Brainscape's Knowledge GenomeTM

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


See full index

PHM 702: Pulm and ToXXX > not all drugs are good drugs: Liver > Flashcards

not all drugs are good drugs: Liver Flashcards

1
Q

Definition of drug-induced liver disease/impairment

A
  • Total bili >2.5 with any ALT, AST elevation or
  • ALT >5x ULN or
  • AST >5x ULN or
  • ALP >2x ULN or
  • INR >1.5 with elevated AST, ALT, OR ALP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Normal bilirubin lab values

A

Just think about 1
- Total bili <1.2
- Conjugated <0.2
- Unconjugated <1.0

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

Normal AST and ALT values

A
  • AST normally 5-40
  • ALT normally 5-40
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Normal albumin value

A

4

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

Normal INR value

A

1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

MOA of APAP induced liver impairment/tox

A

In setting of high doses:
1. conjugation pathway becomes saturated →
2. CYP2E1 pathway is utilized more than it normaly is →
3. more NAPQI (toxic) production →
4. glutathione stores cannot regenerate fast enough to combine with all NAPQI to make them non toxic →
5. NAPQI starts attacking hepatocytes → hepatocyte injury and death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Predisposing factors to APAP overdose

A
  • CYP2E1 induction (anticonvulsants, isoniazid, chronic EtOH)
  • Malnourishment
  • Decreased sulfation and glucoronidation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Toxic levels of APAP

A
  • 7.5g in adults
  • > 150mg/kg in children
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

ABX that can cause liver disase

A
  • Augmentin: can cause cholestatic jaundice and hepatocellular injury
  • Azithromycin
  • Bactrim
  • Cefazolin
  • Cipro
  • Isoniazid
  • Levofloxacin
  • Minocycline
  • Nitrofurantoin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Can dietary supplements cause liver dsiase?

A

Yes
- Body building herbal dietary supplement (HDS) → usually cholestatic injury
- Non-body building HDS → usually hepatocellular injury
- More severe

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

Diclofenac can/cannot cause liver disease

A

CAN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

General treatment for drug induced liver diseases

A

Supportive care
- IV fluids
- management of N/V
- Correction of hypoglycemia
- Vitamin K/FFP
NAC if indicated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Drug rechallenge in drug-induced liver disease

A

If patient had cholestatic or mixed injury (NOT soley hepatic injury), could rechallenge, but avoid doing so unless there is no other alternative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

MOA of NAC in APAP overdose

A

NAC therapy: provides something other than human tissue for NAPQI to bind to, also possibly a precursor to glutathione.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

PO vs IV NAC in APAP overdose

A
  • PO (72 hr protocol): bad n/v and smells really really bad
    • Pre-treat with anti-emetics
  • IV (20 hr protocol): prefered in pts with liver failure, preggers, or can’t tolerate PO
    • Can cause anaphylactoid reactions, just treat with steroids and Benadryl and readmin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

When to start NAC in APAP overdose

A
  • Prior to hour 4:
    • Consider activated charcoal
    • Wait and recheck at hour 4 to assess whether or not NAC is needed
  • After hour 24 (can no longer use the nomogram to figure out if needed) → if AST is elevated regardless of APAP level
    • Begin NAC
  • After hour 24 or unknown late ingestion with detectable APAP level
    • Begin NAC
17
Q

When to continue NAC beyond the 20/72 hr protocol

A
  • On-going liver failure present
    • Elevated PT/INR
    • Encephalopathy present
  • Detectable APAP
    • APAP >10mcg/ml
  • Ongoing hepatocyte damage
    • AST above ULN and not decreaseing
    • AST >1000
18
Q

How to calculate R value?

A

R = [ALT/ULN] / [ALP/ULN]

19
Q

What does the R value tell you?

A

What kind of DILI it is
hepatocellular vs cholestatic vs mixed

20
Q

R≥5 means

A

hepatocellular likely d/t AST/ALT elevation (hepatocytes impacted)

21
Q

R = 2-5 means

A

Mixed presentation

22
Q

R ≤2 means

A

cholestatic d/t ALP elevation (biliary dysfx)

23
Q

ULN for ALT is

A

40

24
Q

ULN for ALP is

A

140

25
Q

Gamma Glutamyl Transpeptidase (GGT)

A

Found in hepato-billiary tree (liver)
Concurrent GGT elevation with ALP = confirm hepatic origin of ALP elevation

26
Q

Causes of liver disease other than drugs

A
  • alcohol
  • hepatitis
  • biliary tract disease
  • NAFLD
  • genetics/metabolic
    - hemochromatosis
    - a1 antitrypsin deficiency
    - wilson’s disease
27
Q

Short latency drugs

Drugs that can cause DILI shortly after iniitation

A

dili ≤ 7 days
azithro
cipro
levo(floxacin)

28
Q

Long latency drugs

drugs that can cause dili years after initiation

A

dili ≥365 days
amiodarone
minocycline
(?) high intensity statin

29
Q

Markers of liver function

A

AST
ALT
ALP
GGT

30
Q

Markers of liver synthesis

A

Bilirubin
Albumin
PT/INR

31
Q

Facts about APAP

A
  • crosses BBB and placenta
  • RAPID PO absorption 2hrs, complete by 4 hrs
  • 25% via first pass
32
Q

An AST of <1000 IU/L (is/ is NOT) clinically significant for APAP hepatotoxicity?

A

IS NOT

PHM 702: Pulm and ToXXX (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions