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 This group of drugs followed and largely superseded another group of medications with similar effects, but a different mode of action called H2-receptor antagonists.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. 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 Contra-Indications of Proton-pump inhibitors Clostridium difficile infection Inadequate Vitamin B12 Low amount of magnesium in the blood Liver problems Interstitial Nephritis Subacute cutaneous lupus erythematosus Systemic Lupus Erythematosus Osteoporosis Broken Bone Allergies to Proton Pump Inhibitors Side Effects of Proton-pump inhibitors The most common Nausea and vomiting Severe stomach ache Severe diarrhea Vaginal thrush Skin rash A headache chest pain constipation a cough diarrhea or loose stools difficulty with breathing dizziness heartburn muscle pain More common Abdominal or stomach pain, discomfort, or tenderness chills or fever difficulty with moving a headache, severe and throbbing joint or back pain muscle aching or cramping muscle pains or stiffness chest pressure or squeezing pain in the chest discomfort in arms, shoulders, neck or upper back excessive sweating feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis sudden tingling or coldness in an arm or leg sudden slow or difficult speech sudden drowsiness or need to sleep fast breathing sharp pain when taking a deep breath fast or slow heartbeat coughing up blood rust colored urine decreased amount of urine Rare Anxiety change in vision seizures abnormal or fast heart rate tremors weight loss chest pain or tightness confusion a cough Agitation arm, back, or jaw pain blurred vision chest pain or discomfort convulsions extra heartbeats fainting hallucinations a headache irritability lightheadedness mood or mental changes muscle pain or cramps muscle spasm or jerking of all extremities Drug Interactions of Proton-pump inhibitors Anti ulcerant may interact with following drugs, supplements, & may change the efficacy of the drug amiodarone azole antifungal medications (e.g., fluconazole, ketoconazole) caffeine calcium channel blockers (e.g., diltiazem, nifedipine, verapamil) carbamazepine carvedilol certain benzodiazepines (alprazolam, chlordiazepoxide, clonazepam, diazepam,flurazepam, midazolam, and triazolam) clopidogrel clozapine dasatinib glyburide (and other “sulfonylurea” diabetes medications) lidocaine metformin metoprolol pentoxifylline phenytoin propranolol salmeterol SSRIs (e.g., citalopram, fluoxetine, sertraline) sucralfate theophyllines (e.g., aminophylline, oxtriphylline, theophylline) tramadol tricyclic antidepressants(e.g., amitriptyline, clomipramine, desipramine, trimipramine) warfarin References https://en.wikipedia.org/wiki/Proton-pump_inhibitor https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855237/ https://www.sciencedirect.com/topics/neuroscience/proton-pump-inhibitors https://www.sciencedirect.com/science/article/pii/S0149291800830258 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855237/ https://www.ncbi.nlm.nih.gov/pubmed/14664653 Show More