Pharmacology
Summary
Gastric acid secretion plays a pivotal role in the digestive process, with parietal cells in the gastric mucosa being the primary source. These cells utilize the H+/K+ ATPase proton pump for this function. Various signaling molecules, including histamine, gastrin, and acetylcholine, serve as activators for these parietal cells, inducing them to produce increase acid secretion. Furthermore, both gastrin and the vagal stimulus exert direct stimulatory effects on the parietal cells. H2 Histamine receptor blockers, recognizable by their "-tidine" suffix (e.g. cimetidine, famotidine, nizatidine), effectively reduce acid secretion. However, they do not provide a comprehensive inhibition of acid production. For cases presenting mild symptoms, H2 blockers can be an intermittent solution. However, for more severe manifestations like erosive esophagitis or pronounced GERD, proton pump inhibitors (PPIs) are the preferred choice. PPIs, bearing the "-prazole" suffix (e.g. omeprazole, lansoprazole, rabeprazole), function by obstructing the final common pathway of acid production, offering a more potent inhibitory effect. Nevertheless, PPIs have associated side effects. Long-term use might heighten the risk of C. diff infections, pneumonia, and may decrease calcium absorption and magnesium absorption. In the context of conditions like gastrinomas, which cause excessive gastric acid secretion due to gastrin-secreting tumors, somatostatin analogs such as octreotide are invaluable therapeutic agents.
Lesson Outline
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FAQs
Gastric acid secretion is a complex process regulated by several mechanisms. The primary cells involved are the parietal cells located in the gastric mucosa, which are responsible for acid secretion. When activated, they release H+ ions into the stomach's lumen through the H+/K+ ATPase or proton pump. Histamine, released by enterochromaffin-like (ECL) cells, stimulates the parietal cells by activating H2 receptors on them. Moreover, gastrin, a hormone released by G cells, can directly stimulate the parietal cells to secrete H+ and also encourage the ECL cells to release more histamine. In addition, vagal stimulation also plays a role; it can prompt the parietal cells to secrete acid via M3 receptors and stimulate the G cells to release gastrin through the action of gastrin releasing peptide (GRP).
Cimetidine, identifiable by its "-tidine" suffix, is a H2 histamine receptor antagonist that inhibits acid secretion by parietal cells. However, with prolonged use, it can cause various side effects. Notably, cimetidine has antiandrogenic side effects, which means it can lead to conditions like gynecomastia and impotence. It can also elevate prolactin levels in the bloodstream. Additionally, cimetidine can inhibit cytochrome P-450, a critical enzyme involved in drug metabolism, potentially affecting the breakdown of other medications in the body.
H2 receptor blockers, such as cimetidine, famotidine, and nizatidine, are H2 histamine receptor antagonists that inhibit acid secretion by parietal cells located in the gastric mucosa. Histamine, released by enterochromaffin-like (ECL) cells, activates H2 receptors on the parietal cell's basolateral membrane. This activation upregulates the H+/K+ ATPase on the luminal membrane, resulting in increased acid secretion into the lumen of the stomach. By blocking these H2 receptors, these drugs effectively decrease gastric acid production. This mechanism is essential in managing conditions like gastroesophageal reflux disease (GERD) and peptic ulcer disease, where excessive gastric acid poses a problem.
H. pylori infections, responsible for peptic ulcer disease, necessitate a combination of treatments. Typically, a regimen includes a proton pump inhibitor (like omeprazole) paired with two antibiotics. PPIs, by inhibiting gastric acid production, enhance the effectiveness of antibiotics, making them the primary choice for this condition.
While both PPIs and H2 receptor blockers aim to reduce gastric acid secretion, their mechanisms differ. PPIs, identified by the "-prazole" suffix (e.g., omeprazole, lansoprazole, rabeprazole), irreversibly inhibit the H+/K+ ATPase, suppressing the entirety of acid secretion. In contrast, H2 receptor blockers mainly target histamine-induced acid production. Regarding risks, long-term use of PPIs can lead to an increased risk of clostridium difficile and respiratory infections like pneumonia. They can also decrease the absorption of minerals such as Ca2+, Mg2+, and Fe2+ due to their effect on stomach acidity. This reduced absorption might elevate the risk of osteoporotic hip fractures, exacerbate osteoporosis, and even cause hypomagnesemia.
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