Stereochemical aspects of drug metabolism MCQs With Answer

Stereochemical aspects of drug metabolism MCQs With Answer

The stereochemical aspects of drug metabolism are vital for B. Pharm students to understand how chirality, enantiomers and diastereomers influence ADME, pharmacodynamics and toxicity. This introduction reviews stereoselective and stereospecific biotransformations mediated by cytochrome P450 enzymes, esterases, UGTs and other Phase I/II systems, and highlights clinical examples (warfarin, thalidomide, ibuprofen, ketamine, omeprazole). Emphasis is placed on concepts such as chiral inversion, enantioselective clearance, prochiral centers, and implications for drug design and therapeutic outcomes. Learn the biochemical basis and practical consequences of stereochemistry in metabolism to excel in exams and real-world pharmacy practice. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which term describes two molecules that are non-superimposable mirror images?

• Conformers
• Enantiomers
• Constitutional isomers
• Mesomers

Correct Answer: Enantiomers

Q2. A metabolic reaction that converts a prochiral center into a chiral center in a drug is called:

• Racemization
• Chiral inversion
• Stereogenic conversion
• Stereoselective transformation

Correct Answer: Stereoselective transformation

Q3. Which cytochrome P450 isoform is primarily responsible for S-warfarin metabolism?

• CYP3A4
• CYP1A2
• CYP2C9
• CYP2D6

Correct Answer: CYP2C9

Q4. Thalidomide’s teratogenicity is associated mainly with which stereochemical fact?

• It is achiral and unstable
• Only the R-enantiomer is active and safe
• It is administered as a racemate and one enantiomer is teratogenic
• It lacks any chiral centers

Correct Answer: It is administered as a racemate and one enantiomer is teratogenic

Q5. What is chiral inversion in drug metabolism?

• Conversion of an achiral drug into a chiral metabolite
• Conversion of one enantiomer to its mirror image enantiomer
• Racemization to form a 50:50 mixture
• Oxidation at a prochiral center

Correct Answer: Conversion of one enantiomer to its mirror image enantiomer

Q6. Which example illustrates chiral inversion in clinical pharmacology?

• Esomeprazole produced from omeprazole
• R-ibuprofen converting to S-ibuprofen
• S-ketamine having higher potency
• S-warfarin being more potent than R-warfarin

Correct Answer: R-ibuprofen converting to S-ibuprofen

Q7. Enantioselective metabolism refers to:

• Only one enantiomer being present in the drug product
• Different metabolic rates or pathways for each enantiomer
• Complete conversion of both enantiomers to same metabolite
• Absence of stereochemical effects on metabolism

Correct Answer: Different metabolic rates or pathways for each enantiomer

Q8. Which phase II enzyme family is known for stereoselective glucuronidation?

• CYP450 enzymes
• UGT (UDP-glucuronosyltransferases)
• SULT (sulfotransferases)
• MAO (monoamine oxidases)

Correct Answer: UGT (UDP-glucuronosyltransferases)

Q9. What is the enantiomeric excess (ee) of a sample containing 70% R and 30% S enantiomers?

• 40%
• 60%
• 70%
• 30%

Correct Answer: 40%

Q10. Which statement describes a stereospecific metabolic reaction?

• Both enantiomers are metabolized to the same product
• Only one stereoisomer undergoes a particular metabolic transformation
• Metabolism is independent of stereochemistry
• Reaction yields a racemic mixture irrespective of substrate

Correct Answer: Only one stereoisomer undergoes a particular metabolic transformation

Q11. Prochiral molecules become chiral upon:

• Removal of a stereocenter
• Attachment or transformation at a specific planar atom
• Formation of a meso compound
• Complete racemization

Correct Answer: Attachment or transformation at a specific planar atom

Q12. Which clinical example shows enantioselective pharmacodynamics as well as metabolism?

• Racemic acetaminophen
• Racemic ketamine where S-ketamine is more potent and differently metabolized
• Racemic caffeine
• Achiral aspirin

Correct Answer: Racemic ketamine where S-ketamine is more potent and differently metabolized

Q13. Which technique is commonly used to separate and analyze enantiomers during metabolic studies?

• Achiral HPLC
• Chiral chromatography (chiral HPLC)
• UV-Vis spectroscopy without chiral reagents
• TLC on silica gel only

Correct Answer: Chiral chromatography (chiral HPLC)

Q14. In stereoselective oxidation of a chiral substrate by CYP450, what determines the product enantiomer formed?

• Only the pH of the medium
• Active-site geometry and substrate orientation
• The drug’s color
• Presence of glucuronide conjugates

Correct Answer: Active-site geometry and substrate orientation

Q15. Which of the following results from stereoselective protein binding?

• Identical free fraction for enantiomers
• Differing plasma protein binding leading to different free drug concentrations
• Total elimination of one enantiomer
• Instant racemization in plasma

Correct Answer: Differing plasma protein binding leading to different free drug concentrations

Q16. Diastereomers differ from enantiomers in that diastereomers:

• Are non-superimposable mirror images
• Are stereoisomers not related as mirror images and have different physical properties
• Always have identical biological activity
• Cannot be separated chromatographically

Correct Answer: Are stereoisomers not related as mirror images and have different physical properties

Q17. Which process can lead to racemization during drug metabolism?

• Enzymatic epimerization at a stereocenter under physiological conditions
• Purely ionic bonding without enzyme involvement
• Hydrogen bonding to albumin
• Formation of a stable meso compound only

Correct Answer: Enzymatic epimerization at a stereocenter under physiological conditions

Q18. Which stereochemical term describes a molecule with an internal plane of symmetry despite stereocenters?

• Enantiomer
• Meso compound
• Prochiral molecule
• Atropisomer

Correct Answer: Meso compound

Q19. Stereoselective glucuronidation might influence drug elimination because:

• Glucuronides are always more lipophilic
• Different enantiomers form glucuronides at different rates, altering clearance
• Glucuronidation removes chirality from all drugs
• Sulfation always overrides glucuronidation

Correct Answer: Different enantiomers form glucuronides at different rates, altering clearance

Q20. Atropisomerism arises from:

• Restricted rotation about a single bond leading to stable stereoisomers
• Presence of multiple stereocenters only
• Conversion of enantiomers to diastereomers
• Racemization by heat

Correct Answer: Restricted rotation about a single bond leading to stable stereoisomers

Q21. Which metabolic pathway commonly shows high stereoselectivity due to steric requirements of the enzyme active site?

• Hydrolysis by nonspecific hydrolases
• CYP450-mediated hydroxylation
• Simple ionization in plasma
• Passive diffusion across membranes

Correct Answer: CYP450-mediated hydroxylation

Q22. The R/S nomenclature is assigned based on:

• Direction of optical rotation measured experimentally
• Cahn-Ingold-Prelog priority rules based on atomic numbers
• Molecular weight comparison only
• Biological activity of the enantiomer

Correct Answer: Cahn-Ingold-Prelog priority rules based on atomic numbers

Q23. Which drug is marketed as a single enantiomer to improve therapeutic profile compared to its racemate?

• Racemic warfarin marketed unchanged
• Esomeprazole marketed as S-enantiomer of omeprazole
• Racemic ibuprofen marketed only
• Racemic acetaminophen marketed as mixture

Correct Answer: Esomeprazole marketed as S-enantiomer of omeprazole

Q24. Stereoselective renal excretion can occur because:

• Kidney glomerulus selectively filters based on chirality
• Transporters and tubular secretion mechanisms can discriminate between enantiomers
• All enantiomers are equally reabsorbed
• Only phase II metabolites are excreted in urine

Correct Answer: Transporters and tubular secretion mechanisms can discriminate between enantiomers

Q25. Which analytical parameter directly measures the proportion of two enantiomers in a sample?

• Area under the curve (AUC)
• Optical rotation or chiral chromatographic peak area ratios
• pKa value determination
• Melting point depression

Correct Answer: Optical rotation or chiral chromatographic peak area ratios

Q26. In stereoselective drug-drug interactions, co-administered drugs can:

• Allow total symmetry in metabolism
• Preferentially inhibit metabolism of one enantiomer leading to altered enantiomeric ratios
• Only affect non-chiral metabolites
• Always increase clearance of both enantiomers equally

Correct Answer: Preferentially inhibit metabolism of one enantiomer leading to altered enantiomeric ratios

Q27. Which reaction type often leads to formation of a new stereocenter during Phase I metabolism?

• Hydrolysis producing achiral fragments
• Oxidative hydroxylation creating a new chiral alcohol
• Glucuronidation at existing polar groups only
• Sulfation of a non-stereogenic hydrogen

Correct Answer: Oxidative hydroxylation creating a new chiral alcohol

Q28. How does stereochemistry influence pharmacokinetic parameters like clearance?

• Stereochemistry has no influence on clearance
• Different enantiomers can have different clearances due to varied metabolism and protein binding
• Clearance depends only on molecular weight
• Clearance is solely determined by renal filtration rate

Correct Answer: Different enantiomers can have different clearances due to varied metabolism and protein binding

Q29. A racemate refers to:

• A mixture containing only one enantiomer
• A 50:50 mixture of two enantiomers
• A compound with no stereocenters
• A diastereomeric excess sample

Correct Answer: A 50:50 mixture of two enantiomers

Q30. Which enzyme class is primarily involved in oxidative Phase I stereoselective metabolism?

• Transferases
• CYP450 monooxygenases
• Hydrolases
• Ligases

Correct Answer: CYP450 monooxygenases

Q31. Stereoselective formation of metabolites can influence toxicity because:

• All metabolites are non-toxic
• One enantiomer may form a toxic metabolite while the other does not
• Toxicity is independent of stereochemistry
• Only conjugation reactions produce toxicity

Correct Answer: One enantiomer may form a toxic metabolite while the other does not

Q32. Which statement about prodrugs with chiral centers is correct?

• Prodrugs are always achiral
• Activation may be stereoselective, producing different active enantiomers
• Prodrugs never undergo stereoselective metabolism
• Chiral prodrugs always racemize before activation

Correct Answer: Activation may be stereoselective, producing different active enantiomers

Q33. The tendency of a drug to undergo stereoselective hepatic uptake is mainly influenced by:

• Only the drug’s color and taste
• Lipophilicity, transporter affinity, and stereochemistry
• The amount of food in stomach only
• Universal transporter that ignores chirality

Correct Answer: Lipophilicity, transporter affinity, and stereochemistry

Q34. Which term describes unequal metabolism leading to enrichment of one enantiomer?

• Enantioselective enrichment
• Chiral dilution
• Complete racemization
• Stereoindifference

Correct Answer: Enantioselective enrichment

Q35. In designing safer chiral drugs, pharmaceutical scientists may:

• Always market only racemates
• Develop single-enantiomer formulations to reduce adverse effects and variability
• Ignore stereochemistry as irrelevant
• Use higher doses of racemates to mask differences

Correct Answer: Develop single-enantiomer formulations to reduce adverse effects and variability

Q36. Which of the following best explains why S-warfarin has greater anticoagulant potency?

• S-warfarin is more water-soluble
• S-warfarin has higher intrinsic activity at the target and is differently metabolized
• R-warfarin is not absorbed
• Only S-warfarin forms glucuronide conjugates

Correct Answer: S-warfarin has higher intrinsic activity at the target and is differently metabolized

Q37. Which metabolic enzyme can perform stereoselective N-dealkylation?

• UDP-glucuronosyltransferase
• CYP450 enzymes
• Carboxylesterase only
• Alcohol dehydrogenase only

Correct Answer: CYP450 enzymes

Q38. Which phenomenon describes conversion of a single enantiomer into a racemic mixture in the body?

• Chiral inversion to opposite enantiomer only
• In vivo racemization
• Prodrug activation
• Phase II conjugation exclusively

Correct Answer: In vivo racemization

Q39. For a drug subject to stereoselective hepatic metabolism, what happens to oral bioavailability of one enantiomer if first-pass metabolism is greater for that enantiomer?

• Its oral bioavailability increases
• Its oral bioavailability decreases relative to the other enantiomer
• Bioavailability remains identical for both enantiomers
• Only renal excretion affects bioavailability

Correct Answer: Its oral bioavailability decreases relative to the other enantiomer

Q40. Which type of stereochemical analysis provides absolute configuration when combined with molecular modeling or standards?

• Chiral HPLC with reference standards
• Simple MS without chiral separation
• Uncalibrated polarimetry only
• Visual inspection of crystals

Correct Answer: Chiral HPLC with reference standards

Q41. Which metabolic reaction is least likely to create a stereocenter?

• Oxidation of a tertiary carbon to a tertiary alcohol
• Hydrolysis of an ester yielding achiral fragments
• Reduction of a ketone at a prochiral carbon creating a chiral alcohol
• Epoxidation across a C=C creating a chiral center

Correct Answer: Hydrolysis of an ester yielding achiral fragments

Q42. Stereochemical considerations are important in regulatory assessment because:

• Regulatory agencies require characterization of stereoisomeric composition and activity
• Stereochemistry is never relevant to safety
• Only achiral drugs are evaluated rigorously
• Enantiomers are always treated as identical by regulators

Correct Answer: Regulatory agencies require characterization of stereoisomeric composition and activity

Q43. Which class of transport proteins is known to show stereoselective substrate recognition affecting distribution and elimination?

• P-glycoprotein and certain uptake transporters (e.g., OATPs)
• Hemoglobin only
• Albumin exclusively without stereoselectivity
• Cellulose-based transporters

Correct Answer: P-glycoprotein and certain uptake transporters (e.g., OATPs)

Q44. A drug with two stereocenters can have how many stereoisomers at maximum (ignoring meso forms)?

• 2
• 3
• 4
• 8

Correct Answer: 4

Q45. Which factor does NOT typically contribute to stereoselective metabolism?

• Enzyme active site chirality
• Substrate orientation within the enzyme
• Ambient room color
• Substituent steric hindrance near stereocenter

Correct Answer: Ambient room color

Q46. Which best describes enantiospecific metabolism?

• Both enantiomers give identical metabolites at identical rates
• Only one enantiomer can be metabolized to a specific product while the other cannot
• Metabolism proceeds randomly without stereochemical preference
• Enantiomers are indistinguishable to metabolic enzymes

Correct Answer: Only one enantiomer can be metabolized to a specific product while the other cannot

Q47. Which therapeutic implication arises from stereoselective toxic metabolite formation?

• Dose adjustment is unnecessary for enantiomeric composition
• Choice of single-enantiomer formulation may reduce toxicity
• Racemates are always safer than enantiopure drugs
• Toxic metabolites cannot be predicted by stereochemistry

Correct Answer: Choice of single-enantiomer formulation may reduce toxicity

Q48. Which process can lead to stereochemical inversion at a carbon adjacent to a carbonyl during metabolism?

• Hydrogen bonding to albumin
• Enolization followed by reprotonation (tautomerization-based epimerization)
• Glomerular filtration
• Simple dilution in plasma

Correct Answer: Enolization followed by reprotonation (tautomerization-based epimerization)

Q49. In preclinical studies, why is it important to test each enantiomer separately for metabolism?

• Because enantiomers always have identical metabolic profiles
• To identify stereoselective pathways, distinct metabolites, and differential toxicity or efficacy
• Only racemates are of regulatory interest
• Metabolism studies are unnecessary for enantiomers

Correct Answer: To identify stereoselective pathways, distinct metabolites, and differential toxicity or efficacy

Q50. Which design strategy uses stereochemistry to minimize formation of a toxic metabolite?

• Developing a racemic mixture to dilute the toxic enantiomer
• Selecting or synthesizing the enantiomer that is less likely to form the toxic metabolite
• Increasing dose to overwhelm metabolic pathways
• Avoiding characterization of stereoselective metabolism

Correct Answer: Selecting or synthesizing the enantiomer that is less likely to form the toxic metabolite

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com