Proton Pump Inhibitors – PPIs
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Proton pump inhibitors (PPIs) are a commonly prescribed medication typically for symptoms of gastro-oesophageal reflux, peptic ulcer disease, and as gastroprotection where conditions or other prescribed drugs increase the risk of gastritis – such as when using steroids or NSAIDs.

Adverse effects are generally unusual, but it should be noted there is an increased risk of osteoporosis associated with long-term use, and that PPIs are known to alter gut flora – although the clinical result of this is unclear (and probably not hugely significant).

Generally you should use the lowest dose for the shortest period of time. Latest guidelines suggest a PRN (As required) approach to usage.

I sometimes use the analogy of “sun burn” when describing inflammation in the stomach caused by dyspepsia or reflux. This helps to explain about intermittent usage of PPIs, and why it seems that symptoms may not be immediately resolved. For example – like sunburn, gastric inflammation may take days to resolve, and may continue indefinitely if the cause isn’t removed (e.g. lifestyle factors +/- PPI use). BY removing factors that cause the inflammation you then allow the mucosa time to recover. – Dr Tom Leach

Esomeprazole proton pump inhibitor PPI
Esomeprazole box. PPIs are widely available and some smaller doses may be available without prescription in some jurisdictions.

Mechanism of action

Proton pump inhibitors act by irreversibly inhibiting H+/K+-ATPase in gastric parietal cells.

  • This proton pump usually secretes hydrogen ions into the stomach – resulting in the production of gastric acid
  • This mechanism is more effective than the reduction in stomach acid that is induced by H2-receptor antagonists (e.g. ranitidine)

Adverse effects

  • Gastrointestinal disturbance
    • Nausea, vomiting constipation, diarrhoea, flatulence
  • Headache
  • May increase risk of infections such as:
  • Hypomagnesia – associated with long-term use
    • If severe can cause tetany and dysrhythmia
  • Increased risk of osteoporosis and fractures in the elderly
  • May decrease B12 absorption in long term use
  • May increase risk of chronic kidney disease


  • Peptic ulcer disease
    • As part of “Triple Therapy” – which usually also involves amoxicillin and clarithromycin
  • GORD
  • Dyspepsia
  • Zollinger-Ellison Syndrome
  • Scleroderma oesophagus
  • Gastroprotection / prophylaxis
    • Usually used in conjunction with other drugs – e.g. steroids or NSAIDs


Generally PPIs have similar therapeutic effects, and mainly differ in their drug interactions (particularly omeprazole appears more likely to interact).

Pantoprazole is traditionally considered the “strongest” PPI.

  • Omeprazole
    • Often first line
    • Typical dose – 10-40mg OD
  • Esomeprazole
  • Lansoprazole
  • Pantoprazole
    • Available as oral or IV preparation
  • Rabeprazole


  • Can reduce symptoms of gastric carcinoma – leading to late diagnosis. Be aware of red flag symptoms before prescribing – such as weight loss, evidence of GI bleeding, age >55 at onset of symptoms
  • Omeprazole appears safe in pregnancy. H2 antagonists have been traditionally preferred, but PPI use is increasing
  • Appears safe in breast feeding
  • Try to use the lowest dose fo rate shortest possible period
    • Consider ceasing in GORD if symptoms are well controlled
    • Use intermittently when symptoms recur
    • Try stepping down to a lower dose


  • May reduce effectiveness of clopidogrel – especially omeprazole. Consider alternative agents in patients taking clopidogrel


  • The Top 100 Drugs. 1st Ed. (2015). Hitchings, A, Lonsdale D, Burrage D, Baker, E.
  • Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
  • Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
  • Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy

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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) FRACGP currently works as a GP and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University, and is studying for a Masters of Sports Medicine at the University of Queensland. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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