How does cyclosporine cause hepatotoxicity?
Cyclosporine undergoes extensive hepatic metabolism and because of its interaction with the cytochrome P450 system (CYP 3A4) is susceptible to severe drug-drug interactions. In animal models, cyclosporine decreases bile flow which may account for the mild hyperbilirubinemia that occurs with high doses.
What mechanism is associated with acetaminophen toxicity?
Patients at Increased Risk. Because the mechanism of acetaminophen toxicity occurs via the formation of NAPQI, any factors that influence the availability of metabolic enzymes will therefore affect toxicity.
Can cyclosporine cause jaundice?
The onset of indirect hyperbilirubinemia promptly after initiation of cyclosporine therapy, its further dose- and time-related exacerbations, its rapid resolution with discontinuation of cyclosporine, its prompt recurrence on rechallenge, and the exclusion of other causes strongly suggest that cyclosporine was the …
What type of reaction is liver injury induced by acetaminophen?
Depletion or deficiency of the compounds responsible for the phase II conjugation reactions may result in accumulation of toxic metabolites. Such is the case in patients who abuse alcohol and ingest acetaminophen. In this example, even low-dose acetaminophen can result in severe liver damage.
What is the mechanism of acetaminophen?
Acetaminophen belongs to a class of drugs called analgesics (pain relievers) and antipyretics (fever reducers). The exact mechanism of action of acetaminophen is not known. It may reduce the production of prostaglandins in the brain. Prostaglandins are chemicals that cause inflammation and swelling.
Why does acetaminophen cause Zone 3 necrosis?
Toxicants requiring bioactivation to cause injury (e.g. acetaminophen) will generally cause zone 3 (centrilobular) hepatic injury, since this area contains higher levels of biotransforming enzymes. This area is also at risk for hypoxic injury due to toxicants that alter oxygen delivery to cells (e.g. carbon monoxide).
What is the mechanism of action of cyclosporine?
Cyclosporine is a potent immunomodulatory agent with an increasing number of clinical applications. Its major mode of action is inhibition of the production of cytokines involved in the regulation of T-cell activation. In particular, cyclosporine inhibits the transcription of interleukin 2.