Pathogenesis

The basis of the pathogenesis of peptic ulcer is the imbalance between aggressive factors and gastric pepsin, on one hand, and the mucosal barrier, on the other. Among the environmental factors leading to increased gastric secretion, are: smoking, excessive use of alcohol, non-steroidal anti-inflammatory drugs (NSAIDs), emotional stress and other psychosocial factors.

The relationship between H.pylori infection and peptic ulcer of the stomach and the duodenum has been demonstrated in epidemiological studies. More than half of the world population is chronically infected with H.pylori, but only 5-10% of the patients develop an ulcer. This is determined by the histology of gastritis, the changes in the homeostasis of the gastric acid secretion and hormones, the gastric metaplasia in the duodenum, the reaction between the mucosal barrier and H.pylori, and genetic factors.

H.pylori leads to inflammatory changes in the gastric mucosa, with an increased secretion of cytokines – interleukin 8 and interleukin 1 beta. The ulcerogenesis is due to the influx of neutrophils and macrophages in the gastric mucosa, with the release of lysosomal enzymes, oxygen radicals and leukotrienes, which disrupt the integrity of the lining.
The local damage and the reduction of the hydrophobicity of the mucus gel of the gastric mucosa were considered the main mechanisms of damage from NSAIDs in the peptic ulcer. Later it was found that drugs act primarily by suppressing the gastric prostaglandin synthesis.

Studies with experimental models have shown that the infiltration of the gastric mucosa with neutrophils is one of the key mechanisms for the emergence of peptic ulcer from NSAIDs. This process results in the release of oxygen free radicals and proteases, as well as the obstruction to blood flow of the capillary.

Clinical Implications

The main symptom in uncomplicated peptic ulcer is epigastric pain, accompanied by other dyspeptic complaints such as fullness, bloating and nausea.

In patients with duodenal ulcer, epigastric pain usually occurs on an empty stomach or at night and is relieved by food or antacid medications. About one third of these patients also have heartburn, most of them without erosive esophagitis.

Chronic ulcers can occur asymptomatically – that is characteristic of NSAID-induced ulcers, the first implication may be gastrointestinal bleeding or perforation. The most common and serious complication is bleeding that occurs in 50 -170 per 100 000 patients, with the highest risk for those who are over 60 years of age.

Perforation occurs with the frequency of 7-10 people per 100 000. The penetration of retroperitoneal organs is characterized by constant severe pain in the abdomen and is a rare complication. Obstruction in the pylorus, the result of ulcer induced fibrosis is also rare, most often due to malignancy.

Diagnosis

A peptic ulcer is diagnosed in the presence of the integrity of the mucosa with size > = 5 mm, covered with fibrin; a break < 5 mm is defined as erosion.
Peptic ulcers can be single or multiple. The typical location of the duodenal is the olfactory where the stomach contents enter the small intestine. Gastric ulcer has a different location, but most often it occurs in the corner of the small curvature.

The so-called “kissing ulcers” are located directly opposite each other in the front and rear wall of bulubus duodeni. If the ulcer is distal to this area, one needs to think about the disease of Crohn, ischemia or the rare syndrome of Zollinger-Ellison.

Treatment of Peptic Ulcer Disease
The basic groups of medicaments for treatment of peptic ulcers are:
• antisecretory agents
– Proton pump inhibitors – Lansoprazole
– H2 blockers
– M-cholinolytics – Pirenzepine

• Gastroduodenal mucosal protectors
– Sucralfate, Bismuth subcitrate colloidal, Misoprostol

• Antihelicobacter preparations
– Amoxicillin, Clarithromycin, Metronidazole

The advent of proton pump inhibitors (PPI) is a key point to treating peptic ulcer as they selectively inhibit H + K + ATP-sins of parietal cells.

Proton Pump Inhibitors:

– inhibit both the basal and the stimulated acid secretion;
– do not exhibit the tachyphylaxis effect (in contrast to H2-blockers);
– lead to the stimulation of restorative processes of the lining;
– lead to the healing of ulcers without forming scars.

These benefits of PPIs define them as drugs of first choice in the current guidance and the most effective and economically advantageous pharmaco-therapy (in terms of the effectiveness of the treatment).

The treatment of the associated with H.pylori peptic ulcer disease is mainly aimed at the eradication of the infection – it is achieved by a combination of suppressing the acid secretion medications and antibiotics.

NSAIDs, including the low-dose of acetylsalicylic acid, are the most important etiologic factors for the complications of peptic ulcer in countries where the incidence of infection with H.pylori is decreasing.

During the treatment of NSAID-induced ulcers the intake of anti-inflammatory drugs should be discontinued, if possible, and treatment with an H2-receptor antagonist, PPI, or sucralfate should be started. Proton pump inhibitors lead to a faster relief of the symptoms and healing of ulcer, as compared with the two other groups of medicaments.

If it is not possible to stop the intake of NSAIDs, the dose required has to be to be reduced to the minimum effective dose by adding also the protective treatment with PPI. If the patient with an NSAID-induced ulcer is positive for H.pylori, an erdication therapy has to be carried out.

Patients at high risk of developing an ulcer on the background of treatment with NSAIDs should be treated at the same time with PPI in order to reduce the risk of developing ulcers or adopt selective COX-2 inhibitors, the use of which, however, is limited due to their relationship with increased cardiovascular risk.

For the treatment of peptic ulcer Tchaikapharma High Quality Medicines offers the Bulgarian market the proton pump inhibitor Lansoprazol with the following trade name:

AF496 LanzAcid (Lansoprolol) 30 mg x 30 tabl. – 9.75 BGN.