Pharm. of Antineoplastic Agents Flashcards
Name the tumor determinants
1) Growth Fraction
2) Mass Doubling Time
3) Tumor Burden
What 3 tissues are most affected and what are the SE?
1) Fair Follicles- alpecia
2) GI tract- Nausea & Vomiting
3) Bone Marrow- myelosuppression
Does an increase in Growth Fraction increase or decrease Doubling Time?
Decrease
Would a slow doubling time respond better or worse to Tx?
worse
what type of tumors (tumor burden) do not respond well to drug therapy
larger, bulky tumors
describe a log cell-kill
a given drug regimen will eliminate a constant proportion of cells, not a constant number of cells (most solid tumors do NOT exhibit exponential growth)
Describe Vinblastine
binds to tubulin->inhibition of mitosis->metaphase arrest, cells accumulate in G-2 and S phases. Then add ARA-C which blocks DNA synthesis that occurs in the S phase
Describe Mechlorethamine
a Alkylating agent (nitrogen mustard), forms highly reactive intermediates; 2-choloroethyl side chain cyclizes via a 1st order SN1 rxn forming highly reactive ethyl eniminium ion which in turn forms a carbonium ion or other reactive intermediate. When the reactive species reacts with DNA or protein, the alkyl gorup is transferred->Covalent bond (on DNA the most susceptible site is the #7 nitrogen of guanine which is highly neutrophilic.
What are the consequences of Alkylation?
1) Ring Opening
2) Depurinization
3) Miscoding
4) Cross-linking
What is a major SE of Mechlorethamine?
powerful vesicant, so avoid extravasation otherwise serious blisters will occur, can Tx with Na Thiosulfate
What is Aldophosphamide (from Cyclophosphamide) metabolized to?
Carboxyphophamide, Phosphoramide mustard, Acrolein
What is Phosphoramide mustard further metabolized to?
nornitrogen mustard (an alkylating agent)
What is the major SE of Acrolein?
Hemorrhagic Cystitis
What are the the 2 Nitrogen Mustards?
Mechlorethamine and Cyclophasphamide
What are the major SE of Nitrogen Mustards?
1) Leukopenia
2) Hemorrhagic Cystitis
3) SIADH
4) Misc.
What is Filgrastim used for?
counter SE of leukopenia from Nitrogen Mustards: counter marrow suppression by acting like G-CSF and producing monocytes, fibroblasts, and endothelial cells by stimulating proliferation and differentiation of neutrophil progenitors
What does Sargramostim do?
counter SE of leukopenia from Nitrogen Mustards: a GM-CSF used to accelerate myeloid recovery after chemotherapy or BMT, multilineage in that it activates granulocytes, macrophages, megakaryocytes and erythrocytes
How do you avoid Hemorrhagic Cystitis?
a) well hydrating
b) MESNA (mercaptoethanesulfonate Na) reacts with the DB of Acrolein
What is SIADH?
syndrome of inappropriate ADH; water intoxication, can cause hypoatremia(low Na) and seizures; Tx with loop diuretic furosemide (Lasix)
Describe Nitrosoureas
main differences from mustards is that, in addition to alkylating DNA, they do carbamoylate proteins, preferred site of attack is the oxygen on the #6 carbon, not the #7 nitrogen of guanine
Describe the MOA of Nitrosoureas
like mustards, are not phase spedific but their effects are seen during the S phase. They are very lipophilic and readily cross the BBB; Nitrosoureas are NOT vesicants
What are the Folic Acid Analogs?
Methotrexate(MTX) and Pralatrexate
what is the importance of N5-N10-methylenetetrahydrofolate(FH4) in Folic Acid Analogs
donates a 1-carbon unit in the form of -CH3 to deoxyuridine monophosphate(dUMP) in the synthesis of thymidine (aka 5-METHYL-uacil)
describe high and low dose MTX
given as high dose followed by leucovorin rescue; low doses of leucovorin are given to selectively “rescue” healthy cells
