Antimetabolites Indian Medical PG Practice Questions and MCQs
Practice Indian Medical PG questions for Antimetabolites. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Antimetabolites Indian Medical PG Question 1: Azathioprine is used as a treatment for which specific condition?
- A. Autoimmune diseases (Correct Answer)
- B. Gout
- C. HIV infection
- D. Cancer
Antimetabolites Explanation: ***Autoimmune diseases***
- **Azathioprine** is a **purine analogue** that acts as an **immunosuppressant**, making it effective in managing various autoimmune conditions by reducing the immune response.
- It is specifically used in diseases like **rheumatoid arthritis** [1], lupus, Crohn's disease, and in **organ transplantation** to prevent rejection [1].
*Gout*
- **Gout** is an inflammatory arthritis caused by the deposition of **urate crystals** in the joints.
- Treatment typically involves **NSAIDs**, **colchicine**, and **allopurinol** (to lower uric acid), not immunosuppressants like azathioprine.
*HIV infection*
- **HIV infection** is a viral disease that attacks the immune system, requiring **antiretroviral therapy (ART)** to control viral replication.
- Azathioprine is not used for HIV treatment as it would further suppress an already compromised immune system.
*Cancer*
- While some **cytotoxic agents** are used in cancer therapy, azathioprine is primarily an immunosuppressant and its role in cancer treatment is limited.
- **Chemotherapy** for cancer involves agents specifically designed to target and kill rapidly dividing cancer cells through various mechanisms.
Antimetabolites Indian Medical PG Question 2: Which of the following is the platinum-based chemotherapeutic agent used as first-line treatment for ovarian carcinoma?
- A. Cyclophosphamide
- B. Methotrexate
- C. Cisplatin (Correct Answer)
- D. Dacarbazine
Antimetabolites Explanation: ***Cisplatin***
- **Cisplatin** is a platinum-based chemotherapy drug that forms **DNA cross-links**, inhibiting DNA synthesis and leading to the death of rapidly dividing cells, making it highly effective against **ovarian carcinoma**.
- It is a cornerstone of chemotherapy regimens for ovarian cancer, often used in combination with other agents such as paclitaxel.
*Methotrexate*
- **Methotrexate** is an **antimetabolite** that inhibits dihydrofolate reductase, thereby interfering with DNA synthesis.
- While it is used in various cancers like leukemia, lymphoma, and some solid tumors (e.g., breast cancer, gestational trophoblastic disease), it is **not a primary recommended drug for ovarian carcinoma**.
*Cyclophosphamide*
- **Cyclophosphamide** is an **alkylating agent** that causes DNA damage, leading to cell death.
- It is used in many cancers, including lymphoma, breast cancer, and some leukemias, but it is **not a first-line or primary agent for ovarian carcinoma** in contemporary treatment guidelines.
*Dacarbazine*
- **Dacarbazine** is an **alkylating agent** primarily used in the treatment of **malignant melanoma** and Hodgkin lymphoma.
- It is **not indicated for the treatment of ovarian carcinoma**.
Antimetabolites Indian Medical PG Question 3: Resistance to Methotrexate develops due to?
- A. Rapid proliferation of cancer cells
- B. Thymidylate kinase deficiency
- C. Thymidylate synthetase deficiency
- D. Increased production of dihydrofolate reductase (DHFR) (Correct Answer)
Antimetabolites Explanation: ***Increased production of dihydrofolate reductase (DHFR)***
- Methotrexate acts by inhibiting **dihydrofolate reductase (DHFR)**, an enzyme essential for **folate metabolism** and DNA synthesis.
- An **increased production of DHFR** (through gene amplification or overexpression) by cancer cells allows them to bypass the drug's inhibitory effects, leading to resistance.
- This is the **most common mechanism** of methotrexate resistance.
*Rapid proliferation of cancer cells*
- While **rapid cell proliferation** is a characteristic of cancer, it doesn't directly explain resistance to methotrexate.
- Methotrexate targets fast-dividing cells (S-phase specific), so rapid proliferation often makes them **more susceptible**, not resistant, as long as the drug's mechanism is effective.
*Thymidylate kinase deficiency*
- **Thymidylate kinase** is involved in the phosphorylation of **thymidine** to produce **dTMP** (deoxythymidine monophosphate).
- A deficiency in this enzyme would likely hinder DNA synthesis, potentially increasing sensitivity to DNA-targeting agents, rather than causing resistance to methotrexate.
*Thymidylate synthetase deficiency*
- **Thymidylate synthetase** converts dUMP to dTMP using **5,10-methylene-THF** as a cofactor.
- Methotrexate **indirectly inhibits** thymidylate synthetase by depleting tetrahydrofolate cofactor pools through DHFR inhibition.
- A **deficiency** of this enzyme would not cause resistance; rather, **increased thymidylate synthetase** expression can be an alternative resistance mechanism, though less common than DHFR overexpression.
Antimetabolites Indian Medical PG Question 4: A 23-year-old female underwent kidney transplantation and developed acute humoral rejection after 8 days, which was successfully managed with tacrolimus and another drug that suppresses both B and T lymphocytes. What is the drug that targets both B and T lymphocytes by inhibiting de novo synthesis of purines?
- A. Prednisone
- B. Methotrexate
- C. Mycophenolate mofetil (Correct Answer)
- D. Cyclophosphamide
Antimetabolites Explanation: ***Mycophenolate mofetil***
- This drug inhibits **inosine monophosphate dehydrogenase**, an enzyme crucial for the **de novo synthesis of guanine nucleotides** in lymphocytes.
- This selective inhibition effectively suppresses the proliferation and function of both **B and T lymphocytes**, making it a cornerstone in preventing transplant rejection.
*Methotrexate*
- **Methotrexate** is an **antimetabolite** that primarily inhibits **dihydrofolate reductase**, interfering with DNA synthesis and cell proliferation.
- While it has immunosuppressive effects, its primary mechanism in inhibiting purine synthesis is not de novo synthesis in the same manner as mycophenolate mofetil.
*Prednisone*
- **Prednisone** is a **corticosteroid** that exerts its immunosuppressive effects through broad anti-inflammatory actions, genomic and non-genomic effects, affecting the function of various immune cells.
- It does not specifically target **de novo purine synthesis** as its primary mechanism of immunosuppression.
*Cyclophosphamide*
- **Cyclophosphamide** is an **alkylating agent** that cross-links DNA strands, leading to cell cycle arrest and apoptosis, particularly in rapidly dividing cells like lymphocytes.
- While it is a potent immunosuppressant affecting both B and T cells, its mechanism does not involve the inhibition of **de novo purine synthesis**.
Antimetabolites Indian Medical PG Question 5: Which antineoplastic agent is known to cause hemorrhagic cystitis?
- A. Cyclophosphamide (Correct Answer)
- B. Methotrexate
- C. Cisplatin
- D. Vincristine
Antimetabolites Explanation: ***Cyclophosphamide***
- Cyclophosphamide is an **alkylating agent** that forms highly reactive metabolites, such as **acrolein**, which is excreted in the urine and causes direct irritation and damage to the bladder urothelium, leading to **hemorrhagic cystitis**.
- This toxicity can be mitigated by co-administration of **mesna** (2-mercaptoethane sulfonate sodium), which inactivates acrolein in the bladder, and aggressive intravenous hydration.
*Methotrexate*
- Methotrexate is a **folate antagonist** primarily known for causing **myelosuppression**, **mucositis**, and **hepatotoxicity**.
- While it can cause renal toxicity at high doses due to precipitation in renal tubules, it is not typically associated with hemorrhagic cystitis.
*Cisplatin*
- Cisplatin is a **platinum-based chemotherapy agent** with significant **nephrotoxicity** and **ototoxicity** as its dose-limiting toxicities.
- It also commonly causes profound nausea and vomiting but is not a primary cause of hemorrhagic cystitis.
*Vincristine*
- Vincristine is a **vinca alkaloid** that interferes with microtubule formation, primarily known for causing **peripheral neuropathy** (e.g., foot drop, paresthesias, constipation due to autonomic neuropathy) and is a vesicant.
- It does not typically cause hemorrhagic cystitis; its bone marrow toxicity is generally less severe compared to other chemotherapeutic agents.
Antimetabolites Indian Medical PG Question 6: The use of which of the following helps in reducing the toxicity of doxorubicin to the heart?
- A. Dexrazoxane (Correct Answer)
- B. Amifostine
- C. Carboplatin
- D. Flucytosine
Antimetabolites Explanation: ***Dexrazoxane***
- **Dexrazoxane** is a **cardioprotective agent** that chelates intracellular iron, thereby reducing the formation of **free radicals** responsible for doxorubicin-induced cardiotoxicity.
- It is specifically approved for reducing the incidence and severity of **cardiomyopathy** associated with doxorubicin use, particularly in patients who have received a high cumulative dose.
*Amifostine*
- **Amifostine** is a **cytoprotective agent** used to reduce the incidence of nephrotoxicity associated with platinum-based chemotherapy (e.g., cisplatin) and to reduce xerostomia in patients undergoing radiation therapy for head and neck cancer.
- Its primary mechanism involves scavenging **free radicals** and detoxifying reactive metabolites in normal tissues, but it is not specifically indicated for doxorubicin-induced cardiotoxicity.
*Carboplatin*
- **Carboplatin** is a **platinum-based chemotherapy agent** similar to cisplatin, primarily used in the treatment of various cancers, including ovarian, lung, and head and neck cancers.
- It causes myelosuppression and nephrotoxicity as major side effects but is a **chemotherapeutic drug itself**, not a protective agent against other chemotherapies.
*Flucytosine*
- **Flucytosine** is an **antifungal medication** used to treat severe systemic fungal infections, often in combination with amphotericin B.
- Its mechanism involves interfering with fungal DNA and RNA synthesis, and it has no known role in mitigating the toxicity of doxorubicin.
Antimetabolites Indian Medical PG Question 7: Mechanism of action of Pemetrexed is:-
- A. Topoisomerase inhibitor
- B. Dihydrofolate reductase inhibitor
- C. Dopamine agonist
- D. Thymidylate synthase inhibitor (Correct Answer)
Antimetabolites Explanation: ***Thymidylate synthase inhibitor***
- **Pemetrexed** is a **multi-targeted antifolate agent** that primarily inhibits **thymidylate synthase (TS)**, the key enzyme responsible for synthesizing thymidine monophosphate, an essential building block for DNA synthesis.
- While pemetrexed also inhibits **dihydrofolate reductase (DHFR)** and **glycinamide ribonucleotide formyltransferase (GARFT)**, its **primary and most clinically significant mechanism** is TS inhibition, making it particularly effective in mesothelioma and non-small cell lung cancer.
- This multi-targeted action enhances its cytotoxic effects compared to single-target antifolates.
*Dihydrofolate reductase inhibitor*
- While pemetrexed does inhibit **DHFR** as part of its multi-targeted mechanism, this is a **secondary action**, not its primary mechanism.
- Classical DHFR inhibitors include **methotrexate** and **trimethoprim**, which specifically target this enzyme.
- In exam contexts, pemetrexed is best classified by its **primary target: thymidylate synthase**.
*Topoisomerase inhibitor*
- **Topoisomerase inhibitors** target enzymes that control DNA topology during replication and transcription.
- Examples include **irinotecan** and **topotecan** (topoisomerase I inhibitors) and **etoposide** (topoisomerase II inhibitor).
- This is not the mechanism of action for pemetrexed.
*Dopamine agonist*
- **Dopamine agonists** activate dopamine receptors and are used in neurological conditions like Parkinson's disease (e.g., **pramipexole**, **ropinirole**).
- This mechanism is completely unrelated to anticancer agents and folate metabolism.
Antimetabolites Indian Medical PG Question 8: Which of the following can be given orally?
- A. Actinomycin D
- B. Cytosine arabinoside
- C. Doxorubicin
- D. Cyclophosphamide (Correct Answer)
Antimetabolites Explanation: ***Cyclophosphamide***
- **Cyclophosphamide** is an **alkylating agent** that can be administered both **orally and intravenously**.
- It has good **oral bioavailability** (>75%) and is commonly given orally in many chemotherapy regimens and immunosuppressive protocols.
- Oral formulation is particularly useful for maintenance therapy and chronic administration.
*Actinomycin D*
- **Actinomycin D** (dactinomycin) is an **intravenous** antineoplastic agent.
- It is a **peptide-containing antibiotic** that intercalates into DNA, and its oral bioavailability is very poor.
*Cytosine arabinoside*
- **Cytosine arabinoside** (cytarabine) is primarily administered **intravenously** or **subcutaneously**.
- It has a high first-pass metabolism when given orally, resulting in very **low oral bioavailability**.
*Doxorubicin*
- **Doxorubicin** is an **anthracycline antibiotic** that is predominantly given **intravenously**.
- It has poor oral bioavailability due to extensive **first-pass metabolism** and is therefore not administered orally.
Antimetabolites Indian Medical PG Question 9: Which of the following drugs act by inhibiting DNA replication?
- A. Mitomycin C
- B. 6-Mercaptopurine (Correct Answer)
- C. Actinomycin D
- D. Asparaginase
Antimetabolites Explanation: ***6-Mercaptopurine***
- This drug is a **purine analog** that acts as an **antimetabolite**, directly interfering with the **synthesis of purine nucleotides** required for DNA replication.
- By inhibiting enzymes like **PRPP amidotransferase** and getting incorporated into DNA as a fraudulent nucleotide, it blocks the **de novo synthesis** pathway, preventing normal DNA replication.
- This represents **direct inhibition of DNA synthesis** at the nucleotide building block level.
*Mitomycin C*
- This agent is an **alkylating agent** that **cross-links DNA** strands, causing DNA damage that prevents strand separation.
- While it does prevent DNA replication, its mechanism is through **DNA damage and structural disruption** rather than inhibition of the DNA synthesis machinery itself.
- It acts by damaging already-formed DNA rather than preventing new DNA synthesis.
*Actinomycin D*
- Actinomycin D is an **intercalating agent** that inserts itself between DNA base pairs, primarily **inhibiting RNA synthesis** by blocking RNA polymerase movement.
- While it binds to DNA, its primary therapeutic action is on **transcription (RNA synthesis)**, not direct inhibition of DNA replication.
*Asparaginase*
- Asparaginase is an enzyme that **depletes asparagine** from the blood, which is an essential amino acid for certain cancer cells (e.g., leukemic cells).
- Its mechanism is to starve cancer cells of asparagine, leading to **inhibition of protein synthesis**, not DNA replication.
Antimetabolites Indian Medical PG Question 10: On chronic use, linezolid leads to which of the following?
- A. Thrombocytopenia (Correct Answer)
- B. Deranged LFT
- C. Nephrotoxicity
- D. Ototoxicity
Antimetabolites Explanation: ***Thrombocytopenia***
- **Linezolid** is known to cause **myelosuppression**, particularly **thrombocytopenia**, with prolonged use (typically >2 weeks).
- This adverse effect is usually **reversible** upon discontinuation of the drug.
- This is the **most characteristic** and **dose-limiting** hematologic toxicity of chronic linezolid therapy.
*Deranged LFT*
- While **linezolid** can occasionally cause **elevated liver enzymes**, this is a **less common** adverse effect compared to myelosuppression.
- **Thrombocytopenia** is far more characteristic of **chronic linezolid use** and is the primary concern requiring monitoring.
- Hepatotoxicity with linezolid is typically mild and less dose-limiting than hematologic effects.
*Nephrotoxicity*
- **Linezolid** is generally considered to have a low risk of **nephrotoxicity** and does not typically cause significant kidney damage.
- **Aminoglycosides** or **vancomycin** are examples of antibiotics more commonly associated with nephrotoxic effects.
*Ototoxicity*
- **Ototoxicity**, characterized by hearing loss or tinnitus, is not a common or recognized side effect of **linezolid** therapy.
- This adverse effect is more frequently associated with drugs like **aminoglycosides** or high-dose **loop diuretics**.
More Antimetabolites Indian Medical PG questions available in the OnCourse app. Practice MCQs, flashcards, and get detailed explanations.
