2-LITERATURE REVEIEW

Gastrointestinal:
The gastrointestinal tract is a long, hollow tube with its lumen inside the
body and its wall acting as an interface between the internal and
external environments. The wall does not normally allow harmful agents
to enter the body, nor does it permit body fluids and other materials to
escape. The process of digestion and absorption of nutrients requires an
intact and healthy gastrointestinal tract epithelial lining that can resist
the effects of its own digestive secretions. The process also involves
movement of materials through the gastrointestinal tract at a rate that
facilitates absorption, and it requires the presence of enzymes for the
digestion and absorption of nutrients (figure. 1). {porth C. M., Kunert M.
P.(2002). Pathophysiology concepts of altered health states,
LIPPINCOTT WILLIAMS & WILKINS , SIXTH EDITION.}
Figure.1 The Digestive System
Peptic Ulcer History:
For more than a century, peptic ulcer disease has been a major cause of
morbidity and mortality. In the early part of the 20th century, when
stress and diet were judged to be important pathogenetic factors for
peptic ulceration, patients with peptic ulcers were treated with
hospitalization, bed rest, and the prescription of “bland” diets. By the
1950s, investigators and clinicians had focused their attention primarily
on the pathogenetic role of gastric acid, and antacid therapy had
become the treatment of choice for peptic ulcer disease. Antacids given
at very high doses healed about 80% of duodenal ulcers after 4 weeks of
therapy in comparison with placebo. The histamine H2 receptor
antagonist cimetidine became available for clinical use in 1977.
H2 receptor antagonists produced good ulcer healing rates, ranging from
80% to 95%, after 6 to 8 weeks of therapy. Acid suppression with
antisecretory therapy rapidly emerged as the treatment of choice for
patients with peptic ulcer disease. With the advent of proton pump
inhibitors (PPIs) in the 1980s, even more potent acid suppression and
higher rates of ulcer healing could be achieved. Although most acute
peptic ulcerations healed with acid suppression therapy, the majority of
patients experienced recurrences within 1 year of discontinuing
treatment with antacids or antisecretory agents alone.
For most of the 20th century, therefore, peptic ulcer disease was
considered a chronic, incurable disorder characterized by frequent
exacerbations and remissions. The discovery of the link between
Helicobacter pylori and peptic ulcer by Marshall and Warren
in the mid-1980s led to another revolution in ulcer therapy. Now there is
overwhelming evidence to support H. pylori infection as the most
important cause of duodenal and gastric ulcers worldwide.
Curing the infection not only heals peptic ulcer but also prevents ulcer
relapse. Although hospitalizations for uncomplicated peptic ulcers in
western countries had begun to decline by the 1950s, there was an
increase in admissions for ulcer hemorrhage and perforation among the
elderly. This increase has been attributed to the greater use of non-
steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin. The
widespread use of NSAIDs has led to an epidemic of ulcer complications
and deaths. In the United States, use of prescription
NSAIDs accounts for about 25% of all reported adverse drug reactions.
Cotherapy with antiulcer drugs and the replacement of NSAIDs with
cyclooxygenase-2 (COX-2) inhibitors have become acceptable
treatments for patients who are at risk for peptic ulcer disease.
With the declining prevalence of H. pylori infection, the proportion of
patients with idiopathic ulcers is growing, at least in the United States,
where the reported proportion is between 20% and 30%.
In Asia, the proportion of idiopathic ulcers is much lower, at 1% to 4%. It
has been argued that as the incidence of H. pylori ulcers falls, a greater
proportion of idiopathic ulcers will be seen.
In a 5-year cohort of 435 patients with duodenal ulcer described in a
study published in 1993, only 6 patients were identified to have H.
pylori–negative idiopathic duodenal ulcers. Their serum gastrin
responses and peak gastric acid output values were significantly higher
than those of H.pylori–negative controls without ulcers. Thus, long-term
prophylaxis with antisecretory drugs is advisable (see later), although
this recommendation is not evidence-based.
{http://www.mdconsult.com/das/book/body/110253190-
6/772031244/1389/370.html}

Peptic Ulcer Definition:

Peptic ulcers are open sores that develop on the inside lining of your
esophagus, stomach and the upper portion of your small intestine. The
most common symptom of a peptic ulcer is abdominal pain.{The Mayo
Clinic.”Peptic Ulcer.”}

It is definiedas mucosal erosions equal to or greater than 0.5cm.As many

as 60-90% of such ulcers are associated with Helicobacter pylori, a
spiral-shaped bacterium that lives in the acidic environment of the
stomach.{Y.H. Kim et al. “long-term stress and Helicobacter pylori
infection independently induce gastric mucosal lesions in C57B-6
mice.”Scandinavian Journal of Gastroenterology.2002, 37 (11):1259-64.}
signs and symptoms of peptic ulcer
disease:
A dull or burning pain in the stomach is the most common symptom of
peptic ulcer disease. A person can feel this pain anywhere between the
navel and the breastbone. The pain usually

 occurs when a person’s stomach is empty—such as between

meals or during the night
 lessens briefly after eating food or taking antacids
 lasts for minutes to hours
 comes and goes for several days, weeks, or months

Other, less common symptoms include

 bloating
 burping
 changes in appetite
 nausea
 vomiting
 weight loss
{1Momtaz H, Souod N, Dabri H, Sarshar M. Study of Helicobacter
pylori genotype status in saliva, dental plaques, stool and gastric
biopsy samples. World Journal of Gastroenterology.
2012;18(17):2105–2111.}
They are two common forms of peptic
ulcers include:
1. Helicobacter pylori infection
2. Non-Steroidal anti-inflammatory drugs (NSAID) intake

 Psychological stress has been associated with increase gastric acid

secretion.
 Cigarette smoking is risk factor for peptic ulcer disease (PUD) and
has been shown to decrease gastric mucus production.
 Other risk factors include type O blood group, alcohol, chronic
pulmonary disease, reflux esophagitis, cirrhosis, and renal failure
transplantation.{clinical application, second edition unit vII 15,
page205-206}

Types of peptic Ulcers:

1- Gastric Ulcer

A Gastric ulcer is damage to the inner lining (the mucosa) of the stomach
or the upper part of the intestine (duodenum). A bacterium,Helicobacter
pylori, is the main cause of ulcers in this area.

Causes

The most common cause is infection with Helicobacter pylori bacteria

and this is responsible for up to 90 per cent of all cases of peptic
ulceration.

The second most common cause is damage inflicted by aspirin (eg

Disprin) or non-steroidal anti-inflammatory drugs (NSAIDs, such as
diclofenac (eg Voltarol) or naproxen (eg Synflex)) used by many for
arthritis, rheumatism, backache, headaches and period pain.Ulcers can
also occur in people weakened by severe disease (such as chronic
respiratory disease or major trauma). This is thought to result from poor
oxygenation to the lining of the stomach. Occasionally (in Europeans), a
stomach ulcer is caused by cancer and rarely, some other specific illness
is found to be responsible. Such conditions include:

 Excessive production of hydrochloric acid in the stomach

(Zollinger-Ellison syndrome)
 Crohn's disease (an inflammatory condition affecting any part of
the gut).

Symptoms And Signs

The symptoms are often described as

 Indigestion,
 Heartburn,
 Hunger pangs or
 Dyspepsia.

Some sufferers find that eating actually helps settle their discomfort for
a while, others find it makes them worse. Citrus drinks, spicy and
smoked foods can make the pain worse.Finally, it is important to stress
that most people with a stomach ache do not have ulcers.An ulcer is
potentially dangerous .

the warning signs are:

 difficulty swallowing or regurgitation

 persistent nausea and vomiting
 vomiting blood or vomit with the appearance of coffee grounds
 black or tar-like stools
 unintended weight loss
 anaemia (paleness and fatigue)
 sudden, severe and incapacitating abdominal pains.

2- Esophagus ulcer:

An esophagus ulcer is the chronic inflammation of the esophagus,

therefore often called esophagitis. Esophagus ulcers can lead to a
condition called Barrett Esophagus(Barrett's esophagus is a serious
complication of GERD, which stands for gastroesophageal reflux
 disease. In Barrett's esophagus, normal tissue lining the esophagus --
the tube that carries food from the mouth to the stomach -- changes
to tissue that resembles the lining of the intestine. About 10% of
people with chronic symptoms of GERD develop Barrett's
esophagus). Synonyms found for esophagus ulcer are Barrett Ulcer,
BE, Chronic Peptic Ulcer and Esophagitis Syndrome or Esophagitis-
Peptic Ulcer.

Causes

The ulceration of the esophagus is mostly caused through chronic

gastroesophageal reflux disease (GERD). GERD is a disease that causes
the stomach acids to reflux into the esophagus, causing heartburn.
However an esophagus ulcer can also be caused through infection with
candida species, the herpes virus (HSV), or the human papillomavirus
(HPV), among others. Infectious esophagus ulcers mainly occur in
patients with a weak immune system.
Other causes can be excessive vomiting, surgery or medications such as
aspirin or ibuprofen.

Symptoms And Signs

Typical symptoms may include:

 Difficulties swallowing(dysphagia) or painful swallowing

(odynophagia)
 sore throat
 hoarse voice
 Heartburn
 acid reflux
 Nausea
 Vomiting
 Abdominal Pain
 chest pain (worse with eating)
 decrease in appetite(Weight Loss)
 Cough
 Eventually the esophagus can narrow and make swallowing
difficult and painful (Barrett Ulcer).
 3- Duodenal ulcer

A duodenal ulcer is a type of peptic ulcer that occurs in the duodenum,

the beginning of the small intestine. Peptic ulcers are eroded areas in
the lining of stomach and duodenum, which result in abdominal pain,
possible bleeding, and other gastrointestinal symptoms.

Causes

The most common cause of duodenal ulcer is a stomach infection

associated with the Helicobacter pylori (H pylori) bacteria.

Other risk factors for duodenal ulcers include overuse of alcohol,

tobacco, and medications such as aspirin and nonsteroidal anti-
inflammatory drugs (NSAIDs). Severe illness has also been implicated as
a risk factor in the development of duodenal ulcer.

Symptoms And Signs

The signs and symptoms of duodenal ulcer can be constant or sporadic,

and the disease course varies among individuals. If H pylori is the cause
of the ulcer, the symptoms will remain as long as the infection is
untreated. Some people with duodenal ulcers have no symptoms at all,
while others may have burning pain, severe nausea, and vomiting.
{Advanced Gastroenterology © Copyright 2014 Advanced . All Rights
Reserved.}
Peptic Ulcer Disease: Causes
1- Protective vs. Hostile Factors
2- Helicobacter pylori
3- Nonsteroidal Anti-Inflammatory Drugs (NSAIDS)
4- Gastrinoma (Zollinger-Ellison Syndrome)
5- Hypercalcemia
6- Genetic factors
7- Smoking
8- Stress
9- Alcohol and Diet

1-Protective vs. Hostile Factors

“No gastric acid, no peptic ulcer” is a misconception. Excessive gastric

acid secretion is only one factor in the pathogenesis of peptic ulcer
disease. Decreased mucosal defense against gastric acid is another
cause. The integrity of the upper gastrointestinal tract is dependent
upon the balance between “hostile” factors such as gastric acid, H.
pylori, NSAIDs and pepsin, and “protective” factors such as
prostaglandins, mucus, bicarbonate, and blood flow to mucosa affecting
gastrointestinal mucosa (Figure 3).

Figure 3. A, Protective factors; B, hostile factors.

Injury to gastric and duodenal mucosa develops when deleterious
effects of gastric acid overwhelm the defensive properties of the
mucosa. Inhibition of endogenous prostaglandin synthesis leads to a
decrease in epithelial mucus, bicarbonate secretion, mucosal blood flow,
epithelial proliferation, and mucosal resistance to injury. Lower mucosal
resistance increases the incidence of injury by endogenous factors such
as acid, pepsin, and bile salts as well as exogenous factors such as
NSAIDs, ethanol and other noxious agents (Figure4).

Figure 4. Pathogenesis of peptic ulcer disease.

2-Helicobacter pylori

H. pylori is the etiologic factor in most patients with peptic ulcer disease
and may predispose individuals to the development of gastric
carcinoma. H. pylori colonizes in the human stomach (Figure 5). The
method of H. pylori transmission is unclear, but seems to be person-to
person spread via a fecal-oral route. The prevalence of H. pylori in adults
appears to be inversely related to the socioeconomic status. It is also
thought that water is a reservoir for transmission of H. pylori.
Figure 5. A, H. pylori resident on the gastric epithelium; B, electron micrograph.
3-Nonsteroidal Anti-Inflammatory Drugs (NSAIDS)

A small but important percentage of patients have adverse

gastrointestinal events associated with NSAID use that results in
substantial morbidity and mortality. Risk factors for the development of
NSAID-associated gastric and duodenal ulcers include advanced age,
history of previous ulcer disease, concomitant use of corticosteroids and
anticoagulants, higher doses of NSAIDs, and serious systemic disorders.
The concept of gastroduodenal mucosal injury has evolved from the
notion of topical injury to concepts that involve multiple mechanisms.
NSAIDs initiate mucosal injury topically by their acidic properties. By
diminishing the hydrophobicity of gastric mucus, endogenous gastric
acid and pepsin may injure surface epithelium. Systemic effects of
NSAIDs appear to play a predominant role through the decreased
synthesis of mucosal prostaglandins. The precursor of prostaglandins,
arachidonic acid, is catalyzed by the two cyclo-oxygenase isoenzymes,
cyclo-oxygenase-1 and cyclo-oxygenase-2.
The gene for cyclo-oxygenase-1,the housekeeping enzyme, maintains
the homeostasis of organs. Cyclo-oxygenase-2, the inflammatory
enzyme, is inducible. Although NSAIDs can inhibit both pathways, only
the gene for cyclo-oxygenase-2 contains a corticosteroid-responsive
repressor element (Figure 6). Literature suggests that the anti-
inflammatory properties of NSAIDs are mediated through inhibition of
cyclo-oxgenase-2, and adverse effects, such as gastric and duodenal
ulceration, occur as a result of effects on the constitutively expressed
cyclo-oxygenase-1.

Figure 6. Prostaglandin synthesis and mechanism of action Cox-2 inhibitors.

H. pylori is prevalent among 22–63% of patients taking NSAIDs. Most
studies do not show a significant difference in H. pylori prevalence
between NSAID users and nonusers. Gastritis in patients on NSAID
therapy appears to be related to underlying H. pylori rather than drug
use. The lower incidence of H. pylori among patients with gastric ulcers
than those with duodenal ulcers is presumably the result of NSAID use.
NSAIDs are more likely to cause gastric than duodenal ulcers. NSAIDs
appear to cause ulcers by a mechanism independent of H. pylori based
on the inhibition of prostaglandin synthesis.

4-Gastrinoma (Zollinger-Ellison Syndrome)

The classic triad of Zollinger-Ellison syndrome involves peptic ulcers in

unusual locations (i.e., the jejunum), massive gastric acid
hypersecretion, and a gastrinproducing islet cell tumor of the pancreas
(gastrinoma). Gastrinoma in the pancreas appears in approximately 50%
of patients. Another 20% of patients have it in the duodenum and others
have it in the stomach, peripancreatic lymph nodes, liver, ovary, or
small-bowel mesentery. Zollinger-Ellison syndrome accounts for only
0.1% of all duodenal ulcer disease. One fourth of patients have this
syndrome as part of the multiple neoplasia syndrome Type I (MEN I).
Patients with gastrinoma may have intractable ulcer disease. Because
gastrin is trophic to the gastric mucosa, endoscopy or x-ray may
demonstrate hypertrophy of the gastric rugae. Patients may also
experience diarrhea (including steatorrhea from acid inactivation of
lipase) and gastroesophageal reflux. These symptoms are episodic in
75% of patients.

5-Hypercalcemia

Hypercalcemia has a direct bearing on the gastric acid hypersecretory

state found in patients with Zollinger-Ellison syndrome and MEN I.
Intravenous calcium infusion in normal volunteers induces gastric acid
hypersecretion. Additionally, calcium has been demonstrated in vivo and
in vitro to stimulate gastrin release directly from gastrinomas.
Resolution of hypercalcemia (by parathyroidectomy) reduces the basal
acid output and serum gastrin concentration in fasting gastrinoma
patients and those with MEN I, suggesting that resolution of
hypercalcemia plays an important role in the therapy of this subgroup of
patients.
6-Genetic factors

Genetic factors play a role in the pathogenesis of ulcer disease. The

lifetime prevalence of developing ulcer disease in first-degree relatives
of ulcer patients is about three times greater than the general
population. Approximately 20–50% of duodenal ulcer patients report a
positive family history; gastric ulcer patients also report clusters of
family members who are likewise affected.

7-Smoking

The literature reveals a strong positive correlation between cigarette

smoking and the incidence of ulcer disease, mortality, complications,
recurrences and delay in healing rates. Smokers are about two times
more likely to develop ulcer disease than nonsmokers. Cigarette
smoking and H. pylori are co-factors for the formation of peptic ulcer
disease. There is a strong association between H. pylori infection and
cigarette smoking in patients with and without peptic ulcers. Cigarette
smoking may increase susceptibility, diminish the gastric mucosal
defensive factors, or may provide a more favorable milieu for H. pylori
infection.

8-Stress

Numerous studies have revealed conflicting conclusions regarding the

role of psychological factors in the pathogenesis and natural history of
peptic ulcer disease. The role of psychological factors is far from
established. Acute stress results in increases in pulse rate, blood
pressure and anxiety, but only in those patients with duodenal ulcers did
acute stress actually result in significant increases in basal acid secretion.
There is no clearly established “ulcer-type” personality. Ulcer patients
typically exhibit the same psychological makeup as the general
population, but they appear to perceive greater degrees of stress. In
addition, there is no evidence that distinct occupational factors influence
the incidence of ulcer disease.
9-Alcohol and Diet

Although alcohol has been shown to induce damage to the gastric

mucosa in animals, it seems to be related to the absolute ethanol
administered (200 proof). Pure ethanol is lipid soluble and results in
frank, acute mucosal damage. Because most humans do not drink
absolute ethanol, it is unlikely there is mucosal injury at ethanol
concentrations of less than 10% (20 proof). Ethanol at low
concentrations (5%) may modestly stimulate gastric acid secretions;
higher concentrations diminish acid secretion. Though physiologically
interesting, this has no direct link to ulcerogenesis or therapy. Some
types of food and beverages are reported to cause dyspepsia. There is
no convincing evidence that indicates any specific diet causes ulcer
disease. Epidemiologic studies have failed to reveal a correlation
between caffeinated, decaffeinated, or cola-type beverages, beer, or
milk with an increased risk of ulcer disease. Dietary alteration, other
than avoidance of pain-causing foods, is unnecessary in ulcer patients.
{ Summary of the National Institutes of Health consensus.
“Helicobacter pylori in peptic ulcer disease.” Maryland Medical Journal.
1994, 43:923-4.}

PEPTIC ULCER DISEASE: ANATOMY

The stomach is located in the upper part of the abdomen just beneath
the diaphragm. The stomach is distensible and on a free mesentery,
therefore, the size, shape, and position may vary with posture and
content. An empty stomach is roughly the size of an open hand and
when distended with food, can fill much of the upper abdomen and may
descend into the lower abdomen or pelvis on standing. The duodenum
extends from the pylorus to the ligament of treitz in a sharp curve that
almost completes a circle. It is so named because it is about equal in
length to the breadth of 12 fingers, or about 25 cm. It is largely
retroperitoneal and its position is relatively fixed. The stomach and
duodenum are closely related in function, and in the pathogenesis and
manifestation of disease.

The stomach may be divided into seven major sections. The cardia is a
1-2 cm segment distal to the esophagogastric junction. The fundus refers
to the superior portion of the stomach thet lies above and imaginary
horizontal plane that passes through the esophagogastric junction. The
antrum is the smaller distal one-fourth to one-third of the stomach. The
narrow 1-2 cm channel that connects the stomach and duodenum is the
pylorus. The lesser curve refers to the medial shorter border of thhe
stomach, whereas the opposite surface is the greater curve. The
angularis is along the lesser curve of the stomach where the body and
antrum meet, and is accentuated during peristalsis (figure 2).

Figure 2. A, Normal anatomy of the stomach and duodenum; B-D, corresponding endoscopic
images.

The duodenum extends from the pylorus to the ligament of Treitz in a

circle-like curve and is divided into four portions. The superior portion is
approximately 5 cm in length, beginning at the pylorus, and passes
beneath the liver to the neck of the gallbladder. The first part of the
superior portion (2–3 cm) is the duodenal bulb. The descending or
second part of the duodenum takes a sharp curve and goes down along
the right margin of the head of the pancreas. The common bile duct and
the pancreatic duct enter the medial aspect of this portion of the
duodenum at the major papilla either separately or together. The
duodenum turns medially, becoming the horizontal portion, and passes
across the spinal column, inclining upward for 5–8 cm. The ascending
portion begins at the left of the spinal column, ascending left of the
aorta for 2–3 cm, and ends at the ligament of Treitz, where the intestine
angles forward and downward to become the jejunum.
{ D.Y. Graham et al. “Recognizing peptic ulcer disease: Keys to clinical
and laboratory diagnosis.” Postgraduate Medicine. 1999, 105(3):113-
133.}

Peptic Ulcer Disease: Complications

Associated Complications

About 25 percent of patients with peptic ulcer disease have a serious

complication such as hemorrhage, perforation, or gastric outlet
obstruction. Silent ulcers and complications are more common in older
patients and in patients taking NSAIDs.
{Hilton D, Iman N, Burke GJ, Moore A, O’Mara G, Signorini D, et al.
Absence of abdominal pain in older persons with endoscopic ulcers: a
prospective study. Am J Gastroenterol 2001;96:380-4.}
{Martinez JP, Mattu A. Abdominal pain in the elderly. Emerg Med Clin
North Am 2006;24:371-88.}

The incidence of seriousupper gastrointestinal complications among

persons in the general population who do not take NSAIDs is extremely
low (less than one per 1,000 person-years).
{ Hernandez-Diaz S, Rodriguez LA. Incidence of serious upper
gastrointestinal bleeding/perforation in the general population: review
of epidemiologic studies. J Clin Epidemiol 2002;55:157-63.}
Bleeding

Upper gastrointestinal bleeding occurs in 15 to 20 percent of patients

with peptic ulcer disease. It is the most common cause of death and the
most common indication for surgery in the disease. In older persons, 20
percent of bleeding episodes result from asymptomatic ulcers.
{Martinez JP, Mattu A. Abdominal pain in the elderly. Emerg Med Clin
North Am 2006;24:371-88.}

Patients may present with hematemesis (bright red or “coffee ground”),

melena, fatigue caused by anemia, orthostasis, or syncope.
There are several risk-stratification schemes that can help physicians
determine the need for urgent intervention and predict continued or
recurrent bleeding after endoscopic therapy. The Rockall risk scoring
system is useful in stratifying patients at higher risk of rebleeding and
death and has been prospectively validated in different populations.
{Rockall TA, Logan RF, Devlin HB, Northfield TC. Risk assessment after
acute upper gastrointestinal haemorrhage. Gut 1996;38:316-21.}

In stable patients with gastrointestinal bleeding, potentially ulcerogenic

medications should be discontinued. A proton pump inhibitor should be
administered intravenously; this reduces transfusion requirements, need
for surgery, and duration of hospitalization, although it does not reduce
mortality.
{Leontiadis GI, Sharma VK, Howden CW. Systematic review and
metaanalysis: proton-pump inhibitor treatment for ulcer bleeding
reduces transfusion requirements and hospital stay—results from the
Cochrane Collaboration. Aliment Pharmacol Ther 2005;22:169-74.}
EGD ( EGD stands for EsophagoGastroDuodenoscopy. An EGD also
called “upper endoscopy”) should be performed to find characteristics
that suggest a high rate of bleeding recurrence (e.g., ulcer larger than
1 cm, visible or actively bleeding vessel).
{Rockall TA, Logan RF, Devlin HB, Northfield TC. Risk assessment after
acute upper gastrointestinal haemorrhage. Gut 1996;38:316-21.}
Patients whose condition is unstable should undergo fluid or
packed-cell resuscitation followed by emergent EGD and coagulation
of bleeding sites through endoscopic ligation; placement of
hemoclips; injection of epinephrine, alcohol, or a sclerosant; or a
combination of methods.
{Eisen GM, Dominitz JA, Faigel DO, Goldstein JL, Kalloo AN, Petersen
BT, et al., for the American Society for Gastrointestinal Endoscopy.
Standards of Practice Committee. An annotated algorithmic approach
to upper gastrointestinal bleeding. Gastrointest Endosc 2001;53:853-
8.}
Oral antisecretory therapy should be initiated as soon as patients
resume oral intake. Treatment of H. pylori infection is more effective
than antisecretory therapy without eradication of H. pylori for
preventing recurrent bleeding. Therefore, patients with bleeding
peptic ulcers should be tested for H. pylori infection and should be
prescribed eradication therapy if results are positive.
{Gisbert JP, Khorrami S, Carballo F, Calvet X, Gene E, Dominguez-
Munoz E. Meta-analysis: Helicobacter pylori eradication therapy vs.
antisecretory non-eradication therapy for the prevention of recurrent
bleeding from peptic ulcer. Aliment Pharmacol Ther 2004;19:617-29.}
If continued administration of aspirin or NSAIDs is required,
concurrent administration of misoprostol or a proton pump inhibitor
should be considered.
{Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bittman
RM, et al. Misoprostol reduces serious gastrointestinal complications
in patients with rheumatoid arthritis receiving nonsteroidal anti-
inflammatory drugs. A randomized, double-blind, placebo-controlled
trial. Ann Intern Med 1995;123:241-9.}
{Rostom A, Dube C, Wells G, Tugwell P, Welch V, Jolicoeur E, et al.
Prevention of NSAID-induced gastroduodenal ulcers. Cochrane
Database Syst Rev 2002;(4):CD002296.}
Patients with nonhealing gastric ulcers should have biopsy to rule out
cancer. Angiographic embolization of bleeding vessels or surgery is
indicated if a patient’s vital signs or laboratory studies suggest continued
or recurrent bleeding.
{Eisen GM, Dominitz JA, Faigel DO, Goldstein JL, Kalloo AN, Petersen
BT, et al., for the American Society for Gastrointestinal Endoscopy.
Standards of Practice Committee. An annotated algorithmic approach
to upper gastrointestinal bleeding. Gastrointest Endosc 2001;53:853-
8.}
Surgical options include gastroduodenotomy and oversewing of the
blood vessel with or without vagotomy and drainage in duodenal ulcer;
and excision of the ulcer with vagotomy and drainage or partial
gastrectomy in bleeding gastric ulcers.
Perforation

Perforation occurs in approximately 2 to 10 percent of peptic ulcers.

{Behrman SW. Management of complicated peptic ulcer disease. Arch
Surg 2005;140:201-8.}
It usually involves the anterior wall of the duodenum (60 percent),
although it may also occur in antral (20 percent) and lesser-curve (20
percent) gastric ulcers. Perforation of ulcers in children is rare. Free
peritoneal perforation and resulting chemical and bacterial peritonitis is
a surgical emergency causing sudden, rapidly spreading, severe upper
abdominal pain exacerbated by movement; the pain may radiate to the
right lower abdomen or to both shoulders. Fever, hypotension, and
oliguria suggest sepsis and circulatory compromise. Generalized
abdominal tenderness, rebound tenderness, board-like abdominal wall
rigidity, and hypoactive bowel sounds (clinical signs of peritonitis) may
be masked in older patients and those taking steroids,
immunosuppressants, or narcotic analgesics.
Upright or lateral decubitus abdominal radiography or erect chest
radiography may demonstrate pneumoperitoneum; however, the
absence of this finding does not rule out perforation.
{Martinez JP, Mattu A. Abdominal pain in the elderly. Emerg Med Clin
North Am 2006;24:371-88.}
Sonography, computed tomography, and gastroduodenography are
confirmatory.
Initial resuscitation with large-volume crystalloids; nasogastric suction;
and administration of intravenous broad-spectrum antibiotics against
gram-negative rods, anaerobes, and oral flora are usually followed by
laparotomy and placement of an omental patch (Graham patch
plication) in patients with perforated duodenal ulcers. In otherwise
healthy patients with a history of chronic ulcer and minimal peritoneal
contamination, a concurrent, definitive, anti-ulcer procedure (e.g.,
vagotomy and drainage, highly selective vagotomy) may also be
considered. Perforated gastric ulcers are treated with an omental patch,
wedge resection of the ulcer, or a partial gastrectomy and
reanastomosis. Coexisting H. pylori infection should be eradicated to
reduce recurrence and minimize the need for long-term antisecretory
therapy and further surgical intervention.
{Behrman SW. Management of complicated peptic ulcer disease. Arch
Surg 2005;140:201-8.}
{Ng EK, Lam YH, Sung JJ, Yung MY, To KF, Chan AC, et al. Eradication
of Helicobacter pylori prevents recurrence of ulcer after simple closure
of duodenal ulcer perforation: randomized controlled trial. Ann Surg
2000;231:153-8.}
In older patients, mortality rates from perforation and its management
may be as high as 30 to 50 percent.
{University of Michigan Health System. Peptic ulcer disease. Accessed
May 4, 2007,
at: http://www.cme.med.umich.edu/pdf/guideline/PUD05.pdf.}

Gastric outlet obstruction

Peptic ulcer disease is the underlying cause in less than 5 to 8 percent of

patients presenting with gastric outlet obstruction. Patients with
recurrent duodenal or pyloric channel ulcers may develop pyloric
stenosis as a result of acute inflammation, spasm, edema, or scarring
and fibrosis. Symptoms suggesting obstruction include recurrent
episodes of emesis with large volumes of vomit containing undigested
food; persistent bloating or fullness after eating; and early satiety.
Weight loss, dehydration, and a hypochloremic, hypokalemic metabolic
alkalosis may result; a tympanitic epigastric mass representing the
dilated stomach with visible gastric peristalsis also may be observed.
EGD or gastroduodenography (using diatrizoate meglumine and
diatrizoate sodium [Gastrografin] or barium) is recommended to
determine the site, cause, and degree of obstruction. Malignancy, a
more common cause of obstruction (responsible for more than 50
percent of cases), should be ruled out.
{Shone DN, Nikoomanesh P, Smith-Meek MM, Bender JS. Malignancy is
the most common cause of gastric outlet obstruction in the era of H2
blockers. Am J Gastroenterol 1995;90:1769-70.}
Obstruction resulting from acute inflammation or edema responds well
to nasogastric decompression, administration of H2 blockers or proton
pump inhibitors, and eradication of H. pylori. Prokinetic agents should be
avoided. Endoscopic pyloric balloon dilatation or surgery (vagotomy
and pyloroplasty, antrectomy, or gastroenterostomy) are options to
relieve chronic obstruction.
{Behrman SW. Management of complicated peptic ulcer disease. Arch
Surg 2005;140:201-8.}
Peptic Ulcer Disease: Diagnosis

Overview

Peptic ulcer disease is suspect in patients with epigastric distress and

pain; however, these symptoms are not specific. Lack of response to
conventional treatment for peptic ulcer disease should suggest
conditions other than benign peptic ulcers, and should warrant
endoscopy or abdominal imaging. { © Copyright 2001-2013 | All Rights
Reserved.600 North Wolfe Street, Baltimore, Maryland 21287}

Types of Diagnosis:
1-History taking
2-Laboratory tests
3-Radiologic imaging
4-Endoscopic examination.{porth C. M., Kunert M. P.(2002).
Pathophysiology concepts of altered health states, LIPPINCOTT
WILLIAMS & WILKINS , SIXTH EDITION.}

1-History taking

The history should include careful attention to aspirin and NSAID use.
Peptic ulcer should be differentiated from other causes of epigastric
pain. .{porth C. M., Kunert M. P.(2002). Pathophysiology concepts of
altered health states, LIPPINCOTT WILLIAMS & WILKINS , SIXTH
EDITION.}

2-Laboratory tests

A health care provider will look to see if H. pylori are present using one
of three simple tests:
 blood test
 urea breath test
 stool test
Blood test

A blood test involves drawing a sample of a patient’s blood at a health

care provider’s office or a commercial facility and sending the sample to
a lab for analysis. The blood test can show the presence of H. pylori.

Urea breath test

For a breath test, the patient swallows a special liquid that contains
urea—a waste product the body produces as it breaks down protein. If
H. pylori are present, the bacteria will convert the urea into carbon
dioxide. A nurse or technician will take samples of a patient’s breath at a
health care provider’s office or a commercial facility and send the
samples to a lab to measure the level of carbon dioxide.

Stool test

A stool test is the analysis of a sample of stool. The health care provider
will give the patient a container to take home for catching and storing
the stool. The patient returns the sample to the health care provider or a
commercial facility, and it is sent to a lab for analysis. Stool tests can
show the presence of H. pylori. {1Momtaz H, Souod N, Dabri H, Sarshar
M. Study of Helicobacter pylori genotype status in saliva, dental plaques,
stool and gastric biopsy samples. World Journal of Gastroenterology.
2012;18(17):2105–2111.}
3-Radiologic imaging

X-ray studies with a contrast medium such as barium are used to detect
the presence of an ulcer crater and to establish a peptic ulcer in the
stomach (Figure 7) or duodenum (Figure 8) and to exclude gastric
carcinoma

Figure 7. A, X-ray of gastric ulcer in the antrum; B, corresponding illustration of a gastric

ulcer.
 Figure 8. A, Duodenal ulcer; B, corresponding x-ray.

Though less invasive than endoscopy, the barium x-ray is limited by

being less sensitive and accurate at defining mucosal disease, or
distinguishing benign from malignant ulcer disease (Figure 9). In patients
who have anatomic deformities from previous gastric surgery or scarring
from chronic inflammation, barium x-rays may be difficult to interpret.
Generally, these x-rays have up to a 30% false negative and a 10% false
positive rate. Until 1970, peptic ulcers were diagnosed almost
exclusively by radiological methods. The most common inaccuracies of
radiological diagnosis include the failure to recognize true ulcers, or the
misdiagnosis of a scar or a deformed duodenal bulb as a true ulcer. Since
the 1970s, increasing numbers of peptic ulcers are diagnosed by
endoscopy. {© Copyright 2001-2013 | All Rights Reserved.600 North
Wolfe Street, Baltimore, Maryland 21287}

Figure 9. Peptic ulcers; A. malignant; B. benign.

4- Endoscopic examination

Endoscopy (i.e., gastroscopy and duodenoscopy) can be used to visualize

the ulcer area and obtin biopsy speciments to test for H.pylori and
exclude ,alignant disease. Methods for establishing the presence of
H.pylori include the C urea breath test using a radioactive isotope (13C
or 14 C), the stool antigen test, and endoscopic biopsy for urease testing.
Blood tests to obtain serologic titers of H.pylori antibodies also can be
done. The serologic test can establish that a person has been infected
with H.pylori, but it cannot distinguish how recently the infection
occurred. {porth C. M., Kunert M. P.(2002). Pathophysiology concepts
of altered health states, LIPPINCOTT WILLIAMS & WILKINS , SIXTH
EDITION.}

An endoscope (a thin, flexible, lighted tube) is passed through the mouth

and pharynx and into the esophagus. The forward-viewing scope
transmits an image of the esophagus, stomach and duodenum to a
monitor visible to the physician (Figure 12). Air may be introduced into
the stomach, expanding the folds of tissue, and enhancing examination
of the stomach. {PDR Medical Staff. PDR Guide to Drug Interactions, Side
Effects and Indications; 2009 edition}

Esophagogastroduodenoscopy (EGD) is the most direct and most

accurate method of establishing the diagnosis of peptic ulcer disease
(Figures 13 and 14). In addition to identifying the ulcer, its location and
size, EGD also provides an opportunity to detect subtle mucosal lesions
and to biopsy lesions to establish histopathological basis. Endoscopic
biopsies are indicated for all gastric ulcers at the time of diagnosis,
whereas duodenal ulcers are almost always benign, not requiring biopsy
in usual circumstances. {K.S. Han. “The effect of an integrated stress
management program on the psychological and physiologic stress
reactions of peptic ulcer in korea.” Journal of holistic Nursing. 2002,
20(1):61-80.
Endoscopic biopsy also appears the best and most accurate diagnostic
method for H. pylori. Histological examination with standard
hematoxylin and eosin staining provides an excellent means of diagnosis
(Figure 15). {K.S. Mota et al. “Flavonoids with gastroprotective
activity.” Molecules. 2009, 3; 14(3):979-1012. Review.
Peptic Ulcer Disease: Treatment s and
drugs
Overview

The treatment of peptic ulcer has changed dramatically over the past
several years, and now aims to eradicate tha cause and effect a
permanent cure for the disease. Pharmacologic treatment focuses on
eradicating H.pylori, relieving ulcer symptoms, and healing the ulcer
crater. Acid-neutralizing, acid-inhibiting drugs and mucosal protective
agents are used to relieve symptoms and promote healing of the ulcer
crater. There is no evidence that special diets are beneficial in treating
peptic ulcer. Aspirin and NSAID use should be avoided when possible.
{porth C. M., Kunert M. P.(2002). Pathophysiology concepts of altered
health states, LIPPINCOTT WILLIAMS & WILKINS , SIXTH EDITION.}
Treatment of peptic ulcer by Natural Remedies:

A variety of nutritional strategies and dietary supplements have a

positive impact on reducing the symptoms and retarding the
development of gastric ulcers. Flavonoids and antioxidants such as
anthocyanidins and resveratrol (found in blueberries, cherries, red
grapes, and tomatoes) inhibit the growth of H. pylori, which can have
dramatic implications for gastric ulcer causality.
{K.S. Mota et al. “Flavonoids with gastroprotective activity.”
Molecules. 2009,3;14(3):979-1012. Review.}
{A. Solmaz et al. “Protective and therapeutic effects of resveratrol on
acetic acidinduced gastric ulcer.” Free Radical Research. 2009,
43(6):594-603.}
Probiotic supplements containing Lactobacillus acidophilus may help
maintain a balance in the digestive system between beneficial and
harmful bacteria, suppress H. pylori infection, and help reduce side
effects from taking antibiotics.
{P. Marteau et al. “Nutritional advantages of probiotics and
prebiotics.” British Journal of Nutrition. 2002, 87(Sup. 2):S153-S157.}
Vitamin C supplements (500 to 1,000 mg 1-3 times daily) deter the
proliferation of H. pylori and are helpful in treating bleeding gastric
ulcers caused by aspirin use.
{M. Jarosz. “Effects of high dose vitamin C treatment on Helicobacter
pylori infection and total vitamin C concentration in gastric juice.”
European Journal of Cancer Prevention. 1999, 7(60):449-454.}
Herbs have also proven helpful with treating gastric ulcers and can be
taken fresh or as dried extracts or tinctures.
 Cranberry (Vaccinium macrocarpon)
 curcumin, enteric coated peppermint (Mentha piperita)
 black pepper (Piper nigrum)
 DGL-licorice (Glycyrrhiza glabra)
 green tea (Camellia sinensis)
 and mastic (Pistacia lentiscus)
all help to inhibit H. pylori growth and protect the stomach against
damage from NSAIDs.
{O. Burger et al. “Inhibition of Helicobacter pylori adhesion to human
gastric mucus by a high-molecular-weight constituent of cranberry
juice.” Critical Reviews in Food Science and Nutrition. 2002, 42(3
Suppl):279-284.}
{C. Cabrera et al. “Beneficial effects of green tea -- a review.” Journal of
the American College of Nutrition. 2006, 25(2):79-99.}
{R. De et al. “Antimicrobial activity of curcumin against Helicobacter
pylori isolates from India and during infections in mice.” Antimicrobial
Agents and Chemotherapy. 2009, 53(4):1592-7.}

The Pharmaceutical Treatment of

Peptic Ulcers:

The modern history of peptic ulcer disease has followed a remarkable

course and lead to widespread acceptance of the notion that the
majority of gastric ulcers are caused by H. pylori and the institution of
treatment protocols such as “triple therapy,” which has had dramatic
effects (greater than 90 percent initial eradication rate and less than 10
percent re-infection rate at five years).
{A. Qasim et al. “Review article: treatment of Helicobacter pylori
infection and factors influencing eradication.” Alimentary
Pharmacological Therapeutics. 2002, 16(Suppl 1):24-30.}
Triple therapy is the use of a proton-pump inhibitor or H2 blocker
(which both reduce gastric acid secretion) with either two different
antibiotics or an antibiotic combined with bismuth salicylate (found in
Pepto-Bismol). The discovery of effective and potent acid suppressants
and the identification of the largely bacteria cause of peptic ulceration
are the two most important developments that are associated with the
overall decreased rates seen with peptic ulcer disease.
{P. Malfertheiner et al. “Peptic Ulcer Disease.” Lancet. 2009, 374:1449-
61.}
Additionally, the morbidity associated with H. pylori infection has
dramatically decreased from 1993 to present due mainly to triple
therapy.
{B. Bashinskaya et al. “Trends in Peptic Ulcer Disease and the
Identification of Helicobacter Pylori as a Causative Organism:
Population-based Estimates from the US Nationwide Inpatient
Sample.” Journal of Global Infectious Diseases. 2011, 3(4):366–370.}
Although the overall rates of peptic ulcer disease have decreased,
incidence of gastric ulceration has increased over the last few decades
due to increased NSAID use. Thus, antibiotics or triple therapy are not
given to patients with gastric ulcers caused by NSAIDs; rather, their pain
medications are either reduced, eliminated or altered, and acid-reducing
medications may be recommended for a few months to allow the
ulceration to heal.

1) Proton-Pump Inhibitors

Proton-pump inhibitors are a group of drugs that display pronounced

and long-lasting reduction of stomach acid production. They are among
the most widely sold drugs in the world and are generally considered the
most potent inhibitors of acid secretion, more so than an earlier class of
inhibitors called H2-receptor antagonists (or simply H2 blockers).
{Canadian Pharmacists Association. Compendium of Pharmaceuticals
and Specialties; 2008 edition.}
Proton-pump inhibitors act by irreversibly blocking the hydrogen /
potassium adenosine triphosphatase enzyme system (commonly called
the gastric proton pump) of the stomach’s parietal cells. The proton-
pump is the final stage in stomach acid secretion, being directly
responsible for secreting hydrogen ions into the gastric lumen and
making it an ideal target for inhibiting acid secretion. Proton-pump
inhibitors reduce gastric acid secretion by up to 99 percent. Proton-
pump inhibitors are given in an inactive form, which readily crosses cell
membranes and enters into parietal cells, where they become activated
by the acidic environment. The lack of stomach acid aids in the healing
of gastric ulcers and reduces the pain from indigestion and heartburn,
but hydrochloric acid is required for the digestion of proteins and
absorption of nutrients, especially vitamin B-12 and calcium. As such,
hypochlorhydria (insufficient hydrochloric acid) can lead to a variety of
side effects such as B-12 deficiency (which often mimics symptoms of
Alzheimer’s), increased risk of bone fracture, increased risk of certain
heart arrhythmias and interstitial nephritis, low serum magnesium levels
(hypomagnesemia), headaches (the most commonly reported adverse
effect), nausea, diarrhea, abdominal pain, flatulence, constipation,
fatigue and dizziness.
{Canadian Pharmacists Association. Compendium of Pharmaceuticals
and Specialties; 2008 edition.}

Furthermore, recent data suggests that there may be a rebound effect

when proton-pump inhibitors are discontinued.
{C. Reimer et al. “Proton-Pump Inhibitor Therapy Induces Acid-Related
Symptoms in Healthy Volunteers after Withdrawal of Therapy.”
Gastroenterology. 2009,137(1):80-87.}
In other words, stopping use can cause an increase in stomach acid
production above that of normal levels that lasts for several weeks.
The most common clinically used proton-pump inhibitors include
omeprazole (Losec, Prilosec, Zegerid, Lomac, Omepral, Omez),
lansoprazole (Prevacid, Zoton, Monolitum, Inhibitol, Levant, Lupizole),
dexlansoprazole (Kapidex, Dexilant), esomeprazole (Nexium, Esotrex),
pantoprazole (Protonix, Somac, Pantoloc, Pantozol, Zurcal, Zentro,
Controloc) and rabeprazole (Zechin, Rabecid, Nzole-D, Aciphex, Pariet,
Rabeloc). The vast majority of these drugs are known as benzimidazole
derivatives, but new research indicates that imidazopyridine derivatives
may be a more effective means of treatment.
{G. Sachs et al. “Review Article: The clinical pharmacology of proton
pump inhibitors.” Alimentary Pharmacological Therapeutics. 2006,
23(2):2–8.}

2) H2 Blockers

H2 blockers, also known as histamine blockers or H2-receptor

antagonists, are competitive antagonists of histamine at the parietal cell
H2-receptors in the stomach. H2 blockers suppress the secretion of
hydrochloric acid by parietal cells by two mechanisms: histamine
released by enterochromaffin-like cells in the stomach is blocked from
binding on parietal cell H2-receptors, which stimulate acid secretion;
and as a consequence, other substances that promote acid secretion
(such as gastrin and acetylcholine) have a reduced effect on parietal cells
when the H2- receptors are blocked. H2 blockers are still commonly
used for the treatment of dyspepsia, but they have been surpassed in
popularity by the more effective proton-pump inhibitors for the
treatment of gastric ulcers.
In the U.S., all four FDA-approved members of the H2 blocker group
(cimetidine, ranitidine, famotidine and nizatidine) are available over-the-
counter in relatively low doses, or by prescription in larger doses. Brand
names for these drugs include Tagamet (cimetidine), Zantac (ranitidine),
Pepcid (famotidine) and Axid (nizatidine). Much like proton-pump
inhibitors, H2 blockers are generally well-tolerated, with the exception
of cimetidine (Tagamet), which was the first H2 blocker developed in the
mid-to-late 1960s. Cimetidine became the first “blockbuster drug”
(adrug generating more than one billion USD of revenue per year), but it
was discovered to interfere with the body's mechanisms of drug
metabolism and elimination through the liver cytochrome P450
pathway. As such, cimetidine use increases the risk of drug toxicity, and
has also been linked to hypotension, gynecomastia in males, loss of
libido, and impotence.
{PDR Medical Staff. PDR Guide to Drug Interactions, Side Effects and
Indications; 2009 edition.}
Ranitidine (Zantac) was introduced in 1981 and was found to have a far
better tolerability profile (fewer adverse drug reactions), longer-lasting
action, and ten-times the biochemical activity of cimetidine. However,
the most common side effects of H2 blockers can be similar to most
proton-pump inhibitors because they too greatly reduce the production
of hydrochloric acid, which is needed for healthy digestion and the
absorption of vitamin B-12 and calcium. Due to their adverse effects on
digestion and nutrient absorption, acid-reducing medications are only
recommended for a consecutive duration of about two months.

Side effects:

Less serious side effects may include:

 Headache (may be severe);

 Drowsiness, dizziness;
 Sleep problems (insomnia);
 Decreased sex drive, impotence, or difficulty having an orgasm; or
 Swollen or tender breasts (in men);
 Nausea, vomiting, stomach pain; or
 Diarrhea or constipation.
{C. Reimer et al. “Proton- Pump Inhibitor Therapy Induces Acid-
Related Symptoms in Healthy Volunteers after Withdrawal of
Therapy.” Gastroenterology. 2009,137(1):80-87.}

3) Antibiotics

Antibiotics are prescribed to kill bacteria such as H. pylori, but due to

resistance and adaptability, more than one type is often recommended
to be taken at the same time. Antibiotic regimens are different
throughout the world, but in the U.S., antibiotics prescribed for treating
H. pylori include amoxicillin, clarithromycin (Biaxin), metronidazole
(Flagyl), furazolidone (Furoxone) and tetracycline. Antibiotics are usually
prescribed for only two weeks at a time in order to avoid side effects.
Relatively common side effects of antibiotic use include acquired
resistance to antibiotic therapy, serious allergic reactions (including
anaphylaxis), nausea, upset stomach, diarrhea, sun sensitivity, disruption
of the intestinal flora and fauna, systemic overgrowth of pathogenic
bacteria (such as Clostridium difficile) and yeast species (such as Candida
albicans), and numerous potential interactions with other drugs.
{PDR Medical Staff. PDR Guide to Drug Interactions, Side Effects and
Indications; 2009 edition.}
In the U.S., clarithromycin-based triple therapy (combined with a
proton-pump inhibitor and either amoxicillin or metronidazole for 10-14
days) is considered the standard treatment for an ulcer caused by H.
pylori; however, other protocols are also popular. Research shows
higher cure rates with 14 days of treatment, although side effects
become much more probable and severe beyond this time frame.
{Canadian Pharmacists Association. Compendium of Pharmaceuticals
and Specialties; 2008 edition.}
At least four weeks after the initiation of antibiotic treatment, the
patient is tested by the doctor using a breath or stool test to be sure the
H. pylori infection has been eradicated. Blood tests are not useful after
treatment because a patient's blood can test positive for H. pylori even
after the bacteria have been eliminated. If the infection remains,
another two-week round of triple therapy is usually recommended, but
typically with a different combination of antibiotics to prevent resistance
(although H. pylori resistance to amoxicillin is considered rare). Another
strategy, called “salvage” or quadruple therapy, involves adding bismuth
salicylate compounds to the treatment protocol.

4) Bismuth Salicylate

Medications that protect the lining of the stomach and small intestine
from the damaging effects of acid are called cytoprotective agents and
include the prescription medications sucralfate (Carafate) and
misoprostol (Cytotec), and over-the-counter agents such as bismuth
salicylate (Pepto-Bismol). Bismuth compounds may also directly kill H.
pylori, although its antibacterial actions should not be viewed as a
replacement for conventional antibiotics. Bismuth salicylate, like all
salicylates (especially aspirin), can cause serious bleeding problems
when used alone in patients with bleeding ulcers. Bismuth quadruple
therapy usually involves combining bismuth salicylate with a proton-
pump inhibitor, tetracycline and metronidazole for 10-14 days.

The main reasons to add bismuth salicylate to a treatment regime for

gastric ulcers is if the patient is still infected with H. pylori after a trial of
triple therapy, or if the patient cannot take amoxicillin (a penicillin-like
antibiotic) because of a penicillin allergy, or if the patient has been
treated before with a macrolide antibiotic, such as clarithromycin.
{PDR Medical Staff. PDR Guide to Drug Interactions, Side Effects and
Indications; 2009 edition.}
Side effects from bismuth salicylate are considered rare, but the most
common are benign and include darkening of the stools and/or tongue,
and a metallic taste in the mouth.

Side effects:

 Anxiety
 Any loss of hearing
 Confusion
 Connstipation (severe)
 Diarrhea (severe or continuing)
 Difficulty in speaking or slurred speech
 Dizziness or lightheadedness
 Drowsiness (severe)
 Fast or deep breathing
 Headache (severe or continuing)
 Increased sweating
 Increased thirst
 Mental depression
 Muscle spasms (especially of face, neck, and back)
 Muscle weakness
 Nausea or vomiting ( severe or continuing)
 Ringing or buzzing in ears (continuing)
 Stomach pain (severe or continuing)
 Trembling
 Uncontrollable flapping movements of the hands (especially in
elderly patients) or other uncontrolled body movements
 Vision problems
 {D.L. Diehl. “Acupuncture for gastrointestinal and hepatobiliary
disorders.” Journal of Alternative and Complementary Medicine.”
1999, 5(1):27-45.}

Summary of Common Pharmaceutical Protocols:

Proton-pump inhibitor / H2-blocker + clarithromycin + metronidazole /

amoxicillin

Proton-pump inhibitor / H2-blocker + metronidazole + tetracycline /

bismuth salicylate

Proton-pump inhibitor / H2-blocker + furazolidone + tetracycline /

bismuth salicylate

5) Antacids:

Antacids are available over-the-counter. They neutralize existing

stomach acid, which can provide relief of burning stomach pain,
heartburn, and indigestion, but they are not considered as a treatment
for gastric ulcers. Antacids do not kill H. pylori nor do they block the
production of stomach acid. Commonly used antacids include aluminum
hydroxide (Amphojel, AlternaGEL), magnesium hydroxide (Milk of
Magnesia), aluminum hydroxide combined with magnesium hydroxide
(Maalox, Mylanta), calcium carbonate (Rolaids, Titralac, Tums), and
sodium bicarbonate (Alka-Seltzer). It is recommended to take antacids at
least one hour before or two hours after taking other medications
because antacids may block the medications from being absorbed and
effectively utilized.
{PDR Medical Staff. PDR Guide to Drug Interactions, Side Effects and
Indications; 2009 edition.}
Other side effects can include constipation or diarrhea, depending on
the main ingredients of the antacids.

Ulcers that Fail to Heal:

Peptic ulcers that don't heal with treatment are called refractory ulcers and may
require surgery. Surgical procedures may involve a vagotomy or cauterization.
Common reasons why ulcers fail to heal include: not taking medications according to
directions, antibiotic resistant H. pylori population, patient’s use of tobacco or pain
relievers that increase the risk of ulcers. Less often, refractory ulcers may be a result
of extreme overproduction of stomach acid, which occurs in Zollinger-Ellison
syndrome.