Drug-Induced liver injury Flashcards
How much time usually passes btw drug exposure and detection of liver damage?
42 days.
What classes of drugs most often cause liver damage?
antibiotics- almost 50% of drug induced liver injury (DILI)
CNS agents (phenytoin) are also a big culprit
herbs and analgesics
What are the mechanisms of DILI?
- direct effects of the chemical structure of a drug or its metabolites. Rare, but important for drugs like acetaminophen. Show dose-dependent response.
- Generation of a transient intermediate medabolite or metabolic/immunoallergice responses to the drug: typically not dose dependent.
What can liver tests tell us about DILI?
elevated ALT/AST usually indicate hepatocyte injury.
Alk phos elevation suggests bile duct injury
high total bilirubin: quesionts about bile duct blockage.
When should I suspect DILI?
ALT or Alk Phos > 3X normal limits
hyperbilirubinemia.
abnormal function tests like hypoalbuminemia or elevated INR (PTT). a presumptive dx, even when you do histopathologic characterizaiton.
5 (6?) phenotypes of DILI
hepatocellular, choestatic, mixed, fibrosis, nodular regenerative hyperplasia. Also, hepatic adaptation: transient abnormal liver function tests despite continued drug administration.
drug induced hepatitis: clinical picutre, onset, definition
hepatocellular injury with biochemical evidence of liver disease. immediate onset with dose-dependent toxins and 2-6 wk latency when due to immunoallergenic/autoimmune mechanisms.
begins with prodromal sympromts: fever, malaise, rash, LAD, then nausea, vomiting, jaundice. ALT> ALP. can culminate in liver failure and cause functional changes.
definition of microvesicular steatosis. histo appearance, other organs involved.
severe form of hepatotoxicity: leads to necrosis rather than apoptosis. resembles acute fatty liver pregnancy and will show red fat globules on oil red stain.
may involve other organs: encephalopathy, pancreatitis, nephrotoxicity, metabolic acidosis
Causes severe, rapid decline
Clinical manifestation of microvesicular steatosis
pain, nausea and vomiting, but then evolves into encepthalopathy. can cause hypoglycemia, coagulopathy, hyperammonemia, and lactic acidosis.
What drugs cause micrvesicular steatosis?
HAART (esp. nucleoside inhibitors), tetracycline in pregnancy, aspirin + influenza B in children (Reye’s syndrome), and valproate in kids
What is macrovesicular steatosis?
similar to non-alcoholic fatty liver disease. triglyceride accumulation from defects in lipoprotein metab, damage to plasma membranes, or incr. lipid delivery to liver.
large, fat vesicles. one fat globule/hepatocyte in oil red stain.
What drugs cause macrovesicular steatosis?
Amiodarone (which can also cause necrosis and fibrosis)
What drugs cause mixed macrovesicular and microvesicular steatosis?
minocycline
Drug-induced cholestasis: types, symptoms
types: bland, cholestatic hepatitis, sclerosing cholangitis.
presentation: pruritis, pale stools, and dark urine.
symptoms take longer to resolve than acute hepatitis symptoms.
may become a chronic problem
What drugs cause choestasis?
Bland cholestasis: no hepatitis symptoms. may be seen iwth OCPs.
Augmentin: cholestasis + reversible jaundice.
