Pharmacological Agents in Leukemia Treatment

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Questions and Answers

Which of the following describes the mechanism of action of anthracyclines?

They intercalate with DNA to inhibit RNA and DNA polymerase. (correct)

They selectively target the cell cycle phase G1.

They enhance the binding of RNA polymerase to DNA.

They inhibit topoisomerase I and promote DNA replication.

What is a significant adverse drug reaction associated with vincristine treatment?

Severe respiratory depression

Significant liver toxicity

Severe neurological toxicity (correct)

Increased risk of infections

Which of the following statements about idarubicin is true?

It cannot be given orally.

It is the least cardiotoxic anthracycline. (correct)

It can be administered intrathecally.

It has the highest incidence of cardiotoxicity among anthracyclines.

What is the primary concern when administering anthracyclines?

Acute cardiotoxicity Signup and view all the answers

Which agent is known to reduce cardiac toxicity resulting from anthracyclines?

Dexrazoxane Signup and view all the answers

When should alemtuzumab be considered for a patient with CLL?

When the patient is refractory to fludarabine and alkylating agents. Signup and view all the answers

What is a common side effect of administering anthracyclines?

Alopecia and rash. Signup and view all the answers

Which of the following describes the administration route of idarubicin?

IV and oral routes. Signup and view all the answers

What should be monitored for patients undergoing treatment with doxorubicin?

Left ventricular function Signup and view all the answers

What is one of the effects of anthracyclines on DNA?

They generate free radicals leading to DNA oxidation. Signup and view all the answers

What is the primary mechanism of action of mercaptopurine in cancer treatment?

Mimics purine structures to interfere with nucleotide synthesis Signup and view all the answers

Which of the following adverse reactions is associated with prolonged use of mercaptopurine?

Secondary acute myeloid leukaemia Signup and view all the answers

What is the significance of testing for thiopurine methyltransferase (TPMT) polymorphism before prescribing mercaptopurine?

To assess the risk of myelosuppression Signup and view all the answers

What is the main indication for the use of cytarabine in treatment protocols?

Acute myeloid leukaemia (AML) Signup and view all the answers

Which of the following statements best describes the action of vincristine in cancer treatment?

Blocks microtubule polymerization during mitosis Signup and view all the answers

What is the primary role of Methotrexate in cancer treatment?

Inhibits critical enzymes in the cell cycle Signup and view all the answers

Which adverse drug reaction is specifically associated with cyclophosphamide?

Hemorrhagic cystitis Signup and view all the answers

In the context of stem cell transplant preparation, which chemotherapy agent is most relevant?

Busulfan Signup and view all the answers

Which of these agents is not typically used as a treatment for chronic lymphocytic leukaemia (CLL)?

Busulfan Signup and view all the answers

What serious adverse effect is associated with high doses of cyclophosphamide?

Cardiotoxicity Signup and view all the answers

How does Methotrexate contribute to cell death in cancer treatment?

By inhibiting the function of dihydrofolate reductase Signup and view all the answers

What is a common reason for providing vigorous IV hydration when administering cyclophosphamide?

To manage the risk of hemorrhagic cystitis Signup and view all the answers

Which mechanism of action defines antimetabolites in cancer therapy?

Structurally resembling normal metabolites Signup and view all the answers

Which of the following actions is primarily associated with rituximab in the treatment of CLL?

Binding to the CD20 receptor Signup and view all the answers

What is a common adverse drug reaction associated with asparaginase treatment?

Hypersensitivity reactions Signup and view all the answers

How does hydroxycarbamide exert its effects in cancer treatment?

By inhibiting ribonucleotide reductase Signup and view all the answers

What kind of antibody is obinutuzumab?

Humanized monoclonal Signup and view all the answers

Which type of cancer is hydroxycarbamide NOT indicated for?

Acute lymphoblastic leukemia Signup and view all the answers

What is a significant limitation of glucocorticosteroids when used in cancer treatment?

The duration of remission is brief compared to cytostatic agents. Signup and view all the answers

What potential complications can arise from the use of asparaginase due to its effects on clotting factors?

Increased risk of bleeding and clotting Signup and view all the answers

Which of the following describes the mechanism of action of glucocorticosteroids?

Binding to cytoplasmic receptors to induce apoptosis Signup and view all the answers

In the context of chronic lymphocytic leukemia (CLL) treatment, what is true about the combination of rituximab with cyclophosphamide and fludarabine?

It is a common initial treatment regimen. Signup and view all the answers

What differentiates humanized monoclonal antibodies like obinutuzumab from mouse chimeric antibodies like rituximab?

They are primarily derived from human sources. Signup and view all the answers

What is the primary mechanism of action of Venetoclax in the treatment of specific leukemias?

Mimics Bax and binds to Bcl-2 Signup and view all the answers

Which drug is known to cause retinoic acid syndrome when used in pregnant patients?

Tretinoin Signup and view all the answers

What adverse effect is commonly associated with Venetoclax?

Tumor lysis syndrome Signup and view all the answers

In treating chronic lymphocytic leukemia (CLL), which of the following statements is correct about Ibrutinib?

It inhibits Bruton’s tyrosine kinase Signup and view all the answers

Which of the following best describes the role of Tretinoin in cancer treatment?

An inducing agent for remission in promyelocytic leukaemia Signup and view all the answers

What is a significant kinetic consideration of Ibrutinib usage?

Avoid interactions with CYP3A4 inducers or inhibitors Signup and view all the answers

What aspect of dexamethasone therapy is critical for its use in cancer treatment?

To reduce edema in critical areas Signup and view all the answers

Which pathway does Ibrutinib significantly impact to inhibit B-cell activation?

NF-ĸB signaling pathway Signup and view all the answers

Which type of leukemia is Venetoclax currently used to treat?

Acute myeloid leukaemia (AML) and Chronic lymphocytic leukaemia (CLL) Signup and view all the answers

What adverse drug reaction is a serious risk associated with Ibrutinib?

Cardiovascular complications like Atrial fibrillation Signup and view all the answers

Study Notes

Pharmacological Agents Used to Treat Leukemia

Imatinib is a tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML). It inhibits the BCR-ABL tyrosine kinase, which is consistently active in many cancers.
Imatinib induces remissions in over 90% of CML patients in the chronic phase.
Other tyrosine kinase inhibitors like dasatinib or nilotinib are used when imatinib fails or is resistant.
Tyrosine kinase inhibitors work by preventing the enzyme from binding to substrates or phosphate donors.
Resistance to these inhibitors can arise from mutations that prevent drug binding.
Imatinib is administered orally at doses between 250-750mg per day. Food does not impede absorption.
Imatinib's half-life is 18-40 hours.
CYP3A4 metabolizes imatinib. Other drugs that inhibit CYP3A4 increase imatinib concentration. Inducers of CYP3A4 (like rifampicin) lower plasma imatinib concentration.
Common adverse drug reactions include myelosuppression (low blood cell count), gastrointestinal distress (diarrhea, nausea, vomiting), liver toxicity, and rash.
Fluid retention (edema), pleural effusions, and congestive heart failure are also possible side effects.

Alkylating Agents

Cyclophosphamide is a prodrug that is converted to an active nitrogen mustard in the liver.
It causes alkylation of DNA, leading to covalent cross-linking between DNA strands, preventing DNA replication.
Cyclophosphamide is used in the treatment of chronic lymphocytic leukemia (CLL).
Adverse drug reactions include myelosuppression (low blood cell count), hemorrhagic cystitis, and cardiotoxicity (at high doses). Mesna and increased fluid intake are used to manage hemorrhagic cystitis.

Antimetabolites

Methotrexate is a folic acid analog that inhibits dihydrofolate reductase, decreasing tetrahydrofolate, an essential coenzyme in DNA synthesis.
This reduces the synthesis of DNA, eventually causing cell death.
Methotrexate is used in the treatment of acute lymphoblastic leukemia.
Common adverse effects include myelosuppression, renal failure, pneumonitis, and mucositis. Leucovorin rescue therapy can help prevent severe toxicities when used with high doses of methotrexate.
Long-term use of low doses of methotrexate in rheumatoid arthritis can cause severe liver toxicity

Plant Products

Vincristine is used in acute leukemia, childhood leukemia, and lymphomas.
It acts during mitosis by binding to beta-tubulin, interfering with microtubule formation, and thus stopping cell division.
Adverse reactions include neurological toxicity, constipation, and myelosuppression among other effects.
Doxorubicin, Daunorubicin, and Idarubicin are cytotoxic antibiotics used in acute leukemia.
These intercalate with DNA, generating free radicals and preventing DNA replication, or preventing re-ligation of DNA strands.
These cause cardiotoxicity.

Other Drugs

Fludarabine is used in combination therapy with cyclophosphamide/rituximab as a first or second-line treatment for B-cell chronic lymphocytic leukemia. It inhibits DNA polymerase, DNA primase, and DNA ligase, incorporated into DNA and RNA.
Mercaptopurine is used in combination therapy with methotrexate to treat acute leukemia, especially acute lymphoblastic leukemia. It is an analogue of the natural purine, hypoxanthine.
Cytarabine (Ara-C) is used to treat acute myeloid leukemia, acute promyelocytic leukemia, and high-grade lymphoma. It is an analog of 2' deoxycytidine. Active form is incorporated into DNA and interferes with base pairing, inducing apoptosis.
Venetoclax is a drug that targets Bcl-2, an anti-apoptotic protein, which is overexpressed in some leukemias, notably CLL. In normal cells, Bcl-2 prevents intrinsic apoptosis. Venetoclax binds to and inhibits Bcl-2, stimulating apoptosis in cells that overexpress Bcl-2.
Ibrutinib inhibits Bruton's tyrosine kinase (BTK). BTK is involved in B-cell activation pathway, stimulating the PIP3-PKC pathway in B-cell leukemia, and contributes to anti-apoptotic signaling, (NF-KB). Ibrutinib inhibits growth factor signaling, thereby inhibiting cell division and decreasing anti-apoptosis signaling.
Midostaurin is a small molecule tyrosine kinase inhibitor used in AML, which is positive for FLT-3
Additionally, there are monoclonal antibodies like Rituximab (targets CD20) and Obinutuzumab (targets CD20).

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Description

Explore the pharmacological agents used to treat leukemia, focusing primarily on Imatinib as a tyrosine kinase inhibitor. Learn about its mechanisms, dosing, metabolism, and resistance as well as other alternatives when treatment fails. This quiz covers key concepts critical for understanding leukemia treatment.