Methotrexate and Purine Analogs Quiz

Questions and Answers

What is the primary action of methotrexate on cellular processes?

Promoting the synthesis of thymidylate

Inhibiting enzyme activity unrelated to folic acid

Enhancing transport of folic acid into cells

Inhibiting dihydrofolate reductase (correct)

Why is the availability of thymidylate critical for cell survival?

It allows for DNA synthesis. (correct)

It regulates cell division rates.

It facilitates protein synthesis.

It is essential for oxygen transport in cells.

What secondary effect does methotrexate have on cells apart from DNA synthesis inhibition?

Stimulating immune response

Enhancing mitochondrial function

Inducing cell differentiation

Inducing apoptosis (correct)

What is the purpose of leucovorin rescue in the context of methotrexate treatment?

To prevent normal cell apoptosis Signup and view all the answers

What is a key reason some neoplastic cells are unresponsive to methotrexate?

They lack the transport system required for drug uptake. Signup and view all the answers

What is the predominant therapeutic use of mercaptopurine?

Maintenance therapy of acute lymphocytic leukemia Signup and view all the answers

Why can massive doses of methotrexate be effective in neoplastic cells despite their resistance?

They force uptake through passive diffusion. Signup and view all the answers

What characteristic of malignant cells contributes to their limited response to leucovorin?

Defective transport system for drug uptake Signup and view all the answers

Which statement accurately reflects the pharmacokinetics of mercaptopurine?

It undergoes erratic absorption and is widely distributed, but not to the CNS. Signup and view all the answers

What primary biochemical process does mercaptopurine disrupt after conversion to its active form?

Purine biosynthesis Signup and view all the answers

Inhibition of which enzyme is fundamentally linked to the action of methotrexate?

Dihydrofolate reductase Signup and view all the answers

Which of the following is NOT a toxicity associated with mercaptopurine?

Hepatic failure Signup and view all the answers

What is the mechanism of action of fluorouracil?

Inhibits biosynthesis of DNA and RNA Signup and view all the answers

In the treatment of what condition are pyrimidine analogs predominantly used?

Solid tumors Signup and view all the answers

Which of the following describes a common trait of pyrimidine analogs?

They are prodrugs that require conversion to their active forms. Signup and view all the answers

Which is a consequence of the incorporation of pyrimidine analogs into nucleic acids?

Disruption of nucleic acid function Signup and view all the answers

Which cancer is specifically mentioned as being approved for treatment with Etoposide?

Refractory testicular cancer Signup and view all the answers

What is the primary mechanism of action for Etoposide?

Inhibits topoisomerase II Signup and view all the answers

Which of the following adverse effects is associated with Amsacrine?

Bone marrow suppression Signup and view all the answers

What distinguishes Mitotane from other anti-cancer drugs listed?

It selectively targets adrenal cortex cells Signup and view all the answers

Which drug inhibits the synthesis of asparagine in tumor cells?

Crisantaspase Signup and view all the answers

What type of leukaemia is Hydroxyurea primarily indicated for?

Chronic myeloid leukaemia Signup and view all the answers

What adverse effect is associated with taking Procarbazine in combination with alcohol?

Generalized cytotoxicity Signup and view all the answers

What unique characteristic of cell sensitivity is noted concerning Etoposide?

Cells in the S and G2 phases are most sensitive Signup and view all the answers

What mechanism is commonly attributed to Methylhydrazine?

Generalized cytotoxic action Signup and view all the answers

What is a critical monitoring requirement during the therapy with Crisantaspase?

Organ function Signup and view all the answers

Which of the following is a competitive inhibitor at oestrogen receptors?

Tamoxifen Signup and view all the answers

What is the effect of adrenocortical steroids like Prednisolone in cancer therapy?

Inhibit growth of lymphoid tissue cancers Signup and view all the answers

Which hormone therapy is effective in treating androgen-dependent prostatic cancer?

Flutamide Signup and view all the answers

Which drug is cited as causing non-specific immunostimulation?

Levamisole Signup and view all the answers

Which approach in immunotherapy utilizes tumor-specific monoclonal antibodies?

Magic-bullet therapy Signup and view all the answers

What role do gonadotropin-releasing hormone (GnRH) analogues play in cancer treatment?

Inhibit GnRH release Signup and view all the answers

Which of the following hormones is used to inhibit endometrial cancer?

Progesterones Signup and view all the answers

What is the primary purpose of using vaccines like BCG in cancer therapy?

To provide non-specific immunostimulation Signup and view all the answers

What is the primary purpose of using recombinant colony stimulating factors in chemotherapy?

To reduce the duration of neutropenia following chemotherapy Signup and view all the answers

Which of the following combinations of drugs is most likely to lead to increased neurotoxicity?

Methotrexate and vincristine Signup and view all the answers

Which of the following is NOT a mechanism of drug resistance in chemotherapy?

Enhanced uptake of the drug by cancer cells Signup and view all the answers

What is a common treatment advantage of administering large doses of chemotherapy intermittently?

Enabling the bone marrow to regenerate between doses Signup and view all the answers

Which drug's resistance mechanism involves mutation leading to less affected cells?

Methotrexate Signup and view all the answers

What is the effect of using Verapamil in relation to chemotherapeutic drugs?

It blocks the efflux of drugs by p-glycoprotein Signup and view all the answers

What is the primary advantage of combination therapy in chemotherapy?

Reduces the risk of drug resistance Signup and view all the answers

Which condition describes primary drug resistance in chemotherapy?

Resistance that occurs when the drug is first administered Signup and view all the answers

Study Notes

Methotrexate

Inhibits dihydrofolate reductase, preventing conversion of dihydrofolic acid (FH2) to tetrahydrofolic acid (FH4).
FH4 is essential for folic acid activation and necessary for DNA, RNA, and protein biosynthesis.
A significant consequence of reduced FH4 is impaired thymidylate biosynthesis, crucial for DNA synthesis.
Methotrexate induces cell death primarily by disrupting DNA synthesis, targeting cells in the S-phase.
Reduced thymidine levels signal apoptosis (programmed cell death).
Leucovorin rescue can enhance methotrexate efficacy; normal cells use leucovorin to bypass methotrexate's metabolic blockage.
Some cancer cells are resistant due to inefficient methotrexate uptake.

Purine Analogs

Key purine analogs include mercaptopurine, cladribine, clofarabine, fludarabine, nelarabine, pentostatin, and thioguanine.
Mercaptopurine (Purinethol):
- Prodrug, converted to active form inside cells.
- Disrupts purine biosynthesis and nucleotide interconversion, being S-phase specific.
- Primarily used for maintenance therapy in acute lymphocytic leukemia (ALL).
- Side effects include bone marrow suppression, mild hepatotoxicity.

Pyrimidine Analogs

Essential pyrimidines: cytosine, thymine, uracil; used in DNA and RNA biosynthesis.
Pyrimidine analogs include cytarabine, fluorouracil, capecitabine, floxuridine, and gemcitabine.
Fluorouracil (Adrucil):
- Fluorinated uracil derivative, effective against solid tumors and specific blood cancers.

Etoposide

Derived from podophyllotoxin; inhibits topoisomerase II, preventing DNA repair.
Cell death occurs through accumulation of irreparable DNA breaks.
Most effective in S and G2 phases, used primarily for refractory testicular and small cell lung cancers.

Miscellaneous Anti-Cancer Agents

Methylhydrazine: Generalized cytotoxic actions with MAO inhibition.
Procarbazine: Inhibits DNA & RNA synthesis, used for lymphoma.
Hydroxyurea: Inhibits ribonucleotide and deoxyribonucleotide synthesis, treating chronic myeloid leukemia (CML).
Crisantaspase: Bacterial asparaginase; treats acute lymphoblastic leukemia (ALL), risk of CNS depression.
Mitotane: Selectively cytotoxic to adrenal cortex tumors.
Amsacrine: Intercalates with DNA; treats acute myeloid leukemia (AML), carries risk of cardiotoxicity.

Endocrine Therapy

Targets hormone-dependent cancers potentially through surgical removal or through hormone antagonism.
Medications include:
- Adrenocortical steroids (e.g., Prednisolone): Treat lymphoid tissue cancers; also manage cancer complications.
- Oestrogen antagonists (e.g., Tamoxifen): Competitive inhibition at estrogen receptors, indicated in metastatic breast cancer for pre-menopausal women.
- Progesterones: Effective against endometrial and some prostate cancers.
- Androgen antagonists (e.g., Flutamide): Treat androgen-dependent prostate cancers.

Immunotherapy

Advances based on the immune system's response to infections leading to tumor regression.
Strategies include:
- Tumor-specific monoclonal antibodies targeting cancer cells.
- Non-specific immunostimulatory vaccines (e.g., BCG).
- Cytokines (e.g., interferon-α) modulating immune responses.

Treatment Schedules in Cancer Chemotherapy

Combines multiple agents to enhance toxicity and reduce resistance.
Example combinations include methotrexate and vincristine, selecting drugs with lower myelotoxicity.
Administering large, intermittent doses allows recovery time for bone marrow.

Drug Resistance in Chemotherapy

Resistance can be primary (present initially) or acquired during treatment.
Mechanisms include:
- Increased drug efflux via P-glycoprotein.
- Decreased drug uptake or activation.
- Increased inactivation or alternative metabolic pathway usage.
- Enhanced target repair and dependency alterations.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Test your knowledge on the mechanisms of action of Methotrexate and purine analogs. This quiz covers their effects on DNA synthesis, cell death, and potential resistance in cancer treatment. Understand the implications of folic acid metabolism and purine biosynthesis.