Proton pump inhibitors

Key examples

• Lansoprazole
• Omeprazole
• Pantoprazole

 

Common indications

Proton pump inhibitors are a first-line treatment for:

1. Prevention and treatment of peptic ulcer disease, including NSAID-associated ulcers.
2. Symptomatic relief of dyspepsia and gastro-oesophageal reflux disease.
3. Eradication of Helicobacter pylori infection, in which they are used in combination with antibiotic therapy.

 

Mechanisms of action

• Proton pump inhibitors (PPIs) reduce gastric acid secretion. 
• They act by irreversibly inhibiting H+/K+-ATPase in gastric parietal cells. 
• This is the ‘proton pump’ responsible for secreting H+ and generating gastric acid. 
• An advantage of targeting the final stage of gastric acid production is that they are able to suppress gastric acid production almost completely. 
• In this respect they differ from H2-receptor antagonists.

 

Important adverse effects

• Common side effects of PPIs include gastrointestinal disturbances and headache. 
• By increasing the gastric pH, PPIs may reduce the body’s host defence against infection; there is some evidence of increased risk of Clostridium difficile infection in patients taking PPIs. 
• Prolonged treatment with PPIs can cause hypomagnesaemia, which if severe can lead to tetany and ventricular arrhythmia.

 

Warnings

• PPIs may disguise symptoms of gastric cancer, so prescribers should enquire about ‘alarm symptoms’ before and during treatment. 
• There is epidemiological evidence that PPIs, particularly when administered at high dose for prolonged courses in the elderly, can increase the risk of fracture. 
• Patients at risk of osteoporosis should therefore be identified and treated as appropriate.

 

Important interactions

• There is some evidence that PPIs, particularly omeprazole, reduce the antiplatelet effect of clopidogrel by decreasing its activation by cytochrome P450 enzymes. 
• Understanding continues to evolve on this issue, but current evidence suggests that lansoprazole and pantoprazole have a lower propensity to interact with clopidogrel. 
• As such, these are the preferred PPIs when prescribing alongside clopidogrel.