CASE 19

A 40 year old man was seen by a physician 12 months ago

complaining of dyspepsia, which occurred sometimes after
eating. The discomfort was relieved by eating a meal or taking
antacids. The physician diagnosed the case as peptic ulcer and
prescribed a drug, which provided rapid for 1 month and had
no further dyspepsia for 6 months. However, over the next few
months, the symptoms recurred and grew progressively worse.
Now, on a return visit to the same physician, further
investigations have demonstrated the presence of a duodenal
ulcer, while the culture showed the presence of Helicobacter
pylori. This time the physician prescribed another therapeutic
regimen

*Discuss drugs that are used to relieve the symptoms of peptic
ulcer?
Explain why the ulcer relapsed? *
Specify the drugs probably prescribed on the second visit? *
*State the chances of cure by the most appropriate drugs
prescribed?





Introduction :
Food passes down the oesophagus (gullet) into the stomach. The
stomach makes acid which is not essential, but helps to digest
food. After being mixed in the stomach, food passes into the
duodenum (the first part of the small intestine). In the duodenum
and the rest of the small intestine, food mixes with enzymes
(chemicals). The enzymes come from the pancreas and from cells
lining the intestine. The enzymes break down (digest) the food
which is absorbed into the body.
peptic ulcer Duodenal Ulcers

An ulcer is where the lining of the gut is
damaged and the underlying tissue is
exposed.
A duodenal ulcer is a sore in the lining of the
intestine. It is in the first part of your small
infection associated with mostly intestine
) bacteria. pylori H ( pylori Helicobacter the
occur in the stomach upper region of the small intestine.
an ulcer looks like a small, red crater on the
inside lining of the gut.
Duodenal ulcers cause an aching, burning,
hunger-like pain in the upper-middle portion
of the abdomen, just below the breastbone.
The pain from these ulcers tends to occur
immediately after eating. eating doesn't
make the pain subside, but tends to
exacerbate it.
(pain happens when the stomach is full)
This pain tends to develop or worsen when the
stomach is relatively empty usually two to five
hours after eating.
(pain occurs when the stomach is empty)
The stomach and the duodenum are both covered by layers of mucous
membranes. When they function properly, those membranes protect the stomach
and the duodenum from the digestive juices and enzymes that break down foods
and beverages.
Duodenal and gastric ulcers are most commonly caused by a bacteria called
Helicobacter pylori, or H. pylori. H. pylori is usually present and doesn't cause any
trouble. Occasionally, though, it causes a disruption in the mucous membranes of
the duodenum and/or stomach that prompts inflammation and, ultimately, ulcers.

Causes:
Lifestyle(risk factor)
Smoking--Studies show that cigarette smoking increases one's chances of getting
an ulcer. Smoking slows the healing of existing ulcers and also contributes to
ulcer recurrence .
Caffeine--Coffee, tea, colas, and foods that contain caffeine seem to stimulate
acid secretion in the stomach, aggravating the pain of an existing ulcer.
However, the amount of acid secretion that occurs after drinking decaffeinated
coffee is the same as that produced after drinking regular coffee. Thus, the
stimulation of stomach acid cannot be attributed solely to caffeine .
Alcohol--Research has not found a link between alcohol consumption and
peptic ulcers. However, ulcers are more common in people who have cirrhosis of
the liver, a disease often linked to heavy alcohol consumption .
Stress--Although emotional stress is no longer thought to be a cause of ulcers,
people with ulcers often report that emotional stress increases ulcer pain.
Physical stress, however, increases the risk of developing ulcers particularly in the
stomach. For example, people with injuries such as severe burns and people
undergoing major surgery often require rigorous treatment to prevent ulcers
and ulcer complications .
Drug(risk factor)
ulcer pain doesn't tend to respond very well
to antacids and other over-the-counter
medications;
sign of a duodenal ulcer is pain that occurs
during the middle of the night, when acid
secretion and production is the most rampant.
Nonsteroidal anti-inflammatory drugs (NSAIDs) make the stomach vulnerable to the
harmful effects of acid and pepsin. NSAIDs such as aspirin, ibuprofen, and
naproxen sodium are present in many non-prescription medications used to
treat fever, headaches, and minor aches and pains. These, as well as prescription
NSAIDs used to treat a variety of arthritic conditions ,
interfere with the stomach's ability to produce mucus and bicarbonate *
* affect blood flow to the stomach and cell repair
They can all cause the stomach's defense mechanisms to fail, resulting in an
increased chance of developing stomach ulcers. In most cases, these ulcers
disappear once the person stops taking NSAIDs


Helicobacter pylori
H. pylori is a spiral-shaped bacterium found in the stomach. Research shows that
the bacteria (along with acid secretion) damage stomach and duodenal tissue,
causing inflammation and ulcers. Scientists believe this damage occurs because
of H. pylori's shape and characteristics:
H. pylori survives in the stomach because it produces the enzyme urease. Urease
generates substances that neutralize the stomach's acid--enabling the bacteria
to survive. Because of their shape and the way they move:
* the bacteria can penetrate the stomach's protective mucous lining. Here, they
can produce substances that weaken the stomach's protective mucus and make
the stomach cells more susceptible to the damaging effects of acid and pepsin
* The bacteria can also attach to stomach cells further weakening the stomach's
defensive mechanisms and producing local inflammation. For reasons not
completely understood, H. pylori can also stimulate the stomach to produce
more acid .

Physiologic factors
stimulates the gastrin The hormone : . Excess acid production in the stomach
production of acid in the stomach; therefore, any factors that increase gastrin
production will in turn increase the production of stomach acid
(Acid and pepsin) Researchers believe that the stomach's inability to defend
itself against the po werful digestive fluids( acid and pepsin) contributes to ulcer
formation. The stomach defends itself from these fluids in several ways .
*One way is by producing mucus--a lubricant-like coating that shields stomach
tissues .
*Another way is by producing a chemical called bicarbonate, This chemical
neutralizes and breaks down digestive fluids into substances less harmful to
stomach tissue. Finally, blood circulation to the stomach lining, cell renewal, and
cell repair also help protect the stomach
In addition to the increased gastric and duodenal acidity observed in some
patients with duodenal ulcers, accelerated gastric emptying is often present. This
acceleration leads to a high acid load delivered to the first part of the
duodenum, where 95% of all duodenal ulcers are located. Acidification of the
duodenum leads to gastric metaplasia(this inflammation results in production of
stomach-like cells called duodenal gastric metaplasia. ), which indicates
replacement of duodenal villous cells with cells that share morphologic and
secretory characteristics of gastric epithelium. Gastric metaplasia may create an
environment with H pylori further tissue damage and inflammation, which may
result in an ulcer.
Genetics: family history of H pylori revealed that their high pepsin levels
were more likely related to H pylori infection .
Less common causes include:

Zollinger-Ellison syndrome

Radiation therapy

Bacterial or viral infections

Tumors

Other medicines such as steroids or medicines to treat
osteoporosis

Severe stress such as surgery, trauma, head injury, shock,
or burns

Symptoms :

Epigastric pain is the most common symptom of both gastric and
duodenal ulcers.

It is characterized by a gnawing or burning sensation and occurs after
mealsclassically, shortly after meals with gastric ulcer and 2-3 hours
afterward with duodenal ulcer.

It may also come in the middle of the night when your stomach is empty

Weight loss

Loss of appetite

Nausea

Vomiting

Bloating

Burping

Dyspepsia
Ulcers can cause serious problems and severe abdominal pain. One problem is
bleeding. Bleeding symptoms may include:

Bloody or black, tarry stools

Vomiting what looks like coffee grounds or blood

Weakness

Lightheadedness

Physiology:
Peptic ulcers are defects in the gastric or duodenal mucosa that extend through
the muscularis mucosa.
The epithelial cells of the stomach and duodenum to reduce injury :
1_ secrete mucus in response to irritation of the epithelial lining and as a result of
cholinergic stimulation. The superficial portion of the gastric and duodenal
mucosa exists in the form of a gel layer, which is impermeable to acid and
pepsin.
2_Other gastric and duodenal cells secrete bicarbonate, which aids in buffering
acid that lies near the mucosa.
3_Prostaglandins of the E type (PGE) have an important protective role,
because PGE increases the production of both bicarbonate and the mucous
layer.
4_ ion pumps in the basolateral cell membrane help to regulate intracellular pH
by removing excess hydrogen ions. Through the process of restitution, healthy
cells migrate to the site of injury.
5_ Mucosal blood flow removes acid that diffuses through the injured mucosa
and provides bicarbonate to the surface epithelial cells.
Under normal conditions, a physiologic balance exists between
gastric acid secretion and gastroduodenal mucosal defense.
Mucosal injury and, thus, peptic ulcer occur when the balance between
the aggressive factors and the defensive mechanisms is disrupted.
Aggressive factors, such as NSAIDs, H pylori infection, alcohol, bile salts, acid, and
pepsin, can alter the mucosal defense by allowing back diffusion of hydrogen
ions and subsequent epithelial cell injury.
The defensive mechanisms include tight intercellular junctions, mucus, mucosal
blood flow, cellular restitution, and epithelial renewa

why the ulcer relapsed? Because sometimes doctor treatment
the symptoms of ulcer not treat cause of ulcer ,,
mean mostly causes of duodenal ulcer (inflammation due increase acidity
associated with H pylori) so use of eradication of H pylori and drug reduce
gastric acidity complete treatment of gastric ulcer and no relapse of ulcer .

Treatment :
Non-pharmacological Treatment of Peptic ulcer:
1-Avoid spicy food.
2-Avoid xanthin containing beverges.
3-Avoid Alcohol.
4-Avoid Smoking.
5-Avoid heavy meals.
6-Encourage small frequent low caloric meals.
7-Avoid ulcerating drugs e.g. NSAIDs, corticosteroids, xanthines and
parasympathomimetics
pharmacological Treatment
The principal physiologic stimulants of gastric acid secretion are
gastrin, acetylcholine,and histamine.
*Gastrin is a hormone secreted by G cells in the gastric antrum, whereas
*acetylcholine is released from vagus nerve terminals. Gastrin and acetylcholine
directly stimulate acid secretion by parietal cells,
they also stimulate the release of histamine from paracrine (enterochromaffin-
like) cells. Histamine stimulates H
2
receptors located on parietal cells and
provokes acid secretion via cyclic adenosine monophosphate (cAMP) stimulation
of the proton pump (H
+
,K
+
-ATPase).
The vagus nerve mediates the cephalic phase of gastric acid secretion evoked by
the smell, taste, and thought of food.
Gastrin mediates the gastric phase of acid secretion evoked by the presence of
food in the stomach.
The level of gastric acidity can be reduced either by
1_ neutralizing gastric acid with antacids
2- inhibiting gastric acid secretion with a histamine H
2
receptor antagonist or a
proton pump inhibitor (PPI).

Cytoprotective Drugs

Sucralfate
This sucralfated polysaccharide Mechanisms
and epithelial cells craters ulcer to adheres - 1
2- it inhibits pepsin-catalyzed hydrolysis of mucosal proteins.
in mucosal cells. synthesis prostaglandin stimulates 3_
These actions contribute to the formation of a protective barrier to acid
and pepsin and thereby facilitate the healing of ulcers.
sucralfate can be used to treat active ulcers or to suppress the recurrence
of ulcers. Because it is somewhat less effective than drugs that inhibit
gastric acid secretion, it is primarily used in patients who cannot tolerate
blockers or PPIs.
2
H
Indications

gastrointestinal constipation and other effects, adverse systemic few
disturbances and laryngospasm have been reported occasionally
Adverse
Effects

Cytoprotective Drugs

Misoprostol

The drug exerts a cytoprotective effect by :
1-inhibiting gastric acid secretion
2- promoting the secretion of mucus and bicarbonate.
Mechanisms
in patients who are ulcers duodenal and gastric for the prevention of
taking NSAIDs on a long-term basis for the treatment of arthritis and
other conditions.
Indications

Diarrhea and intestinal cramping are the most common adverse effects,
but other gastrointestinal reactions can also occur.
Misoprostol can stimulate uterine contractions and induce labor in
pregnant women, so its use is contraindicated during pregnancy.

Adverse
Effects

Proton Pump Inhibitors
esomeprazole, omeprazole, pantoprazole, and rabeprazole

The PPIs are acid-labile prodrugs that are administered orally as
active converted to , preparations coated - enteric release, - sustained
the proton pump. that bind to metabolites
Definition
* The active metabolites of PPIs form a covalent disulfide link with a
in the luminal found ATPase) -
+
,K
+
(H pump proton cysteinyl residue in the
membrane of gastric parietal cells
* The drugs irreversibly inhibit the proton pump
* prevent the secretion of gastric acid for an extended period.
inhibition of up to 95% of gastric acid secretion.and a single dose can
Mechanisms
inhibit acid secretion for 1 to 2 days Hence the PPIs are more efficacious
blockers
2
than the H
treating peptic ulcer disease. They typically heal 80% to 90% of
peptic ulcers in 2 weeks or less when used in combination with
antibiotics, whereas H
2
-blocker combinations heal 70% to 80% in 4
weeks.
PPIs are also the most effective drugs for treating GERD
PPIs can be used to prevent peptic ulcers and bleeding in persons
receiving high-dose or long-term therapy with NSAIDs such as
diclofenac.
treatment of dyspepsia and heartburn.
Indications


Gastric Antacids
) carbonate. calcium and hydroxides magnesium and aluminum (

Gastric antacids chemically neutralize stomach acid. *
* This raises the gastrointestinal pH sufficiently to relieve the pain of
dyspepsia and acid indigestion and to enable peptic ulcers to heal
Mechanisms
* Aluminum hydroxide can cause constipation.
* Magnesium hydroxide often causes diarrhea.
* Calcium carbonate can also cause constipation, and large doses of
calcium carbonate can lead to a rebound in acid secretion.

Adverse Effects
dyspepsia. and indigestion acid treat *
* Nonprescription products containing a low dose of a histamine
antagonist and an antacid used to treat peptic ulcers
2
H
Indications


Histamine H
2
Receptor Antagonists
cimetidine, famotidine, ranitidine, and nizatidine.


drugs to compete with histamine for binding to H
2
receptors on gastric
parietal cells .
The H
2
blockers have been shown to be potent inhibitors of both
Mechanisms
secretion stimulated - meal *
of gastric acid. secretion basal *
When they reduce the volume and concentration of gastric acid, they
because pepsin produce a proportionate decrease in the production of
gastric acid catalyzes the conversion of inactive pepsinogen to pepsin
and can cause activity antiandrogenic Cimetidine has weak *
gynecomastia in elderly men.
P450 cytochrome of inhibitor known - Cimetidine is a well *
These isozymes are involved in the metabolism of numerous isozymes
drugs (The dosage of these drugs may need to be reduced in patients
taking cimetidine.)
Adverse Effects
including production, acid excessive with treat conditions associated
dyspepsia, peptic ulcer disease, and gastroesophageal reflux disease
(GERD).
Indications


Treatment of Helicobacter Pylori Infection

* Studies show that 80% to 90% of patients who undergo monotherapy with a gastric acid
inhibitor have an ulcer recurrence within 1 year after discontinuing this therapy.

* Hence, combination therapy is now the standard of care, and clinicians should use
regimens that have a 90% to 95% cure rate in their locality, The currently recommended
treatment for peptic ulcers consists of a PPI and two or more of the following
antimicrobial agents:
amoxicillin, clarithromycin, metronidazole, tinidazole, bismuth subsalicylate, or
tetracycline
for example : rabeprazole and amoxicillin for 5 days followed by rabeprazole plus
clarithromycin and metronidazole or tinidazole for another 5 days
.