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

B. Xenobiotics

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

A) Filtration

B) Sequestration

C) Metabolism

D) Diffusion

C. Metabolism

Lipophilic xenobiotics are generally transformed into products that are more:

A) Volatile

B) Polar

C) Protein-bound

D) Lipophilic

B. Polar

Biotransformation of lipophilic xenobiotics usually improves their:

A) Tissue storage

B) Renal excretion

C) Protein binding

D) Membrane retention

B. Renal excretion

Some biotransformation reactions can produce metabolites with what unexpected effect?

A) Enhanced activity

B) Reduced absorption

C) Less polarity

D) Impaired distribution

A. Enhanced activity

Some drug biotransformations are clinically important because they can generate:

A) Inert proteins

B) Toxic products

C) Bile salts

D) Digestive enzymes

B. Toxic products

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

B. Renal elimination

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

A. Phase I

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

A) Acidic

B) Polar

C) Reduced

D) Lipophilic

B. Polar

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

B. Phase I reaction

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

B. Phase II

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

C. Polar conjugate

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

C. Before phase I

The principal organ responsible for drug metabolism is the:

A) Kidney

B) Liver

C) Spleen

D) Lung

B. Liver

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

A) Hepatocytes

B) Microorganisms

C) Kupffer cells

D) Goblet cells

B. Microorganisms

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

A) Gastric acid

B) Bile pigments

C) Portal albumin

D) Splenic enzymes

A. Gastric acid

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

B. Intestinal wall

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

A) Nuclear pores

B) Lipophilic ER membrane

C) Lysosomal lumen

D) Mitochondrial matrix

B. Lipophilic ER membrane

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

A) Hydrophilic

B) Lipophilic

C) Ionic

D) Proteinaceous

B. Lipophilic

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

A) Ribosomes

B) Microsomes

C) Lysosomes

D) Peroxisomes

B. Microsomes

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

A) Monooxygenases

B) Hydrolases

C) Kinases

D) Transferases

A. Monooxygenases

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

A) Nitrogen

B) Carbon dioxide

C) Oxygen

D) Hydrogen

C. Oxygen

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

D. P450 reductase and P450

Cytochrome P450 oxidations depend on electron transfer from which enzyme?

A) NADPH P450 oxidoreductase

B) Alcohol dehydrogenase

C) Xanthine oxidase

D) Thiopurine methyltransferase

A. NADPH P450 oxidoreductase

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

B. Carbon monoxide

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

A) Rapid

B) Irreversible

C) Slow

D) Nonenzymatic

C. Slow

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

A) Slower

B) Faster

C) Nonenzymatic

D) Conjugative

A. Slower

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

A) CYP2D6

B) CYP2E1

C) CYP1A2

D) CYP3A4

D. CYP3A4

Which external category can induce P450 enzyme expression?

A) Environmental chemicals

B) Plasma proteins

C) Bile acids

D) Renal solutes

A. Environmental chemicals

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

A) Albumin synthesis

B) P450 enzymes

C) Renal filtration

D) Bile secretion

B. P450 enzymes

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

A) Homodimers

B) Heterodimers

C) Monomers

D) Tetramers

B. Heterodimers

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

A. P450 gene expression

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

B. Imidazole drugs

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

A) Induced

B) Inactive

C) Soluble

D) Excreted

B. Inactive

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

B. Suicide inhibitors

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

A. Suicide inhibitor

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

B. P450 reactions

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

A) Oxidation

B) Sulfation

C) Reduction

D) Hydrolysis

B. Sulfation

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

A) Induced

B) Saturated

C) Deleted

D) Inactivated

B. Saturated

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

A. P450 metabolism

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

A) N-acetylcysteine

B) Vitamin K

C) Deferoxamine

D) Fomepizole

A. N-acetylcysteine

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

C. Genetic polymorphism

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

A) Protein synthesis

B) Bile production

C) Pharmacokinetics

D) Gastric emptying

C. Pharmacokinetics

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

B. Drug response

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

A) Digoxin

B) Warfarin

C) Nicotine

D) Mephenytoin

B. Warfarin

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

C. Single nucleotide polymorphism

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

A) Warfarin

B) Digoxin

C) Nicotine

D) Mephenytoin

C. Nicotine

Tobacco smokers with low CYP2A6 activity tend to consume:

A) More tobacco

B) Less tobacco

C) Equal tobacco

D) No tobacco

B. Less tobacco

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

A) Colon cancer

B) Liver failure

C) Lung cancer

D) Renal cancer

C. Lung cancer

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

A) Lower

B) Absent

C) Equal

D) Higher

D. Higher

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

A) 10%

B) 25%

C) 50%

D) 90%

C. 50%

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

A. High northern latitudes

The slow acetylator phenotype is inherited as which trait?

A) X-linked dominant

B) Autosomal recessive

C) Autosomal dominant

D) Mitochondrial

B. Autosomal recessive

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

A. Human gut microbiome

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

A. Two-fold

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

A) Nephrotoxicity

B) Cardiotoxicity

C) Ototoxicity

D) Hepatotoxicity

B. Cardiotoxicity

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

A) Renal filtration

B) Enzyme induction

C) Protein displacement

D) Gastric emptying

B. Enzyme induction

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

C. Competitive inhibition

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

C. Higher doses

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

A. Enzyme induction

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

B. St. John’s wort

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

A) Hypertension

B) Depression

C) Constipation

D) Insomnia

B. Depression

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

A) Own metabolism

B) Renal secretion

C) Protein binding

D) Receptor affinity

A. Own metabolism

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

A) Dependence

B) Resistance

C) Tolerance

D) Withdrawal

C. Tolerance

Which substance is a CYP3A4 substrate inhibitor?

A) Rifampin

B) Ketoconazole

C) Phenobarbital

D) Carbamazepine

B. Ketoconazole

Which antibiotic is a CYP3A4 substrate inhibitor?

A) Erythromycin

B) Penicillin

C) Cefazolin

D) Vancomycin

A. Erythromycin

Which dietary exposure can inhibit CYP3A4 substrates?

A) Cranberry juice

B) Grapefruit juice

C) Orange juice

D) Apple juice

B. Grapefruit juice

Liver disease and pulmonary disease may affect which pharmacologic process?

A) Drug metabolism

B) Drug ingestion

C) Drug formulation

D) Drug packaging

A. Drug metabolism

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

A) P450s

B) Ribosomes

C) Hemoglobin

D) Aquaporins

A. P450s

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

B. Inactivating enzymes

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

A) Translation

B) Degradation

C) Conjugation

D) Excretion

B. Degradation

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

A) Fully ionized

B) Lipophilic

C) Proteinaceous

D) Highly polar

B. Lipophilic

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

A) Fully oxidized

B) Fully conjugated

C) Partially ionized

D) Irreversibly bound

C. Partially ionized

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

A. First-pass effect

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

C. Intestinal metabolism

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

B. Smooth microsomes

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

A. Water

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

D. P450 reductase and P450

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

B. P450 reductase

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

C. P450 heme reduction

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

A. P450, reductase, NADPH, oxygen

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

C. Combines with drug substrate

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

D. Activated oxygen complex

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

B. High lipid solubility

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

B. P450 isoforms

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

A. Cytochrome P450

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

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.

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

A. Transcription, translation, heme synthesis

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

C. Prosthetic cofactor

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

A) CAR

B) PXR

C) AhR

D) RXR

C. AhR

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

A. Arnt

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

B. CYP1A

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

C. CYP3A

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

A. Lipid-lowering drugs

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

A) AhR

B) Arnt

C) RXR

D) PAPS

C. RXR

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

B) The enzyme gets broken down slower

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

A. Bind P450 heme iron

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

B. Suicide inhibitors

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

A. Drug conjugates

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

B. Cytosolic and microsomal GSH transferases

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

D. Aromatic amine or hydrazine

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

A. NAT1 and NAT2

N-acetyltransferases use which endogenous cofactor during acetylation reactions?

A) NADPH

B) PAPS

C) Acetyl-CoA

D) SAMe

C. Acetyl-CoA

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

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

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

D. Epoxide hydrolases

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

A. P450-catalyzed oxidations

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

B. Nutrition and diet

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

A. P450-dependent GSH conjugation

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

C. Depleted faster than regenerated

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

A) Acetyl-CoA

B) NAPQI

C) PAPS

D) SAMe

B. NAPQI

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

A) Cellular proteins

B) Plasma albumin

C) Bile acids

D) Ribosomal RNA

A. Cellular proteins

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

A) Nitric oxide

B) Bile salts

C) Reactive oxygen species

D) Acetyl-CoA

C. Reactive oxygen species

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

D. Autosomal recessive

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

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

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

B. Phase I drug metabolism

Debrisoquin-sparteine oxidation polymorphism is inherited in which pattern?

A) Autosomal recessive

B) Autosomal dominant

C) X-linked recessive

D) Mitochondrial

A. Autosomal recessive

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

A) CYP3A4

B) CYP2C19

C) CYP2D6

D) CYP1A2

C. CYP2D6

Which CYP2C19 allele variant is associated with increased CYP2C19 activity?

A) CYP2C19*2

B) CYP2C19*3

C) CYP2C19*17

D) CYP2C19*5

C. CYP2C19*17

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

A. Increased bleeding risk

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

A) Heme synthesis

B) Splicing

C) Sulfation

D) Acetylation

B. Splicing

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

B. Flavin monooxygenase

“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

A. Ziegler’s enzyme

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

C. Butyrylcholinesterase

Succinylcholine is clinically used primarily as which type of drug?

A) Anticoagulant

B) Muscle relaxant

C) Antidepressant

D) Antifungal

B. Muscle relaxant

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

A) Severe hepatotoxicity

B) Respiratory paralysis

C) Bladder cancer

D) Peripheral neuritis

B. Respiratory paralysis

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

A) Ultrarapid metabolizer

B) Fast acetylator

C) Slow acetylator

D) CYP3A5 expresser

C. Slow acetylator

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

A. Slow acetylator

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

A) BCHE

B) TPMT

C) CYP1A

D) NAT1

B. TPMT

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

A) Thiopurines

B) Macrolides

C) Barbiturates

D) Antipsychotics

A. Thiopurines

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

A. Biotransform drugs

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

A. Beta-glucuronidases

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

A) Oxidases

B) Hydrolases

C) Ligases

D) Reductases

B. Hydrolases

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

A. Portal circulation

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

B. Enterohepatic recycling

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

A) More toxicity

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

A) CYP3A

B) CYP2D6

C) CYP1A

D) CYP2C19

C. CYP1A

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

A. CYP2C9 and CYP2C19

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

A. Pharmacologic effects

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

A) CYP1A2

B) CYP2D6

C) CYP3A4

D) CYP2C9

C. CYP3A4

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

A. First-pass effect

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

A) Ionization

B) Bioavailability

C) Protein synthesis

D) Glucuronidation

B. Bioavailability

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

A. Drug metabolism

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

A. Heavy metal poisoning

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

A. Drug metabolism

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

A) P450s

B) Albumin

C) Hemoglobin

D) Aquaporins

A. P450s

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

(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.

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

(A) Be associated with increased smooth endoplasmic reticulum

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

(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.

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

(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).

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

(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.

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

(B) Ethanol

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

(B) Ethanol

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

(H) Verapamil