The incidence of gastric or duodenal ulcers has decreased in the last few years following the discovery of Helicobacter pylori. However, the incidence of the most serious complications, such as bleeding and defects in the lining of the stomach or duodenum (peptic ulcer), did not decrease. An indispensable attribute of peptic ulcer disease is ulcer niche, and its essence is its recurrence.
An ulcer is a defect in the stomach or duodenum wall that extends beyond the muscular layer of the mucosa and extends into the submucosa or deeper.
Stomach ulcers are characterized by damage to the inner lining of the digestive tract due to the secretion of stomach acid or pepsin. It reaches up to the muscle layer of the gastric epithelium. It may involve the lower esophagus, distal duodenum, or jejunum. In patients with gastric ulcers, upper abdominal pain usually occurs within 15–30 minutes after a meal. In contrast, pain associated with a duodenal ulcer usually occurs 2-3 hours after a meal. Currently, testing for Helicobacter pylori is recommended in all patients with gastric ulcer disease. Some people may need an endoscopy to confirm the diagnosis, especially in patients with severe symptoms.
Ulcer formation pathogenesis
The mechanism of formation results from the imbalance between the protective and destructive factors for the gastric mucosa. With peptic ulcers, there is usually a defect in the mucosa that covers the muscular mucosa. After damage to the protective superficial layer of the mucosa, the inner layers are prone to acidification. In addition, the ability of mucosal cells to secrete bicarbonate is impaired.
H. pylori is known to colonize the gastric mucosa and cause inflammation. It also impairs the secretion of bicarbonates, promoting the development of gastric acidity and metaplasia. The aggressive factors include: hydrochloric acid, pepsin, bile, NSAIDs, Helicobacter pylori. In turn, the defense factors include: mucus, bicarbonates, blood supply, cell renewal, cell membrane.
The main causes of gastric and duodenal ulcers:
pylori infection – this bacterium is responsible for 90% of duodenal ulcers and about 70% -90% of gastric ulcers. H. pylori infection is more common among people of lower socioeconomic status and more common in childhood. The body has a broad spectrum of virulence factors that allow it to adhere and become inflamed with the stomach lining.
NSAIDs – The use of non-steroidal anti-inflammatory drugs is the second most common cause after pylori infection. The secretion of prostaglandins normally protects the gastric mucosa. NSAIDs block the synthesis of prostaglandins by inhibiting the COX-1 enzyme, which reduces the secretion of gastric mucus and bicarbonate and reduces blood flow in the mucosa,
Apart from NSAIDs, corticosteroids, bisphosphonates, potassium chloride, steroids and fluorouracil are also involved in the etiology of peptic ulcer disease. Alcohol and smoking can irritate the gastric mucosa and cause acidity,
stress ulcers,
pathological hypersecretion (e.g., gastrinoma).
Rare causes of gastric and duodenal ulcers:
- Crohn’s disease
hypercalcemia,
lymphoma,
cancer, sarcoma, carcinoid,
foreign body,
cirrhosis of the liver, kidney failure, HIV, celiac disease (duodenum), diabetes mellitus (stomach).
Peptic ulcer symptoms:
- pain and discomfort (incidence rate: 100%),
pain in the upper abdomen (upper abdomen) (67%),
pain occurring shortly (30 minutes) after meals (20%)
pain relieved after meals (2-48%),
night pain (32-43%),
pain that periodically worsens (68%),
pain relieved by agents that neutralize gastric acid (36-87%),
loss of appetite (46-57%),
nausea (54-70%),
vomiting (38-73%),
belching (50%),
heartburn (19%),
indigestion.
Alarm symptoms (suspected cancer):
anemia,
bleeding from the upper gastrointestinal tract,
tarry (black) stools
weight loss (24-61%),
palpable tumor in the abdomen,
the appearance of symptoms of the disease for the first time after the age of 45,
Complications of peptic ulcer disease:
- bleeding from ulcers
anemia,
perforation (perforation) of ulcers
digestive (benign) stenosis of the pylorus.
Basic goals of peptic ulcer treatment
The aim of the therapy is to heal the ulcer niche as quickly as possible and to relieve clinical symptoms of the disease, mainly pain. The aim is to minimize relapses and complications resulting from this disease. If you have symptoms that may indicate this disease, consult a doctor.
Pharmacotherapy
Proton pump inhibitors – H + / K + – ATPase blockers. All available compounds are benzimidazole derivatives and are classified as PROLUGES:
Omeprazole (Bioprazole, Helicid 20),
Lansoprazole (Dexilant),
Pantoprazole (Anesteloc, Controloc),
Rabeprazole,
Esmoprazole (Emanera).
They are the drugs of first choice in the treatment of peptic ulcer and reflux oesophagitis. Their use ALMOST completely inhibits the secretion of hydrochloric acid. By inhibiting H + secretion, the pH in the stomach increases and the eradication of H. pylori is facilitated. The side effects that may result from the use of these preparations are: gastrointestinal discomfort, dizziness, nausea, headache.
Histamine H Receptor Antagonists The following drugs are available:
Cimetadine,
Ranitadine,
Famotidine,
Nizatidine,
They are drugs of second choice. They maintain the pH of the stomach above 5 for 4-6 hours (famotidine: 12 hours). The mechanism of action is based on blocking competing histamine receptors in the parietal cells of the gastric mucosa, inhibiting both basal and histamine-stimulated secretion of hydrochloric acid. Their mechanism of action does not completely inhibit gastric acid secretion, and thus the acid barrier that protects the stomach from being colonized by bacteria is preserved. They are usually served in the evening. Side effects after the use of cimetidine may be taste disturbance or impaired potency, oligospermia and gynecomastia.
Neutralizing drugs. This group of medications includes substances that neutralize or bind hydrochloric acid in the stomach. Belong to them:
Magnesium compounds (Maalox – oral suspension in sachets, Manti),
Aluminum compounds (Maalox, Gelatum Aluminii Phosphorici, Alugastrin),
Alginates (Gaviscon with mint flavor,
They are used only for the immediate relief of pain, until the proton pump inhibitors work. Take them 1-3 hours after a meal. Due to their absorption properties, they should not be used with other drugs.
Sucralfate (Ulgastran – oral suspension). It creates complex connections with basic proteins on the ulcer surface and thus prevents aggressive agents, such as pepsin and hydrochloric acid, from penetrating the mucosa. Side effects include constipation.
Prostaglandin E derivatives. The only available substance is MISOPROSTOL. It works by activating the protective factors and by receptors acting on parietal cells and inhibiting the secretion of HCl.
Eradication of H. pylori. The following procedure is recommended:
Proton pump inhibitors (PPIs) + 2 antibiotics from: amoxicillin, clarithromycin, metronidazole.
In case of failure of the first option, the following are used: PPI + bismuth salts + metronidazole + tetracycline.
In order to avoid the development of peptic ulcer disease, first of all, the use of NSAIDs should be limited. Early detection and intervention for patients diagnosed with ulcers are critical to preventing complications. After the diagnosis of peptic ulcer disease has been made, a gastroenterologist and nutritionist should be consulted.
Literature:
Gisela A. Ocasio Quinones, A. Woolf, Duodenal Ulcer,
Talia F. Malik; Karthik Gnanapandithan; Kevin Singh, Peptic Ulcer Disease
Michelle A. Bernshteyn; Umair Masood, Pantoprazole,
Mutschler, G. Geisslinger, H. K. Kroemer, P. Ruth, Mutschler Pharmacology and Toxicology.
Szczeklik, P. Gajewsk, Interna Szczeklik.
Pharmacodynamics, a textbook for Students of Pharmacy
