Gastric acid inhibitors

Esomeprazole (Nexium) [Gastric Acid Inhibitor/Proton Pump Inhibitor] Uses Short-term (4-8 wk) for erosive esophagitis/GERD H. pylori Infxn in combo w/ antibiotics Action Proton pump inhibitor, gastric acid Dose Adults. GERD/erosive gastritis 20 0 mg/d PO x 4-8 wk 20 0 mg IV 10-30 min inf or >3 min IV push, 10 d max Maint 20 mg/d... 

Avanafil, 127 Dasantafil, 204 Tadalafil, 229 Vardefanil, 205 Fibrinogen Inhibitor Melagartan, 16 Ximelagattan, 16 Gastric Acid Inhibitor Revapiazan, 122 Glaucoma Treatment Bimatoprost, 24 Travoprost, 22... 

From biomedical experience with different kinds of gastric acid inhibitors, the conscious dog seems to be the most relevant animal species for the prediction of the antisecretory potential of a test compoimd in humans. Gastric acid secretion can be studied in the dog with a chronic gastric fistula or with a Heidenhain pouch [40]. 

Test Assays for Studying Gastric Acid Inhibitors... 

TEST ASSAYS FOR STUDYING GASTRIC ACID INHIBITORS... 

Gastric acid inhibitor therapy or elevated gastric pH V... 

For control of gastric acid secretion, the H2 antagonists have encountered competition from the potent -ATPase inhibitors such as... 

Moreover, receptors also control gastric acid release, although some marked species dependence is noticed (8). However, appHcation of agonists in this area does not seem to be probable the antagonists and the proton pump inhibitors serve quite weU. 

Ketoconazole. For treatment of systemic mycoses with amphotericin B or miconazole, the patient must be admitted to a hospital. This is not always possible, particularly in areas where systemic mycoses occur frequently, nor is it always desirable, because of the expense. For these reasons, it was desirable to find an antimycotic that combined safety and broad-spectmm activity with oral adraiinistration. Ketoconazole (10), which is orally active, met most of these requirements. This inhibitor of the ergosterol biosynthesis is an A/-substituted imidazole, that differs from its precursors by the presence of a dioxolane ring (6,7). Ketoconazole is rapidly absorbed in the digestive system after oral adrninistration. Sufficient gastric acid is required to dissolve the compound and for absorption. Therefore, medication that affects gastric acidity (for example, cimetidine and antacids) should not be combined with ketoconazole. 

In addition, Pfister and coworkers investigated 3-hydroxyflavone-6-carboxylic acids as histamine induced gastric secretion inhibitors. After condensing 3-acetyl-4-hydroxybenzoic acid (45) with a variety of aldehydes 46 to deliver the chalcones 47, these purified chalcones were then subjected to the standard AFO conditions to afford flavonols 48 in 51-80% yield. Subsequent alkylation of 48 with methyl iodide or isopropyl iodide followed by saponification of the corresponding esters gave the target compounds. 

The proton pump inhibitors suppress gastric acid secretion by blocking the final step in the production of gastric acid by the gastric mucosa... 

Use peptic ulcer therapeutic, gastric acid secretion inhibitor... 

The search for specific inhibitors of gastric H,K-ATPase has a dual purpose. First, with the help of suitable inhibitors it is possible to get insight into the molecular mechanisms of H,K-ATPase, and second, a specific inhibitor might be clinically useful for inhibition of gastric acid secretion in anti-ulcer therapy. 

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... 

The histamine2-receptor antagonists or H2RAs (cimetidine, famotidine, nizatidine, and ranitidine) and proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, pantopra-zole, and rabeprazole) reduce the amount of acid secreted into the stomach by gastric parietal cells. These agents are also helpful for nausea and vomiting related to gastric acid secretion. 

The incidence of community-associated C. difficile infection (defined as occurring in patients not hospitalized in the year prior to diagnosis) is increasing.36 In addition to antibiotic use, community-associated C. difficile cases are associated with the use of gastric acid suppressive agents (e.g., proton pump inhibitors and H2-receptor antagonists). 

The anti-ulcer agents omeprazole, lanzoprazole, and pantoprazole have been introduced during the past decade for the treatment of peptic ulcers. Gastric acid secretion is efficiently reduced by prazole inhibition of H+K+-ATPase in the parietal cells of the gastrointestinal mucosa [75]. The prazoles themselves are not active inhibitors of the enzyme, but are transformed to cyclic sulfenamides in the intracellular acidic compartment of parietal cells [76]. The active inhibitors are permanent cations at pH < 4, with limited possibilities of leaving the parietal cells, and thus are retained and activated at the site of action. In the neutral body compartments the prazoles are stable, and only trace amounts are converted to the active drugs. (For a review on omeprazole, see Ref. [77].)... 

Gram-negative bacilli are in general not recovered or only occasionally and at low counts in studies of healthy individuals on acid inhibitors [34, 40, 43, 44] (table 2). This pattern has also been shown in healthy old people with hypochlorhydria secondary to chronic gastritis, of whom the great majority only harbored URT flora despite gastric pH >6 [32],... 

Selective failure of the gastric acid barrier, as seen in otherwise healthy individuals on proton pump inhibitors or with H. pylori-induced corpus gastritis, results in gastric colonization of swallowed oropharyngeal bacteria. In otherwise healthy subjects this will be mainly Gram-positive bacteria belonging to the URT flora and strict anaerobic bacteria of oral origin. 

Concurrent colonization by Gram-negative bacilli occurs in some patients with failure of the gastric acid barrier, suggesting additional deficiencies of host defense abnormal oral flora, malnutrition, general illness, or diseases or medication interfering with intestinal peristalsis and clearance. This type of microflora is also seen in 10-30% of patients on acid inhibitors, for which mucosal injury and functional changes related to peptic ulcer and reflux disease may be responsible. 

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