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Titolo:
Improving on PPI-based therapy of GORD
Autore:
Sachs, G;
Indirizzi:
Univ Calif Los Angeles, Ctr Ulcer Res & Educ, Membrane Biol Lab, Los Angeles, CA 90024 USA Univ Calif Los Angeles Los Angeles CA USA 90024 Los Angeles, CA 90024 USA
Titolo Testata:
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY
, volume: 13, anno: 2001, supplemento:, 1
pagine: S35 - S41
SICI:
0954-691X(200105)13:<S35:IOPTOG>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
GASTRIC-ACID SECRETION; PROTON-PUMP INHIBITORS; 24-H INTRAGASTRIC ACIDITY; CONTROLLED TRIAL; GENE-EXPRESSION; ALPHA-SUBUNIT; BETA-SUBUNIT; OMEPRAZOLE; SOMATOSTATIN; ESOMEPRAZOLE;
Keywords:
PPI; GORD; acid suppression; H+,K+-ATPase; enantiomer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Sachs, G Vet Adm Wadsworth Hosp Ctr, Bldg 113,Room 326, Los Angeles, CA 90073 USA Vet Adm Wadsworth Hosp Ctr Bldg 113,Room 326 Los Angeles CA USA 90073
Citazione:
G. Sachs, "Improving on PPI-based therapy of GORD", EUR J GASTR, 13, 2001, pp. S35-S41

Abstract

Blockade of the gastric acid pump, hydrogen-potassium adenosine triphosphatase (H+,K+-ATPase), by proton pump inhibitors (PPIs) is one of the most effective treatments for gastro-oesophageal reflux disease (GORD), In ideal terms, however, the inhibition of acid secretion should occur rapidly, on the first dose, and remain virtually complete in a dose-dependent manner, Several aspects of PPI biochemistry prevent the achievement of this ideal. PPIs target the final step of acid secretion and, due to the covalent nature of their inhibition of H+,K(+-)ATPase, cause suppression of acid secretion long after the drug has been eliminated. Their disadvantages stem from theirmechanism of action: they require accumulation and activation in active parietal cells and have short plasma half-lives, hence a relatively slow onset of action, An extension of PPI plasma half-lives is an obvious goal, possibly via exploitation of probable differences in the metabolism of the two enantiomers (structural mirror images) present in current PPI formulations:e,g., clinical data on the S-enantiomer of omeprazole (esomeprazole) suggest some improvement in acid control, An alternative is to generate a pro-drug of a PPI; plasma levels of the PPI would thus depend on release of the active metabolite from the pro-drug, again extending drug half-life. Anotherarea of active investigation is the development of acid-pump antagonists to inhibit acid secretion at its final step. Eur J Gastroenterol Hepatol 13 (suppl 1):S35-S41 (C) 2001 Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 01:27:50