Adverse digestibility effects, drug-food interactions and long-term safety of proton pump inhibitors. Issue 2 (12th March 2012)

• Record Type: Journal Article
• Authors: Jenzer, H.; Sadeghi, L.; Krause, C.; Stute, P.; Joray, M.; Leuenberger, M.; Stanga, Z.
• Is Part Of: European journal of hospital pharmacy. Volume 19:Issue 2(2012)
• Page Start: 187
• Page End: 188
• Publication Date: 2012-03-12
• Subjects: Pharmacy -- Periodicals; Hospital pharmacies -- Periodicals; 615.1
• DOI: 10.1136/ejhpharm-2012-000074.270
• Languages: English
• ISSNs: 2047-9956

Abstract

Abstract : Background: Gastric acidity is mandatory for pepsin activation, bactericidal effect, secretin and pancreatic enzymes' release. PPIs (proton pump inhibitors) change gastric pH permanently to >3-4. Purpose: The aim of this work is to assess the impact of permanent high gastric pH on absorption and bioavailability (except of CYP450-interactions) and to recommend nutrition support options. Materials and methods: A systematic online literature research was performed on usual platforms. Recommendations rely on a multidisciplinary focus group assessment. Results: Risk factors assigned to long-term inhibition of gastric acidity arise from · cleavage-resistance of peptide and glycosidic bonds · mucosal degeneration and leak · loss of bactericidal action and comprise · bacterial overgrowth · community and hospital-acquired pneumonia · childhood asthma related to PPI treatments of mothers in pregnancy · sensitisation to food allergens in the older and in pregnant women (progesterone slows down gastric emptying) · deterioration of lactose intolerance, celiac disease, atrophic gastritis, rheumatoid arthritis, diabetes mellitus · modified bioavailability o malabsorption of micronutrients, for example vit C and B12, folate, Zn, Fe, Mg, Ca o lower bioavailability, for example ketoconazole, itraconazole, posaconazole, (not: voriconazole), atazanvir, cefpodoxime, cinnarizine, enoxacin, dipyridamole o higher bioavailability, for example nifedipine, digoxin, penicillins, erythromycin, alendronate. To prevent these complications, the focus group recommends: · alternative antacids, step-down, intermittent and on-demand strategies: o MgCO3 and H2 -antagonists have a shorter onset and time of pH>3-4 than pantoprazole 40mg (median pH=3.7, pH>4 for 10.8h) or esomeprazole 40mg (median pH=4.7, pH>4 for 16.1h). · to avoid high allergenic food o that is c rustacean, eggs, fish, milk, peanuts, soybeans, tree nuts or fruits, and wheat · buffering, pepsin replacement, stimulation of digestion and peristalsis o Carbonated beverages, quinine water, aperitifs, appetisers, and bitter substances (amara) o Prokinetic agents (domperidone, bromopride, metoclopramide, quinine, erythromycin) o Mucosal protectors (curcumin, quercetin, alginates, pectins, glycyrrhizin) o Melatonin (regulates digestion and has structural similarity to omeprazole) o Pepsin in HCl preparations · nutrition and dietary approach combined with physical activity o High-fibre-, low-fat-, low-carb diet · reassessment of pharmacotherapy o Weak acids (pKa <4.5) lose their undissociated state required for diffusion across membranes. o Absorption is impaired by membrane-bound CYP3A4, 5, 7 and efflux transporter P-gp. (a log-conc-diagram, structure formula, tables of relevant drugs and nutrients, as well as references are provided on the poster) Conclusions: PPI safety profiles are troubled by risk factors arising from inappropriate long-term use. Drugs may be more bioavailable as a result of mucosal hyperpermeability, or less bioavailable as a result of altered dissociation. Care should be given to substrates with pKa <4.5. At least children and pregnant women should prefer alternatives to PPIs.