Proton Pump Inhibitors
The final common pathway in gastric acid secretion is the proton pump adenosine triphosphatase. Th e physiological essence of this enzyme is the exchange of hydrogen ions for potassium ions. Th us, hydrogen is secreted by the parietal cell into the gastric lumen in exchange for potassium. Proton pump inhibitors should be taken prior to meals, because these drugs are more potent when taken orally prior to meals. Th ey are also absorbed more effectively in the morning.
Mechanism of Action
Proton pump inhibitors or gastric pump inhibitors inhibit H+ and K+ ions, which generate gastric acids.
Proton pump inhibitors are widely used in the short-term therapy of duodenal and gastric ulcers. Proton pump inhibitor agents are also used in the treatment of gastroesophageal refl ux disease, gastric ulcer, and for long-term treatment of pathologic hypersecretory conditions such as Zollinger-Ellison syndrome.
- Omeprazole is used in the treatment of acid peptic disorders. It is approved for the short-term treatment of duodenal ulcers, severe gastroesophageal refl ux, and hypersecretory conditions. It is also eff ective in the prevention of NSAID ulcers and their complications. The antisecretory effect of omeprazole occurs within one hour, with maximum eff ect occurring within two hours.
- Lansoprazole suppresses gastric acid formation in the stomach. Lansoprazole is indicated for the short-term treatment of acute duodenal ulcer, gastric ulcer, and erosive esophagitis. It is most effective given 30 to 60 minutes prior to a meal. Like other proton pump inhibitors, it is very effective in healing acid peptic disease.
Th ere are numerous adverse effects of the proton pump inhibitors, but they occur infrequently. Headache, diarrhea, abdominal pain, dizziness, rash, and constipation are seen with nearly the same frequency as is seen with the H2-blockers.
- Adverse reactions to omeprazole include headache, diarrhea, abdominal pain, nausea, dizziness, vomiting, and constipation. It is contraindicated for long-term use in patients with gastroesophageal refl ux disease, duodenal ulcers, and in lactating women.
- Adverse effects of lansoprazole are fatigue, dizziness, headache, nausea, diarrhea, constipation, anorexia, or increased appetite.
Proton pump inhibitors are contraindicated in long-term use for gastroesophageal reflux disease (GERD) and duodenal ulcers. They are also contraindicated in patients with hypersensitivity to these agents and
children younger than two years, and during pregnancy (categories B and C). Lansoprazole should be avoided in patients with severe hepatic impairment.
Proton pump inhibitors are used with caution in patients with dysphasia, metabolic or respiratory alkalosis, and hepatic disease, and during pregnancy. Safety and effi cacy in children under the age of 18 years are not established.
- Omeprazole increases serum levels and potentially increases the toxicity of benzodiazepines, phenytoin, and warfarin. Th is agent shows decreased absorption with sucralfate (these drugs should be given at least 30 minutes apart).
- Lansoprazole decreases serum levels if taken concurrently with sucralfate. It decreases serum levels of ketoconazole and theophylline.
Rabeprazole increases serum levels and potentially increases the toxicity of benzodiazepines when taken concurrently.