102proton pump inhibitors - gi effects

Adverse Drug Reaction Alert Bulletin (ADRAB)
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Proton pump inhibitors – remember GI adverse effects and rebound
Omeprazole, pantoprazole, lanzoprazole

Key points
° Adverse effects, including gastrointestinal upset, are relatively common (greater than 1% of people)
° Other serious adverse effects include interstitial nephritis, Clostridium difficile and increased risk of
° Use and dosage of proton pump inhibitors should be reviewed constantly (consider an H2 antagonist)
° Rebound and hypersecretion can occur when proton pump inhibitors are discontinued – down titrate

Usual adverse effects
The practical implications of this is that down titration of proton pump inhibitors needs to be slow While proton pumps seem relatively innocuous, it is (conservatively halve dose every three months if worth remembering that some of their frequent
treatment has been long-term) or the rebound adverse effects involve the gastrointestinal
symptoms will suggest that the original GORD system. This is an age-response relationship.1
symptoms have recurred. Persistence on the part of
Common (> 1%) adverse effects include:
the patient is required if drug use is to be Nausea / GI upset, (some references, up to 10%), Need for therapy?
Bloating, nausea and reflux may be due to reduced Uncommon / rare but serious adverse effects
gastric emptying (e.g. in the elderly). These symptoms may respond better to a prokinetic Before starting a proton pump inhibitor: Check if there is a clear indication that this is a condition in which lowering gastric acidity further will be of More recently there has been an association with
benefit – or if the symptom independent of acid? ° Clostridium difficile infection If the proton pump inhibitor doesn’t ‘work’ – check that the gastric symptom has not changed and whether the person is now experiencing a PPI Rebound and hypersecretion after proton pump
inhibitors treatment
Review three monthly – and try slow dose down
For some time there has been evidence of rebound hypersecretion after PPI therapy, particularly longer
term therapy.1-8 There is no evidence of rebound Martin R et al., The rates of common adverse events reported during treatment with after one week of proton pump inhibitor treatment9,10 proton pump inhibitoprs used in general practice in England: cohort studies. Br J Clin Pharmacol. 2000; 50: 366-72 but rebound hypersecretion has been demonstrated Fossmark R et al., Rebound acid hypersecretion after long-term inhibition of gastric acid secretion. Aliment Pharmacol Ther. 2005; 21: 149-54 after eight weeks,6 and this effect can last more Sandvik A et al. Review article: the pharmacological inhibition of gastric acid secretion – tolerance and rebound. Aliment Pharmacol Ther. 1997; 11: 1013-8 than eight weeks, but less than six months after Qvigstad G, Waldrum H. Rebound hypersecretion after inhibition of gastric acid secretion. Basic Clin Pharmcol Toxicol. 2004; 94: 201 Gillen D, McColl K. problems related to acid rebound and tachyphylaxis. Best Pract Res The theory is that long-term acid inhibition results in Reimer C et al. Proton pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009; Apr 10th (e-pub) increased serum gastrin concentrations, leading to Gillen D et al. rebound hypersecretion after omeprazole and its relation to on-treatment acid suppression and Helicobacter pylori status. Gastroenterology. 1999; 116: 239-47 enetrochromaflin-cell like activation & proliferation, Waldrum H et al. Marked increase in gastric acid secretory capability after omeprazole treatment. Gut. 1996; 39: 649-53 and subsequently increased histamine mobilisation Hunfeld N et al. Systematic review: rebound acid hypersecretion after therapy with proton pump inhibiotors. Aliment Pharmacol Ther. 2007; 25: 39-46 from these cells stimulating parietal cells.1,3-5 Orr W et al. patterns of 24-hour oesophageal acid exposure after withdrawal of acid suppression. Aliment Pharmacol Ther. 1995; 9; 571-4

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