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830 > DILI/ALI > Flashcards

DILI/ALI Flashcards

1
Q

Hepatotoxicity Causers

A
  • > 1000 medications/supplements known to cause it
  • Many cases are idiosyncratic where patients are on multiple medications
  • Diet supplements and OTCs are also often the cause in many cases
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2
Q

Risk Factors for Hepatotoxicity

A
  • Advanced age
  • Sex
  • Alchohol use
  • Pregnancy
  • Genetic predisposition
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3
Q

Diagnosing DILI

A
  • Can be difficult

- Patients range from asymptomatic elevations in enzymes to fulminant hepatic failure

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4
Q

ALF + Severe Complications

A
  • INR >= 1.5
  • Hepatic encephalopathy
  • <26 weeks of illness without apparent CLD
  • Common causes: DILI, viral hepatitis, autoimmune liver disease, shock, hypoperfusion
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5
Q

Things to Consider for DILI

A
  • Time to onset
  • Time to recovery
  • Clinical pattern
  • Exclusion to other causes of liver injruy
  • If a drug is known to be the cause
  • Response to re-exposure
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6
Q

Time to Onset

A
  • Typically between 5 day to 3 months of starting a medication
  • Can be 24-72 hours for allergic reactions
  • Exceptions can occur 3-12 months or even years after starting (isoniazid, amiodarone)
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7
Q

Time to Recovery

A
  • Time to FULL recovery
  • Typically see improvement within days to weeks
  • FULL improvement seen in 2-3 months
  • Tylenol and niacin are examples that have rapid improvement
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8
Q

Clinical Pattern of Injury

A
  • Refers to histological features of injury
  • Described with patterns of liver enzymes
  • Hepatocellular, cholestatic, or mixed
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9
Q

Hepatocellular Injury

A
  • ALT > 2x ULN or ALT:ALK ratio > 5

- EX: isoniazid, methyldopa

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10
Q

Cholestatic Injury

A
  • ALK > 2x ULN or ALT:ALK ratio <2

- EX: Augmentin, erythromycin

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11
Q

Mixed Injury

A
  • ALT and ALK elevated, ALT > 8x ULN

- EX: Phenytoin, Enalapril

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12
Q

Exclusions to Other Causes

A
  • Viral Hepatitis (A, B, or C)
  • Alcohol use
  • Weight gain
  • History of autoimmune diseases
  • History of cardiac failure, shock, or septicemia
  • History of ALL drug intake within last 3 months
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13
Q

Re-exposure

A
  • Usually not recommended since rapid injury and potentially fatal outcomes can occur
  • If multiple medications are suspected, reintroduce in order of least likely to cause the outcome
  • Inadvertent re-exposure is also possible on the patient’s part
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14
Q

Medication Categories with Hepatotoxic Effects

A
  • Antibiotics
  • Antituberculosis Drugs
  • Tylenol
  • Statins
  • Anticonvulsants
  • Metformin
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15
Q

Antibiotics

A
  • Rare, usually asymptoatic, transient, and cause mild impairment
  • Augmentin is most common to cause liver injury
  • Injury usually occurs days to weeks after use
  • Host factors can increase likelihood, like Bactrim-induced injury is more likely in HIV patients
  • Initial injury may be transient but reexposures may increase liver injury risk
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16
Q

Antituberculosis Drugs

A

-Well known for hepatotoxic effects
-Ranges from asymptomatic to fulminant hepatic failure
-EX: isoniazid, pyrazinamide, and rifampicin
-Occurs within first few weeks of therapy and main cause for early TB treatment termination
-Host factors increase susceptibility: age (>60), female, malnutrition
-Possible factors: pre-existing liver disease, HIV, acetylator status,
CYP2E1 polymorphisms, alcohol consumption, concomitant hepatotoxic
meds
-Combo therapies also increase the risk
-Ethambutol and streptomycin are not associated with hepatotoxicity

17
Q

Tylenol

A
  • Enzyme elevations are common with concurrent use
  • Usually asymptomatic and resolve rapidly with stopping therapy, reducing dose, or even when continuing the dose sometimes
  • STILL the preferred analgesic with liver disease since it is safer than alternatives
18
Q

Tylenol + Toxic Metabolite

A

-5-9% of Tylenol is converted to a toxic metabolic, N-acetyl-p-benzoquinone
imine
-Usually rapidly metabolized/conjugated with glutathione and excreted
-N-acetylcysteine = antidote, prevents toxicity if used early
-Glutathione availability, alcohol use, and other medications that induce P450 enzymes increase risk for toxicity

19
Q

Statins

A
  • Vague recommendations against use in patients with liver disease
  • Fat deposits on the liver that these patients have would make them benefit from statins
  • Liver transaminase elevations are rare (<1%)
  • No data suggesting to avoid statins in patients with liver disease
20
Q

Anticonvulsants

A
  • Rare, idiosyncratic, and often accompanied by signs of allergic reaction
  • May be a genetic predisposition
21
Q

Anticonvulsant Drug Examples

A
  • Phenytoin: reactive metabolite leads to immune reaction mostly in adults, can be severe and lead to ALF/death
  • Carbemazepine: asymptomatic rises in liver enzymes (Oxcarb. is less toxic)
  • Lamotrigine: one of the most common causers of DILI, can also cause allergic reactions
  • Valproic acid: Can cause many distinct forms of DILI
22
Q

Valproic Acid Risk Factors

A
  • <2 children
  • Combo therapy with enzyme inducer anticonvulsant
  • Developmental delay
  • Carnitine deficiency
23
Q

Metformin

A
  • Historically avoided due to concerns about lactic acidosis
  • Metformin may decrease liver enzymes
  • Data overall says that patients with liver disease may benefit from it and experience lower risk of cancer and higher survival in HCV
24
Q

DILI General Management

A
  • D/C offending agent
  • In ALF, hold/discontinue all unnecessary medications
  • Administer antidote if possible
  • Offer supportive care, steroids are helpful for autoimmune hepatitis
  • UDSA can help reduce itching in cholestatic injury patients
  • Give tenofovir for HBV
25
Q

Drugs Known to Cause Liver Disease

A
  • Do not necessary need to be avoided

- Usually not predominantly metabolized by liver

26
Q

Furosemide

A
  • Concern: electrolyte abnormalities

- Effect in Cirrhotic Patients: electrolyte disturbances, hepatorenal syndrome

27
Q

ACE-I

A
  • Concern: + RAS effect

- Effect in Cirrhotic Patients: hypotension

28
Q

NSAIDs

A
  • Concern: renal failure, increased bleeding risk

- Effect in Cirrhotic Patients: hepatorenal syndrome, fatal GI bleeds, anemia

29
Q

Aminoglycosides

A
  • Concern: renal failure

- Effect in Cirrhotic Patients: hepatorenal syndrome

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