(FETT) Proton Pump Inhibitors

GI Agents

OMEPRAZOLE

LANSOPRAZOLE

• 1 Tablet/day taken in the morning on an empty stomach

• Duration

  • 1–12 weeks depending on the underlying condition

  • Long-term administration for complicated disease, but should generally be avoided

• Irreversible inhibition of H+/K+ATPase in parietal cells → increases stomach pH

PPIs are given in an inactive form, which is activated and takes effect in an acidic environment (e.g., the canaliculi of the apical parietal cells). The lower the pH level is, the higher the enrichment of PPIs in the parietal cells (high specificity of PPIs). The highest levels of H+/K+ ATPase enzyme activity are reached in the parietal cell after a period of prolonged fasting. Therefore, administering PPIs before the first meal of the day achieves highest efficacy.

• Complete suppression of gastric acid secretion

The proton pump, which is responsible for the secretion of H+ ions into the gastric lumen, is the last stage in gastric acid secretion. PPIs target this terminal step irreversibly and thus cause almost complete inhibition of acid secretion. This makes them significantly more effective than H2 antagonists.

• Gastrointestinal

  • Nausea, diarrhea, abdominal pain, flatulence

  • ↑ Risk of C. difficile infection

  • Reactive hypergastrinemia

  • ↓ Absorption of iron and vitamin B12

  • ↓ Absorption of calcium and magnesium → ↑ risk of osteoporosis in long-term use→ ↑ risk of fractures in elderly individuals

• Neurological

  • Lightheadedness, headaches

  • Possibly increased risk of developing cognitive impairment/dementia

• Others

  • Exanthema

  • Visual disturbances (rare)

  • ↑ Risk of pneumonia

  • In rare cases, acute interstitial nephritis

• Peptic ulcer disease (gastric and duodenal ulcers)

• Prevention of stress ulcers

• Gastroesophageal reflux disease

• Gastritis

• Combination treatment in Helicobacter pylori eradication therapy

• Zollinger-Ellison syndrome (gastrinoma)

• Gastropathy caused by NSAIDs

• Special indication: MALT lymphoma (stages I and II)

Although several drug interactions are suspected, those with omeprazole and esomeprazole have proven to be of clinical significance, mainly in CYP2C19-mediated interactions:

• Clopidogrel: ↓ activation

• Warfarin, phenprocoumon: ↓ clearance

• Phenytoin, carbamazepine: ↑ clearance

• Nifedipine: ↑ absorption, ↓ clearance

• Diazepam: ↓ clearance