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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 The group followed and has largely superseded another group of pharmaceuticals with similar effects, but different mode-of-action, called H₂ antagonists.

1 Clinical Use

These drugs are utilized in the treatment of many conditions such as:

dyspepsia
peptic ulcer disease (PUD)
Zollinger-Ellison syndrome
gastroesophageal reflux disease (GORD/GERD)

2 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%

The lack of the acid in the stomach will aid in the healing of duodenal ulcers, and reduces the pain from indigestion and heartburn; which is caused by excess stomach acid.

3 Examples of proton pump inhibitors

Clinically used proton pump inhibitors:

Omeprazole (brand names: Losec®, Prilosec®)
Lansoprazole (brand names: Prevacid®, Zoton®)
EsomeprazoleEsomeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease (PUD), GORD and Zollinger-Ellison syndrome. Esomeprazole magnesium trihydrate is marketed by AstraZeneca under the tradename Nexium . Esomeprazole is the S en (brand names: Nexium®)
PantoprazolePantoprazole is a proton pump inhibitor drug used for short-term treatment of erosion and ulceration of the esophagus caused by gastroesophageal reflux disease. Initial treatment is generally of eight weeks' duration, after which another eight week course (brand names: Protonix®, Somac®)
RabeprazoleRabeprazole is a proton pump inhibitor sold (as its sodium salt) under the brand name Aciphex. Proton pump inhibitors. (brand names: Aciphex®, Pariet®)

4 Adverse effects

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 antagonists and proton pump inhibitors, is associated with an increased risk of community-acquired pneumoniaPneumonia is defined as an infection involving the alveoli of the lungs. It occurs in patients of all age groups, but young children and the elderly, as well as immunocompromised and immune deficient patients, are especially at risk. Causal therapy is wit. 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)

5 References

Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. BooksEnthsiast.com.
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. JAMAJAMA is the acronym for the Journal of the American Medical Association a leading medical journal. Its official name is now JAMA and is referred to by this name in reference lists. It is published weekly by--as its name implies--the American Medical Assoc 292 (16), 1955-1960.

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