Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

GI > Week 5: Drug induced liver injury > Flashcards

Week 5: Drug induced liver injury Flashcards

1
Q

Epidemiology of DILI

A
  • major cause of acute liver failure. Mimics all forms of liver disease.
  • Acetaminophen accounts for 46% of acute liver failure. 1/2 unintentional.
  • Can be Hepatocellular, mixed, or cholestatic pattern of injury
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Drugs and their clinical-pathological signature of DILI

A

ACUTE
-hepatitis: Acetaminophen, INH
-cholestatic/mixed: erythromycin, sulindac
CHRONIC
-chronic hepatitis: methyldopa, nitrofurantoin, minocycline, diclofenac, germander
-ductopenic cholestasis: rare, after acute
-NASH: amiodarone, methotrexate, tamoxifen
-nodular regen. hyperplasia: thiopurines, oxaliplatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Hy’s Law

A

Acute drug hepatitis with jaundice is life threatening- 10% mortality -Hy’s Law

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Chronic DILI

A
  1. Acute hepatitis can lead to chronic hepatitis if not taken off drug
  2. cholestatic reactions resolve slowly and can lead to chronic ductopenia cholestasis if continued on drug.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Diagnosis of DILI

A
  1. Latency: usually new drug started and continued within 6 months (2 days to 12 months)
    - some antibiotics (augmenting, erythromycin) have onset delayed 1-2 months after course of treatment
  2. Dechallenge: stop drug and see if improves
    - improvement in cholestatic pattern is slower
  3. Rechallenge: Shouldn’t do, not safe!
  4. Previous knowledge about drug
  5. Exclusions of other disease
    - liver biopsy usually not helpful
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Classification of DILI

A
  1. Predictable: dose related, frequent injury. Few examples: acetaminophen, cyclosporin
  2. Unpredictable (idiosyncratic): threshold dose but not dose related.
    - Allergic: fever,r eash, eosinophilia, autoantibodies. 1-4 week latency, positive rechallenge
    - Non allergic: absence of immune features, often long latency.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Temple’s Corollary

A
  • mild injury that reverses with continued use- adaptation

examples: statins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Risk factors in DILI

A
  • age: isoniazid (old) vs valproate (young)
  • gender: female 60 for cholestasis
  • Diseases: HBV, HCV, HIV- isoniazid, sulfonamides
  • alcohol: acetaminophen, methotrexate
  • concomitant drugs: phenobarbital and valproate. rifampin and INH
  • obesity/diabetes: methotrexate, tamoxifen
  • genetics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Allergic DILI

A
  1. acute allergic DILI: +/- systemic features of allergy-rash, eosinophilia
  2. autoimmune hepatitis like: no systemic features of allergy
    - acute or chronic hepatitis
    - ANA, SMA, female predominance, elevated IgG. Distinguish from AIH by + dechallenge.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Hepatic drug metabolism

A

phase 1: modification, P450 common phase 1 reaction

phase2: conjugation, more commonly detoxification
phase3: excretion from cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Pathogenesis of drug induced liver injury

A
  • Drug itself can be toxic or its metabolite can induce immune response or cause covalent binding, GSH depletion, ROS
  • leads to inflammatory mediators->injury
  • Common pathway?
  • Drug specific exposure leads to cellular stress and injury.–>systemic organ effects–>symptomatic DILI-> ALF
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Pathogenesis of cholestatic DILI

A
  1. Bland cholestatsis- inhibition of bile acid excretion
    e. g. cyclosporin
  2. Inflammatory cholestasis (cholangitis)
    - cholangiocyte damage by drug or metabolite
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Acetaminophen toxicity (APDP)

A
  • safe up to 4g/day in normal people
  • Safe up to 2g/day: CYP2E1 inducers (chronic EtOH, INH), starvation (decreased GSH and glucuronic acid)
  • presentation: towering transaminases begin day 2, INR abnormal early, minimal hyperbilirubinemia
  • poor prognosis: acidotic, PT>100sec, Serum Cr> 3.4mg/dL, coma, Serum phosphate> 1.2 mM
  • Treatment: follow nomogram for suicidal overdose. Give NAC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Metabolism of acetominophen

A

Phase 2 metabolism: to glucuronide or sulfate

  • if system overwhelmed, metabolism by Cyt P450 2E1: this depletes glutathione
  • fasting also depletes glutathione. Chronic EtOH induces Cyt P450 2E1
  • body vulnerable to ROS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Isoniazid Hepatotoxicity

A

Classic idiosyncratic nonallergic hepatotoxin

  • clinical: 10% ALT> 3x normal
  • half of cases after 2 months
  • increased risk in alcoholics, concomitant TB meds (rifampin), chronic Hep, HIV, older age, slow acetylator
  • rifampin induces enzymes that metabolize isoniazid to a toxic metabolite
  • monitor ALT in >35 monthly or if have other risks. Stop if ALT increases 5x or 3x with symptoms
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Augmentin (amoxicilin -clavulanic acid) toxicity

A
  • most common cause of idiosyncratic DILI
  • allergic features (HLA association)
  • broad signature: hepatitis/cholestasis/mixed
  • 1/2 cases delayed, onset up to 8 weeks after cessation.
  • Early-hepatitis, female, 55

GI (52 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions