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Hepatotoxicity
N/A
47
Aerospace Engineering
1st Grade
02/08/2013

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Term
Interference with bilirubin handling; cytotoxicity; cholestasis; steatosis; hepatitis, cirrhosis, and necrosis; phospholipidosis; carcinoma
Definition
Hepatotoxicity
Term
a potentially toxic product of hemoglobin degradation
Definition
Bilirubin
Term
attaches to albumin binding sites and is then transported to hepatocyte
Definition
unconjugated bilirubin (UCB)
Term
couples UCB to glucuronic acid to become conjugated bilirubin
Definition
Hepatic UDP glucoronyl transferase
Term
excreted into the bile and enters the small intestine
Definition
conjugated bilirubin
Term
converts conjugated bilirubin to urobilinogen
Definition
intestinal flora
Term
is excreted in the stool; some is renally excreted
Definition
urobilinogen
Term
inhibits transport proteins at the hepatocyte membrane, giving rise to elevated plasma levels of both conjugated and unconjugated bilirubin
Definition
Rifampin (Rifadin)
Term
contraindicated in infants less than 2 months old because they compete with bilirubin for binding to albumin
Definition
Sulfonamides
Term
The unconjugated hyperbilirubinemia results in deposition of bilirubin in brain tissue and causing kernicterus and permanent brain damage
Definition
competition for plasma protein binding
Term
inhibition of bilirubin transport; competition for plasma protein binding; inhibition of UDP glucuronyl transferase
Definition
Drugs interfere with bilirubin handling
Term
inhibits UDP glucuronyl transferase and prevents glucoronidation of bilirubin
Definition
Novobiocin (Albamycin, withdrawn)
Term
unconjugated hyperbilirubinemia, especially in neonates, predisposes to kernicterus and permanent brain damage
Definition
inhibition of UDP glucoronyl transferase
Term
metabolized by three pathways: sulfration, glucuronidation, and CYPE2EI
Definition
Acetaminophen
Term
produce a similar hepatocellular, cytotoxic type of damage as acetaminophen
Definition
Isoniazid and iproniazid
Term
condition in which the secretion and/or flow of bile is reduced. The bile accumulates in the body leading to jaundice and itching.
Definition
Cholestasis
Term
typically interfere with the liver cell's secretion of bile without causing hepatitis or liver cell necrosis
Definition
Drug causing cholestasis
Term
suspected of being a hypersensitivity response; not dose-related
Definition
Phenothiazine-induced cholestasis
Term
Phenothiazine-induced cholestasis
Definition
common symptoms are jaundice, rash, fever, eosinophilia and blood dyscrasias
Term
dose related; develops after initial sensitization; mild, reversible jaundice when the drug is discontinued
Definition
Steroid-induced cholestasis
Term
alcoholic fatty liver, non-alcoholic steatoepatitis, non-alcoholic fatty liver disease
Definition
Steatosis classes
Term
common response to ethanol; can lead to hepatitis and cirrhosis of liver
Definition
alcoholic fatty liver
Term
progressive liver disease resulting from steatosis in non-alcoholics can ultimately lead to cirrhosis and liver failure
Definition
non-alcoholic steatohepatitis (NASH)
Term
possibly 20% of US population, partly due to obesity
Definition
non-alcoholic fatty liver disease (NAFLD)
Term
produces large amounts of NADH, which signals the cell to inhibit breakdown of fatty acids and increase synthesis of fatty acids
Definition
Ethanol-induced steatosis
Term
can cause dose-dependent steatosis after large IV doses; inhibition of protein synthesis, notably transporters of VLDL out of the hepatocyte
Definition
Tetracycline-induced steatosis
Term
inflammation of the liver, characterized by presence of inflammatory cells
Definition
Hepatitis
Term
acute hepatitis can lead to
Definition
acute liver failure
Term
chronic hepatitis can lead to
Definition
permanent liver damage and cirrhosis
Term
chronic liver disease in which damaged liver tissue is replaced by fibrosis, scar tissue, and regenerative nodules, leading to loss of hepatic function
Definition
Cirrhosis
Term
most common example of drug-induced cirrhosis
Definition
alcoholic cirrhosis
Term
can cause chronic liver diseases and cirrhosis
Definition
methotrexate, amiodarone and methyldopa
Term
a lysosomal storage disorder characterized by the excess accumulation of phospholipids in tissues
Definition
phospholipidosis
Term
involves trapping or selective uptake of drugs into lysosomes and acidic vesicles of affected cells
Definition
drug-induced phospholipidosis
Term
Drug-induced phospholipidosis side effects
Definition
QT prolongation, myopathy, hepatotoxicity, nephrotoxicity, or pulmonary dysfunction
Term
potential to cause QT prolongation (can also cause phospholipidosis)
Definition
erythromycin, amiodarone, imipramine, fluoxetine, haloperidol, chlorpromazine
Term
cause phospolipidosis, myopathy and neurological damage
Definition
chloroquine, hydroxychloroquine, quinine
Term
phosholipidosis of the renal proximal tubules and glomeruli can occur frequently during nephrotoxicity with these drugs
Definition
aminoglycosides: gentamicin, tobramycin, and amikacin
Term
majority of primary liver cancers arises from hepatocytes
Definition
hepatocarcinoma
Term
may be due to mutagenic or genotoxic effect of acetaldehyde or production of reactive oxygen and nitrogen species
Definition
ethanol-induced carcinoma
Term
has been implicated as responsible for hepatocellular carcinomas and adenomas
Definition
regular, long-term anabolic steroid use
Term
connected with benign liver tumors
Definition
oral contraceptive-induced carcinoma
Term
macrolide antibiotics, natiarrhythmic drugs, antidepressants, antipsychotics, anti-malarials, and aminoglycosides all can contribute to this
Definition
phospholipidosis
Term
selective uptake of drugs into lysosomes and acidic vesicles of affected cells; followed by a gradual accumulation of drug-phospholipid complexes within the internal lysosomal membranes
Definition
Drug Trapping
Term
can cause drug trapping
Definition
drugs that can cause QT longation (antibiotics, antiarrhythmics, antimalarials, aminoglycosides..)
Term
3rd most common cancer in the world and is almost invariably fatal within a year
Definition
Hepatoccellular carcinoma
Term
connected with benign liver tumors
Definition
use of contraceptive steroids, particularly the estrogenic components
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