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Hepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.
All the PPIs except tenatoprazole are rapidly metabolized in the liver by CYP enzymes (mostly by CYP2C19 and 3A4). [82] Dissociation of the inhibitory complex is probably due to the effect of the endogenous antioxidant glutathione which leads to the release of omeprazole sulfide and reactivation of the enzyme. [83] [84]
Omeprazole also inhibits both basal and stimulated acid secretion irrespective of the stimulus [52] as it blocks the last step in acid secretion. [52] The drug binds non-competitively so it has a dose-dependent effect. [53] The inhibitory effect of omeprazole occurs within 1 hour after oral administration. The maximum effect occurs within 2 hours.
The effects on the CYP3A4 in the liver could, in principle, cause interactions with non-oral drugs (e.g. parenteral, inhaled substances, transdermal), [citation needed] and non-CYP3A4-mediated effects also exist. [31] Cytochrome isoforms affected by grapefruit components include CYP3A4, CYP1A2, CYP2C9, and CYP2D6. [21]
A derivative of timoprazole, omeprazole, was discovered in 1979, and was the first of a new class of drug that control acid secretion in the stomach, a proton pump inhibitor (PPI). [11] [12] Addition of 5-methoxy-substitution to the benzimidazole moiety of omeprazole was also made and gave the compound much more stability at neutral pH. [6]
In Western populations, GERD affects approximately 10% to 20% of the population and 0.4% newly develop the condition. [9] For instance, an estimated 3.4 million to 6.8 million Canadians have GERD. The prevalence rate of GERD in developed nations is also tightly linked with age, with adults aged 60 to 70 being the most commonly affected. [ 81 ]
Ludwig Roemheld characterized this particular syndrome shortly before his death; one of his research topics around this time was the effects of calorie intake on the heart. In Elsevier publications, there is no current research or publishing under the name Roemheld syndrome, and as a result, many cases go undiagnosed.
First-pass metabolism may occur in the liver (for propranolol, lidocaine, clomethiazole, and nitroglycerin) or in the gut (for benzylpenicillin and insulin). [4] The four primary systems that affect the first pass effect of a drug are the enzymes of the gastrointestinal lumen, [5] gastrointestinal wall enzymes, [6] [7] [8] bacterial enzymes [5] and hepatic enzymes.
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