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DABT 2025 > Liver Toxicity > Flashcards

Liver Toxicity Flashcards

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1
Q

What is the mechanism of ethanol-induced liver toxicity?

A

Induces CYP2E1, increases fatty acid synthesis, causes steatosis and fibrosis via stellate cell activation.

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2
Q

What are biomarkers for liver toxicity?

A

Elevated ALT, AST, ALP, GGT, total bilirubin; decreased clotting factors.

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3
Q

What are testing methods for liver toxicity?

A

Liver function tests (LFTs), biopsy, BSP/ICG dye clearance, imaging (ultrasound, CT).

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4
Q

What are endpoints for liver toxicity?

A

Acute liver failure, chronic hepatitis, cirrhosis, hepatocellular carcinoma.

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5
Q

How is aflatoxin B1 toxic to the liver?

A

Metabolized to epoxide, forms DNA adducts, leading to hepatotoxicity and cancer.

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6
Q

What is the treatment for acetaminophen-induced DILI?

A

N-acetylcysteine to replenish GSH and detoxify NAPQI.

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7
Q

What are common hepatotoxic agents?

A

Acetaminophen, carbon tetrachloride, aflatoxin, ethanol, thioacetamide, d-limonene, chloroform, methotrexate, amiodarone.

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8
Q

What is the primary mechanism of acetaminophen hepatotoxicity?

A

CYP2E1 bioactivation to NAPQI, depleting glutathione, causing necrosis.

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9
Q

How does carbon tetrachloride cause liver toxicity?

A

CYP450 metabolism to trichloromethyl radical, inducing lipid peroxidation.

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10
Q

What is the mechanism of aflatoxin-induced hepatotoxicity?

A

Forms DNA adducts, causing mutations and hepatocellular carcinoma.

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11
Q

How does ethanol affect the liver?

A

Metabolized to acetaldehyde, causing oxidative stress and steatosis.

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12
Q

What biomarkers indicate hepatotoxicity?

A

Elevated ALT, AST, bilirubin, ALP, GGT, microRNA-122.

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13
Q

What are standard testing methods for hepatotoxicity?

A

Liver function tests, serum enzyme assays, histopathology, imaging.

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14
Q

What are key endpoints of hepatotoxicity?

A

Hepatocellular necrosis, fibrosis, cirrhosis, hepatocellular carcinoma.

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15
Q

How does thioacetamide cause liver toxicity?

A

Metabolized to reactive intermediates, causing centrilobular necrosis.

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16
Q

What is the toxic effect of d-limonene on the liver?

A

Induces hyaline droplet nephropathy in male rats, not relevant to humans.

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17
Q

How does chloroform induce hepatotoxicity?

A

CYP2E1 metabolism to phosgene, causing necrosis at high doses.

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18
Q

What is the mechanism of methotrexate-induced liver toxicity?

A

Inhibits folate metabolism, causing steatosis and fibrosis.

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19
Q

What are clinical signs of hepatotoxicity?

A

Jaundice, fatigue, nausea, abdominal pain, dark urine.

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20
Q

How does amiodarone cause liver toxicity?

A

Accumulates in lysosomes, causing phospholipidosis and steatosis.

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21
Q

What is a key biomarker for acetaminophen overdose?

A

Elevated serum acetaminophen levels and AST:ALT ratio >2.

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22
Q

How does galactosamine cause hepatotoxicity?

A

Depletes UDP-glucuronate, causing acute liver injury.

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23
Q

What testing method detects liver fibrosis?

A

FibroScan measures liver stiffness.

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24
Q

How does vinyl chloride affect the liver?

A

Forms DNA adducts, causing angiosarcoma.

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25
What is a long-term endpoint of ethanol exposure?
Cirrhosis due to chronic inflammation and fibrosis.
26
What agent causes cholestasis?
Chlorpromazine, via bile duct obstruction.
27
What is the role of histopathology in hepatotoxicity?
Identifies necrosis, steatosis, or fibrosis in liver tissue.
28
What biomarker indicates cholestasis?
Elevated serum bilirubin and ALP.
29
How does isoniazid cause liver toxicity?
CYP2E1 metabolism to hydrazine, causing hepatitis.
30
What is the mechanism of bromobenzene hepatotoxicity?
Forms reactive epoxides, causing centrilobular necrosis.
31
What test confirms aflatoxin exposure?
Serum aflatoxin-DNA adducts via ELISA.
32
How does troglitazone cause hepatotoxicity?
Mitochondrial dysfunction, causing idiosyncratic liver injury.
33
What biomarker reflects oxidative stress in liver?
Elevated malondialdehyde (MDA) in liver tissue.
34
How does valproic acid cause liver toxicity?
Inhibits beta-oxidation, causing microvesicular steatosis.
35
What is an endpoint of carbon tetrachloride exposure?
Hepatocellular carcinoma in chronic exposure.
36
How does nitrofurantoin cause liver toxicity?
Induces autoimmune hepatitis via immune-mediated injury.
37
What test evaluates liver function?
Prothrombin time (PT) measures clotting factor synthesis.
38
How does phenytoin cause liver toxicity?
CYP450 metabolism to arene oxides, causing hepatitis.
39
What biomarker monitors methotrexate toxicity?
Elevated serum transaminases (ALT, AST).
40
How does halothane cause liver toxicity?
Forms trifluoroacetyl adducts, triggering immune-mediated hepatitis.
41
What is an endpoint of aflatoxin exposure?
Hepatocellular carcinoma due to p53 mutations.
42
How does cyclosporine cause liver toxicity?
Inhibits bile salt export pump, causing cholestasis.
43
What test detects steatosis?
Ultrasound shows fatty liver.
44
How does ketoconazole cause liver toxicity?
Inhibits CYP3A4, causing idiosyncratic hepatitis.
45
What biomarker indicates acute liver injury?
Elevated microRNA-122 in serum.
46
How does diethanolamine cause liver toxicity?
Depletes choline, causing tumors in rodents.
47
What is an endpoint of methotrexate exposure?
Liver fibrosis in chronic use.
48
How does pyrrolizidine alkaloids cause liver toxicity?
Forms pyrrole adducts, causing veno-occlusive disease.
49
What test assesses drug-induced liver injury?
Roussel Uclaf Causality Assessment Method (RUCAM).
50
How does troleandomycin cause liver toxicity?
Inhibits CYP3A4, causing cholestasis.
51
What biomarker monitors ethanol-induced liver damage?
Elevated GGT in serum.
52
How does allyl alcohol cause liver toxicity?
Metabolized to acrolein, causing periportal necrosis.
53
What is an endpoint of amiodarone exposure?
Steatohepatitis due to mitochondrial dysfunction.
54
How does tamoxifen cause liver toxicity?
Induces steatosis via altered lipid metabolism.
55
What biomarker indicates biliary obstruction?
Elevated conjugated bilirubin.
56
How does dimethylnitrosamine cause liver toxicity?
Forms DNA adducts, causing hepatocellular carcinoma.
57
What are common toxic agents for liver toxicity?
Acetaminophen, ethanol, carbon tetrachloride, aflatoxin B1, amoxicillin-clavulanate, isoniazid, valproate, halothane, herbal supplements, pyrrolizidine alkaloids.
58
What is the mechanism of acetaminophen-induced liver toxicity?
Metabolized to NAPQI by CYP2E1, depletes GSH, causes mitochondrial oxidative stress and necrosis.
59
What is the mechanism of ethanol-induced liver toxicity?
Induces CYP2E1, increases fatty acid synthesis, causes steatosis and fibrosis via stellate cell activation.
60
What is the mechanism of carbon tetrachloride toxicity?
Metabolized to trichloromethyl radical by CYP2E1, causes lipid peroxidation and hepatocyte damage.
61
What are endpoints for liver toxicity?
Acute liver failure, chronic hepatitis, cirrhosis, hepatocellular carcinoma.
62
How is aflatoxin B1 toxic to the liver?
Metabolized to epoxide, forms DNA adducts, leading to hepatotoxicity and cancer.
63
What is the treatment for acetaminophen-induced DILI?
N-acetylcysteine to replenish GSH and detoxify NAPQI.
64
What are risk factors for DILI?
Old age, female gender, chronic alcoholism, pregnancy, certain HLA types (e.g., HLA-B*5701).

DABT 2025 (16 decks)

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