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Anti Ulcerant, PPIs, Proton Pump Inhibitors; Types, Uses

Proton-pump inhibitors (PPIs) are a group of drugs whose main action is a pronounced and long-lasting reduction of stomach acid production. Within the class of medications, there is no clear evidence that one agent works better than another. They are the most potent inhibitors of acid secretion available. This group of drugs followed and largely superseded another group of medications with similar effects, but a different mode of action called H₂-receptor antagonists.

Classification of Proton Pump Inhibitors

Drugs for peptic ulcer and GERD/GORD
H₂ antagonists (“-tidine”)	Cimetidine Famotidine Lafutidine Lavoltidine (loxtidine) Niperotidine Nizatidine Ranitidine Roxatidine
Prostaglandins (E)/analogues (“-prost-“)	Misoprostol Enprostil
Proton-pump inhibitors (“-prazole”)	Azeloprazole Dexlansoprazole Esomeprazole Ilaprazole Lansoprazole Omeprazole Pantoprazole Pantoprazole Rabeprazole Tenatoprazole Timoprazole
Potassium-competitive acid blockers (“-prazan”)	Linaprazan Revaprazan Soraprazan Vonoprazan
Others	Aceglutamide aluminum Acetoxolone Alginic acid Arbaclofen placarbil Bismuth substrate Carbenoxolone Cetraxate Gefarnate Lesogaberan Pirenzepine Proglumide Rebamipide Sucralfate Sulglicotide Telenzepine Teprenone Troxipide Zinc L-carnosine Zolimidine
Combinations	Bismuth subcitrate/metronidazole/tetracycline

Mechanism of Action of Proton-pump inhibitors

Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H⁺/K⁺ATPase, or, more commonly, the gastric proton pump) of the gastric parietal cells. The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H⁺ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.

Targeting the terminal step in acid production, as well as the irreversible nature of the inhibition, results in a class of drugs that are significantly more effective than H₂ antagonists and reduce gastric acid secretion by up to 99%.

Decreasing the acid in the stomach can aid the healing of duodenal ulcers and reduce the pain from indigestion and heartburn. However, stomach acids are needed to digest proteins, vitamin B₁₂, calcium, and other nutrients, and too little stomach acid causes the condition hypochlorhydria.

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The PPIs are given in an inactive form, which is neutrally charged (lipophilic) and readily crosses cell membranes into intracellular compartments (like the parietal cell canaliculus) with acidic environments. In an acid environment, the inactive drug is protonated and rearranges into its active form. As described above, the active form will covalently and irreversibly bind to the gastric proton pump, deactivating it.

Medical Uses of Proton-pump inhibitors

These drugs are used in the treatment of many conditions, such as:

Dyspepsia
Peptic ulcer disease including after endoscopic treatment for bleeding
As part of Helicobacter pylori eradication therapy
Gastroesophageal reflux disease (GERD or GORD) including symptomatic endoscopy-negative reflux disease and associated laryngopharyngeal reflux causing laryngitis and chronic cough
Barrett’s esophagus
Eosinophilic esophagitis
Stress gastritis and ulcer prevention in critical care
Gastrinomas and other conditions that cause hypersecretion of acid including Zollinger–Ellison syndrome (often 2–3x the regular dose is required)

Specialty professional organizations recommend that people take the lowest effective PPI dose to achieve the desired therapeutic result when used to treat gastroesophageal reflux disease long-term. In the United States, the Food and Drug Administration has advised that no more than three 14-day treatment courses should be used in one year.

Despite their extensive use, the quality of the evidence supporting their use in some of these conditions is variable. The effectiveness of PPIs has not been demonstrated for every case. For example, although they reduce the incidence of esophageal adenocarcinoma in Barrett’s esophagus, they do not change the length affected