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54 Cards in this Set

  • Front
  • Back
what are the 2 forms of Alkylating Agents
Nitrogen Mustards

Nitrosoureas
what kind of drug is:

Cyclophosphamide
Alkylating Agent

Nitrogen Mustards
what kind of drug is:

Mechlorethamine
Alkylating Agent

Nitrogen Mustards
what kind of drug is:

Melphalan
Alkylating Agent

Nitrogen Mustards
what kind of drug is:

Carmustine
Alkylating Agents

Nitrosoureas
what kind of drug is:

Lomustine
Alkylating Agents

Nitrosoureas
MOA for the alkylating agents?

**
covalently bind to DNA and Alkylate** it

they hit the N7 position of GUANINE primary

leads to DNA MODIFICATION*
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
do alkylating angents hit cycling or noncycling cells?
Hits BOTH

Replicating cells are most susceptible
Unique toxicity for alkylating agents?

**
Vascular endothelial damage that may precipitate veno-occlusive disease`(VOD)** of the liver (often fatal)
what drugs has strong Vesicant properties?*** what does this produce?
Alkylating Agents (particularly nitrosoureas)

have strong vesicant properties, damage veins with repeated use an if extravasated, produce ulceration**, necrosis**
which nitrogen mustard alkylating agent requires hepatic activation (P450)****
Cyclophosphamide

prodrug requiring activation in liver
what is the dose limiting effect of cyclophosphamide?
bone marrow depeltion
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)**
what nitrosourea can cross the BBB and can treat the CNS?

**
Lomustine

note: it SPONTANEOUSLY BREAKS DOWN
what drugs cause profound and DELAYED bone marrow depression?**
Carmustine (BCNU) & Lomustine (CCNU)

must monitor for at least 6 weeks after a dose
what is dose limiting for Carmustine (BCNU) & Lomustine (CCNU)

***
CNS, renal, hepatic & pulmonary toxicity
for what drugs are Bone marrow and pulmonary toxicities are a function of lifetime cumulative dose
Carmustine (BCNU) & Lomustine (CCNU)
Testicular, ovarian and bladder cancer are treated with what?

***
Cisplatin

(Alkylating Agent--> Platinum analogs)
what favors the process of creating a reactive molecule for Cisplatin?

**
Low chloride concentrations favor process

inside cells
urine
note: Cisplatin Causes inter- and intra-strand DNA crosslinks
was underlined
what alkylating agent is responsible for SEVERE NV?
Cisplatin
what alkylating agent can cause anaphylactic like reactions?
Cisplatin
2 MAJOR delayed toxicities of Cisplatin?

**
Nephrotox: renal tubular damage

Neurotoxiticy: peripheral motor & sensory neuropathy
Ototoxicity (hearing loss)
what is a pretreatment for cisplatin to prevent nephrotox?

**
Abrogated by hydration** (pretreatment) and chloride diuresis**
what is a cytoprotective agent that stops nephrotoxicity from cisplatin
Amifostine
what type of drug is methotrexate?
antifolate
what type of drug is

5-Fluorouracil & capecitabine
Pyrimidine Antimetabolites
what type of drug is

Cytarabine
Pyrimidine Antimetabolites
what type of drug is

Gemcitabine
Pyrimidine Antimetabolites
what type of drug is

6-Mercaptopurine
Purine Antimetabolites
what type of drug is

6-Thioguanine
Purine Antimetabolites
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
Methotrexate major uses (4)? where

**
leukemias;
lymphomas
Psoriasis
Rheumatoid arthritis

BREAST
what can reduce the toxicity (DHFR inhibition) in normal cells with use of methotrexate?

***
Leucovorin rescue

replenishes intracellular pool of tetrahydrofolate cofactors
Dose limiting for methotrexate?
BMD
Major side effects of methotrexate?

***
GI ulceration, mucositis
Capecitabine is the oral form of what drug?
5-Fluorouracil (5-FU)
3 major uses for 5-Fluorouracil (5-FU)?

**
Topical treatment of basal cell carcinoma

Breast cancer

One of few with effect in colorectal cancer
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**
2 major side effects of 5-Fluorouracil?

**
GI mucositis – dose limiting with infusion
BMD – dose limiting with IV bolus
what effect will leucovorin have when used with 5-FU?
Leucovorin enhances cytotoxic effects as well as toxicities
this drug is a prodrug, that is a C analog, and inhibits DNA synthesis

**
Cytarabine
major uses of Cytarabine?

**
Hematological (AML, ALL, non-Hodgkin’s lymphoma)

**
major dose limiting side effect of Cytarabine
BMD
MOA of Gemcitabine?

**
**inhibits ribonucleotide reductase
--decreases dNTPs

**inhibits DNA polymerase

**incorporates into DNA (chain termination)
major tox of Gemcitabine?

**
Myelosuppression (neutropenia)
clinical uses of 6-Mercaptopurine & 6-thioguanine?? 3

**
ALL , AML , CML
MOA of 6-Mercaptopurine & 6-thioguanine?

*
Inhibits synthesis of purine nucleotides
the parent form of these drugs are inactive... nucleobase --> nucleotide analog
6-Mercaptopurine & 6-thioguanine
what metabolizes (inactivates) 6-Mercaptopurine?

**
xanthine oxidase
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
3 toxiciteis with the purine analogs (6-Mercaptopurine & 6-thioguanine
)?

*
BMD (dose limiting)
Hyperuricemia (potential for crystaluria)
Hepatotoxicity
~ 1/3 pts show some cholestatic jaundice with this drug


****TESTTTT
6-Mercaptopurine & 6-thioguanine