirm H.
pylori eradication.