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;
28 Cards in this Set
- Front
- Back
|
What is the MOA of Nitrogen Mustards?
|
crosslinking of DNA strands which is the main cause of toxicity; monoalkylated guanine can form anomalous base pairs with thymidine; depurination can also occur leading to strand breaks
|
|
|
How does resistance develop to nitrogen mustards?
|
alkylated DNA can be repaired by excision of the alkylated nucleotides; resistance occurs with increased repair activity, decreased drug permeability, and increased production of thiols
|
|
|
What phase to alkylating agents target?
|
NONE! HA! They are most cytotoxic to rapidly proliferatin cells, cels die by apoptosis or by failure to replicate heavily damaged DNA. It'll also suppress your bone marrow. Yum.
|
|
|
How will alkylating agents fuck you the second time around?
|
They are highly mutagenic and can cause secondary cancer (esp. leukemia), sterility later in life
|
|
|
What is the special characterisitic of Mechlorethamine?
|
Extremely unstable! Active for only a few minutes;
|
|
|
What is Mechlorethamine used in?
|
IV in Hodgkin's and other lymphomas. MOPP!!! (mechlorethamine, vincristine (oncovan), procarbazine, prednisone)
|
|
|
How is Cyclophosphamide compared to mechlorethamine?
|
Much longer t1/2; less thrombocytopenia, nausea, and vomiting less severe but still common, not a vesicant more alopecia.
|
|
|
Why doesn't cyclophosphamide work right away?
|
needs to be metabolically activated in the liver! Converted to toxic metabolites phosphoramide mustard and acrolein
|
|
|
What does acrolein, the toxic metabolite of cyclophosphamide cause?
|
sterile hemorrhagic cystitis that can be alleviated with actylcysteine or mesna
|
|
|
How is cyclophosphamide taken?
|
Oral, IV, or IM; it's is the most widely used nitrogen mustard
|
|
|
How does Melphalan/cholarambucil differ from mechlorethamine?
|
Presence of aromatic ring stabilizes the compound. It is given orally
|
|
|
What is Melphalan/cholrambucil used to treat?
|
Multiple Myeloma
|
|
|
What is the MOA of Alkylsulfonates?
|
Alkylation of 7-nitrogen of guanine; formation of intrastrand DNA crosslinks predominate
|
|
|
How are alkylsulfonates excreted?
|
In the Urine as methane sulfonic acid; they are less reactive than nitrogen mustards
|
|
|
How are alkylsulfonates uniquley myelosuppressive?
|
selective depression of granulocytopoiesis; lymphocytes are spared
|
|
|
What is a weird complication of alkysulfonates? Think Zoolander.
|
"Sulfan lung" (FIBROSIS) a rare by sometimes fatal complication; bone marrow depression is dose limiting.
|
|
|
Names the Nitroureas. Do it now.
|
Carmustine, Lomustine, Semustine
-ustine = nitroureas |
|
|
What is the MOA of Nitroureas?
|
Alkylation of DNA; carbamylation of proteins
|
|
|
Where do the Nitroureas soak into?
|
THE BRAIN! Crosses the blood brain barrier; highly lipophilic
|
|
|
As far as toxicity, how do Nitroureas creep around and then get ya!
|
Dose limiting toxicity; Profound cumulative myelosuppression that may be delayed (6 weeks); phelbitis at injection; long term use can produce renal failure
|
|
|
What are nitroureas especially useful in the treatment of?
|
TUMORS of the CNS. That's the brain.
|
|
|
What is the MOA of dacarbazine?
|
Alkylating activity by oxidative demethylation in the liver which decomposes to form the active metabolite, diazomethane; Diazomethane, the metabolite, forms carbonium ions to alkylate DNA
|
|
|
What is the MOA of procarbazine?
|
alkylates 7-nitrogen of guanine; produces DNA strand breaks; inhibits DNA, RNA, and protein synthesis
|
|
|
What is procarbazine used for?
|
penetrates CSF; component of MOPP regimen for Hodgkin's; it's the first P!!!
|
|
|
What is the MOA of Cisplatin?
|
activated in low CHLORIDE environments; can alkylate DNA; also produces intrastrand and interstrand DNA crosslinks
|
|
|
What is the toxicity of Cisplatin?
|
Damaged to proximal tubule of kidney; ototoxic, causes intense nausea and vomiting
|
|
|
What is Cisplatin mainly used for?
|
Testicular cancer and ovarian cancer
|
|
|
What is Mitomycin?
|
Natural antibiotic derived from streptomyces; activated intracellularly to bifunctional alkylating agent; also causes single strand breaks by free radical mechanism
|
