Essay on the Treatment of Peptic Ulcer | Types | Ulcer | Medical Science

In this essay we will discuss about the drugs used for the treatment of peptic ulcer.

Essay # 1. H₂ Receptor Antagonists:

The H₂ receptor antagonist drugs block the production of acid by parietal cells and produce gastric acidity up to 24 hours. These drugs are usually given as a single dose at night. They can also be given twice a day in divided doses. Cimetidine, the first H₂ antagonist, is the least potent, is liable to give rise to side effects and inhibits hepatic microsomal enzymes leading to important drug interactions. The adverse effects include mental confusion, hepatotoxicity, allergic reaction, bone marrow depression, rashes, GIT disorders, impotence and gynecomastia.

Drug interaction results in delaying the oxidative metabolism of a large member of drugs, the important of which are warfarin, phenytoin and theophylline, which have a narrow therapeutic index and margin of safety.

With the availability of more potent and less toxic drug which lack drug interaction properties, cimetidine is not preferred in therapy. Ranitidine is a potent H₂ antagonist; side effects are minimal and rarely cause drug interactions. It is given in doses of 300 mg at night or 150 mg twice a day.

Nizatidine in its potency, doses and therapeutic efficacy is comparable with ranitidine. Pharmacologically its actions are almost exclusively confined to the stomach, with little evidence of effects on cardiovascular or central nervous system. Unlike cimetidine and ranitidine, it does not bind to hepatic cytochrome P450.

Famotidine is the most potent H₂ antagonist, given in a single dose of 40 mg at night. It has no effect on the elimination of drugs metabolized by the liver (no drug interaction). Toxic effects include altered bowel habits, dizziness, headache and more importantly occasional blood dyscrasia. The potency, lack of serious toxic effects and uniformity of uptake, bioavailability, and elimination make famotidine a H₂ antagonist of choice.

Therapeutic uses:

Famotidine is the drug of choice. H₂ antagonists are used in:

a. Duodenal and peptic ulcers. Healing rate may be as high as 95% with treatment for 4 to 8 week therapy.

b. Prophylaxis and treatment of NSAIDs induced duodenal ulcers.

c. Gastroesophageal reflex disease.

d. Prophylactically to reduce the frequency of bleeding from gastro-duodenal erosions in hepatic coma.

e. Zollinger- Ellison syndrome, but proton pump inhibitors are preferred.

Essay # 2. Proton Pump Inhibitors:

H⁺/K⁺ ATPase, a proton pump, is found in the gastric fundal mucosa. Proton pump inhibitors bind to parietal H⁺/K⁺ ATPase, inhibiting secretion of hydrogen into the gastric lumen. Proton pump inhibitors irreversibly inhibit proton pump and inhibit gastric acid secretion more powerfully than H₂ antagonists. Omeprazole (20-40 mg), lansoprazole (30 mg), pantoprazole (40 mg), esomaprazole (40 mg) and rabeprazole (20 mg) are proton pump inhibitors available. They are given orally once a day. Proton pump inhibitors have direct antibacterial against H. pylori but do not cure the infection when used alone.

Therapeutic uses:

Proton pump inhibitors provide significantly better rate and completeness of healing of peptic ulcer than that obtained by H₂ antagonists. They are indicated in resistant peptic ulcers, resistant gastro-esophageal reflex disease and in combination with antibiotics for eradication of H. pylori infection. They are the best drugs for Zollinger-Ellison syndrome, where there is gross over secretion of acid. The incidence of side effects is very low and includes headache, nausea, diarrhea and rashes.

Essay # 3. Selective Antimuscarinics:

Selective antagonists of M₁ receptor in parietal cells are as effective as atropine or other nonselective muscarinic antagonists, but are less likely to produce adverse effects. Pirenzepine is a selective M₁ anticholinergic drug, clinically, was found to possess relatively weak acid-inhibiting action and significant side effects (dry eyes, dry mouth, and urinary retention). It has now been discontinued.

Essay # 4. Mucosal Protection:

These groups of drugs enhance the mucosal protective mechanism of gastro-duodenal mucosa by enhancing mucosal thickness and secretion of mucus and bicarbonate and by promoting the regeneration of epithelial cells. They have also been termed cytoprotective.

Essay # 5. Prostaglandins:

The gastric and intestinal mucosa both synthesize large amounts of prostaglandin, which exerts protective effect on the gastric mucosa and also inhibit acid secretion from gastric parietal cells. Misoprostol (800 micrograms in 2-4 divided doses), a synthetic prostaglandin analogue, is used in peptic ulcers particularly in NSAIDs associated ulcers. The mechanism by which it provides its therapeutic effect is through enhancement of mucosal defense and repair.

Misoprostol enhances mucous bicarbonate secretion, stimulate mucosal blood flow, and decreases mucosal cell turnover. The most common toxicity noted with this drug is diarrhea. Other major toxicities include uterine bleeding and contractions. It is contraindicated during pregnancy. It is given in a dose of 200 μg four times a day.

Essay # 6. Sucralfate:

Sucralfate is a compound of aluminum and sucrose. Its mode of action is not fully understood but seems to be related to enhanced production of endogenous prostaglandin and increased secretion of mucus and bicarbonate, and enhancing mucosal defense and repair. Sucralfate is insoluble in water and becomes a viscous paste within the stomach and duodenum, binding primarily to sites of active ulceration, thus protecting the ulcer crater from autolysis by acid, pepsin and bile.

Toxicity from this drug is rare, with constipation being reported in 2 to 3% cases. It should be avoided in patients with chronic renal insufficiency to prevent aluminum-induced neurotoxicity. Sucralfate is given in doses of 1 g four times a day.

Essay # 7. Bismuth Compound:

Bismuth subsalicylate or sub citrate relieves the symptoms of peptic ulcers by causing coagulation of protein and mucogly-coproteins at the base of the ulcer and acts as a barrier to the diffusion of acid/pepsin, by binding of pepsin, and stimulation of prostaglandins, bicarbonate, and mucous secretion.

The most important claim for bismuth is that it kills the organism H. pylori, which is not true of H₂ antagonists or sucralfate. However, the bactericidal action against H. pylori is temporary and for its eradication a combination therapy of antiulcer drugs and antibiotics is employed. The main side effect of bismuth is constipation. Encephalopathy and neurotoxicity may occur in patients with renal failure and the drug should not be used for long-term maintenance therapy.

H. pylori eradication:

Helicobacter pylori, a spiral, gram-negative, urease-producing bacillus, are thought to be responsible for approximately 80% of ulcers that are not due to NSAIDs. Eradication of H. pylori promotes healing and markedly reduces recurrence of gastric and duodenal ulcers.

No single agent is effective in eradicating the organism and the treatment requires combination of two antimicrobial drugs with an anti-secretory drug, usually a proton pump inhibitor.

The antimicrobial drugs used with the greatest frequency include amoxicillin, metronidazole, tetracycline and clarithromycin. One of the major problems for the failure of eradication of the infection is the development of resistance to one of the major antimicrobial drugs (e.g. clarithromycin or metronidazole).

The other factor responsible for the treatment failure is the duration of treatment. The minimum duration of therapy should be at least 10 days, though 14 days of therapy provides better cure rates.

Anti-secretory therapy provides rapid relief of pain, accelerates healing, and, with many drug (e.g. proton pump inhibitors or bismuth) combination improves the cure rate.

Many combination therapies are available for the treatment of H. pylori infections. However, failure of therapy to cure the infection is an increasing problem, which is due to the presence of antimicrobial-resistant H. pylori and poor compliance with therapy.

The available eradication regimens for H. pylori include dual, triple and quadruple therapies. Dual therapy is associated with a high failure rate and is no longer recommended.

Triple therapy with a minimum duration of 10 days yields a cure rate as high as 91% among patients who comply with the full protocol. A good example of triple therapy is omeprazole 20 mg, clarithromycin 500 mg and amoxicillin 1g taken twice a day for 10 days. Metronidazole is generally not included in the regimen because more than 90% of the H. pylori isolates are resistant to it.

Patients, who fail to respond to triple therapy for more than two attempts, require quadruple therapy consisting of omeprazole (20 mg once or twice daily), tetracycline (500 mg four times daily), metronidazole (500 mg three times daily) and bismuth (e.g., bismuth subsalicylate, 2 tablets four times daily) for 14 days. Because this regimen generally has a higher cure rate than traditional triple therapies, it can also be initial therapy.

An alternative salvage therapy uses high-dose omeprazole (40 mg three times daily) plus amoxicillin (1 g three times daily). Either approach has a high rate of success, even in the face of metronidazole resistance.

Essay # 8. NSAID Associated Ulcers:

NSAID should be stopped as the first step in the therapy of an active NSAID-induced ulcer. If that is possible, then treatment with one of the acid inhibitory agents (H₂ blockers or proton pump inhibitors) is indicated. For patients with rheumatoid arthritis who require active anti-inflammatory therapy, prednisone (5-10 mg/day) can be given without apparently adversely affecting ulcer healing. Once the ulcer has healed, the patient can be given a selective COX-2 inhibitor or a traditional NSAID with concomitant misoprostol with or without one of the acid-inhibitory agents (H₂ blockers, proton pump inhibitors).