Lecture 5

Question 1

What are the normal metabolic pathways for acetaminophen?

Answer 1

Phase II: glucuronidation and sulfation

Question 2

What happens during an acetaminophen overdose?

Answer 2

Excess shifts metabolism to Phase I (CYP450 enzymes) → toxic intermediates

Question 3

What do toxic intermediates from acetaminophen overdose damage?

Answer 3

Cell membranes & proteins → hepatocyte death

Question 4

How does the body detoxify toxic intermediates from acetaminophen?

Answer 4

Glutathione conjugation (a Phase II pathway)

Question 5

What is a clinical point regarding glutathione in acetaminophen metabolism?

Answer 5

Glutathione is limited—once depleted, liver injury occurs

Question 6

What medication replenishes glutathione in acetaminophen overdose?

Answer 6

N-acetylcysteine (NAC)

Question 7

What does the FDA database list regarding pharmacogenomics?

Answer 7

Drugs with required or recommended pharmacogenomic testing

Question 8

Which drugs are examples of those requiring pharmacogenomic testing?

Answer 8

• Warfarin (CYP2C9, VKORC1 polymorphisms) * Certain statins * Many anticancer and seizure drugs

Question 9

What is the clinical relevance of pharmacogenomic polymorphisms?

Answer 9

Affect drug metabolism (poor vs. ultra-rapid metabolizers)

Question 10

What is a key aspect of ethnic variations in pharmacogenomics?

Answer 10

CYP2C19 alleles in East Asian populations

Question 11

What did traditional classification of breast cancer rely on?

Answer 11

Histology, grade, lymph node involvement

Question 12

What modern classification method is used for breast cancer?

Answer 12

Receptor status (ER, PR, HER2)

Question 13

What type of breast cancer tumors respond to hormone therapy?

Answer 13

ER/PR-positive tumors

Question 14

What is the effectiveness of hormone therapy dependent on?

Answer 14

CYP450 metabolism

Question 15

What characterizes HER2-positive tumors?

Answer 15

Gene amplification → excess HER2 receptors

Question 16

What is the function of trastuzumab (Herceptin)?

Answer 16

Blocks HER2 signaling

Question 17

When is trastuzumab effective?

Answer 17

Only if tumor biopsy confirms HER2 amplification

Question 18

What roles do drug transporters play in the body?

Answer 18

• Absorption * Distribution * Metabolism * Excretion

Question 19

What are the two types of drug transport mechanisms?

Answer 19

• Facilitated diffusion (no energy) * Active transport (ATP-dependent)

Question 20

What are efflux pumps, and what do they do?

Answer 20

ABC transporters that pump drugs/toxins out of cells

Question 21

Which transporter has the broadest specificity?

Answer 21

ABCB1 (P-glycoprotein)

Question 22

What is the role of ABCC transporters?

Answer 22

Mainly anticancer drug transport

Question 23

What does ABCG2 transport?

Answer 23

Breast cancer resistance protein, folate transport

Question 24

What do SLC transporters carry?

Answer 24

Organic anion/cation carriers

Question 25

What is the clinical relevance of overexpression of efflux pumps in tumors?

Answer 25

Multidrug resistance

Question 26

What can transporter inhibitors cause?

Answer 26

Drug interactions

Question 27

What happens to digoxin levels if ABCB1 is inhibited?

Answer 27

Levels ↑ → risk of arrhythmia

Question 28

What is a potential consequence of loperamide abuse?

Answer 28

ABCB1 inhibition can allow opioid effects

Question 29

What is the blood-brain barrier (BBB) composed of?

Answer 29

* Tight junctions * Astrocytes * Pericytes

Question 30

What prevents drug entry into the brain at the BBB?

Answer 30

Active efflux transporters

Question 31

Which types of molecules can cross the BBB?

Answer 31

* Small/lipophilic molecules (O₂, CO₂, ethanol, nicotine) * Large molecules need receptor-mediated endocytosis (e.g., insulin, transferrin)

Question 32

What is a major challenge in therapy related to the BBB?

Answer 32

Getting anticancer drugs across the BBB

Question 33

What does the placental barrier do?

Answer 33

Protects fetus from xenobiotics

Question 34

What essential nutrients does the placental barrier allow?

Answer 34

* Glucose * Amino acids

Question 35

What prevents teratogenicity at the placental barrier?

Answer 35

Many drugs blocked by efflux transporters

Question 36

What is the role of genetic testing in clinical applications?

Answer 36

Guides therapy (personalized medicine)

Question 37

What do drug interactions often involve?

Answer 37

Transporter or enzyme inhibition/induction changes drug levels

Question 38

What is a consequence of efflux pump mutations in tumors?

Answer 38

Treatment failure

Question 39

What study tools are recommended for exam prep?

Answer 39

PowerPoints + FDA resources

Question 40

What type of questions should one expect in exams based on the content?

Answer 40

Higher-level reasoning questions (application, not just recall)

Question 41

What is a key takeaway regarding Tylenol toxicity?

Answer 41

Phase I → toxic metabolites; detox via glutathione

Question 42

How is pharmacogenomics shaping prescribing practices?

Answer 42

Increased requirements/recommendations for testing

Question 43

What are the key factors in breast cancer classification?

Answer 43

* ER * PR * HER2

Question 44

What do transporters regulate in the body?

Answer 44

Drug absorption & resistance

Question 45

What similarities do the BBB and placenta share?

Answer 45

Both are physical + transporter barriers

Question 46

What is the clinical relevance of personalized therapy?

Answer 46

Drug interactions, genetic testing