Pharmacotherapy 3

1. Dr.Sowmya
spoorthi M
Assistant Professor
KLE College of
Pharmacy
Belagavi

4.  Acid-related diseases (gastritis , erosions and
peptic ulcer) of the upper GI tract require gastric
acid for their formulation.
 Peptic ulcer disease differs from gastritis and
erosions in that ulcers typically extend deeper
into the muscularis mucosa.
 There are three common forms of peptic ulcers
 Helocobacter Pylori Positive
 Non-sterioidal antiinflammatory drugs induced
 Stress –related musocal damage(SRMD)

9.  The epidemiology of PUD is complicated and
difficult to estimate given the variability in the
prevalence of H.pylori infection,NSAID use,
and cigarette smoking as well as the various
methods used to dectect ulcers for ex
endoscopy, radiology, symptoms or
complications.

10.  The prevalence and incidence of PUD in the
united States also reflects improvements in
drug therapy, the dramatic shift to
ambulatory management, and changes in the
criteria and coding system for mortality and
hospitalization data.

11.  Recent trends suggest a shift from
predominance in men to a similar occurrence
in men and women with increasing rate of
disease in older individuals and a decrease in
the younger population.

12.  Despite a modest decline in mortality,
Hospitalizations, and office visits, PUD
remains one of the most common GI
Diseases, resulting in impaired quality of life,
work loss and high –cost medical care.

14.  Most peptic ulcers occur in the presence of
acid and pepsin when H.pylori,NSAIDS or
other factors disrupt the normal mucosal
defence and healing mechanisms.
 Hypersecretion of acid is the primary
pathogenic mechanism in hypersecretory
states such as Zollinger-Ellison syndrome.

15.  Benign gastric ulcers can occur anywhere in
the stomach,although most are located on
the lesser curvature, just distal to the juction
of the antral and acid-secreting mucosa.
 Most duodenal ulcers occur in the first part of
the duodenum(duodenal bulb).

17.  The 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.
 Members of the same household are likely to
become infected when someone in the same
household is infected.
 H.pylori can also be transmitted by the use of
inadequately sterilized endoscopes.

18.  H.pylori infection causes chronic gastritis in
infected individuals and is causally linked to
PUD ,MALT lymphoma and gastric cancer.
 The majority of infected individuals remain
asymptomatic,but 10 % to 20% will develop
PUD during their lifetime and about 1%will
develop gastric ulcer.

22.  Cigarette Smoking
 Psychological Stress
 Dietary Factors

23.  A physiologic imbalance between aggressive
(gastric acid and pepsin) and protective
(mucosal defense and repair) factors remains
an important issue in the patho physiology of
gastric and duodenal ulcers.
 Gastric acid is secreted by the parietal cells,
which contain receptors for histamine, gastrin
and acetylcholine.
 Acid (as well H.pylori infection and NSAID
use) is an independent factor that contributes
to the disruption of mucosal integrity.

24.  This organism is a gram-negative ,pH sensitive ,
spiral- shaped bacteria that resides between the
mucus layers and surface epithelial cells in the
stomach or any location where gastric type
epithelium is found.
 The combination of its spiral shape and flagellum
permits it to move from the lumen of the
stomach , where the pH is low, to the mucus
layer, where the local pH is neutral.
 H.pylori produces large amounts of urease, which
hydrolyzes urea in the gastric juice and converts
it to ammonia and carbon dioxide.

25.  The local buffering effect of ammonia
creates a neutral micro-environment within
and surrounding the bacterium, protecting it
from the lethal effect of gastric acid.
 H.pylori also produces acid-inhibitory
proteins, which allow it to adapt to the low-
pH environment of the stomach.

26.  H.Pylori binds to specific regions within the stomach.
 It attaches to gastric-type epithelium by adherence
pedestals,which prevent the organism from being
shed during cell turnover and mucus secretion.
 Colonization of the antrum and corpus of the
stomach is associated with gastric ulcer and cancer.
 Antral organisms colonize gastric metaplastic tissue
(Gastric tissue that develops in the duodenum
secondary to changes in gastric acid or bicarbonate
secretion) leading to duodenal ulcers.
 Although H.pylori causes chronic gastric mucosal
inflammation in all infected individuals, only a
minority actually develop an ulcer or gastric cancer.

27.  The underlying pathophysiology associated with
H.pylori infection involves the production of
cytotoxin- associated gene A (CagA) proteins and
vocuolating cytotoxins, such as vac A, which
activate the inflammatory cascae.
 Cag A status and one genotype of the vac A gene
are also predictors of ulcerogenic capacity of a
strain.
 In addition , a number of enzymes produced by
H.pylori may be involved in causing tissue
damage and include urease , haemolysins,
neuraminidase and fucosidase.