Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
66 Cards in this Set
- Front
- Back
|
What are the 3 classes of alkylating agents?
|
1. nitrogen mustards
2. alkyl sulfonates 3. nitrosureas |
|
|
What is MoA of alkylating agents?
|
attach an alkyl group to DNA - causes fragmentation, mutation, and cross linking
|
|
|
What are the nitrogen mustards? (6)
|
1. cyclophosphamide
2. ifosphamide 3. chlorambucil 4. melphalan 5. mechlorethamine 6. bendamustine |
|
|
What are the typical alkylating agent toxicities?
|
myelosuppression, N/V/D, anorexia, mucositis, alopecia, infertility, risk of secondary leukemia
|
|
|
Which two alkylating agents require liver metabolism to their active form and cause hemorrhagic cystitis?
|
cyclophosphamide, ifosfamide
|
|
|
What is a unique toxicity of cyclophosphamide/ifosfamide?
|
bladder irritation
|
|
|
When is mechlorethamine used?
|
salvage therapy of HD
|
|
|
When is chlorambucil used?
|
older patients with CLL, rarely in lymphomas
|
|
|
When is cyclophosphamide used?
|
HD/NHL, acute and chronic leukemias, mycosis fungoides, multiple myeloma
|
|
|
When is melphalan used?
|
multiple myeloma
|
|
|
When is bendamustine used?
|
recently approved in CLL and NHL
|
|
|
What is an example of an Alkyl sulfonate?
|
Busulfan
|
|
|
When is busulfan used?
|
CML and myeloproliferative disorders
|
|
|
What is busulfans unusual AE?
|
Pulmonary fibrosis (can be years after exposure)
|
|
|
What are two examples of nitrosoureas?
|
carmustine, lomustine
|
|
|
When are the nitrosoureas used?
|
brain tumors (good CNS penetration)
|
|
|
What is an example of an atypical alkylating agent?
|
procarbazine
|
|
|
When is procarbazine used?
|
HD and NHL
|
|
|
How do the platinum analogs work?
|
cross link DNA preventing replication
|
|
|
What are the platinum analogs? (3)
|
1. cisplatin
2. carboplatin 3. oxaliplatin |
|
|
What are the platinum analog AEs? (5)
|
1. neuropathy
2. myelosupression 3. NVD 4 hypersensitivity 5 extreme cold sensitity |
|
|
What are the antimetabolites?
|
cytotoxic agents from natural sources resembling vitamins, nucleosides, or amino acids
|
|
|
Which 2 antimetabolites are folic acid analogs?
|
methetrexate and pemetrexed
|
|
|
How does methotrexate work?
|
competitively inhibits DHFR which inhibits thymidine sythesis, purines, and AA synthesis
|
|
|
How is pemetrexed an improvement on methotrexate?
|
multi-targeted antifolate, when given with B12 and folate has less toxicity and equal efficacy with methotrexate
|
|
|
What are the purine inhibitors?
|
6-mercaptopurine
6-thioguanine |
|
|
How do 6-mercaptopurine and 6-thioguanine work?
|
feedback inhibition stops purine biosynthesis, inhibit DNA and RNA synthesis, block chromosomal replication
|
|
|
What happens if you give 6-mercaptopurine with allopurinol?
|
blocks metabolism, toxic build up of 6-MP
|
|
|
What are the purine analogues?
|
fludarabine and cladribine
|
|
|
How do fludarabine and cladribine work?
|
inhibit DNA and RNA synthesis, inhibit adenosine deaminase
|
|
|
Why are fludarabine and cladribine particularly effective in lymphoid cells?
|
inhibition of adenosine deaminase leads to toxic accumulation of adenosine in lymphoid cells
|
|
|
What is the major AE of fludarabine and cladribine?
|
major immunosuppression with risk of PCP and fungal infections, viral reactivation
|
|
|
How can you help limit toxicity of methotrexate?
|
give leucovorin (folinic acid) 24 hours after administration
|
|
|
What are the pyrimidines? (5)
|
1. 5-fluorauracil
2. capecitabine 3. gemcitabine 4. cytarabine 5. 5-azacitidine |
|
|
How does 5-fluorouracil work?
|
binds to thymidylate synthase, can't make thymidine from uracil, can't make DNA
|
|
|
What happens if you give leucovorin with 5-FU?
|
stabilizes drug and increases toxicity
|
|
|
What is the PO form of 5-FU?
|
capecitabine
|
|
|
What is gemcitabine and analog of?
|
cytidine
|
|
|
How does 5-azacitidine, decitabine work?
|
incorporated into DNA causing termination, also causes demethylation of gene promotor sequences, can rescue tumor supressor genes
|
|
|
How does gemcitabine work?
|
incorporates into DNA and causes "masked chain termination"
|
|
|
How does cytarabine work?
|
incorporates into DNA and causes chain termination
|
|
|
What is a major concern with cytarabine?
|
neurotoxicity
|
|
|
What does dactinomycin do?
|
intercalates in double strand DNA preventing replication and transcription
|
|
|
How does Bleomycin work?
|
complexes with free radicals and binds to and breaks DNA
|
|
|
What is a serious AE with bleomycin?
|
pulmonary inflammation and fibrosis (low bleomycin hydrolase, high O2)
|
|
|
What are two anthracyclins?
|
doxorubicin, daunorubicin
|
|
|
How do anthracyclines work?
|
inhibit topoisomerase II, intercalate in DNA, generate free radicals
|
|
|
What is the worrying AE of the anthracyclines?
|
cardiac toxicity (based on cumulative dose)
|
|
|
What is etoposide (VP-16)?
|
a topoisomerase II inhibitor that causes DNA damage
|
|
|
Name two vinca alkaloids
|
vincristine, vinblastine
|
|
|
How do the vinca alkaloids work?
|
bind to microtubules and block mitotic spindle formation, block mitosis
|
|
|
What is the major AE of the vinca alkaloids?
|
peripheral neuropathy
|
|
|
Name two taxanes
|
paclitaxel, docetaxel
|
|
|
How do the taxanes work?
|
bind to tubulin and cause M phase mitotic arrest
|
|
|
What are the major AEs of the taxanes? (2)
|
1. acute allergic reactions to solvents
2. neuropathies |
|
|
How does hydroxyurea work?
|
inhibits ribonucleotide reductase, depletes DNA building blocks
|
|
|
When is hydroxyurea used?
|
to bring down blood counts in leukemias, CML, sickle cell
|
|
|
What drug is an improvement on thalidomide?
|
lenalidomide
|
|
|
When are thalidomide and lenalidomide used?
|
multiple myeloma
|
|
|
What are two SERMS?
|
tamoxifen, raloxifene
|
|
|
How do the SERMS work?
|
bind to ERs, block normal binding and activation by estrogen
|
|
|
What are some side effects of SERMS?
|
hot flashes, vaginal dryness, osteoprotective, increase endometrial cancer, increase clots
|
|
|
What does fulvestrant do?
|
not only blocks ERs (like SERMS) but also degrades ERs by preventing dimerization
|
|
|
Name 2 aromatase inhibitors?
|
anastrazole, letrozole
|
|
|
What do anastrazole and letrozole do?
|
block conversion of androgens to estrogen lowering estrogen levels in post-menopausal women
|
|
|
Name two long acting LHRH analogs?
|
goserelin, leuprolide
|
