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DOWNLOAD PDFGI disturbances like diarrhea, nausea, vomiting, and abdominal pain are common with macrolide use like erythromycin because it is a motilin agonist, encouraging hypermotility and the unpleasant collateral damage. These GI disturbances are commonly the cause of patientsâ noncompliance and preference toward discontinuation.
Macrolides, especially erythromycin and clarithromycin, adversely perpetuate the QT interval and can progress to a potentially fatal torsade de pointes if untreated.
Macrolides are potent inhibitors of the cytochrome P450 system, especially CYP3A4, potentially causing elevations of other drugs metabolized by the P450 system. One particular combination to be avoided due to this interaction is macrolides with statins, HMG-CoA reductase inhibitors used for lowering cholesterol, as this combination can lead to debilitating myopathy. Other important interactions include the potential serum elevation of PT/INR in patients on oral anticoagulants, and delayed clearance of theophylline.
Cholestasis, the impairment of bile flow or production, is a well recognized presentation of macrolide-induced liver disease. Laboratory evaluation typically manifests with elevations in alkaline phosphatase, bilirubin and hepatic transaminases. Specific to the transaminases ALT and AST, these two components are capable of elevations up to 10 times the upper limit of normal during hepatic inflammation.
As part of the pathophysiology involving hepatotoxicity secondary to macrolide use: a direct cytotoxic effect and an immuno-allergic reaction occur producing a peripheral eosinophilia accompanied with a skin rash.
The pathogenesis of hepatotoxicity with macrolide exposure involves both a direct cytotoxic effect as well an immuno-allergic reaction. Macrolide-induced hepatotoxicity aroused by an immuno-allergic reaction is typically accompanied by the release of eosinophils from their mostly tissue-based habitat, resulting in peripheral eosinophilia. This is also associated with skin eruptions primarily in the form of maculopapular exanthems.
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