Hepatic Drug Metabolism - 5

Question 1

• Blood flows out of the liver through ___ veins into the inferior vena cava
• Bile flows out of the liver via a ___ duct
• oxygen rich blood flows into the liver through the ___ artery (20%)
• Nutrient rich blood coming from the bowel flows into the liver via ___ vein (80%)

Answer 1

• hepatic
• bile
• hepatic
• portal

Question 2

Bile composition and function

Answer 2

composition
* water
* bile salts
* bilirubin
* fats

function
* surfactants
* helps fat digestion
* bilirubin elimination

Question 3

Hepatocytes for drug metabolism

hepatocyte responsibilities
* synthesis of albumin and ____ factors
* regulation of ___ metabolic balance
* synthesis of ___ acids
* detoxification of bilirubin
* detoxification of xenobiotics

Answer 3

• coagulation
• nutrient
• bile

Question 4

Principles of drug metabolism

Converts lipophilic chemicals into hydrophilic chemicals, which are readily excreted in urine or bile. Phase 1 (OH) and 2 (bulky)

Answer 4

Question 5

Principles of drug metabolism

Can be divided into 4 categories based on the chemical reaction

Answer 5

1. oxidation (major)
2. conjugation (major)
3. hydrolysis
4. reduction

Question 6

what enzymes does oxidation

Answer 6

CYP450

Question 7

What enzyme does conjugation

Answer 7

UDP glucuronosyl transferase (UGT)

Question 8

What enzyme does hydrolysis

Answer 8

carboxyesterase

Question 9

what enzymes does reduction?

Answer 9

carbonyl reductase

Question 10

Cyp450s

CYP ___ and CYP ___ metabolize over half the orally effective drugs in current use

Answer 10

CYP3A4, CYP2D6

Question 11

CYP3A4 can also do ____ hydroxylation

Answer 11

aromatic

Question 12

CYP2D6 mediates ___ hydroxylation, ___ and ___ dealkylation,

Answer 12

alipathic, N, O

Question 13

Glucuronidation mediated by UGT

UGT takes chonky group from UDPGA and adds it to drug

Answer 13

Question 14

Principles of drug metabolism

Certain drug-metabolizing enzymes’ expression can be upregulated, leading to increased metabolism of drugs
* Enzyme inducing drugs such as ___ activates transcription factor ___, leading to upregulation of enzyme CYP3A4

Answer 14

rifampin, PXR

decreased exposure to enzyme substrates

Question 15

Principles of drug metabolism

Drug-metabolizing enzymes’ activities can be inhibited by drugs
* ___ inhibits CYP3A4

Answer 15

ketoconazole

leading to increased substrate drug exposure

Question 16

Principles of drug metabolism

Gut microbiota mediates certain drug metabolism, mainly ___ and ___

Answer 16

reduction and hydrolysis

Question 17

“Double peak phenomenon” is often caused by ___ cycling of drugs and metabolites

Answer 17

enterohepatic

Question 18

Kupffer cells are the primary cells in the liver responsible for drug metabolism.

Answer 18

False; hepatocytes

Question 19

Choose two main (most common) drug metabolism reactions in the liver.

Answer 19

oxidation and conjugation

Question 20

T or F: Among cytochrome P450 enzymes, CYP3A4 metabolizes the largest fraction of drugs.

Answer 20

true

Question 21

T or F: The Portal triad comprises the bile duct, portal vein, and central vein.

Answer 21

False; Hepatic artery (not central vein)

Question 22

T or F: Enzyme inducers of CYP3A4 would likely decrease the systemic
exposure of CYP3A4 substrates.

Answer 22

true

Question 23

T or F: Enzyme inhibitors of CYP3A4 would likely increase the systemic
exposure of CYP3A4 substrates.

Answer 23

true