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CASE 19

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

complaining of dyspepsia, which occurred sometimes aftereating. 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 duodenalulcer, 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?

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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 u cerDuo ena U cers

An ulcer is where the lining of the gut isdamaged and the underlying tissue isexposed.

A duodenal ulcer is a sore in the lining of theintestine. It is in the first part of your small

infection associated withmostlyintestine) bacteria.pyloriH(pyloriHelicobacterthe

occur in the stomachupper region of the small intestine.an ulcer looks like a small, red crater on theinside 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 occurimmediately after eating. eating doesn'tmake the pain subside, but tends toexacerbate it.(pain happens when the stomach is full)

This pain tends to develop or worsen when thestomach is relatively empty usually two to fivehours after eating.

(pain occurs when the stomach is empty)

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The stomach and the duodenum are both covered by layers of mucousmembranes. 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.

CausesLifestyle(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 wellto antacids and other over-the-countermedications;

sign of a duodenal ulcer is pain that occursduring the middle of the night, when acidsecretion and production is the most rampant.

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Nonsteroidal anti-inflammatory drugs (NSAIDs)make the stomach vulnerable to the

harmful effects of acid and pepsin. NSAIDs such as aspirin, ibuprofen, and

naproxensodiumare 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 bacteriato 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 mucusand 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 mechanismsand producing local inflammation. For reasons not

completely understood, H. pylori can also stimulate the stomach to produce

more acid.

Physiologic factors

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stimulates thegastrinThe 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 defenditself 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 levelswere 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

http://medicine.med.nyu.edu/conditions-we-treat/conditions/duodenal-ulcer?ChunkIID=102706http://medicine.med.nyu.edu/conditions-we-treat/conditions/duodenal-ulcer?ChunkIID=14855http://medicine.med.nyu.edu/conditions-we-treat/conditions/duodenal-ulcer?ChunkIID=14855http://medicine.med.nyu.edu/conditions-we-treat/conditions/duodenal-ulcer?ChunkIID=102706

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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 hoursafterward 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 isbleeding. 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 throughthe 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 ofcholinergic stimulation.The superficial portion of the gastric and duodenalmucosa exists in the form of a gel layer, which is impermeable to acid andpepsin.

2_Other gastric and duodenal cells secrete bicarbonate, which aids in bufferingacid that lies near the mucosa.

3_Prostaglandinsof the E type (PGE) have an important protective role,because PGE increases the production of both bicarbonate and the mucouslayer.

http://medicine.med.nyu.edu/conditions-we-treat/conditions/duodenal-ulcer?ChunkIID=165446http://medicine.med.nyu.edu/conditions-we-treat/conditions/duodenal-ulcer?ChunkIID=165038http://medicine.med.nyu.edu/conditions-we-treat/conditions/duodenal-ulcer?ChunkIID=22574http://medicine.med.nyu.edu/conditions-we-treat/conditions/duodenal-ulcer?ChunkIID=22574http://medicine.med.nyu.edu/conditions-we-treat/conditions/duodenal-ulcer?ChunkIID=165038http://medicine.med.nyu.edu/conditions-we-treat/conditions/duodenal-ulcer?ChunkIID=165446

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4_ ion pumps in the basolateral cell membrane help to regulate intracellular pHby removing excess hydrogen ions.Through the process of restitution, healthycells migrate to the site of injury.

5_ Mucosal blood flow removesacid that diffuses through the injured mucosaand provides bicarbonate to the surface epithelial cells.

Under normal conditions, a physiologic balance exists between

gastric acid secretion and gastroduodenal mucosal defense.

Mucosal injuryand, thus, peptic ulcer occur when the balance between

the aggressive factors and the defensive mechanisms is disrupted.

Aggressive factors, such as NSAIDs, H pyloriinfection, alcohol, bile salts, acid, andpepsin, can alter the mucosal defense by allowing back diffusion of hydrogenions and subsequent epithelial cell injury.

The defensive mechanisms include tight intercellular junctions, mucus, mucosalblood flow, cellular restitution, and epithelial renewa

why the ulcer relapsed?Because sometimes doctor treatmentthe 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.

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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 TreatmentThe principal physiologic stimulants of gastric acid secretion are

gastrin, acetylcholine,and histamine.

*Gastrinis a hormone secreted by G cells in the gastric antrum, whereas

*acetylcholineis 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 H2receptors 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 H2receptor antagonist or a

proton pump inhibitor (PPI).

Cytoprotective DrugsSucralfate

This sucralfated polysaccharideMechanisms

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and epithelial cellscratersulcertoadheres-12- it inhibits pepsin-catalyzed hydrolysis of mucosal proteins.

in mucosal cells.synthesisprostaglandinstimulates3_These actions contribute to the formation of a protective barrier to acidand pepsin and thereby facilitate the healing of ulcers.

sucralfate can be used to treat active ulcers or to suppress the recurrenceof ulcers. Because it is somewhat less effective than drugs that inhibitgastric acid secretion, it is primarily used in patients who cannot tolerate

blockers or PPIs.2H

Indications

gastrointestinalconstipation and othereffects,adversesystemicfewdisturbances and laryngospasm have been reported occasionally

AdverseEffects

Cytoprotective DrugsMisoprostol

The drug exerts a cytoprotective effect by :1-inhibiting gastric acid secretion2- promoting the secretion of mucus and bicarbonate.

Mechanisms

in patients who areulcersduodenalandgastricfor the prevention oftaking NSAIDs on a long-term basis for the treatment of arthritis andother 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 inpregnant women, so its use is contraindicated during pregnancy.

AdverseEffects

Proton Pump Inhibitorsesomeprazole, omeprazole, pantoprazole, and rabeprazole

The PPIs are acid-labile prodrugs that are administered orally as

activeconverted to,preparationscoated-entericrelease,-sustainedthe proton pump.that bind tometabolites

Definition

* The active metabolites of PPIs form a covalent disulfide link with ain the luminalfoundATPase)-

+,K+

(Hpumpprotoncysteinyl residue in themembrane 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

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inhibit acid secretion for 1 to 2 days Hence the PPIs are more efficaciousblockers2than the H

treating peptic ulcer disease. They typically heal 80% to 90% ofpeptic ulcers in 2 weeks or less when used in combination with

antibiotics, whereas H2-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.calciumandhydroxidesmagnesiumandaluminum(

Gastric antacids chemically neutralize stomach acid.** This raises the gastrointestinal pH sufficiently to relieve the pain ofdyspepsia 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.andindigestionacidtreat** Nonprescription products containing a low dose of a histamine

antagonist and an antacid used to treat peptic ulcers2H

Indications

Histamine H2Receptor Antagonistscimetidine, famotidine, ranitidine, and nizatidine.

drugs to compete with histamine for binding to H2receptors on gastric

parietal cells .

The H2blockers have been shown to be potent inhibitors of both

Mechanisms

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secretionstimulated-meal*of gastric acid.secretionbasal*

When they reduce the volume and concentration of gastric acid,theybecausepepsinproduce a proportionate decrease in the production of

gastric acid catalyzes the conversion of inactive pepsinogen to pepsin

and can causeactivityantiandrogenicCimetidine has weak*gynecomastia in elderly men.

P450cytochromeofinhibitorknown-Cimetidine is a well*These isozymes are involved in the metabolism of numerousisozymes

drugs (The dosage of these drugs may need to be reduced in patientstaking cimetidine.)

Adverse Effects

includingproduction,acidexcessivewithtreat conditions associated

dyspepsia, peptic ulcer disease, and gastroesophageal reflux disease(GERD).

Indications

Treatment of Helicobacter PyloriInfection

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

* Hence, combination therapy is now the standard of care, and clinicians should useregimens that have a 90% to 95% cure rate in their locality, The currently recommendedtreatment for peptic ulcersconsists of a PPI and two or more of the followingantimicrobial agents:

amoxicillin, clarithromycin, metronidazole, tinidazole, bismuth subsalicylate, ortetracyclinefor example :rabeprazole and amoxicillin for 5 days followed by rabeprazole plusclarithromycin and metronidazole or tinidazole for another 5 days

.