Microsoft powerpoint - ppi rational use (dubai)

Healing of acid-related disorders directly related to degree and duration of acid suppression and length of treatment Introduction in 1989 of proton pump inhibitors, covalent inhibitors of gastric H+,K+-ATPase, resulted in significant improvement in management of acid-related disorders PPI produce significantly more effective and prolonged acid suppression than H2-receptor antagonists without evidence of Spurt of new releases (“second-generation”) with big claims. More PPI released in last 7 years than in previous 15 years PPI prescriptions for questionable indications in 40%-70% of hospitalized patients (Aliment Pharmacol Ther doi: 10.1111/j.1365- Enteric-coated acid-labile pro-drugs, so peak levels after 2-5 h Weak bases; require acid environment for conversion to active 5% pumps active on fasting, 60%-70% after meal Plasma half-life <2 h; acid inhibition >24 h; 1 week therapy Best administration, therefore, immediately before meals; esomeprazole administration 1 h before, because food No interference with concomitant antacids Significant genetic polymorphisms for one of the CYP Food may delay absorption of lansoprazole, pantoprazole and isoenzymes involved in PPI metabolism, CYP2C19 rabeprazole, but this does not alter area under plasma ~3% of white persons and 15% of Asians deficient in CYP2C19 Generally no dose adjustment for renal or hepatic failure, or in This substantially raises plasma levels of omeprazole, lansoprazole and pantoprazole, but not of rabeprazole and Eradicating H. pylori renders PPI less effective in elevating gastric pH in patients with duodenal ulcer generally more effective than H2RA, but difference not significant in non-ulcer dyspepsia and peptic ulcers preferred for GERD, with night-time H2RA if required reduce risk of NSAID-associated endoscopic ulcer disease but there is less evidence for reduction in bleeding events (Cochrane preferred for primary and secondary prevention, and for treatment, of non-variceal upper GI bleed (Aliment Pharmacol Ther 2008;28:629-7; Health Technol Assess 2007;11:1-164) preferred in treatment for H. pylori In vitro activation time at acidic pH (1.2) abeprazole
At acidic pH (as obtained in parietal cells), activation half-life for PPI Omeprazole, pantoprazole and lansoprazole have equivalent potency for normalizing intra-oesophageal acid exposure after 3 days of treatment in non-erosive reflux disease patients; the former two act earlier (Aliment Pharmacol Ther 2008;28:250-5) Hence, no functional significance in differences in activation time All current PPI equally recommended for H. pylori eradication Recently available fast preparations (coupled with alkalis) useful regimens. In a recent study, omeprazole-based triple therapy gave higher eradication rate in non-ulcer dyspepsia (Korean J • Although recommended doses of PPI vary, data suggest • Different dose recommendations based on different strategies to balance optimal dosage with safety • No real difference in milligram-related efficiencies -- Gastroenterology 2000;118:A5895 Median % time pH >4 in 24 h after single dose (Indian) Few studies indicate that low doses of PPI are as effective as standard doses in management of acid-related diseases Low doses are inferior to standard doses in healing esophagitis Low doses may be therapeutically similar to standard doses in maintenance therapy of GERD and peptic ulcer disease Intravenous formulations of all PPI currently available IV PPI is currently mainstay in management of upper GI bleeding in peptic ulcer patients who have undergone endoscopic hemostasis (Ann Intern Med 2003;139:843-57) Use of similar regimen prior to endoscopy may reduce high-risk stigmata at endoscopy (N Engl J Med 2007;356:1631-40) Unfortunately, IV PPI commonly used where not indicated, and even where recommended, are used in higher doses and for longer durations than recommended (Can J Gastroenterol Once-daily IV PPI may give same benefit as continuous infusion (Am J Gastroenterol 2008;103:3011-8 and 3019-21) Conceivably, oral PPI may offer same benefit (Aliment Pharmacol Ther 2008;28:326-33; BMJ 2005;330:568) Tolerance not seen during short-term treatment Tolerance not seen during short-term treatment Rebound acid hypersecretion by 14 days after cessation of Rebound acid hypersecretion by 14 days after cessation of therapy. Found in H. pylori-negative, but not -positive, subjects; therapy. Found in H. pylori-negative, but not -positive, subjects; can persist for >2 months after prolonged therapy can persist for >2 months after prolonged therapy H. pylori shift from antrum to body / fundus – acid cell atrophy H. pylori shift from antrum to body / fundus – acid cell atrophy May decrease mineral and cobalamin absorption May decrease mineral and cobalamin absorption Significant increase in Clostridium difficile infection in antibiotic • In settings with low rates of such infection, benefit of PPI recipients who receive PPI, but absolute risk increase is modest (Aliment Pharmacol Ther doi: 10.1111/j.1365-2036.2008.03924) PPI may increase risk of nosocomial pneumonia in ICU • Still, inappropriate use of PPI in hospitalized patients must populations, but evidence is controversial (J Crit Care Gastric and jejunal bacterial overgrowth follows PPI use in compromised environs (Indian J Gastroenterol 1995;14:134-6) Tolerance not seen during short-term treatment • PPI use decreases absorption of protein-bound vitamin Rebound acid hypersecretion by 14 days after cessation of B12 in short-term studies (Aliment Pharmacol Ther therapy. Found in H. pylori-negative, but not -positive, subjects; can persist for >2 months after prolonged therapy • Screening for vitamin B12 deficiency recommended on H. pylori shift from antrum to body / fundus – acid cell atrophy long-term PPI treatment (Basic Clin Pharmacol Toxicol May decrease mineral and cobalamin absorption • Results of long-term studies are, however, inconsistent Gastric carcinoid tumors reported in rats on prolonged PPI – Some report decline in serum vitamin B12 (Ann – Not clear whether decline is clinically significant (Clin No evidence of carcinoid tumors or carcinogenesis in humans Elevated gastrin returns to normal within 4 weeks after – Recent studies suggest screening may not be required (Aliment Pharmacol Ther 2008;27:491-7) • PPI use associated with increased serum gastrin levels and bacterial overgrowth, resulting in more toxic bile salt – facilitates digoxin absorption, resulting in higher plasma levels Potential to alter metabolism of drugs eliminated by CYP formation, which may increase risk of colorectal neoplasia • No association between use of PPI and risk of colorectal – Omeprazole delays clearance of warfarin, diazepam and phenytoin; clinically important drug interactions uncommon cancer (Am J Gastroenterol 2008;103:966-73) – Lansoprazole, pantoprazole and rabeprazole do not interact Omeprazole in FDA category C (contraindicated) PPI have advantages over H2RA in many situations All PPI equipotent for standard treatment of acid-peptic disorders Other PPI in FDA category B (use with caution) and for H. pylori eradication regimens PPI excreted in breast milk; discontinue use if not essential Second-generation PPI have advantages of consistency in Recent data suggest that PPI do not represent major teratogenic response and lower drug interactions, but at higher cost risk in humans, including when used in first trimester (Aliment Low-dose PPI may suffice in many situations in Indians with lower parietal cell mass and possibly CYP2C19 deficiency IV PPI have well-defined roles, but should not be overused Safety issues (including potential for drug interactions, nosocomial infections, and micronutrient deficiency) preclude injudicious use

Source: http://isgme.org/PPI-rational-use-Jan-18.pdf