Which chemotherapeutic agent is used to treat colorectal cancer and works by inhibiting thymidylate synthase?… - RRB Nsg. Superintendent -29 April-2025 (shift-2nd)

RRB Nsg. Superintendent -29 April-2025 (shift-2nd)

Pharmacology

Medium

Appeared in: RRB Nsg. Superintendent -29 April-2025 (shift-2nd)

Explanation

5-Fluorouracil (5-FU) is an antimetabolite chemotherapeutic agent, classified as a pyrimidine analog.
It is a cornerstone treatment for solid tumors, especially colorectal cancer.
Its primary mechanism of action is the inhibition of the enzyme thymidylate synthase (TS) after being converted to its active metabolite, FdUMP.
By blocking thymidylate synthase, 5-FU prevents the synthesis of thymidine, a crucial component of DNA, leading to the death of rapidly dividing cancer cells.

Option A: Paclitaxel's mechanism is completely different; it targets the cell's structural components (microtubules) rather than a specific enzyme in the DNA synthesis pathway.
Option B: Etoposide targets topoisomerase II, an enzyme involved in managing DNA tangles during replication, not thymidylate synthase.
Option D: Cyclophosphamide is an alkylating agent that directly damages DNA by forming cross-links, a mechanism distinct from enzyme inhibition for nucleotide synthesis.

Visual 1: Diagram - Mechanism of 5-Fluorouracil. This visual would show the metabolic pathway where 5-FU is converted to FdUMP, which then forms a complex with thymidylate synthase, blocking the conversion of dUMP to dTMP and thus halting DNA production.

Clinical Relevance

Nursing practice connection: This is primarily an exam-oriented knowledge point with limited direct bedside application, so retain Mechanism of Action of Chemotherapeutic Agents as background academic context rather than a clinical decision trigger.
Knowing the specific mechanism of action helps nurses anticipate and manage unique side effects. For 5-FU, inhibiting DNA synthesis leads to common toxicities like myelosuppression (low blood counts) and mucositis (mouth sores).
Nurses play a critical role in monitoring for signs of toxicity and educating patients on managing these side effects, such as practicing good oral hygiene to minimize mucositis.
What if? If a patient has a known DPD (dihydropyrimidine dehydrogenase) deficiency, the answer changes dramatically. 5-FU would be contraindicated or require a significant dose reduction. A nurse seeing this in a patient's chart must flag it immediately, as DPD is the enzyme that breaks down 5-FU, and its deficiency can lead to severe, life-threatening toxicity.

How to Approach the Question

This is a factual recall question that tests your knowledge of pharmacology.
First, break down the question into its key components: 1) the drug class (chemotherapeutic agent), 2) the disease (colorectal cancer), and 3) the specific mechanism (inhibiting thymidylate synthase).
Next, evaluate each option against these three criteria.
Recall the mechanism of action for each drug. Paclitaxel affects microtubules, Etoposide affects topoisomerase II, and Cyclophosphamide is an alkylating agent.
Identify that 5-Fluorouracil is the only option that is an antimetabolite known for inhibiting thymidylate synthase and is a standard treatment for colorectal cancer.

Concept Tested & Keywords

Concept Tested: Mechanism of Action of Chemotherapeutic Agents
Stem keywords: chemotherapeutic agent, colorectal cancer, inhibiting thymidylate synthase
Lead-in keywords: Which

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