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1.

Introduction and Literature review

1.1 Introduction:

Peptic ulcer disease embraces both gastric and duodenal ulcers and has been a
major threat to the world’s population over the past two centuries, with a high
morbidity and substantial mortality. Epidemiological data for this disease and its
complications have shown striking geographical variations in incidence and
prevalence (Malfertheiner et al,2009).
Peptic ulcer has unquestionably been a disease of the twentieth century. Rare

before the end of the previous century, peptic ulcer became increasingly frequent,

reaching a peak during the next 50 years and afflicting as many as 10 per cent of

men. (Christie and Tansey, 2002). Every year peptic ulcer disease (PUD) affects 4

milion people around the world (Di Saverio et al, 2014).

Peptic ulcer disease represents a serious medical problem. Interestingly, those at

the highest risk of contracting peptic ulcer disease are those generations born

around the middle of the 20th century. Ulcer disease has become a disease

predominantly affecting the older population, with the peak incidence occurring

between 55 and 65 years of age.

The complications of peptic ulcer were an important cause of death, severe

haemorrhage being common and perforation, particularly of duodenal ulcers, being


a frequent surgical emergency. Obstruction of the stomach by pyloric stenosis

might also occur

The disease continues to have a substantial impact on our society’s health care

system. Although 70% of ulcer patients are between the ages of 25 and 64, the

peak prevalence of complicated ulcer disease requiring hospitalization is in the age

group 65 to 74 years.

Although morbidity from PUD is decreasing in the west, the incidence of


perforated ulcer remains relatively constant (Ngerageza, 2011).
Despite substantial advances, this disease remains an important clinical problem,
largely because of the increasingly widespread use of non-steroidal anti-
inflammatory drugs (NSAIDs) and low dose aspirin.
1.2-Literature Review

1.2.1. Peptic Ulcer Disease:

Peptic ulcer disease is one of several disorders of the upper gastrointestinal tract

that is caused, at least partially, by gastric acid.

Gastric and duodenal ulcers are breaks in the gastric and duodenal mucosa. Both

gastric and duodenal ulcers relate to the corrosive action of pepsin and

hydrochloric acid on the mucosa of the upper gastrointestinal tract. Ulcers

generally range between 3 mm and several centimeters in diameter.


Ulcers can develop in the esophagus, stomach or duodenum, at the margin of a

gastroenterostomy, in the jejunum, in Zollinger-Ellison syndrome, and in

association with a Meckel's diverticulum containing ectopic gastric mucosa.

Peptic ulcer disease (PUD) results from an imbalance of acid secretion and

mucosal defenses that resist acid digestion. Moreover, studies have confirmed the

strong association between gastric antral infection with H pylori and peptic

ulceration. More than 90% of patients with peptic ulcer disease are infected with H

pylori, and eradication of this infection not only heals most uncomplicated ulcers

but also significantly decreases the likelihood of recurrent ulceration (Ngerageza J.

G, Md (2011)

1.2.1.1.Symptoms

Most patients with peptic ulcer disease present with abdominal discomfort, pain or

nausea. The pain is located in the epigastrium and usually does not radiate.

However, these symptoms are neither sensitive nor specific. Pain radiating to the

back may suggest that an ulcer has penetrated posteriorly, or the pain may be

pancreatic in origin. Pain radiating to the right upper quadrant may suggest disease

of the gallbladder or bile ducts.

Patients may describe the pain of peptic ulcer as burning or gnawing, or as hunger

pains slowly building up for 1–2 hours, then gradually decreasing. Use of antacids
may provide temporary relief. Classically, gastric ulcer pain is aggravated by

meals, whereas the pain of duodenal ulcers is relieved by meals. Hence, patients

with gastric ulcers tend to avoid food and present with weight loss, while those

with duodenal ulcers do not lose weight. It is important to remember that although

these patterns are typical, they are not pathognomonic. The nature of the presenting

symptoms alone does not permit a clear differentiation between benign ulcers and

gastric neoplasm.

1.2.1.2. Causes of Peptic Ulcer Disease:

1.2.1.2.1.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

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.

1.2.1.2.2.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. 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.

1.2.1.2.3.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.

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.

1.2.1.2.4.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.

1.2.1.2.5.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.

1.2.1.2.6.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.

1.2.1.2.7.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.

1.2.1.2.8.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.

1.2.1.2.9.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.

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Risk factors for peptic gastroduodenal ulcer perforation

NSAIDS

1.2.1.3.Sites of peptic ulceration:


1.2.1.3.1. Duodenum:
Ulceration of the first part is the commonest form of PU. While ulceration of the
more distal duodenum is exceptional without the rare (Zollinger- Ellison
Syndrome)

1.2.1.3. 2.The stomach:


It’s the second commonest form of peptic ulcer, classified into four types:
Type I: This develops a long the lesser curve probably due to damage to mucosal
defenses by bile reflux. It is usually associated with gastritis. It’s found in the
junction between acid secreting and non-acid secreting gastric mucosa.
Type II: These are seen in the middle of the corpus; they are secondary to
duodenal ulceration and usually arise because of stasis due to duodenal deformity.
Type III: Occurs in the pyloric channel or prepyloric area, they may be associated
with normal or increase gastric acid secretion.
Type IV: Occur high in the lesser curve below the gastrooesophageal junction.
In contrast to type I and IV, type II and III GU are the result of acid induced
epithelial injury and are treated similarly to DU.
1.2.1.3.3.Oesophagus:
Oesophageal ulcers are due to reflux of acid and pepsin from the stomach. They
are small and superficial but may be large and penetrating when they occur in
columnar mucosa (as in Barrett’s oesophagus in which columnar metaplasia
occurs. It’s considered premalignant).
1.2.1.3.4.Jejunum and ileum:
Jejunal ulcers are uncommon but can develop in Zollinger-Ellison Syndrome and
in gastrojejunal anastomosis, whilst ileal ulcers occur adjacent to Mechel's
diverticulum with ectopic acid secreting mucosa.
1.2.1.4. Diagnosis of Peptic Ulcer Disease:

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.

1.2.1.2.2.1.Types of Diagnosis:

1.2.1.2.2.1.1.History taking

The history should include careful attention to aspirin and NSAID use. Peptic ulcer

should be differentiated from other causes of epigastric pain.

1.2.1.2.2.1.2.Laboratory tests

Laboratory findings of hypochromic anemia and occult blood in the stools indicate

bleeding.

1.2.1.2.2.1.3.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 or

duodenum and to exclude gastric carcinoma

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. 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.

1.2.1.2.2.1.4. 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.
The Pharmaceutical Treatment of Gastric 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).37 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.14 Additionally, the

morbidity associated with H. pylori infection has dramatically decreased from

1993 to present due mainly to triple therapy.11

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).38 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.38 Furthermore,

recent data suggests that there may be a rebound effect when proton-pump

inhibitors are discontinued.39 In other words, stopping use can cause an increase in

stomach acid production above that of normallevels 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.40

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” (a drug 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.22

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.

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.22


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.38

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.22 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.

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

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.22 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.
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.27,28

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.29 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.30

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.31,32,33

Although few scientific studies have examined the effectiveness of specific

homeopathic tinctures for gastric ulcers, many years of anecdotal reports suggests

the following may be of help: Argentum nitricum (for bloating, belching and
gastric pain), Arsenicum album (for ulcers with intense burning pain and nausea),

Kali bichromicum (for burning or shooting abdominal pain that is worse in the

night), Lycopodium (for bloating after eating), Nitric acid (for sharp, shooting pain

that is worse at night), Nux vomica (for heartburn and indigestion), Phosphorus

(for burning stomach pain that worsens at night), Pulsatilla (for symptoms that

change abruptly).34

Other natural therapies which may be of some benefit for those who suffer from

gastric ulcers include acupuncture (used traditionally for a variety of conditions

related to the digestive tract, including peptic ulcers) and chiropractic spinal

manipulation.35,36 The nerves that innervate the stomach travel out from the

thoracic spine, where they may become impinged and cause digestive dysfunction.

Chiropractic spinal adjustments may take pressure off spinal nerves and restore

normal organ function.

Prevention

Prevention of gastric ulcers often involves reducing NSAID use and finding

different medications or alternative approaches to relieve pain. For example,

acetaminophen (Tylenol, others) has not been linked to peptic ulcers. If NSAIDs

need to be taken long-term, H2 blockers or proton pump inhibitors may also be

prescribed to prevent the development of peptic ulcers.


Patients may also receive a prescription for Misoprostol, a drug than can prevent

NSAID induced gastric ulcers.22

Lifestyle is also important for reducing the risks of peptic ulcers. Doctors used to

recommend eating bland foods, dairy products and small portions during meals,

but newer recommendations include eating foods rich in fiber, especially fruits and

vegetables. Fruits, vegetables and whole grains are also vitamin-rich, which may

enhance the body’s ability to heal stomach irritation and prevent ulceration. Foods

containing flavonoids, such as apples, cranberries, onions, garlic and tea may

inhibit the growth of H. pylori. Avoiding refined foods (white breads, pastas and

sugar), eating less red meat and more cold-water fish, using healthy oils (olive oil

or coconut oil), and reducing trans-fatty acids are all common dietary

recommendations for reducing the risk of peptic ulcers.

Quitting smoking is also an important strategy because compounds in cigarettes

interfere with the protective lining of the stomach, making it more susceptible to

the development of ulcers. Smoking also increases stomach acid production.

Reducing alcohol, coffee, and soda pop consumption can also help prevent ulcers

as excessive use of these acidic beverages irritates and erodes the mucous lining of

the stomach and intestines, leading to inflammation, ulceration and bleeding.25

Controlling stress and anxiety is also an important part of ulcer prevention,

although not as vital as once thought. At the very least, stress may worsen the signs
and symptoms of gastric ulcers. Relaxation techniques such as meditation, yoga,

and tai chi are known to be able to reduce stress levels and impact peptic ulcer

symptomatology.

Objective:
References:

Christie D A, Tansey E M. (eds) (2002) Peptic Ulcer: Rise and Fall. Wellcome

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bleeding peptic ulcers: 2013 WSES position paper

Salomone Di Saverio1*†, Marco Bassi7†, Nazareno Smerieri1,6, Michele

Masetti1, Francesco Ferrara7, Carlo Fabbri7,

Luca Ansaloni3, Stefania Ghersi7, Matteo Serenari1, Federico Coccolini3, Noel

Naidoo4, Massimo Sartelli5,

Gregorio Tugnoli1, Fausto Catena2, Vincenzo Cennamo7 and Elio Jovine

Peptic ulcer disease


Peter Malfertheiner, Francis K L Chan, Kenneth E L McColl
www.thelancet.