Review of Pharmacology - 9E (2015)

Chemotherapy C: Antineoplastic Drugs
Explanations
1. Ans. (b) Laryngotracheal stenosis (Ref: American College of Chest Physicians, 2008)
• Application of topical mitomycin C after endoscopic dilation of laryngotracheal stenosis reduces the rate of restenosis.
• It is also useful for anal carcinoma and superficial bladder cancer.
2. Ans. (a) Oral alkylating agent (Ref: Goodman Gilman 12/e p1687)
Temozolomide is an alkylating agent that can be given orally.
3. Ans. (c) Sickle cell anemia (Ref: Katzung 12/e p645, 989)
Methotrexate is used for the management of:
• Rheumatoid arthritis • Psoriasis
• Juvenile chronic arthritis • Psoriatic arthritis
• Ankylosing spondylitis • Polymyositis
• Dermatomyositis • Wegener’s granulomatosis
• Giant cell arteritis • Systemic lupus Erythematosis
• Vasculitis • Graft versus host disease
• Cancers (choriocarcinoma, breast cancer etc.)
4. Ans. (b) Less neurotoxic than cyclophosphamide (Ref: Goodman and Gilman 12/e p1684)
Ifosfamide is more neurotoxic than cyclophosphamide
• Mechlorethamine, ifofamide and cyclophosphamide are examples of nitrogen mustard group of alkylating agents.
• These are metabolized by cytochrome p450 enzymes.
• Ifosfamide produces chloracetaldehyde and acrolein as metabolites. Acrolein results in hemorrhagic cystitits whereas
chloracetaldehyde is responsible for nephrotoxicity.
• Ifosfamide has same toxicity profile as cyclophosphamide although it causes GREATER platelet suppression, neurotoxicity,
nephrotoxicity and hemorrhagic cystitis.
5. Ans. (d) Methotrexate (Ref: Goodman and Gilman, 12/e p85)
Alkalinization of urine speeds the clearance of weakly acidic drugs like aspirin, phenobarbitone, chlorpropamide and
methotrexate etc.
6. Ans. (a) Bleomycin (Ref: Katzung, 11/e p953)
Bleomycin is a marrow sparing drug but it causes pulmonary fibrosis and skin toxicity as adverse effects. Another anticancer
drug causing pulmonary fibrosis is busulfan.
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7. Ans (b) Overproduction of DHFRase (Ref: Goodman and Gilman, 11/e p1336)
Mechanisms of methotrexate resistance
• Impaired transport of methotrexate into cells
• Production of altered forms of DHFR that have decreased affinity for the inhibitor
• Increased concentrations of intracellular DHFR through gene amplification or altered gene regulation
• Decreased ability to synthesize methotrexate polyglutamates
• Increased expression of a drug efflux transporter, of the MRP (multidrug resistance protein) class.
8. Ans (a) Cyclophosphamide (Ref: Katzung, 11/e p500)
Cyclophosphamide is a prodrug and is activated by hepatic biotransformation to aldophosphamide. One of its degradation
products is acrolein that is responsible for hemorrhagic cystitis (its characteristic adverse effect). This adverse effect
can be decreased by vigorous hydration and by the use of mercapto ethane sulfonic acid (mesna).
9. Ans. (c) Bone Marrow suppression (Ref: CMDT 2010/1499)
Depression of bone marrow is usually the most significant dose limiting toxicity with cancer chemotherapy.
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Chemotherapy General C: Pharmacology
Antineoplastic Drugs
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