BIIC Pharmacology Lecture 10_Chemotherapy of Lukemias Flashcards
What is the goal of therapy with Acute Lymphoblastic Leukemia (ALL)?
complete clinical and hematologic remission. This is often acheived in children but less frequently in adults
Doxorubicin, Daunorubicin, Epirubicin are all what kind of drug?
Anthracyclines
Drugs ending in -rubicin are typical of what drug class?
Anthracyclines
What is the MOA for Anthracyclines?
- Intercalation into DNA
- Inhibition of topoisomerase II
- Generation of semiquinone free radicals and oxygen free radicals
Why do anthracyclines negativly effect the heart so strongly?
Anthracyclines create free radical O2 which creates H2O2. The heart does not have catalase. The only way for the heart to process the H2O2 is through the fenton pathway. This forms a hydroxy radical.
When giving anthracyclines, what medication can be used to protect the heart?
dexrazoxane
What are the three main ADRs of anthracyclines?
Mucositis
Stomatitis
Cardiotoxicity
What is unique about Mitoxantrone?
It works like an anthracycline but it does not generate free radicals
What is the function of Imatinib?
It is a protein tyrosine kinase inhibitor that is used against the BCR-ABL gene. It results in cellular apoptosis.
What are the two main applications of imatinib?
- Chronic myelogenous leukemia (CML)
* Gastrointestinal stromal tumors (GIST)
What is the purpose of Intrathecal methotrexate ± cranial irradiation in ALL treatment?
It can be used to irradicate cancer cells that are sequestered in immune privliged areas
What is the MOA of Methotrexate?
directly inhibits dihydrofolate reductase (stopes purine synthesis) and causes indirect inhibition of thymidylate synthase
What are the three main ADRs of Methotrexate?
o Mucositis
o Photosensitivity
o Nephrotoxicity
What is the “antidote” of Methotrexate?
Leucovorin
6-Mercaptopurine and 6-Thioguanine are both what kind of drug?
Purine Antagonists with a structure similar to guanine
Thiopurine methyl transferase does what?
It is the enzyme that metabolizes Thiopurines (like purine antagonists). Patients with reduced activity thiopurine get therapudic treatment at much lower levels of the purine antagonist.
What is the main ADR of 6-Mercaptopurine
Hepatotoxicity (elevated liver enzymes)
Cyclophosphamide & Ifosfamide are both matabloized into what? Why does this matter?
They are matabloized into Acrolein which causes hemorrhagic cystitis in the bladder.
How can the effects of acroline be minimized?
Hydration and administration fo mensa
What is the main ADR of Cyclophosphamide & Ifosfamide?
Hemorrhagic cystitis
What is the clinical goal of Acute Myeloid Leukemia (AML)?
complete clinical and hematologic remission
Cytarabine & Gemcitabine are both what kind of drugs>
Cytidine analogs
What is the main ADR of Cytarabine?
Hand and Foot Syndrome
Fludarabine, Cladribine, Clofarabine are what kind of drugs?
Halogenated adenosine analogs
