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17 Cards in this Set
- Front
- Back
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Case I |
ddx viral hep, cellulities, choleangitits tests; ultrasound rx; cholestryamine for the itch and excess bile salts, then naltrexone for itch and IV sedation
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Incidence of DILI |
most drugs exhibit a low incidence of liver injury
4-8% of patients hopsitalized for jaundice had DILI
leading cause of acute liver failure referred for transplantation
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Hepatic drug metabolism |
Phase 1 increase the solubility via addition of polar head groups, mainly by cytochrome p450 superfamily of MFOs CYP 1-3
Phase 2 conjugation to a large polar group, glucaronic acid, sulfate, acetate, glutathione
Phase 3; transport into bile, ATP depedent transporters in the bile canaliculi |
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Factors affects phase 1-3 rxns |
diet; induction or inhbition of CYP enzymes by foods, chronic alcohol increase CYP2E1 and depletes glutathione
presence of other drugs
age; infants have immaturity of CPY eznymes, decrease in CYP with aging, age relating differences in phase 2 rxns
genetics; SNPs, fast and slow acetylators, gilbert syndrome with diminished capacity for glucrondination is linked to irnotectan tox
underlying liver disease |
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Case 2 |
increased UC meds, was terrible UC, started steroids which slight improved, wanted to use anti-TNF antibodies but had latent Tb, treated on isoniazid for the latent Tb
at 6 weeks the aminotransferases rose to 2x normal, but continued to watch |
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Types of DILI |
predicted; occur in most people after a threshold dose is reached, dose related, latent period between exposure and reaction is brief, acetaminophen
unpredictable; unrelated to dose, latency period of a few days to 12 month, may or may not be due to hypersensitivity or immunology injury |
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Mechanisms of DILI injury |
intrinsic = necrosis of hepatocytes
idiosyncratic = necrotic or cholestatic, can be hypersensitive or hyposensititve |
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Patterns of injury |
hepatocellular = elevated ALT
mixed = elevated ALP an ALT
cholestatic = Elevated ALP and TBL |
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Common histo features |
microvesicular fat
acute hep
cholestasis
eosinophilic rich infiltrate |
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Case 3 |
NSAID used for arthritis |
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Herbals and Hepatic injury |
little monitoring, minimal recording, not often reported by the patient because they do not realize their potentil potency |
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Etiology of liver failure |
acetaminophen, other drugs, then Hep B then A |
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Acetaminophen metabolism |
at therapeutic doses, 90% conjugated with sulfate or glucuronide and excreted in urine,
but remainder is metabolized in the CYP450 pathway to N acetyl p benzoquineoneimine
but if you have reduced glutathione due to other conjugation the toxic metabolite and overpopulate |
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acetaminophen toxicity |
with toxic doses, sulfation and glucuronidation pathways are saturated and more is metabolized to NAPQI
reduced stores in teh chronically ill, starved, and alcoholics
effects the hepatocytes around the central vein where the clotting factors arise |
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factors influencing tox |
excessive intake, CYP activity, decreased glucuronidation or sulfation, depletion of glutathione stores |
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Rumack-Matthew normogram |
single acute overdose of an immediate release prep of acetaminophen at 4 to 24 hrs after ingestion
sustained prep measure at 4 and 8 hrs
chronic overdose, serum levels may be normal |
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Rx for acetaminophen poisoning |
activated charcoal within 4hrs of ingestion to decrease absorption
acetylcysteine for those with a risk for of hepatotoxicity, (glutathione derivative) restores levels
given orally and IV, liver transplantaiton for those with progressive liver failure |
