Pharmacology of acid suppression in the hospital setting: focus on proton pump inhibition.
The more potent and longer-lasting inhibition of gastric acid secretion provided by proton pump inhibitors (PPIs) as compared with histamine-2-receptor antagonists is caused in large part by differences in their mechanism of action. PPIs block histamine-2-, gastrin-, and cholinergic-mediated sources of acid production and inhibit gastric secretion at the final common pathway of the H+/K+ adenosine triphosphatase proton pump. In contrast, histamine-2-receptor antagonists cannot block receptor sites other than those mediated by histamine. It seems that the rapid loss of acid suppression activity by the histamine-2-receptor antagonists may be attributed to tolerance. Such tolerance has not occurred in patients receiving PPIs because these agents are irreversible inhibitors of the H+/K+ adenosine triphosphatase proton pump. For these reasons, patients who have acid-related disorders that require high levels of acid suppression do not respond well to intravenous histamine-2-receptor antagonists and would be excellent candidates for intravenous PPI therapy. Candidates for intravenous PPIs also include patients who cannot receive oral PPIs and those who may need the higher acid suppression therapy provided by the intravenous rather than the oral route. Clinical studies have demonstrated the efficacy of intravenous pantoprazole in maintaining adequate control of gastric acid output during the switch from oral to intravenous therapy in patients with severe gastroesophageal reflux disease or the Zollinger-Ellison syndrome. Intragastric administration of solutions prepared from oral PPIs has been used as an alternative to the intravenous route in critical care settings. However, decreased bioavailability may limit the value of intragastric delivery of PPIs because of the high frequency of gastric emptying problems in critically ill patients.
Pisegna
Joseph R
JR
Division of Gastroenterology and Hepatology, Greater Los Angeles Veterans Administration, Los Angeles, CA 90073, USA. jpisegna@ucla.edu
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000863:Antacids / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D002986:Clinical Trials as Topic; D005744:Gastric Acid / Q000502:physiology; D006760:Hospitalization; D006801:Humans; D007362:Intensive Care Units; D009853:Omeprazole / Q000031:analogs & derivatives; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D013454:Sulfoxides / Q000494:pharmacology; D016896:Treatment Outcome
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000863:Antacids; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D000077402:Pantoprazole; D009853:Omeprazole