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Flashcards in Drug induced liver injury Deck (18):
1

What are the three forms of liver injury

Hepatocellular injury
cholestasis
Mixed

2

What might hepatocellular injury result from

Drug or its metabolites

3

What do paracetamol and methotrexate cause

direct hepatocellular toxicity

4

What are the mechanisms of drug-induced liver injury

Disruption of the cell membrane
Production of immune targets by covalent binding of the drug to cell proteins
Inhibition of cellular pathways of drug metabolism
Abnormal bile flow due to disruption of subcellular actin filaments or interruption of transport pumps
Programmed cell death (apoptosis) mediated by tumour necrosis factor and Fas pathways
Inhibition of mitochondrial function causing accumulation of reactive oxygen species, lipid peroxidation, fat accumulation and cell death

5

What is the most important factor for susceptibility to DILI

Genetic variability

6

What are the clinical features of DILI

Acute hepatitis
Cholestasis
A mixed condition resembling acute viral hepatitis

7

What is the prognosis dependent on in DILI

The presence of jaundice

8

What is hepatocellular injury defined as

A rise in ALT of more than 2 fold or
ALT/AP ratio >5

9

What is acute cholestatic injury defined as

An increase in the ALP >2 x ULN or an ALT/ALP

10

What are the main causative agents in DILI

Antibiotics
NSAIDs
Antiseizure medication
Herbal preparations

11

When might a liver biopsy be useful

Where there is a suspicion of an underlying liver disease

12

What is the management for DILI

No effective treatment other than stopping the implicated drug and providing supportive care

13

What is the leading cause of acute liver failure

Paracetamol overdose

14

What dose of paracetamol results in serious or fatal adverse effects

150mg/kg

15

What are the clinical features of a paracetamol overdose

Asymptomatic for the first 24hours after infestion
Hepatic necrosis begins after 24h resulting in RUW pain, jaundice and elevated transaminases

16

What are the investigations for a paracetamol overdose

paracetamol elvels are sampled after 4h of ingestion
Basline FBC, U&E, creatinine, LFTs
Prothrombin time is the best indicator of severity of liver failure

17

Why is blood glucose measured in Paracetamol overdoses

Hypoglycaemia is common

18

What is the management of a paracetamol overdose

Urine output and blood glucose are monitored hourly
U&E, LFT and INR checked 12 hourly
N-acetylcysteine (NAC is given to patients:
with lelvels above the treatment line, immediately at presentation if the overdose is more than 150mg/kg or the overdose is staggered or the patient presents more than 15h after ingestion