Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients undergoing percutaneous coronary intervention and in those with acute coronary syndromes, clopidogrel plus aspirin is the first-line antiplatelet therapy for reducing cardiovascular events. Although clopidogrel is generally well tolerated, with rash, indigestion, vomiting, diarrhea, and bleeding being the most common adverse effects, rare but serious complications may occur. We describe a 78-year-old woman who underwent percutaneous coronary intervention with drug-eluting stents; clopidogrel and aspirin were started as antiplatelet therapy. Three weeks later, the patient developed mixed hepatocellular and cholestatic liver injury. Clopidogrel was discontinued, and her liver profile results began to improve. Her diagnostic work-up included screening for hepatitis, infectious mononucleosis, and rheumatologic diseases, as well as ultrasonography, magnetic resonance imaging, and endoscopic retrograde cholangiopancreaticography; all results were normal. On day 5 of hospitalization, because of the patient's risk for thrombosis secondary to the drug-eluting stents, clopidogrel was reintroduced; her liver enzyme levels increased. In the absence of any biliary obstruction or other obvious causes of hepatic injury, drug-induced hepatocellular injury and cholestatic jaundice were suspected, and clopidogrel was again discontinued. The patient's liver function tests gradually improved 3 days later and showed marked improvement at her 2-week follow-up visit after discharge. Use of the Maria and Victorino scale for diagnosis of drug-induced hepatotoxicity indicated a probable (score of 14) relationship between clopidogrel and mixed hepatocellular injury and cholestatic jaundice in this patient. Although routine liver function testing is not recommended in patients who receive clopidogrel, having a high index of clinical suspicion, drug rechallenge, and excluding other obvious causes are required to establish the diagnosis of a rare drug complication such as clopidogrel-induced hepatic injury.
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PMID:Clopidogrel-induced hepatocellular injury and cholestatic jaundice in an elderly patient: case report and review of the literature. 1939 67

Clopidogrel is a thienopyridine, which inhibits the platelet P2Y adenosine diphosphate (ADP) receptor termed P2Y(12). It is taken as a prodrug that requires biotransformation to an active metabolite by cytochrome P450 (CYP) isoenzymes. In addition, esterases shunt the majority of clopidogrel to an inactive pathway, whilst the remaining prodrug requires two separate CYP-dependent oxidative steps. PPIs might diminish the antiplatelet effects and the clinical effectiveness of clopidogrel possibly through inhibition of CYP2C19 and CYP3A4 isoenzymes. Treatment with clopidogrel and aspirin decreases recurrent cardiovascular events after an acute coronary syndrome. However, an inherent increment of major bleeding is also associated with antiplatelet therapy, as well as dyspepsia with aspirin. Also, major bleeding has been associated with high risk for ischemic events and mortality. For this reason, a proton pump inhibitor (PPI) is often co-prescribed to reduce the risk of gastrointestinal tract bleeding, but its concomitant use might reduce the inhibitory effect of clopidogrel on platelet aggregation. Nevertheless, doubts exist about the possible interaction of concomitant PPI use that may reduce the inhibitory effect of clopidogrel on platelet aggregation. Indeed, there is some controversy with regard to the true risk of cardiovascular adverse events arising from a potential drug-drug interaction between clopidogrel and PPI. In this article, we will review the current status and controversies in relation to a possible interaction between clopidogrel and PPIs.
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PMID:Interactions between clopidogrel and proton pump inhibitors: a review of evidence. 2156 18