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Proton Pump Inhibitors (PPIs)


There are 4 PPIs

  • Lansoprazole 15mg - 30mg daily
  • Omeprazole 20mg - 40mg daily
  • Pantoprazoe 40mg - 80mg daily
  • Esomeprazole - 20mg daily
  • Use the lowest effective dose and shortest duration of therapy to minimise risk
  • Annual blood test for B12, magnesium & calcium (as it decreases their absorbtion)

Prevention of NSAID-associated ulcers

PPI should be prescribed for the following patients 

  • 45 years of age when on LONG-TERM steroid or NSAID
  • ≥65 years of age when on SHORT TERM and LONG TERM steroid or NSAID
  • When TWO of the following risk factors are present:
    • ≥65 years of age
    • History of gastroduodenal ulcer, GI bleeding, or gastroduodenal perforation
    • Helicobacter pylori infection
    • High risk of GI adverse effects
    • Severe co-morbidity (malignancy, Heart failure (NYHA III-IV)
    • significant liver or renal disease (e.g. CKD 4&5 and cirrhosis, CVD, diabetes, or hypertension)
    • Heavy smoking or excess alcohol consumption
    • Any medications known to cause GI bleed or ulceration:
      • Antiplatelets - eg Aspirin, clopidogrel, prasugrel
      • SSRIs - eg Citalopram, fluoxetine, paroxetine
      • Anticoagulants - eg Warfarin, dabigatran, apixaban, rivaroxaban
      • Corticosteroids - eg Prednisolone
      • NSAIDs- eg Aspirin, ibuprofen, diclofenac, naproxen, indometacin
      • Potassium-channel activator - eg nicorandil 

The risks associated with LONG TERM PPIs

  • muscle twitching
  • tremors
  • vomiting
  • fatigue
  • loss of appetite
  • Upon discontinuation, magnesium levels normalized within 1 to 2 weeks, but reoccurred within days after attempts to restart PPI therapy
  • Caution should be taken when coadministering with other agents that may lower magnesium levels, such as digoxin and diuretics

Increased risk of fractures


especially when used

  • at high doses
  • for over a year
  • in the elderly

Clostridium difficile infection

  • due to the effect of decreasing gastric acidity


  • caused by gastric acid suppression
  • causes rebound hyperacidity
  • after discontinuing PPI therapy patients may experience worsening GERD symptoms (even in short 8 week courses) taper PPI slowly


  • increased risk of developing community-acquired pneumonia (CAP)
  • Acid suppression leads to an increase in gastric pH; allowing for the overgrowth of non-Helicobacter pylori bacteria
  • Can potentially lead to microaspiration and lung colonization

C difficile

  • Gastric acid protects against pathogens colonizing the stomach and intestinal tract
  • Higher gastric pH can lead to a more virulent strain of bacteria
  • The delay in gastric emptying can prolong exposure to the bacteria
  • For example those taking broad-spectrum antibiotics


  • An increased risk in hip, spine, and wrist fractures in patients on high does and/or long- term therapy
  • Reduced absorption of mineral calcium in the diet
  • There may be as much as a 41% reduction in calcium absorption after 14 days of omeprazole therapy
  • Calcium citrate formulations are better than carbonate with PPI 


  • Due to decreased intestinal absorbtion of calcium

Vitamin B12 Deficiency

  • Malabsorption of vitamin B12 may result from atrophic gastritis and achlorhydria, promoting bacterial overgrowth that allows for the increased digestion of cobalamin
  • Results from studies have been inconsistent and appear to not be clinically significant
  • Routine screening of vitamin B12 may be considered in the elderly or malnourished patients


  • Recent data has suggested a link between PPI use and dementia
  • Biologically, PPIs may increase the production and degradation of amyloid and bind to tau
  • The possibility of reduced levels of vitamin B12 and other nutrients may also play a role in the increased risk

Other PPI Indications 

  • short-term treatments for gastric and duodenal ulcers
  • in combination with antibacterials for the eradication of Helicobacter pylori
  • treatment of dyspepsia and gastro-oesophageal reflux disease
  • treatment of NSAID-associated ulcers (in patients who need to continue NSAID treatment after an ulcer has healed, the dose of proton pump inhibitor should normally not be reduced because asymptomatic ulcer deterioration may occur)
  • to reduce the degradation of pancreatic enzyme supplements in patients with cystic fibrosis
  • to control excessive secretion of gastric acid in Zollinger–Ellison syndrome; high doses are often required

Drug Interactions

  • several protease inhibitors; itraconazole, ketoconazole, isoniazid
  • oral iron supplements
  • clopidrogrel
    • PPIs may inhibit the hepatic cytochromes although not confirmed yet
    • Lansoprazole is safer than omeprazole
  • If alternative therapies cannot be used, patients receiving these medications should be counseled to take them towards the end of the PPI dosing interval

H2-receptor antagonists can be used as an alternative

  • ranitidine 150mg - 300mg daily
  • famotidine 20mg- 40mg daily
  • nizatadine 150mg - 300mg daily
  • cimetidine 400mg - 800mg daily

PPI review

Bear in mind 

  • Sometimes they need a ppi for 3-6 months 
  • Review the dose - may be give them lower PPI dose? 
  • can be NSAID related - Infection in the lining of the stomach - refer for H Pylori test

Find out


  • What are they eating and how are they living their lives? 
  • How much are they sleeping/are they doing night shifts ?
  • Do they smoke?
  • Are they under a lot of stress is there anything in their life style they can do ? 
  • Usually diet and stress is the main cause
  • Are we masking any symptoms?


Red Flags

  • Weight loss, appetite loss, difficulty swallowing, persistent vomiting, - refer for endoscopy for stomach cancer
  • Fullness after meal, bloating, wind, bowel changes, acid, indigestion after stopping antacids / PPI - do an H pylori test (stop PPI for two weeks first) 
  • If there are no red flags then it is usually dyspepsia or GORDeflux/


DYSPEPSIA - Indigestion


  • prop up with pillow / diet / weight / smoking /stress 
  • Metoclopramide / domperidone speed up the emptying of the stomach
  • Amitriptiline for blocking the signals of dyspepsia - so good for abdominal pain  
  • PPI / H2 receptor blocker
  •  Patient leaflet https://www.nhs.uk/conditions/heartburn-and-acid-r


  • Excessive burping / sore throat / cough / pressure or lump in throat
  • Full dose PPI for 4 weeks
  • May be repeated for another 4 weeks or double PPI for 4 weeks or add H2RA at night if bedtime symptoms
  • persistent or recurrent symptoms refer for endoscopy and do H Pylori test
  • endoscopy-negative consider switching to an H2RA for one month
  • if still symptomatic refer to gastroenterologist 

Isoniazid Itraconazole Ketoconazole Digoxin Omeprazole clopidrogrel Lansoprazole

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