Drugs in the Liver

Question 1

What is metabolism?

Answer 1

All chemical reactions involved in maintaining the living state of cells and the organism.

Question 2

What is intrinsic clearance?

Answer 2

The theoretical maximum clearance of unbound drug by an organ, without limitations from blood flow or protein binding.

Question 3

What is conjugation in drug metabolism?

Answer 3

The addition of chemical groups to drugs, making them more water-soluble for excretion.

Question 4

What is hydrolysis in drug metabolism?

Answer 4

The chemical breakdown of a compound due to a reaction with water.

Question 5

What is reduction in a chemical reaction?

Answer 5

The gain of electrons or loss of oxygen.

Question 6

What is oxidation in a chemical reaction?

Answer 6

The loss of electrons or gain of oxygen.

Question 7

What factors determine hepatic clearance of oral drugs?

Answer 7

Liver blood flow, intrinsic clearance, and protein binding.

Question 8

What does a high extraction ratio indicate?

Answer 8

Drug is rapidly cleared in a single liver pass; clearance depends mostly on hepatic blood flow.

Question 9

Give an example of a drug with a high extraction ratio.

Answer 9

Morphine, verapamil, or propranolol.

Question 10

What does a low extraction ratio indicate?

Answer 10

Drug is poorly cleared; clearance depends on liver’s metabolic capacity and free drug fraction.

Question 11

Give an example of a drug with a low extraction ratio.

Answer 11

Warfarin or phenytoin.

Question 12

What does an intermediate extraction ratio mean?

Answer 12

Clearance is influenced by both hepatic blood flow and intrinsic metabolism.

Question 13

Give an example of a drug with intermediate extraction ratio

Answer 13

Aspirin or codeine.

Question 14

What are CYP450 enzymes?

Answer 14

A family of enzymes responsible for Phase 1 drug metabolism, primarily oxidation.

Question 15

What is the main role of CYP450 enzymes in metabolism?

Answer 15

Conversion of drugs into inactive metabolites.

Question 16

Where are CYP450 enzymes found?

Answer 16

Mostly in the liver.

Question 17

What reactions are typically catalyzed by CYP450 enzymes?

Answer 17

Oxidation, reduction, and hydrolysis.

Question 18

How can drugs interact through CYP450 enzymes?

Answer 18

By competing for the same enzyme binding site.

Question 19

What happens to the drug with lower enzyme affinity in a drug-drug interaction?

Answer 19

It is metabolized more slowly, leading to prolonged effects.

Question 20

What is a potential consequence of CYP450 competition?

Answer 20

Increased risk of toxicity or prolonged drug action.

Question 21

What is the main purpose of Phase II metabolism?

Answer 21

Detoxification via conjugation to make drugs more water-soluble for excretion

Question 22

What happens to the drug in Phase II metabolism?

Answer 22

It is conjugated with molecules like glycine, glutamine, or sulfur compounds.

Question 23

What is glucuronidation?

Answer 23

glucuronic acid is added to a drug.

Question 24

Where are glucuronides eliminated?

Answer 24

In bile and urine.

Question 25

What is amino acid conjugation?

Answer 25

Conjugation of drugs with amino acids like glycine or glutamine for urinary excretion.

Question 26

Why are neonates vulnerable to drugs like chloramphenicol?

Answer 26

Slow glucuronidation can lead to toxic accumulation.

Question 27

What is sulfoconjugation?

Answer 27

Conjugation of drugs with sulfate, making them polar and easily excreted in urine.

Question 28

What is biliary excretion?

Answer 28

The excretion of drugs directly into bile, especially after conjugation.

Question 29

What drugs are more likely to be excreted in bile?

Answer 29

Polar and lipophilic drugs with molecular weight > 200 kDa.

Question 30

What happens to drugs with smaller molecular weight?

Answer 30

They are more likely to be excreted via urine.

Question 31

What kind of transport is used in biliary excretion?

Answer 31

Active, energy-dependent transport that can become saturated.

Question 32

What are risk factors for impaired drug metabolism in liver disease?

Answer 32

Hepatocellular failure, reduced blood flow, impaired enzyme function, low protein binding.

Question 33

What effect does liver disease have on plasma protein binding?

Answer 33

Decreases it, increasing free drug and volume of distribution.

Question 34

How does malnutrition affect liver metabolism?

Answer 34

It reduces availability of essential micronutrients.

Question 35

What is Drug-Induced Liver Injury (DILI)?

Answer 35

Liver damage caused by medications, from mild enzyme elevation to acute liver failure.

Question 36

What is the most common cause of acute liver failure in the U.S. and Europe?

Answer 36

Drug-induced liver injury.

Question 37

What is idiosyncratic DILI (IDILI)?

Answer 37

Rare, unpredictable liver injury not clearly related to drug dose.

Question 38

How common is significant liver damage from methotrexate?

Answer 38

Rare – about 1 in 300 patient years.

Question 39

What are methotrexate-related liver risks?

Answer 39

Fatty liver disease, fibrosis, cirrhosis (with cumulative doses > 2g).

Question 40

What increases liver risk with methotrexate?

Answer 40

Alcohol, obesity, age.

Question 41

How is methotrexate liver risk monitored?

Answer 41

LFTs, serum fibrosis markers, and liver biopsy.

Question 42

What dose of paracetamol can cause hepatic necrosis?

Answer 42

10 grams.

Question 43

How long before toxicity signs appear after paracetamol overdose?

Answer 43

Up to 48 hours.

Question 44

What predicts poor prognosis in paracetamol toxicity?

Answer 44

Prolonged prothrombin time and acidosis.

Question 45

Who is more prone to paracetamol toxicity?

Answer 45

Alcoholics, fasting patients, or those on enzyme-inducing drugs.

Question 46

What is the antidote for paracetamol toxicity?

Answer 46

IV Acetylcysteine (21-hour or 12-hour infusions).

Question 47

What tool helps guide paracetamol overdose treatment?

Answer 47

TOXBASE.

Question 48

How does chronic alcohol use affect liver enzymes?

Answer 48

Induces them, increasing hepatotoxicity risk.

Question 49

How does acute alcohol use affect enzyme activity?

Answer 49

Inhibits enzymes.

Question 50

Which common analgesic is metabolized via glucuronidation and sulfation?

Answer 50

Aspirin.

Question 51

What condition makes glucuronidation inefficient in infants?

Answer 51

Immature liver function.