Proton Pump Inhibitors

The first PPI, omeprazole, was launched in the late 1980s, and PPIs are currently the world's largest-selling pharmaceutical drug group. Several other PPIs, such as lanzoprazole, pantoprazole, rabeprazole and esomeprazole have since been developed.

Although the primary therapeutic indication of PPIs is in the treatment of peptic ulcers, PPIs are effective both in relieving symptoms of GORD and healing oesophagitis.

Mode of action

Interaction of PPIs with the parietal cell
FIGURE 4 – Interaction of
PPIs with the parietal cell
(click to enlarge)

PPIs exert their effects by inhibiting the action of the gastric parietal cell proton pump (H+ATPase), thus reducing the production of acid by the stomach (Figure 4).

Efficacy

All PPIs are now indicated for the treatment of reflux oesophagitis, and because this proton pump is common to all routes of acid secretion (histamine-, gastrin- and acetylcholine-mediated), PPIs have the greatest capacity to reduce acid secretion in the stomach, and do so by approximately 80–85% of normal.[Chiba N, 1997]

As for the H2-RAs, the primary indication for PPIs is benign gastric and duodenal ulcers. Usually PPIs produce symptomatic relief within days and most benign ulcers heal within 6 weeks.[Salas M, 2002] Ulcer healing rates are better and occur slightly faster than with H2-RAs; however, relapse is as common as with H2-RAs.

PPIs are also effective in ulcers resulting from NSAID therapy, and in Zollinger-Ellison syndrome.[Welage LS, 2000]

Dosing

For the treatment of GORD, PPIs are usually prescribed once daily.

Adverse effects

PPIs have proved to be well tolerated with a good safety record. The most common side effects (for all of the group) are:

  • Nausea
  • Diarrhoea and constipation
  • Headache
  • Skin rashes

There have been recent reports on effects of long-term usage of PPIs;

  • increased association with community acquired diseases, which include clostridium difficile and pneumonia
  • 44% increased risk of having a fractured hip among those who used a PPI for more than 12 months; this risk was 2.6 times more for those patients on high doses.

Precautions

PPIs are not recommended for use during pregnancy and lactation, or in children.

Omeprazole interacts with a number of commonly used medicines including diazepam, phenytoin and warfarin, therefore, it is best to use an alternative treatment in patients already taking one of these drugs. These interactions do not occur with pantoprazole and are only weak with lanzoprazole.

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