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Proton pump inhibitor
Proton pump inhibitors are a group of drugs whose main action is pronounced and long-lasting reduction of gastric acid production. The group followed and has largely superseded another group of pharmaceuticals with similar effects, but different mode-of-action, called H2-receptor antagonists.
These drugs are utilized in the treatment of many conditions such as:
- peptic ulcer disease (PUD)
- Zollinger-Ellison syndrome
- gastroesophageal reflux disease (GORD/GERD)
Mechanism of action
Proton pump inhibitors act by irreversibly blocking the hydrogen-potassium adenosine triphosphatase enzyme system (the K+/H+-ATPase, or more commonly just proton pump) of the gastric parietal cell. The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.
Targeting the terminal-step in acid production, as well as the irreversible nature of the inhibition, result in a class of drugs that is significantly more effective than H2 antagonists and reduces gastric acid secretion by up to 99%
Examples of proton pump inhibitors
Clinically used proton pump inhibitors:
- Omeprazole (brand names: Losec®, Prilosec®)
- Lansoprazole (brand names: Prevacid®, Zoton®)
- Esomeprazole (brand names: Nexium®)
- Pantoprazole (brand names: Protonix®, Somac®)
- Rabeprazole (brand names: Aciphex®, Pariet®)
Proton pump inhibitors are generally well tolerated, and the incidence of adverse effects is relatively uncommon. The range and occurrence of adverse effects are similar for all of the proton pump inhibitors, though they have been reported more frequently with omeprazole. This may be due to its longer availability and hence clinical experience.
Common adverse effects include: headache, nausea, diarrhoea, abdominal pain, fatigue, dizziness. (Rossi, 2004)
Infrequent adverse effects include: rash, itch, flatulence, constipation. (Rossi, 2004)
Recently it has been observed that gastric acid suppression, using H2-receptor antagonists and proton pump inhibitors, is associated with an increased risk of community-acquired pneumonia. It is suspected that acid suppression results in insufficient elimination of pathogenic organisms. It has therefore been suggested that patients at higher risk of pneumonia should only be prescribed proton pump inhibitors at lower doses and only when necessary. (Laheij et al., 2004)
- Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
- Laheij RJF, Sturkenboom MCJM, Hassing R-J, Dieleman J, Stricker BHC, Jansen JBMJ, (2004). Risk of Community-Acquired Pneumonia and Use of Gastric Acid–Suppressive Drugs. JAMA 292 (16), 1955-1960.
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