Alkylating agents such as mechlorethamine are cornerstone cytotoxic drugs in chemotherapy, notable for DNA alkylation and cross-linking that disrupts replication and transcription. Mechlorethamine (a nitrogen mustard) is a highly reactive bifunctional alkylator used historically in lymphoma and topically for certain cutaneous T‑cell lymphomas. B. Pharm students must understand its pharmacology, mechanism (N7 guanine alkylation, interstrand cross-links), pharmacokinetics (instability in aqueous solution, rapid hydrolysis), dose-limiting toxicities (myelosuppression, vesicant effects, mucositis), resistance mechanisms, and safe handling during preparation. This topic reinforces principles of drug mechanism, adverse effects, clinical uses, and patient safety for safe dispensing and counseling. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which chemical class does mechlorethamine belong to?
- Nitrogen mustard alkylating agent
- Platinum coordination compound
- Antimetabolite pyrimidine analogue
- Topoisomerase inhibitor
Correct Answer: Nitrogen mustard alkylating agent
Q2. What is the primary molecular target of mechlorethamine in DNA?
- Phosphate backbone
- N7 position of guanine
- 3′ hydroxyl end of DNA strand
- Thymine dimer formation site
Correct Answer: N7 position of guanine
Q3. Mechlorethamine exerts cytotoxicity mainly by:
- Inhibiting dihydrofolate reductase
- Intercalating between base pairs
- Forming interstrand and intrastrand cross-links in DNA
- Blocking microtubule polymerization
Correct Answer: Forming interstrand and intrastrand cross-links in DNA
Q4. Which cell-cycle phase is mechlorethamine most active against?
- S phase only
- M phase only
- Cell cycle nonspecific (all phases)
- G1 phase only
Correct Answer: Cell cycle nonspecific (all phases)
Q5. A major dose-limiting toxicity of mechlorethamine is:
- Cardiotoxicity
- Hepatotoxicity
- Myelosuppression (bone marrow suppression)
- Peripheral neuropathy
Correct Answer: Myelosuppression (bone marrow suppression)
Q6. Mechlorethamine is described as a vesicant. This means it can cause:
- Reduced renal clearance
- Tissue blistering and severe local necrosis on extravasation
- Systemic allergic reactions when inhaled
- Permanent hearing loss
Correct Answer: Tissue blistering and severe local necrosis on extravasation
Q7. Which factor contributes to mechlorethamine’s instability and need for immediate preparation before use?
- High lipid solubility in plastics
- Rapid hydrolysis in aqueous solution
- Heat-induced polymerization
- Slow enzymatic activation in plasma
Correct Answer: Rapid hydrolysis in aqueous solution
Q8. Resistance to mechlorethamine in tumor cells can result from:
- Increased expression of dihydropyrimidine dehydrogenase
- Increased DNA repair and glutathione-mediated detoxification
- Overexpression of PPAR-gamma
- Loss of thymidylate synthase
Correct Answer: Increased DNA repair and glutathione-mediated detoxification
Q9. Which clinical use is historically associated with systemic mechlorethamine?
- Acute promyelocytic leukemia as first-line monotherapy
- Hodgkin’s lymphoma and certain lymphoproliferative disorders
- Metastatic colon cancer exclusively
- Chronic myeloid leukemia targeting BCR-ABL
Correct Answer: Hodgkin’s lymphoma and certain lymphoproliferative disorders
Q10. Topical mechlorethamine formulations are used primarily for:
- Psoriasis vulgaris
- Mycosis fungoides (cutaneous T‑cell lymphoma)
- Alopecia areata
- Contact dermatitis
Correct Answer: Mycosis fungoides (cutaneous T‑cell lymphoma)
Q11. Metabolic detoxification of mechlorethamine in cells commonly involves:
- Conjugation with glutathione
- Beta-oxidation in mitochondria
- Deamination by monoamine oxidase
- Glycosylation in the Golgi apparatus
Correct Answer: Conjugation with glutathione
Q12. Which adverse effect is especially monitored due to long-term alkylator exposure?
- Secondary malignancies such as therapy-related leukemia
- Development of pulmonary fibrosis after a single dose
- Immediate cataract formation
- Permanent hyperglycemia
Correct Answer: Secondary malignancies such as therapy-related leukemia
Q13. The primary pharmacodynamic action of mechlorethamine can best be described as:
- Enzyme inhibition by covalent enzyme binding
- Alkylation of nucleophilic sites on DNA leading to cross-linking
- Competitive antagonism at cell-surface receptors
- Reversible intercalation inhibiting topoisomerase
Correct Answer: Alkylation of nucleophilic sites on DNA leading to cross-linking
Q14. Which protective precaution is most important when preparing mechlorethamine in the pharmacy?
- Wearing UV-protective goggles only
- Use of biological safety cabinet, gloves, and protective gown to prevent exposure
- Preference for glassware over plastic to accelerate reaction
- Heating the solution to ensure sterility
Correct Answer: Use of biological safety cabinet, gloves, and protective gown to prevent exposure
Q15. Mechlorethamine preferentially cross-links which DNA structures to exert cytotoxicity?
- Telomeric repeats only
- Interstrand cross-links between guanine bases on opposite strands
- RNA:DNA hybrids exclusively
- Mitochondrial DNA exclusively
Correct Answer: Interstrand cross-links between guanine bases on opposite strands
Q16. A pharmacist counseling a patient about mechlorethamine should emphasize which common acute side effect?
- Severe hypoglycemia
- Nausea and vomiting (acute emesis)
- Instantaneous hair regrowth
- Improved renal function
Correct Answer: Nausea and vomiting (acute emesis)
Q17. Which DNA repair pathway is mainly responsible for repairing alkylation cross-links caused by mechlorethamine?
- Nucleotide excision repair and homologous recombination
- Mismatch repair exclusively
- Base excision repair only
- Photoreactivation repair
Correct Answer: Nucleotide excision repair and homologous recombination
Q18. Incompatibility issues with mechlorethamine preparation are mainly due to:
- Precipitation with saline
- Covalent reaction with water and reactive containers leading to loss of potency
- Formation of stable chelates with calcium
- Rapid crystallization at room temperature
Correct Answer: Covalent reaction with water and reactive containers leading to loss of potency
Q19. Which laboratory parameter should be monitored closely before and during mechlorethamine therapy?
- Serum amylase only
- Complete blood count (CBC) for neutropenia and thrombocytopenia
- Fasting lipid profile
- Thyroid function tests
Correct Answer: Complete blood count (CBC) for neutropenia and thrombocytopenia
Q20. Why is mechlorethamine considered bifunctional?
- It requires two metabolic activations to work
- It contains two reactive chloroethyl groups capable of forming two covalent bonds
- It binds to both RNA and proteins preferentially
- It acts on two different enzymes simultaneously
Correct Answer: It contains two reactive chloroethyl groups capable of forming two covalent bonds
Q21. Which statement about mechlorethamine pharmacokinetics is correct?
- It has a long plasma half-life permitting weekly dosing
- It is highly stable in aqueous intravenous solutions
- It is rapidly inactivated by hydrolysis requiring immediate use after reconstitution
- It is exclusively excreted unchanged in urine
Correct Answer: It is rapidly inactivated by hydrolysis requiring immediate use after reconstitution
Q22. For an extravasation injury caused by mechlorethamine, pharmacists should be aware that the drug is:
- A non-vesicant and harmless on skin contact
- A vesicant requiring immediate management to limit tissue damage
- Neutralized by exposure to light only
- Effectively treated by oral antihistamines alone
Correct Answer: A vesicant requiring immediate management to limit tissue damage
Q23. Which adverse effect is characteristic of alkylating agents including mechlorethamine?
- Reversible ototoxicity without hematologic toxicity
- Gonadal toxicity and potential infertility
- Exclusive cardiac arrhythmias without other toxicity
- Selective sparing of rapidly dividing cells
Correct Answer: Gonadal toxicity and potential infertility
Q24. Mechlorethamine’s clinical effectiveness is primarily due to its ability to:
- Promote rapid angiogenesis in tumors
- Induce DNA cross-links that prevent replication and trigger apoptosis
- Act as a reversible competitive inhibitor of DNA polymerase
- Stimulate immune checkpoints to enhance T‑cell response
Correct Answer: Induce DNA cross-links that prevent replication and trigger apoptosis
Q25. Which patient counseling point is appropriate for topical mechlorethamine therapy?
- Apply to broken open wounds to enhance penetration
- Wear gloves during application and avoid sun exposure to treated skin
- Store the cream at high temperature to increase potency
- Combine with other topical immunosuppressants without consulting the physician
Correct Answer: Wear gloves during application and avoid sun exposure to treated skin
Q26. Which laboratory mechanism contributes to tumor resistance specifically against mechlorethamine?
- Increased expression of drug influx transporters
- Upregulation of glutathione S-transferase and DNA repair enzymes
- Decreased expression of cytochrome P450 enzymes
- Enhanced deposition of extracellular matrix
Correct Answer: Upregulation of glutathione S-transferase and DNA repair enzymes
Q27. In formulation terms, why might glass containers be preferred over certain plastics for mechlorethamine?
- Plastics increase oncologic potency
- Some plastics can bind or react with the drug, reducing its potency
- Glass accelerates hydrolysis making drug safer
- Plastic leaches nutrients that stabilize the drug
Correct Answer: Some plastics can bind or react with the drug, reducing its potency
Q28. Which clinical feature suggests long-term complications from prior alkylator therapy?
- New-onset hyperthyroidism
- Development of treatment-related acute myeloid leukemia (t-AML)
- Immediate rash within minutes of exposure
- Rapid hair thickening after therapy
Correct Answer: Development of treatment-related acute myeloid leukemia (t-AML)
Q29. Which of the following best describes an important pharmacy safety practice with mechlorethamine?
- Preparing large batches and storing for weeks to optimize workflow
- Using closed-system transfer devices and preparing doses immediately before administration
- Allowing open-air reconstitution on the benchtop to speed up processing
- Wearing cotton gloves only while handling vials
Correct Answer: Using closed-system transfer devices and preparing doses immediately before administration
Q30. The mutagenic potential of mechlorethamine is primarily due to its:
- Ability to inhibit ribosomal RNA synthesis only
- Formation of covalent DNA adducts and cross-links that cause mutations
- Stimulation of telomerase activity in somatic cells
- Activation of antiviral immune pathways
Correct Answer: Formation of covalent DNA adducts and cross-links that cause mutations
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.
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