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Pharm 4

front 1

Substances absorbed across the lungs or skin, or ingested in food, drink, therapeutic drugs, or recreational drugs, are called:

A) Autacoids

B) Xenobiotics

C) Eicosanoids

D) Cofactors

back 1

B. Xenobiotics

front 2

A drug’s biologic activity may be terminated or altered by which alternative process after absorption?

A) Filtration

B) Sequestration

C) Metabolism

D) Diffusion

back 2

C. Metabolism

front 3

Lipophilic xenobiotics are generally transformed into products that are more:

A) Volatile

B) Polar

C) Protein-bound

D) Lipophilic

back 3

B. Polar

front 4

Biotransformation of lipophilic xenobiotics usually improves their:

A) Tissue storage

B) Renal excretion

C) Protein binding

D) Membrane retention

back 4

B. Renal excretion

front 5

Some biotransformation reactions can produce metabolites with what unexpected effect?

A) Enhanced activity

B) Reduced absorption

C) Less polarity

D) Impaired distribution

back 5

A. Enhanced activity

front 6

Some drug biotransformations are clinically important because they can generate:

A) Inert proteins

B) Toxic products

C) Bile salts

D) Digestive enzymes

back 6

B. Toxic products

front 7

Metabolic biotransformations usually occur between drug absorption into the circulation and which final process?

A) Hepatic uptake

B) Renal elimination

C) Gut secretion

D) Plasma binding

back 7

B. Renal elimination

front 8

Which phase usually introduces or unmasks a functional group on the parent drug?

A) Phase I

B) Phase II

C) Phase III

D) Enterohepatic cycling

back 8

A. Phase I

front 9

Phase I reactions usually convert the parent drug into a metabolite that is more:

A) Acidic

B) Polar

C) Reduced

D) Lipophilic

back 9

B. Polar

front 10

A drug undergoes oxidation that unmasks a hydroxyl group before conjugation. This first reaction is best classified as:

A) Phase II metabolism

B) Phase I reaction

C) Renal elimination

D) Microsomal storage

back 10

B. Phase I reaction

front 11

Which metabolic phase combines an endogenous substrate with a functional group to form a polar conjugate?

A) Phase I

B) Phase II

C) Phase III

D) Phase IV

back 11

B. Phase II

front 12

The major functional result of many phase II reactions is formation of a highly:

A) Lipophilic conjugate

B) Volatile compound

C) Polar conjugate

D) Reactive radical

back 12

C. Polar conjugate

front 13

Although often taught as sequential, phase II reactions may sometimes occur when relative to phase I reactions?

A) Always after

B) Never independently

C) Before phase I

D) Only after excretion

back 13

C. Before phase I

front 14

The principal organ responsible for drug metabolism is the:

A) Kidney

B) Liver

C) Spleen

D) Lung

back 14

B. Liver

front 15

The lower gut can metabolize drugs partly because it contains intestinal:

A) Hepatocytes

B) Microorganisms

C) Kupffer cells

D) Goblet cells

back 15

B. Microorganisms

front 16

Besides lower-gut microorganisms, which gut factor can directly metabolize some drugs?

A) Gastric acid

B) Bile pigments

C) Portal albumin

D) Splenic enzymes

back 16

A. Gastric acid

front 17

Drug metabolism in the gut can also be mediated by digestive enzymes and enzymes in the:

A) Colonic lumen

B) Intestinal wall

C) Portal vein

D) Pancreatic duct

back 17

B. Intestinal wall

front 18

Many drug-metabolizing enzymes are located in which cellular structure?

A) Nuclear pores

B) Lipophilic ER membrane

C) Lysosomal lumen

D) Mitochondrial matrix

back 18

B. Lipophilic ER membrane

front 19

The endoplasmic reticulum location of many drug-metabolizing enzymes is important because many substrates are:

A) Hydrophilic

B) Lipophilic

C) Ionic

D) Proteinaceous

back 19

B. Lipophilic

front 20

After cell fractionation, which structures retain many morphologic and functional features of intact ER membranes?

A) Ribosomes

B) Microsomes

C) Lysosomes

D) Peroxisomes

back 20

B. Microsomes

front 21

Smooth microsomes contain which important class of drug-metabolizing enzymes?

A) Monooxygenases

B) Hydrolases

C) Kinases

D) Transferases

back 21

A. Monooxygenases

front 22

Microsomal monooxygenase activity requires NADPH as a reducing agent and molecular:

A) Nitrogen

B) Carbon dioxide

C) Oxygen

D) Hydrogen

back 22

C. Oxygen

front 23

Which pair participates in microsomal oxidation-reduction drug metabolism?

A) NADH and catalase

B) Glutathione and transferase

C) Aldehyde and dehydrogenase

D) P450 reductase and P450

back 23

D. P450 reductase and P450

front 24

Cytochrome P450 oxidations depend on electron transfer from which enzyme?

A) NADPH P450 oxidoreductase

B) Alcohol dehydrogenase

C) Xanthine oxidase

D) Thiopurine methyltransferase

back 24

A. NADPH P450 oxidoreductase

front 25

Which molecule binds reduced cytochrome P450 to produce its characteristic 450-nm absorbance?

A) Nitric oxide

B) Carbon monoxide

C) Molecular oxygen

D) Carbon dioxide

back 25

B. Carbon monoxide

front 26

P450 enzymes are relatively sluggish catalysts, so their biotransformation reactions are generally:

A) Rapid

B) Irreversible

C) Slow

D) Nonenzymatic

back 26

C. Slow

front 27

Compared with many phase II reactions, P450-catalyzed reactions are generally:

A) Slower

B) Faster

C) Nonenzymatic

D) Conjugative

back 27

A. Slower

front 28

Which cytochrome P450 isoform metabolizes over half of liver-metabolized prescription drugs?

A) CYP2D6

B) CYP2E1

C) CYP1A2

D) CYP3A4

back 28

D. CYP3A4

front 29

Which external category can induce P450 enzyme expression?

A) Environmental chemicals

B) Plasma proteins

C) Bile acids

D) Renal solutes

back 29

A. Environmental chemicals

front 30

Environmental chemicals and pollutants can alter drug metabolism mainly by inducing:

A) Albumin synthesis

B) P450 enzymes

C) Renal filtration

D) Bile secretion

back 30

B. P450 enzymes

front 31

After ligand binding, PXR, CAR, and PPAR-alpha induce P450 genes by forming:

A) Homodimers

B) Heterodimers

C) Monomers

D) Tetramers

back 31

B. Heterodimers

front 32

PXR, CAR, and PPAR-alpha are best described as ligand-regulated receptors that affect:

A) P450 gene expression

B) Ribosomal assembly

C) Lysosomal acidification

D) Albumin filtration

back 32

A. P450 gene expression

front 33

Which drug class binds tightly to P450 heme iron and competitively inhibits endogenous substrate metabolism?

A) Beta-lactams

B) Imidazole drugs

C) Loop diuretics

D) Bile resins

back 33

B. Imidazole drugs

front 34

Macrolide antibiotics can be metabolized into complexes that render cytochrome P450 catalytically:

A) Induced

B) Inactive

C) Soluble

D) Excreted

back 34

B. Inactive

front 35

Inactivators that attack the heme or protein portion of cytochrome P450 are called:

A) Competitive blockers

B) Suicide inhibitors

C) Allosteric activators

D) Phase II cofactors

back 35

B. Suicide inhibitors

front 36

A compound irreversibly damages the protein moiety of a P450 enzyme during metabolism. This compound is best classified as a:

A) Suicide inhibitor

B) Reducing agent

C) Response element

D) Polar conjugate

back 36

A. Suicide inhibitor

front 37

Phase II reactions usually accelerate drug biotransformation because they are generally faster than:

A) Gastric hydrolysis

B) P450 reactions

C) Renal filtration

D) Plasma diffusion

back 37

B. P450 reactions

front 38

At therapeutic doses, acetaminophen is mainly cleared through glucuronidation and:

A) Oxidation

B) Sulfation

C) Reduction

D) Hydrolysis

back 38

B. Sulfation

front 39

When acetaminophen intake exceeds therapeutic doses, glucuronidation and sulfation pathways become:

A) Induced

B) Saturated

C) Deleted

D) Inactivated

back 39

B. Saturated

front 40

Acetaminophen overdose becomes dangerous partly because saturation of conjugation pathways increases reliance on:

A) P450 metabolism

B) Bile acid transport

C) Albumin binding

D) Digestive enzymes

back 40

A. P450 metabolism

front 41

After acetaminophen overdose, which treatment protects against fulminant hepatotoxicity and death?

A) N-acetylcysteine

B) Vitamin K

C) Deferoxamine

D) Fomepizole

back 41

A. N-acetylcysteine

front 42

A population has a variant allele frequency above 1% that changes gene expression or function. This is called:

A) Epigenetic silencing

B) Drug tolerance

C) Genetic polymorphism

D) Enzyme induction

back 42

C. Genetic polymorphism

front 43

Genetic polymorphisms in phase I enzymes can alter which drug property?

A) Protein synthesis

B) Bile production

C) Pharmacokinetics

D) Gastric emptying

back 43

C. Pharmacokinetics

front 44

Polymorphisms in phase I metabolism can change pharmacokinetics and the magnitude or duration of:

A) Bile flow

B) Drug response

C) Albumin binding

D) Renal perfusion

back 44

B. Drug response

front 45

Patients with CYP2C9*3 have much lower tolerance for which drug?

A) Digoxin

B) Warfarin

C) Nicotine

D) Mephenytoin

back 45

B. Warfarin

front 46

CYP3A5 polymorphism is known to result from what type of intron 3 change?

A) Frameshift deletion

B) Promoter methylation

C) Single nucleotide polymorphism

D) Trinucleotide expansion

back 46

C. Single nucleotide polymorphism

front 47

The CYP2A6 gene is especially responsible for oxidation of which substance?

A) Warfarin

B) Digoxin

C) Nicotine

D) Mephenytoin

back 47

C. Nicotine

front 48

Tobacco smokers with low CYP2A6 activity tend to consume:

A) More tobacco

B) Less tobacco

C) Equal tobacco

D) No tobacco

back 48

B. Less tobacco

front 49

Low CYP2A6 activity in smokers is associated with a lower incidence of:

A) Colon cancer

B) Liver failure

C) Lung cancer

D) Renal cancer

back 49

C. Lung cancer

front 50

Women, particularly Hispanic American women, express what hepatic CYP2B6 protein level compared with men?

A) Lower

B) Absent

C) Equal

D) Higher

back 50

D. Higher

front 51

The slow acetylator phenotype occurs in about what percentage of Black and White Americans?

A) 10%

B) 25%

C) 50%

D) 90%

back 51

C. 50%

front 52

Slow acetylator phenotype is common in Europeans living in which region?

A) High northern latitudes

B) Equatorial coastal regions

C) Low southern latitudes

D) Tropical island regions

back 52

A. High northern latitudes

front 53

The slow acetylator phenotype is inherited as which trait?

A) X-linked dominant

B) Autosomal recessive

C) Autosomal dominant

D) Mitochondrial

back 53

B. Autosomal recessive

front 54

Besides host genetics, what plays a significant role in drug responses?

A) Human gut microbiome

B) Pulmonary surfactant

C) Bone marrow reserve

D) Plasma sodium

back 54

A. Human gut microbiome

front 55

Co-treatment of certain antibiotics with digoxin can raise serum digoxin by about:

A) Two-fold

B) Four-fold

C) Ten-fold

D) Twenty-fold

back 55

A. Two-fold

front 56

Antibiotic-induced increases in serum digoxin raise the risk of which toxicity?

A) Nephrotoxicity

B) Cardiotoxicity

C) Ototoxicity

D) Hepatotoxicity

back 56

B. Cardiotoxicity

front 57

Cigarette smokers metabolize some drugs faster than nonsmokers primarily because of:

A) Renal filtration

B) Enzyme induction

C) Protein displacement

D) Gastric emptying

back 57

B. Enzyme induction

front 58

Residual drug at an active site may inhibit metabolism of another simultaneous drug by what mechanism?

A) Allosteric activation

B) Irreversible binding

C) Competitive inhibition

D) Gene induction

back 58

C. Competitive inhibition

front 59

Patients routinely ingesting certain antipsychotics or barbiturates may require what warfarin dose adjustment?

A) Lower doses

B) No doses

C) Higher doses

D) Alternate-day doses

back 59

C. Higher doses

front 60

A chronic barbiturate user starts warfarin and needs a higher dose. The best explanation is:

A) Enzyme induction

B) Phase II blockade

C) Renal failure

D) Gut sterilization

back 60

A. Enzyme induction

front 61

Which over-the-counter herbal medicine for depression causes many drug-drug interactions?

A) Kava

B) St. John’s wort

C) Valerian root

D) Ginkgo biloba

back 61

B. St. John’s wort

front 62

St. John’s wort is commonly taken as an herbal treatment for:

A) Hypertension

B) Depression

C) Constipation

D) Insomnia

back 62

B. Depression

front 63

An inducer may enhance metabolism of other drugs and also its:

A) Own metabolism

B) Renal secretion

C) Protein binding

D) Receptor affinity

back 63

A. Own metabolism

front 64

Progressively reduced therapeutic effectiveness from enhanced metabolism of the same drug is called:

A) Dependence

B) Resistance

C) Tolerance

D) Withdrawal

back 64

C. Tolerance

front 65

Which substance is a CYP3A4 substrate inhibitor?

A) Rifampin

B) Ketoconazole

C) Phenobarbital

D) Carbamazepine

back 65

B. Ketoconazole

front 66

Which antibiotic is a CYP3A4 substrate inhibitor?

A) Erythromycin

B) Penicillin

C) Cefazolin

D) Vancomycin

back 66

A. Erythromycin

front 67

Which dietary exposure can inhibit CYP3A4 substrates?

A) Cranberry juice

B) Grapefruit juice

C) Orange juice

D) Apple juice

back 67

B. Grapefruit juice

front 68

Liver disease and pulmonary disease may affect which pharmacologic process?

A) Drug metabolism

B) Drug ingestion

C) Drug formulation

D) Drug packaging

back 68

A. Drug metabolism

front 69

Viral infection, bacterial infection, cancer, and inflammation can impair drug metabolism by affecting:

A) P450s

B) Ribosomes

C) Hemoglobin

D) Aquaporins

back 69

A. P450s

front 70

Inflammatory mediators, cytokines, and nitric oxide impair drug metabolism partly by doing what to P450s?

A) Activating transcription

B) Inactivating enzymes

C) Enhancing absorption

D) Increasing secretion

back 70

B. Inactivating enzymes

front 71

Inflammation can impair P450-mediated metabolism by inactivating P450s and enhancing their:

A) Translation

B) Degradation

C) Conjugation

D) Excretion

back 71

B. Degradation

front 72

Pharmacologically active organic molecules tend to have which property at physiologic pH?

A) Fully ionized

B) Lipophilic

C) Proteinaceous

D) Highly polar

back 72

B. Lipophilic

front 73

At physiologic pH, many pharmacologically active organic molecules remain unionized or:

A) Fully oxidized

B) Fully conjugated

C) Partially ionized

D) Irreversibly bound

back 73

C. Partially ionized

front 74

After oral administration, many drugs are absorbed from the small intestine and carried through the portal system to the liver for extensive metabolism before systemic circulation. This is called:

A) First-pass effect

B) Renal clearance

C) Phase II conjugation

D) Enterohepatic recycling

back 74

A. First-pass effect

front 75

Intestinal metabolism can contribute to first-pass elimination, and patients with impaired liver function may rely more on which site for drug elimination?

A) Renal tubules

B) Pulmonary alveoli

C) Intestinal metabolism

D) Splenic macrophages

back 75

C. Intestinal metabolism

front 76

Microsomes retain rough and smooth ER features. Which microsomes are relatively rich in enzymes responsible for oxidative drug metabolism?

A) Rough microsomes

B) Smooth microsomes

C) Ribosomal microsomes

D) Nuclear microsomes

back 76

B. Smooth microsomes

front 77

In a typical microsomal monooxygenase reaction, one oxygen atom enters the drug product while the other oxygen atom becomes:

A) Water

B) Carbon monoxide

C) Carbon dioxide

D) Hydrogen peroxide

back 77

A. Water

front 78

Which two microsomal enzymes are central to the mixed-function oxidase system

A) Catalase and peroxidase

B) Glucuronidase and sulfatase

C) Dehydrogenase and reductase

D) P450 reductase and P450

back 78

D. P450 reductase and P450

front 79

In the microsomal mixed-function oxidase system, NADPH donates electrons through which flavoprotein enzyme?

A) Cytochrome b5

B) P450 reductase

C) Alcohol dehydrogenase

D) Glutathione reductase

back 79

B. P450 reductase

front 80

In the microsomal drug oxidation system, which step is rate-limiting for hepatic drug oxidations?

A) Drug binding to P450

B) Oxygen release from water

C) P450 heme reduction

D) Product diffusion away

back 80

C. P450 heme reduction

front 81

Which set contains the four required components for microsomal drug oxidation?

A) P450, reductase, NADPH, oxygen

B) P450, glucuronide, ATP, oxygen

C) NADH, transferase, sulfate, oxygen

D) CYP3A4, albumin, ATP, water

back 81

A. P450, reductase, NADPH, oxygen

front 82

In the first major step of microsomal drug oxidation, oxidized Fe3+ P450 does what?

A) Releases oxidized product

B) Forms water immediately

C) Combines with drug substrate

D) Conjugates with glucuronide

back 82

C. Combines with drug substrate

front 83

During microsomal drug oxidation, a second electron from NADPH via P450 reductase reduces oxygen, producing what intermediate?

A) Polar conjugate

B) Free drug radical

C) Inactive heme complex

D) Activated oxygen complex

back 83

D. Activated oxygen complex

front 84

The microsomal oxidase system can oxidize many unrelated substrates because substrate specificity is very low; the main shared substrate feature is:

A) High water solubility

B) High lipid solubility

C) Strong protein binding

D) Complete ionization

back 84

B. High lipid solubility

front 85

Which enzyme family catalyzes the bulk of hepatic drug and xenobiotic metabolism, including isoforms such as CYP1A2, CYP2C9, and CYP3A4?

A) UDP transferases

B) P450 isoforms

C) Sulfotransferases

D) Alcohol dehydrogenases

back 85

B. P450 isoforms

front 86

In drug metabolism terminology, the abbreviation CYP refers to which hepatic xenobiotic-metabolizing enzyme family?

A) Cytochrome P450

B) Cytosolic phosphatase

C) Conjugated pyridoxal

D) Carbamoyl phosphate

back 86

A. Cytochrome P450

front 87

A drug repeatedly administered to a patient induces its own P450 metabolism. What is the expected effect on substrate metabolism and pharmacologic action?

A) Decreased metabolism, increased action

B) Increased metabolism, decreased action

C) Increased metabolism, increased action

D) Decreased metabolism, decreased action

back 87

B. Increased metabolism, decreased action

If a drug induces its own P450 metabolism, it makes the liver better at breaking down that same drug over time.

front 88

For increased P450 synthesis during enzyme induction, what cellular processes must increase?

A) Transcription, translation, heme synthesis

B) Translation, excretion, bile secretion

C) Degradation, oxidation, conjugation

D) Filtration, secretion, reabsorption

back 88

A. Transcription, translation, heme synthesis

front 89

In P450 induction, increased synthesis of heme is important because heme functions as the enzyme’s:

A) Competitive inhibitor

B) Endogenous substrate

C) Prosthetic cofactor

D) Nuclear receptor

back 89

C. Prosthetic cofactor

front 90

Cruciferous vegetables and omeprazole induce CYP1A through a cytoplasmic receptor for polycyclic aromatic hydrocarbons called:

A) CAR

B) PXR

C) AhR

D) RXR

back 90

C. AhR

front 91

During CYP1A induction, the inducer-AhR complex translocates into the nucleus and dimerizes with which nuclear protein?

A) Arnt

B) RXR

C) PAPS

D) POR

back 91

A. Arnt

front 92

After AhR-Arnt dimerization in CYP1A induction, the complex activates regulatory genes for which P450 isoform family?

A) CYP2B

B) CYP1A

C) CYP3A

D) CYP2C

back 92

B. CYP1A

front 93

Pregnane X receptor, a steroid-retinoid-thyroid receptor family member, mediates induction of which P450 isoform family?

A) CYP1A

B) CYP2A6

C) CYP3A

D) CYP2D6

back 93

C. CYP3A

front 94

PPAR-alpha is highly expressed in the liver and kidneys and uses which type of drugs as ligands?

A) Lipid-lowering drugs

B) Beta-lactam antibiotics

C) Opioid analgesics

D) H2 blockers

back 94

A. Lipid-lowering drugs

front 95

A PPAR-alpha ligand induces P450 gene expression by forming a heterodimer with which nuclear receptor?

A) AhR

B) Arnt

C) RXR

D) PAPS

back 95

C. RXR

front 96

P450 enzymes can be increased when a drug/substrate makes the enzyme more stable. What does this mean?

A) The enzyme gets broken down faster
B) The enzyme gets broken down slower
C) The enzyme is blocked by competition
D) The enzyme is permanently destroyed

back 96

B) The enzyme gets broken down slower

front 97

How do imidazole-containing drugs inhibit P450-mediated metabolism of endogenous substrates and drugs?

A) Bind P450 heme iron

B) Deplete sulfate donors

C) Destroy UGT genes

D) Activate CAR receptors

back 97

A. Bind P450 heme iron

front 98

Substrates that irreversibly inhibit P450s through reactive intermediates attacking apoprotein or heme moieties are called:

A) Substrate stabilizers

B) Suicide inhibitors

C) Nuclear ligands

D) Polar conjugates

back 98

B. Suicide inhibitors

front 99

Phase I metabolites often undergo conjugation with endogenous substances to form polar, readily excreted, usually inactive products called:

A) Drug conjugates

B) Free radicals

C) Active intermediates

D) Lipid stores

back 99

A. Drug conjugates

front 100

Which glutathione transferases are involved in metabolism of drugs/xenobiotics and leukotrienes/prostaglandins, respectively?

A) NAT1 and NAT2

B) Cytosolic and microsomal GSH transferases

C) UGT and SULT enzymes

D) Methyltransferase and epoxide hydrolase

back 100

B. Cytosolic and microsomal GSH transferases

front 101

N-acetyltransferases most directly catalyze metabolism of substrates containing which chemical moiety?

A) Sulfate ester or hydrazine

B) Epoxide ring or hydrazine

C) Steroid nucleus or hydrazine

D) Aromatic amine or hydrazine

back 101

D. Aromatic amine or hydrazine

front 102

N-acetyltransferases are encoded primarily by which two genes?

A) NAT1 and NAT2

B) CYP1A2 and CYP3A4

C) UGT1 and UGT2

D) SULT1 and SULT2

back 102

A. NAT1 and NAT2

front 103

N-acetyltransferases use which endogenous cofactor during acetylation reactions?

A) NADPH

B) PAPS

C) Acetyl-CoA

D) SAMe

back 103

C. Acetyl-CoA

front 104

SAMe-mediated xenobiotic metabolism can include which methylation reactions?

A) O-, N-, and S-methylation

B) N-, P-, and C-methylation

C) O-, C-, and P-methylation

D) S-, P-, and C-methylation

back 104

A. O-, N-, and S-methylation

front 105

A P450-catalyzed oxidation generates a reactive epoxide from a xenobiotic. Which enzyme class hydrolyzes this epoxide?

A) Sulfotransferases

B) Glutathione transferases

C) N-acetyltransferases

D) Epoxide hydrolases

back 105

D. Epoxide hydrolases

front 106

Epoxide hydrolases are important because they hydrolyze epoxides generated by which process?

A) P450-catalyzed oxidations

B) UGT-mediated conjugations

C) NAT-mediated acetylations

D) SAMe-mediated methylations

back 106

A. P450-catalyzed oxidations

front 107

Which factor plays a critical role in regulation of drug conjugation reactions?

A) Pulmonary pressure

B) Nutrition and diet

C) Gastric motility

D) Splenic filtration

back 107

B. Nutrition and diet

front 108

Acetaminophen is normally metabolized by glucuronidation, sulfation, and which third pathway?

A) P450-dependent GSH conjugation

B) NAT-dependent acetylation

C) SAMe-dependent methylation

D) Epoxide hydrolase cleavage

back 108

A. P450-dependent GSH conjugation

front 109

In acetaminophen overdose, hepatic injury begins because hepatic GSH is:

A) Overproduced rapidly

B) Converted to sulfate

C) Depleted faster than regenerated

D) Secreted into bile

back 109

C. Depleted faster than regenerated

front 110

The toxic reactive metabolite that accumulates during acetaminophen overdose is best known as:

A) Acetyl-CoA

B) NAPQI

C) PAPS

D) SAMe

back 110

B. NAPQI

front 111

NAPQI directly injures hepatocytes by reacting with nucleophilic groups on which target?

A) Cellular proteins

B) Plasma albumin

C) Bile acids

D) Ribosomal RNA

back 111

A. Cellular proteins

front 112

Acetaminophen-induced hepatotoxicity involves direct hepatocellular damage and generation of:

A) Nitric oxide

B) Bile salts

C) Reactive oxygen species

D) Acetyl-CoA

back 112

C. Reactive oxygen species

front 113

Defects in phase I oxidative metabolism are commonly inherited as which type of trait?

A) X-linked dominant

B) Autosomal dominant

C) Mitochondrial

D) Autosomal recessive

back 113

D. Autosomal recessive

front 114

Which group of six liver CYPs accounts for about 75% of clinically relevant drug metabolism?

A) 3A4, 2C9, 2D6, 2C19, 1A2, 2B6

B) 2A6, 2E1, 4A, 1B1, 2J2, 3A5

C) 1A1, 2F1, 2S1, 3A7, 4F2, 11A1

D) 2R1, 2U1, 4B1, 8B1, 17A1, 21A2

back 114

A. 3A4, 2C9, 2D6, 2C19, 1A2, 2B6

front 115

Polymorphisms in CYP3A4, CYP2C9, CYP2D6, CYP2C19, CYP1A2, and CYP2B6 significantly influence which process?

A) Phase II conjugation

B) Phase I drug metabolism

C) Renal tubular secretion

D) Gastric drug absorption

back 115

B. Phase I drug metabolism

front 116

Debrisoquin-sparteine oxidation polymorphism is inherited in which pattern?

A) Autosomal recessive

B) Autosomal dominant

C) X-linked recessive

D) Mitochondrial

back 116

A. Autosomal recessive

front 117

Debrisoquin-sparteine oxidation polymorphism involves impaired oxidations dependent on which CYP enzyme?

A) CYP3A4

B) CYP2C19

C) CYP2D6

D) CYP1A2

back 117

C. CYP2D6

front 118

Which CYP2C19 allele variant is associated with increased CYP2C19 activity?

A) CYP2C19*2

B) CYP2C19*3

C) CYP2C19*17

D) CYP2C19*5

back 118

C. CYP2C19*17

front 119

CYP2C19*17 is associated with higher prodrug activation and which clinical risk?

A) Increased bleeding risk

B) Severe nicotine dependence

C) Lower acetaminophen toxicity

D) Reduced P450 transcription

back 119

A. Increased bleeding risk

front 120

CYP3A5 variation is due to a single nucleotide polymorphism in intron 3 that alters:

A) Heme synthesis

B) Splicing

C) Sulfation

D) Acetylation

back 120

B. Splicing

front 121

Trimethylamine oxidation polymorphism causes “fish odor syndrome” in slow metabolizers because trimethylamine is largely metabolized by which enzyme?

A) Butyrylcholinesterase

B) Flavin monooxygenase

C) Thiopurine methyltransferase

D) Beta-glucuronidase

back 121

B. Flavin monooxygenase

front 122

“Fish odor syndrome” suggests genetic variants can affect oxidative drug metabolism through non-P450 enzymes such as:

A) Ziegler’s enzyme

B) CYP3A4

C) CYP1A2

D) NAT2

back 122

A. Ziegler’s enzyme

front 123

A patient has prolonged paralysis after succinylcholine. Genetic deficiency of which enzyme most likely explains slower succinylcholine metabolism?

A) CYP3A4

B) NAT2

C) Butyrylcholinesterase

D) Beta-glucuronidase

back 123

C. Butyrylcholinesterase

front 124

Succinylcholine is clinically used primarily as which type of drug?

A) Anticoagulant

B) Muscle relaxant

C) Antidepressant

D) Antifungal

back 124

B. Muscle relaxant

front 125

Patients with butyrylcholinesterase deficiency metabolize succinylcholine slowly and are especially susceptible to:

A) Severe hepatotoxicity

B) Respiratory paralysis

C) Bladder cancer

D) Peripheral neuritis

back 125

B. Respiratory paralysis

front 126

Which phenotype is associated with higher isoniazid-induced peripheral neuritis risk?

A) Ultrarapid metabolizer

B) Fast acetylator

C) Slow acetylator

D) CYP3A5 expresser

back 126

C. Slow acetylator

front 127

A patient takes isoniazid and gets nerve problems, like tingling or numbness, plus autoimmune-like side effects. Which type of drug-metabolism patient is this most likely?

A) Slow acetylator
B) CYP3A4 inducer
C) TPMT overexpresser
D) Fast flavin monooxygenase metabolizer

back 127

A. Slow acetylator

front 128

Lack of S-methylation of aromatic sulfhydryl compounds is caused by polymorphism of which gene?

A) BCHE

B) TPMT

C) CYP1A

D) NAT1

back 128

B. TPMT

front 129

TPMT gene polymorphism increases risk of fatal hematopoietic toxicity from which drug class?

A) Thiopurines

B) Macrolides

C) Barbiturates

D) Antipsychotics

back 129

A. Thiopurines

front 130

The human gut microbiome can significantly influence drug response because gut microflora can:

A) Biotransform drugs

B) Synthesize heme

C) Destroy P450 genes

D) Block filtration

back 130

A. Biotransform drugs

front 131

Drugs glucuronidated in the liver may enter bile and reach the gut, where microbial enzymes remove glucuronide groups. Which enzymes do this?

A) Beta-glucuronidases

B) Flavin monooxygenases

C) N-acetyltransferases

D) Butyrylcholinesterases

back 131

A. Beta-glucuronidases

front 132

Gut microbial beta-glucuronidases are best classified as which enzyme type?

A) Oxidases

B) Hydrolases

C) Ligases

D) Reductases

back 132

B. Hydrolases

front 133

After gut de-glucuronidation, the pharmacologically active parent aglycone may be reabsorbed into which circulation?

A) Portal circulation

B) Pulmonary circulation

C) Coronary circulation

D) Lymphatic circulation

back 133

A. Portal circulation

front 134

Reabsorption of active aglycone after gut de-glucuronidation can extend drug action through:

A) Renal filtration

B) Enterohepatic recycling

C) Pulmonary diffusion

D) Splenic sequestration

back 134

B. Enterohepatic recycling

front 135

If a drug keeps getting recycled between the liver, bile, intestine, and back into the blood, the body is exposed to the drug for longer. If that drug is already close to the toxic range, what can happen?

A) More toxicity
B) Less absorption
C) Faster drug removal
D) Loss of an enzyme

back 135

A) More toxicity

front 136

Charcoal-broiled foods and cruciferous vegetables induce which enzyme family?

A) CYP3A

B) CYP2D6

C) CYP1A

D) CYP2C19

back 136

C. CYP1A

front 137

St. John’s wort is used for depression and induces CYP3A4, with lesser induction of which enzymes?

A) CYP2C9 and CYP2C19

B) CYP1A2 and CYP2D6

C) CYP2A6 and CYP2E1

D) CYP3A5 and CYP2B6

back 137

A. CYP2C9 and CYP2C19

front 138

Simultaneous administration of two or more drugs can impair elimination of the more slowly metabolized drug and prolong its:

A) Pharmacologic effects

B) Gastric absorption

C) Protein synthesis

D) Renal uptake

back 138

A. Pharmacologic effects

front 139

Furanocoumarins in grapefruit juice irreversibly inactivate which P450 isoform in intestinal mucosa?

A) CYP1A2

B) CYP2D6

C) CYP3A4

D) CYP2C9

back 139

C. CYP3A4

front 140

Grapefruit furanocoumarins enhance proteolytic degradation of intestinal CYP3A4, thereby impairing which process?

A) First-pass effect

B) Renal clearance

C) Biliary secretion

D) Gastric motility

back 140

A. First-pass effect

front 141

Impairment of intestinal first-pass metabolism by grapefruit juice tends to increase oral drug:

A) Ionization

B) Bioavailability

C) Protein synthesis

D) Glucuronidation

back 141

B. Bioavailability

front 142

Cardiac disease can alter drug metabolism primarily by affecting physiologic delivery and function of metabolizing organs, so it belongs among diseases that affect:

A) Drug metabolism

B) Drug formulation

C) Drug naming

D) Drug packaging

back 142

A. Drug metabolism

front 143

Which exposure is listed among common disease-related causes of altered drug metabolism?

A) Heavy metal poisoning

B) Lactose intolerance

C) Seasonal allergy

D) Iron deficiency

back 143

A. Heavy metal poisoning

front 144

Endocrine dysfunction can alter drug handling because it is one of the conditions that affects:

A) Drug metabolism

B) Drug taste

C) Capsule dissolution

D) Tablet coating

back 144

A. Drug metabolism

front 145

Inflammatory mediators, cytokines, and nitric oxide impair drug metabolism mainly by inactivating:

A) P450s

B) Albumin

C) Hemoglobin

D) Aquaporins

back 145

A. P450s

front 146

Drug metabolism in humans usually results in a product
that is
(A) Less lipid soluble than the original drug
(B) More likely to distribute intracellularly
(C) More likely to be reabsorbed by kidney tubules
(D) More lipid soluble than the original drug
(E) Less water soluble than the original drug

back 146

(A) Less lipid soluble than the original drug

Most drug metabolism happens in the liver and is meant to make drugs easier to eliminate. The body usually converts lipid-soluble drugs into more water-soluble (polar) metabolites so they can be excreted in urine or bile.

front 147

If therapy with multiple drugs causes induction of drug
metabolism in your depressed patient, it will
(A) Be associated with increased smooth endoplasmic reticulum
(B) Be associated with increased rough endoplasmic reticulum
(C) Be associated with decreased enzymes in the soluble
cytoplasmic fraction
(D) Require 3–4 months to reach completion

back 147

(A) Be associated with increased smooth endoplasmic reticulum

front 148

Which of the following factors is likely to increase the duration of action of a drug that is metabolized by CYP3A4 in the
liver?
(A) Chronic administration of rifampin during therapy with
the drug in question
(B) Chronic therapy with amiodarone
(C) Displacement from tissue-binding sites by another drug
(D) Increased cardiac output
(E) Chronic administration of carbamazepin

back 148

(B) Chronic therapy with amiodarone

Amiodarone is recognized as an inhibitor of
P450. Rifampin and carbamazepine can induce drug-metabolizing enzymes and thereby may reduce the duration of drug action.

front 149

Which of the following agents, when used in combination
with other anti-HIV drugs, permits dose reductions?
(E) Quinidine
(F) Ritonavir
(G) Succinylcholine
(H) Verapamil

back 149

(F) Ritonavir

Ritonavir inhibits hepatic drug metabolism, and its use at low
doses in combination regimens has permitted dose reductions of other HIV protease inhibitors (eg, indinavir).

front 150

Which of the following drugs may inhibit the hepatic microsomal P450 responsible for warfarin metabolism?
(A) Amiodarone
(B) Ethanol
(C) Phenobarbital
(D) Procainamide
(E) Rifampin

back 150

(A) Amiodarone

Amiodarone is an important antiarrhythmic drug and has a
well-documented ability to inhibit the hepatic metabolism of
many drugs. The answer is A.

front 151

Which of the following drugs, if used chronically, is most
likely to increase the toxicity of acetaminophen?
(A) Cimetidine
(B) Ethanol
(C) Ketoconazole
(D) Procainamide

back 151

(B) Ethanol

front 152

Which of the following drugs has higher first-pass metabolism in men than in women?
(A) Cimetidine
(B) Ethanol
(C) Ketoconazole
(D) Procainamide

back 152

(B) Ethanol

front 153

Which of the following drugs is an established inhibitor of
P-glycoprotein (P-gp) drug transporters?
(E) Quinidine
(F) Ritonavir
(G) Succinylcholine
(H) Verapamil

back 153

(H) Verapamil