Download Causes of ulcers

ANTI-ULCER
Stomach ulcer re also known as a peptic ulcer or a gastric ulcer, it is small erosion (hole)
in the gastrointestinal tract. The duodenal ulcers are most common type of stomach ulcer.
Duodenal ulcers occur in the first 12 inches of small intestine beyond the stomach. An ulcer that
produces in the stomach is called gastric ulcers. An ulcer is not cancerous or contagious.
Duodenal ulcers are benign, whereas the stomach ulcers may become malignant.
Causes of ulcers:
 Ulcers may occur when an imbalance between digestive fluids in the stomach and
duodenum. Most ulcers are caused by an infection with a type of bacteria called H. pylori
(Helicobacter pylori).
 Use of painkillers such as aspirin, naproxen (NSAIDs), and ibuprofen can frequently
cause ulcers.
 Excess acid production from tumors of the acid producing cells of the stomach
,gastrinomas, that increases acid output (Zollinger-Ellison syndrome)
 Radiation treatment to the area
 Excessive drinking of alcohol
 Smoking or chewing tobacco
 Serious illness
Symptoms: Heartburn, Nausea or vomiting, Bloating, Vomiting blood, Dark or black stool (due
to bleeding), Weight loss, severe pain in the mid to upper abdomen.
Diagnosis: Endoscopy
Treatment: The goal of ulcer treatment is to relieve pain, heal the ulcer, and prevent
complications. The primary goal of a treatment involves the reduction of risk factors (NSAIDs
and cigarettes). The next step is medications.
Antacids: Commonly used antacids are salts of aluminum and magnesium, such as aluminum
hydroxide (usually a mixture of Al(OH)3 and aluminum oxide hydrates) or magnesium
hydroxide [Mg(OH)2], either alone or in combination. Calcium carbonate [CaCO3] reacts with
HCl to form CO2 and CaCl2 and is a commonly used preparation. Antacids are weak bases that
react with gastric acid to form water and a salt, thereby diminish the gastric acidity. Because
pepsin is inactive at a pH greater than 4, antacids also reduce pepsin activity. Systemic
absorption of sodium bicarbonate [NaHCO3] can produce transient metabolic alkalosis;
therefore, this antacid is not recommended for long-term use.
Therapeutic uses: Aluminum- and magnesium-containing antacids are used for symptomatic
relief of peptic ulcer disease and GERD; they may promote healing of duodenal ulcers, but the
evidence for efficacy in the treatment of acute gastric ulcers is less compelling; therefore, these
agents are used as last-line therapy.
Adverse effects: Aluminum hydroxide tends to be constipating, and magnesium hydroxide tends
to produce diarrhea. Preparations that combine these agents aid in normalizing bowel function.
The binding of phosphate by aluminum-containing antacids can lead to hypophosphatemia. In
addition to the potential for systemic alkalosis, sodium bicarbonate liberates CO2, causing
belching and flatulence. In patients with renal impairment, caused by accumulation of
magnesium, sodium, calcium, and other electrolytes. Excessive intake of calcium carbonate
along with calcium foods can result in hypercalcemia.
H2 blockers: H2 blockers are effective in ulcer healing; they have a limited role in eradicating
H. pylori without antibiotics. Histamine antagonists (H2 blockers) are drugs designed to block
the action of histamine on gastric cells and reduce the production of acid, the H2 blockers are
cimetidine, nizatidine, ranitidine, and famotidine.
Cimetidine: Cimetidine and the other H2 antagonists are given orally, distribute widely
throughout the body including into breast milk and across the placenta, and are excreted mainly
in the urine. Cimetidine normally has a short serum half-life, which is increased in renal failure.
Cimetidine inhibits cytochrome P450 and can slow metabolism (and, thus, potentiate the action)
of several drugs (for example, diazepam, warfarin, phenytoin, quinidine, carbamazepine,
theophylline, and imipramine).
Ranitidine: Ranitidine is longer acting and is five- to ten-fold more potent Compared to
cimetidine. Ranitidine has minimal side effects and does not produce the antiandrogenic or
prolactin-stimulating effects of cimetidine.
Famotidine: This is similar to ranitidine in its pharmacologic action, but it is 20 to 50 times
more potent than cimetidine, and 3 to 20 times more potent than ranitidine.
Nizatidine: It is similar to ranitidine in its pharmacologic action and potency. In contrast to
cimetidine, ranitidine, and famotidine, which are metabolized by the liver, nizatidine is
eliminated principally by the kidney. Because little first-pass metabolism occurs with nizatidine,
its bioavailability is nearly 100 percent. No intravenous preparation is available.
Side effects: Confusion, headache, lethargy, or hallucinations. At higher doses cimetidine may
rarely cause breast swelling or impotence.
Proton-pump inhibitors: PPIs (Proton-pump inhibitors) such as omeprazole, pantoprazole,
lansoprazole, esomeprazole, and rabeprazole are the most potent than H2 blockers in suppressing
acid secretion. These drugs are comparable to H2 blockers in effectiveness in treating gastric and
duodenal ulcers, they are superior to H2 blockers in treating esophageal ulcers. Esophageal
ulcers are more sensitive than gastric and duodenal ulcers to minute amounts of acid. Therefore,
more complete acid suppression accomplished by proton-pump inhibitors is important for
esophageal ulcer healing.
Omeprazole is the first of a class of drugs that bind to the H+/K+-ATPase enzyme system
(proton pump) of the parietal cell, thereby suppressing secretion of hydrogen ions into the gastric
lumen. The membrane-bound proton pump is the final step in the secretion of gastric acid.
Side effects: Headache, constipation, diarrhea, nausea and rash.
Antimicrobial agents: Currently, either quadruple therapy of bismuth subsalicylate and
metronidazole plus tetracycline plus a PPI, or triple therapy consisting of a PPI with
metronidazole or amoxicillin plus clarithromycin, are administered for a 2-week course. This
usually results in a 90% or greater eradication of H.Pylori bacterial rate. Bismuth salts do not
neutralize stomach acid, but they inhibit pepsin and increase the secretion of mucus, thus helping
to form a barrier against the diffusion of acid in the ulcer. Treatment with a single antimicrobial
drug is less effective (20-40 % eradication rates), results in antimicrobial resistance and is
absolutely not recommended.
Prostaglandins: PGE2, (cytoprotective effect) produced by the gastric mucosa, inhibits
secretion of HCl and stimulates secretion of mucus and bicarbonate. A deficiency of
prostaglandins is thought to be involved in the pathogenesis of peptic ulcers. Misoprostol, a
stable analog of prostaglandin E1, as well as some PPIs, are approved for prevention of gastric
ulcers induced by NSAIDs.
Anticholinergic drugs (Antimuscarinic agents): Stimulation of muscarinic receptors increases
gastrointestinal motility and secretory activity. A cholinergic antagonist, such as dicyclomine,
can be used in the management of peptic ulcer disease and Zollinger-Ellison syndrome,
particularly in patients who are refractory to standard therapies.
Side effects: Constipation, dry mouth, cardiac arrhythmias, and urinary retention.
Mucosal protective agents: These agents are also known as cytoprotective compounds, they
have several actions that enhance mucosal protection mechanisms, thereby preventing mucosal
injury, reducing inflammation, and healing existing ulcers.
Bismuth subsalicylate: Preparations of this compound effectively heal peptic ulcers. In addition
to their antimicrobial actions, they inhibit the activity of pepsin, increase secretion of mucus, and
interact with glycoproteins in necrotic mucosal tissue to coat and protect the ulcer crater.
Sucralfate: This complex of aluminum hydroxide and sulfated sucrose binds to positively
charged groups in proteins of both normal and necrotic mucosa. By forming complex gels with
epithelial cells, sucralfate creates a physical barrier that impairs diffusion of HCl and prevents
degradation of mucus by pepsin and acid. It also stimulates prostaglandin release as well as
mucus and bicarbonate output, and it inhibits peptic digestion. By these and other mechanisms,
sucralfate effectively heals duodenal ulcers and is used in long-term maintenance therapy to
prevent their recurrence. The drug is absorbed systemically. It is very well tolerated.