These drugs acts by inhibiting gastric acid secretion or by promoting ulcer healing.
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:
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.
Gastric ulcer, duodenal ulcer
