Ulcers, peptic proton pump inhibitors

Antacids are neutralizing agents. Examples are magnesium hydroxide, magnesium trisylicate and aluminium hydroxide. Prior to the introduction of histamine-H2 receptor antagonists and proton pump inhibitors, they were the standard drugs for the treatment of duodenal/ peptic ulcers. Today their clinical use is limited to the treatment of dyspepsia and the symptomatic relieve for patients with peptic ulcers. 

The proton pump inhibitors are particularly important in the treatment of Helicobacter pylori in patients with active duodenal ulcers. Helicobacter pylori (H. pylori) has been implicated as a causative organism in a type of chronic gastritis and in a large number of cases of peptic and duodenal ulcers. 

Less common causes of peptic ulceration include Zollinger-Ellison syndrome (ZES), cancer chemotherapy, radiation, and vascular insufficiency. ZES is caused by a gastrin-producing tumor called a gastrinoma and results in gastric acid hypersecretion. High-dose oral proton pump inhibitor (PPI) therapy is the initial treatment of choice for ZES intermittent intravenous PPI therapy may be required for any patient in whom oral therapy is contraindicated.1... 

H2RA, histamine2-receptor antagonist NSAID, nonsteroidal anti-inflammatory drug PPI, proton pump inhibitor. (Adapted from Berardi RR, Welage LS. Peptic ulcer disease. In DiPiro JT, Talbert RL,... 

The analgesic effects of NSAIDs are attributed to inhibition of the COX-2 enzyme, whereas the negative GI effects are due to inhibition of COX-1.28 Patients taking oral anticoagulants, those with a history of peptic ulcer disease, or others at high risk for GI complications may be considered candidates for a COX-2 inhibitor or a combination of a nonselective NSAID with a gastroprotective agent such as a proton pump inhibitor (PPI). Because most PPIs are available by prescription only, such patients should be referred to a physician. 

GNB = Gram-negative bacilli PPI = proton pump inhibitor Hp = H. pylori. a Patients with peptic ulcer disease and reflux esophagitis. b Early stage of atrophic corpus gastritis of limited extension (less common). 

Although the risk of GI complications is relatively small with short-term therapy, coadministration with a proton pump inhibitor should be considered in elderly patients and others at increased GI risk. NSAIDs should be used with caution in individuals with a history of peptic ulcer disease, heart failure, uncontrolled hypertension, renal insufficiency, coronary artery disease, or if they are receiving anticoagulants concurrently. 

Proton pump inhibitors (PPIs), such as omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole, are commonly prescribed to treat symptoms of heartburn, acid reflux, chest pain, dyspepsia, and chronic cough. PPIs inhibit the transfer of protons into the stomach lumen. Pharmacological acid suppression is thus used to treat gastroesophageal reflux disease (GERD) and esophagitis, peptic ulcers, and Helicobacter pylori infection as well as to prevent ulcer development with concurrent nonsteroidal anti-inflammatory drug use. 

Localised upper abdominal pain is the most common symptom of peptic ulcer disease. The pain is relieved by antacids, proton pump inhibitors and H2 antagonists. The pain may or may not be relieved by food and is often v/orse during the night. Peptic ulceration may be accompanied by occasional vomiting, anorexia and weight loss. Diffuse abdominal pain is not a characteristic symptom of peptic ulcer disease. 

Omeprazole is an antiulcer drug. It is a proton pump inhibitor. This substituted benzimidazole inhibits gastric acid secretion to help acid/peptic disorders and duodenal ulcers. It interferes with the proton pump in the mucous lining of the stomach, the last stage of acid production. It can turn off stomach acid in as little as one hour. Lansoprazole (no. 12) has a similar structure. 

Lazzaroni M, Bianchi Porro G. Treatment of peptic ulcer in the elderly. Proton pump inhibitors and histamine H2 receptor antagonists. Drugs Aging 1996 9(4) 251-61. 

There is increasing evidence that eradication of Helicobacter pylori with combination therapy of two antibiotics (often amoxicillin with clarithromycin) with a proton pump inhibitor (e.g. pantoprazol) during one week will heal and prevent peptic ulcer disease. 

Answer Peptic ulcer disease is most frequently secondary to either Helicobacter pylori infection or use of NSAIDs. The patient does admit to NSAID use (naproxen), but should also be checked for concomitant H. pylori infection at time of endoscopy or by a serology test. If the patient was found to have H. pylori, an appropriate eradication regimen should be prescribed. The patient should also be counseled to avoid NSAIDs. The patient should be prescribed a proton pump inhibitor for 8 weeks to heal the ulcer. A repeat endoscopy should be done at that time to document ulcer healing and rule out gastric cancer. In addition, the patient should be counseled to stop smoking, which is a risk factor for more severe peptic ulcer disease. 

Revaprazan is a reversible proton pump inhibitor. It is currently in Phase 111 clinical development as a treatment for peptic ulcer (Figure 8.70). 

Asymptomatic peptic ulceration develops in 10-20% of people taking frequent NSAIDs, and ulcer-related complications (bleeding, perforation) develop in 1-2% of persons per year. Proton pump inhibitors taken once daily are effective in reducing the incidence of ulcers and ulcer complications in patients taking aspirin or other NSAIDs. 

Proton pump inhibitors (PPIs), eg, omeprazole, lansoprazole Irreversible blockade of H +, K+-ATPase pump in active parietal cells of stomach Long-lasting reduction of stimulated and nocturnal acid secretion Peptic ulcer, gastroesophageal reflux disease, erosive gastritis Half-lives much shorter than duration of action low toxicity reduction of stomach acid may reduce absorption of some drugs and increase that of others... 

Finally, it is universally accepted at present that Helicobacter pylori infection has a definitive ethiological role in peptic ulcer disease, and that erradication therapy is warranted in these clinical scenarios. The majority of therapeutic trials have included the application of triple therapy with proton pump inhibitors or ranitidine bismuth citrate, clarithromycin and either amoxycillin or metronidazol and is to date the treatment of choice. However, recent studies have reported antibiotic resistance which can be one reason for failure of treatment of Helicobacter pylori infection [101-103], and new treatment strategies are therefore Wellcome. Flavonoids, in addition to their gastroprotective activity previously commented, have been also shown to inhibit Helicobacter pylori growth in vitro. In this way, Beil et al. [50]... 

AstraZeneca (formerly Astra) has launched the proton-pump inhibitor esomeprazole (19) (as Nexium) as a treatment for peptic ulcer, gastroesophageal reflux disease, duodenal ulcer, and esophagitis. Esomeprazole is the (S)-enantiomer of omeprazole and was developed as a result of its improved pharmokinetic profile and better potency after oral dosing than (f )-form of omeprazole or the racemate. The dosage is higher than would be expected for a simple chiral switch. The stereogenic center is at sulfur. Detailed accounts of the development of the process have been published.189190... 

Omeprazole inhibits the secretion of gastric acid and acts as a proton pump inhibitor. It is highly effective for ulcerative reflux esophagatis and peptic ulcer... 

Infection with the bacterium H. pylori is associated with ulcer development. Treatment of peptic ulcers may involve a course of antibiotics to eradicate this organism. Agents such as H2 (histamine) antagonists, for example ranitidine, and proton pump inhibitors, such as omeprazole, are also used to heal peptic ulcers. 

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