A new medication, drug A, is being developed for the treatment of peptic ulcer disease. During initial testing, gastric acid secretion in experimental animals is stimulated by vagal stimulation, histamine infusion, or gastrin infusion. Before the stimulus is administered, the animals are divided into 2 groups, one group receives pretreatment with drug A, and the second one serves as the control and is given an injection of an equivalent volume of normal saline. The effects of the drug on hydrochloric acid (HCl) output by the stomach mucosa are recorded and shown in the graphs below. Drug A is most similar to which of the following medications?

Question

A new medication, drug A, is being developed for the treatment of peptic ulcer disease.  During initial testing, gastric acid secretion in experimental animals is stimulated by vagal stimulation, histamine infusion, or gastrin infusion.  Before the stimulus is administered, the animals are divided into 2 groups, one group receives pretreatment with drug A, and the second one serves as the control and is given an injection of an equivalent volume of normal saline.  The effects of the drug on hydrochloric acid (HCl) output by the stomach mucosa are recorded and shown in the graphs below.  Drug A is most similar to which of the following medications?

Quizplus · Accepted Answer

11ec160b_3bd4_b5de_9249_4708fd13d56b_MD0001_00 Gastric parietal cells secrete hydrochloric acid (HCl) in response to 3 major stimulants: histamine, vagal output, and gastrin. Histamine is released from enterochromaffin-like (ECL) cells and binds to H2 receptors on the basolateral parietal cell membrane. Vagal stimulation causes acetylcholine release, which directly stimulates HCl secretion by binding to parietal cell muscarinic (M3) receptors. In addition, vagal stimulation indirectly promotes HCl secretion via gastrin-releasing peptide (GRP), which stimulates gastrin release from G cells. G cells also release gastrin in response to protein-rich meals. Gastrin primarily stimulates HCl secretion by binding to the CCK_B receptor on ECL cells (promotes histamine release). It also directly binds to the CCK_B receptor on parietal cells, but this mechanism is less significant for acid secretion. The final common pathway for HCl secretion is the H⁺/K⁺-ATPase proton pump, located on the apical membrane of the parietal cell. Based on the graphs shown above, drug A inhibits gastric acid secretion in response to all 3 major stimulants. Therefore, drug A is most similar to a proton pump inhibitor (eg, lansoprazole, omeprazole) as it is likely inhibiting the H⁺/K⁺-ATPase proton pump. (Choice A) Atropine is a nonselective antimuscarinic agent often used to produce mydriasis/cycloplegia or reverse bradycardia. Atropine may reduce gastric acid secretion in response to vagal stimulation by blocking parietal cell M3 receptors; however, it would not significantly decrease acid secretion during histamine or gastrin infusion. (Choice B) Bethanechol is a cholinomimetic muscarinic agonist used to treat ileus and urinary retention. Bethanechol would promote gastric acid secretion by stimulating parietal cell M3 receptors. (Choice C) Cimetidine treats gastroesophageal reflux and peptic ulcer disease by blocking parietal cell H2 receptors. Although H2 receptor blockade would reduce gastric acid secretion in response to histamine or gastrin infusion, it would not significantly reduce acid secretion in response to vagal stimulation. (Choice E) Sucralfate may promote peptic ulcer healing by binding to the base of mucosal ulcers and providing physical protection against gastric acid; however, it does not inhibit gastric acid secretion. Educational objective: Proton pump inhibitors (eg, omeprazole, lansoprazole) block the final common pathway of gastric acid secretion from parietal cells, which is stimulated by acetylcholine, histamine, and gastrin. __________ References: Control of gastric acid secretion: the gastrin-ECL cell-parietal cell axis. (http://www.ncbi.nlm.nih.gov/pubmed/11246041) Cell biology of gastric acid secretion. (http://www.ncbi.nlm.nih.gov/pubmed/8386569) Revisiting the parietal cell. (http://www.ncbi.nlm.nih.gov/pubmed/19889964)

A New Medication, Drug A, Is Being Developed for the Treatment