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phm 702 pulm, tox & rheumatoid > Week 4 Drug induced Liver Injury > Flashcards

Week 4 Drug induced Liver Injury Flashcards

1
Q

Role of Liver

A
  • Metabolism
  • Synthesis
  • Detoxification
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2
Q

Problems associated with diseased liver

A
  • Dec AA metabolism
  • Dec Protein synthesis
  • Inc Bili
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3
Q

What are the effects of dec protein synthesis

A
  • Dec clotting factors causing an inc in PT/INR
  • Dec albumin conct
  • Dec thrombpopoietin synthesis causing dec in platelets
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4
Q

Normal AST and ALT

A

<40

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5
Q

What is an inc in AST and ALT associated with?

A

Hepatocyte injury

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6
Q

What is an inc in ALP associated with?

A

Cholestatic injury

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7
Q

Normal ALP

A

<140

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8
Q

normal Albumin

A

4

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9
Q

Normal INR

A

4

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10
Q

Normal bili

A

<1

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11
Q

Causes of Liver Disease

A
  • alcohol and hepatitis ( most common)
  • biliary tract disease
  • fatty liver disease
  • drug induced
  • genetics
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12
Q

DILI clinical pearls

A
  • responsible for 13% of liver failure — #1 cause of death in Acute LF
  • Responsible for 16% of liver transplants
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13
Q

DILI definitions (4)

A

-total bili >2.5 w/ any inc in AST, ALP, ALP
- ALT or AST >5x ULN
- ALP > 2x ULN OR
- INR >1.5 w/ any inc in AST, ALP

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14
Q

What is the equation for deciding the type of DILI

A

R = (ALT/ULN) / (ALP/ULN)

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15
Q

Hepatocellular injury R value

A

R >/= 5

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16
Q

Mixed R value

A

R = 2-5

17
Q

Cholestatic injury R value

A

</= 2

18
Q

Augmentin DILI pearls

A
  • causes both types of injury
  • 2 nd most common drug to cause DILI
  • GENE HLA-DRBI*15
  • onset 2-45 days
19
Q

Augmentin DILI treatment

A

self resolving, supportive care

20
Q

Drugs that cause DILI (in order )

A
  1. APAP
  2. Antimicrobals
    • Augmentin
    • Isoniazid
    • Nitrofurantoin
    • Bactrim
    • Minocycline
  3. NSAIDs : Diclofenac
21
Q

DILI mortality/transplants

A
  • Most common with hepatocellular injury and when bili >2.5
22
Q

APAP pk

A
  • rapid absorption
  • during overdose MOA unchanged. total absorption w/ 4 hrs
  • crosses BBB and placenta
23
Q

APAP Metabolism

A

90% undergoes glucuronidation & sulfation
5-15% oxidized by CYP2E1 to NAPQI
- Combines w/ glutathion to form non-toxic cysteine/mercaptate and is then eliminated in urine

24
Q

APAP toxicity MOA

A
  • glucuronidation pa thway over saturated
  • more CYP2E1 metabolism
  • inc NAPQ1
  • hepatocyte injury
  • DEATH
25
Q

What APAP dose is toxic

A

> 7.5 g adults
150mg/kg in kids

26
Q

Predisposing factors for APAP tox

A
  • CYP2E1 induction
  • Malnourished
  • dec glucuronidation & sulfation
27
Q

What drugs causes CYP2E1

A

Anticonvulsants , Isoniazid , ETOH

28
Q

What labs are seen w/in 24-36 post ingestion of APAP?

A

AST> 1000 (untreated; liver injury)

29
Q

When does maximal hepatoxicity happen and symptoms/labs associated with it?

A
  • w/in 72- 96 post ingestion (untreated)
  • encephalopathy, coma, cerebral edema, hemorrhage
  • AST, ALT> 10,000
  • inc INR, Bili, pH, Lactate
30
Q

APAP toxicity management options

A
  • NAC
  • Activated charcoal
  • Supportive care
31
Q

When is activated charcoal used?

A

pt presents <4 hrs after ingestion

32
Q

How do we determine when to use NAC

A
  • Rumack Matthew Nomogram
  • start w/in 8 hrs post ingestion for best efficacy
33
Q

In what patients should NAC be used after 24 hrs of therapy?

A
  • AST still elevated (>1000 or above ULN and not decreasing)
  • APAP detectable (>10mcg/ ml)
  • On going liver failure
  • on PO therapy (72 hr duration)
34
Q

What 2 features identify liver failure

A
  • inc in PT/INR and Encephalopathy
35
Q

NAC MOA

A

Precursor to glutathione, incs it production
-detoxifies NAPQI

36
Q

PO NAC pearls

A
  • straight to liver
  • super bad taste (cover it, dilute it 5%, pre-treat with antiemetics, put in NG tube)
37
Q

IV NAC pearls

A
  • loading dose over 60 minutes to avoid Anaphylactoid rxns
    • pause inf, give Benadryl, resume
    • typically doesnt happen twice
38
Q

Who gets IV NAC

A
  • pregnant
  • liver failure (which is…)
  • inability to tolerate PO

phm 702 pulm, tox & rheumatoid (15 decks)

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