A 48-year-old man presents for evaluation of heartburn. He reports a burning feeling in his chest after eating. It is worse when he eats spicy foods or tomato sauce. He is sometimes awakened at night with these symptoms. He has tried over-the-counter antacids and histamine H2 blockers with partial relief. He is on no medications regularly. His examination today is normal. An upper gastrointestinal (GI) x-ray series reveals gastroesophageal reflux. Along with appropriate diet and lifestyle modification recommendations, you prescribe omeprazole.
What is the mechanism of action of omeprazole?
What is the mechanism of action of antacid medications?
What is the mechanism of action of histamine H2-receptor antagonists?
Answers to case: Agents for upper GI disorders
Summary: A 48-year-old man with gastroesophageal reflux disease (GERD) is prescribed omeprazole.
Mechanism of action of omeprazole:
Irreversible inhibition of the H+, K+-ATPase proton pump in parietal cells, reducing transport of acid from the cell into the lumen.
Mechanism of action of antacids:
Weak bases that directly neutralize gastric acid and reduce pepsin activity.
Mechanism of action of histamine H2-receptor antagonists:
Competitive antagonists of histamine at the parietal cell histamine H2 receptor.
Clinical correlation
GERD, a common cause of recurrent heartburn and dyspepsia, is caused by gastric acid irritating the lining of the esophagus. It can be treated by numerous medications. Antacid medications, widely available without a prescription, usually contain aluminum hydroxide, magnesium hydroxide, calcium carbonate, or combinations thereof. They are weak bases that partially neutralize gastric acid. Histamine H2-receptor antagonists, available over-the-counter or by prescription, competitively antagonize the effect of histamine (released from nearby gastric mucosa enterochromaffin-like [ECL] cells) at the histamine H2 receptor in gastric parietal cells.
Omeprazole was the first medication in a class known as proton pump inhibitors (PPIs). PPIs directly and irreversibly inhibit the action of the H+, K+-ATPase that transports H+ from gastric parietal cells into the lumen of the stomach thus reducing both the basal and stimulated release of gastric acid. PPIs are used for the treatment of refractory gastroesophageal reflux disease, hypersecretory conditions such as Zollinger-Ellison syndrome, for peptic ulcer disease, and as a part of the treatment regimen (in combination with antibiotics) for Helicobacter pylori infections. Helicobacter pylori is the most common cause of non-drug-induced peptic ulcer disease.
Approach to pharmacology of agents for upper GI disorders
Objectives
- List the antacid agents and describe their mechanisms of action, therapeutic uses, and adverse effects.
- List the histamine H2-receptor antagonists and PPIs that inhibit gastric acid production and describe their mechanisms of action, therapeutic uses, and adverse effects.
- List the drugs used therapeutically to promote the defense of the gastrointestinal tract from the effects of acid, and describe their mechanisms of action, therapeutic uses, and adverse effects.
Definitions
Prodrugs:
Inactive compounds that are metabolized in the body to therapeutically active agents.
Continuation: Case: Agents for upper GI disorders. Class
Jennifer is a clinical pharmacologist. She helps doctors of all medical specialties choose medications. Jennifer consults about drug dosage, interactions, and side effects.