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;
52 Cards in this Set
- Front
- Back
|
Which chemotherapy drugs work on the mitosis part of the cell cycle?
|
Vinca alkaloids
Taxanes |
|
|
Which classes of drugs within the DNA synthesis portion of the cell cycle?
|
Anti-metabolites
Epipodophyllotoxins Camptothecins |
|
|
Which chemotherapy drugs are cell cycle non specifc?
|
Alkylating Agents
Anthracyclines |
|
|
What is the function of topoisomerases?
|
Unwinds DNA and recoils the DNA
|
|
|
What is the function of polymerases?
|
matches DNA base pairs
a-t, g-c |
|
|
What are the purines?
|
Adenosine
Guanine |
|
|
Which are the pyrimidines?
|
Thymine
Cytosine |
|
|
What are the alkylating agents?
|
Cyclophosphamide* (CTX, Cytoxan®)
Ifosfamide Platinums Cisplatin (CDDP) Carboplatin Oxaliplatin Nitrosureas Lomustine* (CCNU) Carmustine (BCNU) |
|
|
What are the alkylating agents 2?
|
Mechlorethamine
Melphalan (ALkeran) Mechlorethamine Melphalan* (Alkeran®) Chlorambucil* (Leukeran®) Busulfan* (Myleran®) Thiotepa Procarbazine* Dacarbazine (DTIC) Temozolamide* |
|
|
What are the potential outcomes of the alkylating agents?
|
Template being replicated is misread or mispaired during DNA synthesis
Cross-linking prevents DNA strands from unwinding Single or double-strand breaks in DNA occur |
|
|
What is the mechanism of action of Cyclophosphamide?
|
Parent drug is converted by hepatic microsomal enzymes to 4-hydroxycyclophosphamide (4-HCP)
4-HCP is converted to acrolein and phosphoramide mustard Phosphoramide mustard alkylates DNA Acrolein is responsible for causing hemorrhagic cystitis |
|
|
what is the mechanism of action of phohphoramide mustard?
|
alkylates the DNA
|
|
|
What is the major side effect of acrolein?
|
hemorrhagic cystitis-
|
|
|
What is the mechanism of action of ifosfamide?
|
Parent drug is converted to acrolein and ifosforamic mustard
There is more acrolein formed with ifosfamide Acrolein is responsible for causing hemorrhagic cystitis |
|
|
What are the clinical uses of
Cyclophosphamide? |
leukemia, lymphomas, solid tumors
bone marrow transplant treat graft-versus-host-disease Rheumatic disorders & autoimmune nephritis |
|
|
What are the clinical uses of Ifosphamide?
|
Solid tumors
|
|
|
What is the dose limiting toxicity of Cyclophosphamide?
|
myelosuppression
|
|
|
What is the dose limiting toxicity of Ifosphamide?
|
hemorrhagic cystitis
|
|
|
What is hemorrhagic cystitis?
|
Caused by accumulation of acrolein
Binds to thiol in bladder wall Hematuria, urinary frequency & irritation Prevent with vigorous hydration (≥2 L/day) & MESNA Treat with bladder irrigation, alum irrigation, and other therapies Heme test urine while on therapy |
|
|
What is MESNA?
|
Uroprotectant containing sulfhydryl group
Binds to acrolein in the bladder to form a nontoxic compound Not systemically absorbed so does not interfere with cytotoxic activity Use with cyclophosphamide >2 g/m2/dose, ifosfamide ALWAYS Effective in prevention only |
|
|
what drugs are the platinums?
|
Cisplatin
Carboplatin Oxaliplatin |
|
|
What are the side effects of of Cisplatin?
|
Filtered by glomerulus & concentrated in renal tubules; incompletely cleared
Nephrotoxicity – ↓ GFR, electrolyte losses (Mg, K), and renal failure Prevent with aggressive hydration (NaCl) |
|
|
How is carboplatin dosed?
|
Dosing based on area under the curve
--based on the patients renal function --not concentrated in the renal tubules, more efficiently cleared |
|
|
What are the clinical uses of the platinums?
|
Testicular, ovarian, metastatic bladder, lung and other solid tumors
Cisplatin – most active single agent in cervical cancer Oxaliplatin – colorectal cancer Non-Hodgkin’s lymphoma |
|
|
What are the dose limiting toxicity of Cisplatin?
|
Vomiting
Nephrotoxicity |
|
|
What is the dose limiting toxicity of Carboplatin?
|
Myelosuppression
|
|
|
What is the dose limiting toxicity of oxaplatin?
|
Peripheral neuropathy
|
|
|
What is Amofostine (Ethylol)?
|
chemoprotectant agent that is metabolized to an active free thiol which binds to cisplatin and prevents damage to normal tissue
free radical scavenger side effects include hypotension and nausea and vomiting also used to prevent radiation-associated xerostomia |
|
|
What is Chlorambucil (Leukeran) ?
|
Used for the treatment of chronic lymphocytic leukemia
|
|
|
What is Busulfan (Myleran)
|
Used for treatment of leukemia and transplant
Also available IV form (used more for transplant) toxicity is decreasing seizure threshold |
|
|
What is Melphalan (Alkeran)?
|
Used for the treatment of multiple myeloma
8 mg/m2 PO daily day 1-4 repeat every 28 days All three of these medications come as 2 mg tablets (watch dispensing by brand name) |
|
|
What is Temozolomide (Temodar)?
|
Used for treatment of brain tumors
150 mg/m2 PO daily days 1-5 a cycle repeat cycle every 28 days |
|
|
What are the anthracyclines?
|
Doxorubicin (Adriamycin®, hydroxy-daunorubicin)
Daunorubicin Idarubicin Epirubicin Mitoxantrone |
|
|
What is the mechanism of Action of the anthracyclines?
|
Inhibition of topoisomerase II
Intercalation between DNA base pairs, interfering with DNA synthesis Formation of free radicals that damage DNA and cell membranes |
|
|
What are the clinical uses of Doxorubicin?
|
Breast cancer
Most active agent Sarcomas GI tumors Lymphoma |
|
|
What are the dose limiting toxitities?
|
Myelosuppression
Cardiotoxocity Extravasation injury |
|
|
What is acute cardiotoxicity?
|
Acute
arrhythmias within 24 hours of administration Related more to peak concentrations |
|
|
What is the chronic cardiotoxitcity?
|
secondary to free radical formation
cumulative doses > 550 mg/m2 |
|
|
What is Dexrazoxane (Zinecard®)?
|
Cardioprotectant
Disrupts iron-anthracycline complex Prevents free radical formation without interfering with cytotoxic activity Used in leukemia with patients who have underlying heart dysfunction |
|
|
What is Liposomal doxorubicin (Doxil®)?
|
Liposomal delivery system not as readily taken up by cardiac tissue and decreases the risk of cardiotoxicity
Used in breast, ovarian cancer |
|
|
What is Bleomycin?
|
Used in testicular cancer, Hodgkin’s Disease
Test dose needed only for Hodgkin’s disease Watch for pulmonary toxicity and N/V |
|
|
What is Mitoxantrone?
|
Similar ring structure to anthracyclines
Similar mechanism of action, with decreased tendency for free radical formation Decreased cardiotoxicity and extravasation Decreased nausea and vomiting Blue-green urine discoloration |
|
|
Mitomycin C?
|
used in gastrointestinal tumors
used intravesicularly in bladder cancer Sent to OR for shake and bake |
|
|
What are the antimetabolites?
|
antifolates
purine analogs pyrimidine antagonists? |
|
|
Which drugs are the antifolates?
|
Methotrexate MTX
Pemetrexed (Alimta) |
|
|
What is the mechanism of action of Methotrexate?
|
Taken up intracellularly by cancer & healthy cells
Inhibits dihydrofolate reductase tetrahydrofolate purine & thymidylate Lack of purines & thymidylate prevents DNA synthesis Leucovorin rescue |
|
|
What is leukovorin rescue?
|
Reduced folate that bypass MTX inhibition of tetrahydrofolate synthesis
Uptake healthy cells > cancer cells |
|
|
What are the clinical uses of Methotrexate?
|
Hematological and solid malignancies
ALL, non-Hodgkin’s lymphoma Breast and bladder CA Osteosarcoma (high-dose) Non-oncologic uses |
|
|
What does dihydrofolate reductase do?
|
converts dihydrofolate to tetrahydrofolate--important in pyrimidine synthesis!
|
|
|
Toxicities of Methotrexate
|
Myelosuppression and mucositis
Nephrotoxicity (crystallization of MTX) |
|
|
How do you prevent the toxicities with methotrexate?
|
prevent renal damage by alkalinizing the urine with sodium bicarbonate solutions
avoid drugs that can interfere with excretion of methotrexate: Bactrim, NSAIDS, etc. leucovorin rescue with high doses (yellow card) can accumulate in fluid and leach out over time causing serious toxicity – ensure patient has no fluid collections (ascitis, pleural effusions, etc.) Make sure CXR is obtained prior to dose |
|
|
How do you use Leukovorin Rescue?
|
needed when administering high-doses of methotrexate > 100-500 mg/m2
directly converted into tetrahydrofolate without the need for dihydrofolate reductase begin 24 hours after methotrexate given should be given until methotrexate level is < 0.05 micromolar (5 x 10-8M) Refer to yellow card May give carboxypeptidase (from NCI) Needs IRB approval prior to dose |
