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54 Cards in this Set
- Front
- Back
what are the 2 forms of Alkylating Agents
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Nitrogen Mustards
Nitrosoureas |
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what kind of drug is:
Cyclophosphamide |
Alkylating Agent
Nitrogen Mustards |
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what kind of drug is:
Mechlorethamine |
Alkylating Agent
Nitrogen Mustards |
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what kind of drug is:
Melphalan |
Alkylating Agent
Nitrogen Mustards |
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what kind of drug is:
Carmustine |
Alkylating Agents
Nitrosoureas |
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what kind of drug is:
Lomustine |
Alkylating Agents
Nitrosoureas |
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MOA for the alkylating agents?
** |
covalently bind to DNA and Alkylate** it
they hit the N7 position of GUANINE primary leads to DNA MODIFICATION* |
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What 3 things does alkylation do?
*** |
1)***Excessive cross-linking (bifunctional)
Cytotox correlates very closely with interstrand cross-linkage of DNA 2)***DNA strand breaks (monofunctional) Depurination by excision of guanine residues, leading to strand breakage by repair enzymes 3)Miscoding of DNA -modified guanine mispairs with thymine |
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do alkylating angents hit cycling or noncycling cells?
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Hits BOTH
Replicating cells are most susceptible |
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Unique toxicity for alkylating agents?
** |
Vascular endothelial damage that may precipitate veno-occlusive disease`(VOD)** of the liver (often fatal)
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what drugs has strong Vesicant properties?*** what does this produce?
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Alkylating Agents (particularly nitrosoureas)
have strong vesicant properties, damage veins with repeated use an if extravasated, produce ulceration**, necrosis** |
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which nitrogen mustard alkylating agent requires hepatic activation (P450)****
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Cyclophosphamide
prodrug requiring activation in liver |
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what is the dose limiting effect of cyclophosphamide?
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bone marrow depeltion
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what is an acute dose-limiting effect of cyclophophamide? What causes this? What 3 things can help this?
****** |
**Hemorrhagic cystitis
caused by metabolite acrolein** Limit toxicity with aggressive hydration** and use Mesna** or N-acetylcysteine (NAC)** |
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what nitrosourea can cross the BBB and can treat the CNS?
** |
Lomustine
note: it SPONTANEOUSLY BREAKS DOWN |
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what drugs cause profound and DELAYED bone marrow depression?**
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Carmustine (BCNU) & Lomustine (CCNU)
must monitor for at least 6 weeks after a dose |
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what is dose limiting for Carmustine (BCNU) & Lomustine (CCNU)
*** |
CNS, renal, hepatic & pulmonary toxicity
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for what drugs are Bone marrow and pulmonary toxicities are a function of lifetime cumulative dose
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Carmustine (BCNU) & Lomustine (CCNU)
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Testicular, ovarian and bladder cancer are treated with what?
*** |
Cisplatin
(Alkylating Agent-->Platinum analogs) |
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what favors the process of creating a reactive molecule for Cisplatin?
** |
Low chloride concentrations favor process
inside cells urine |
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note: Cisplatin Causes inter- and intra-strand DNA crosslinks
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was underlined
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what alkylating agent is responsible for SEVERE NV?
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Cisplatin
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what alkylating agent can cause anaphylactic like reactions?
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Cisplatin
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2 MAJOR delayed toxicities of Cisplatin?
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Nephrotox: renal tubular damage
Neurotoxiticy: peripheral motor & sensory neuropathy Ototoxicity (hearing loss) |
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what is a pretreatment for cisplatin to prevent nephrotox?
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Abrogated by hydration** (pretreatment) and chloride diuresis**
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what is a cytoprotective agent that stops nephrotoxicity from cisplatin
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Amifostine
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what type of drug is methotrexate?
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antifolate
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what type of drug is
5-Fluorouracil & capecitabine |
Pyrimidine Antimetabolites
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what type of drug is
Cytarabine |
Pyrimidine Antimetabolites
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what type of drug is
Gemcitabine |
Pyrimidine Antimetabolites
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what type of drug is
6-Mercaptopurine |
Purine Antimetabolites
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what type of drug is
6-Thioguanine |
Purine Antimetabolites
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MOA for Methotrexate?
** |
Folic acid analog (antagonist)
inhibits dihydrofolate reductase (DHFR) leads to partial depletion of tetrahdyrofolate cofactors interrupts de novo synthesis of TMP and purine nucleotides |
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Methotrexate major uses (4)? where
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leukemias;
lymphomas Psoriasis Rheumatoid arthritis BREAST |
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what can reduce the toxicity (DHFR inhibition) in normal cells with use of methotrexate?
*** |
Leucovorin rescue
replenishes intracellular pool of tetrahydrofolate cofactors |
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Dose limiting for methotrexate?
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BMD
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Major side effects of methotrexate?
*** |
GI ulceration, mucositis
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Capecitabine is the oral form of what drug?
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5-Fluorouracil (5-FU)
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3 major uses for 5-Fluorouracil (5-FU)?
** |
Topical treatment of basal cell carcinoma
Breast cancer One of few with effect in colorectal cancer |
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MOA of 5-Fluorouracil (5-FU)?
*** i will put * on everything in the answer that was underlined |
Converted in target cells to 5F-dUMP
ie nucleobase --> nucleoside --> nucleotide 5F-dUMP covalently binds to **thymidylate synthetase** with FH4 (reduced folate) **Blocks conversion of dUMP to TMP** **DECREASED TTP & inhibition of DNA synthesis** thymineless death Also converted to FdUTP and FUTP Can incorporate into DNA and RNA **Inhibits DNA & RNA synthesis** |
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2 major side effects of 5-Fluorouracil?
** |
GI mucositis – dose limiting with infusion
BMD – dose limiting with IV bolus |
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what effect will leucovorin have when used with 5-FU?
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Leucovorin enhances cytotoxic effects as well as toxicities
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this drug is a prodrug, that is a C analog, and inhibits DNA synthesis
** |
Cytarabine
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major uses of Cytarabine?
** |
Hematological (AML, ALL, non-Hodgkin’s lymphoma)
** |
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major dose limiting side effect of Cytarabine
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BMD
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MOA of Gemcitabine?
** |
**inhibits ribonucleotide reductase
--decreases dNTPs **inhibits DNA polymerase **incorporates into DNA (chain termination) |
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major tox of Gemcitabine?
** |
Myelosuppression (neutropenia)
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clinical uses of 6-Mercaptopurine & 6-thioguanine?? 3
** |
ALL , AML , CML
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MOA of 6-Mercaptopurine & 6-thioguanine?
* |
Inhibits synthesis of purine nucleotides
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the parent form of these drugs are inactive... nucleobase --> nucleotide analog
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6-Mercaptopurine & 6-thioguanine
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what metabolizes (inactivates) 6-Mercaptopurine?
** |
xanthine oxidase
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The dose of 6-MP must be lowered when _____ is used concurrently
*** |
allopurinol
this is a xanthine oxidase, which metabolizes the drug allopurinol is used To protect the kidneys against uric acid damage |
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3 toxiciteis with the purine analogs (6-Mercaptopurine & 6-thioguanine
)? * |
BMD (dose limiting)
Hyperuricemia (potential for crystaluria) Hepatotoxicity |
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~ 1/3 pts show some cholestatic jaundice with this drug
****TESTTTT |
6-Mercaptopurine & 6-thioguanine
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