chemotherapy Flashcards
what are the 4 main therapeutic agents used in chemotherapy?
alkylating agents
antimetabolites
cytotoxic antibodies
plant derivatives
what do alkylating agents do to cause conformational changes in DNA?
they form covalent bonds with nucleophilic substances in the cell and cross link DNA which prevents DNA polymerase accessing to replicate the DNA
how exactly is the DNA changed by alkylating agents?
modifies guanine so it mispairs with Thymine which causes the cell to undergo apoptosis
what type of alkylating agent is cyclophosphamide?
a nitrogen mustard
what enzyme in the liver activates cyclophosphamide?
p450 enzymes
what is the cytotoxic product of nitrogen mustards?
phosphor amide mustartd
what is the toxic by-product of the activation of nitrogen mustards which is counteracted by mesna?
acrolein
which alkylating agent is used in chronic granulocyte leukaemia to prevent formation of granulocytes and platelets in low dosage and RBCs in high dosage?
Busulphan (an alkylsulphonate)
which type of alkylating agent is used to treat brain tumours because of its lipid soluble properties which allow it to cross the blood-brain barrier?
nitrosoureas (eg lomustine and carmustine)
what class of alkylating agent is a water soluble complex?
platinum based compounds (e.g. cisplatin)
what are the three classes of antimetabolite chemotherapy drugs?
antifolates
antipyrimidines
antipurines
what is an example of the drug which is a competitive inhibitor of the folate pathway and is giving orally usually?
methotrexate
what are two examples of antipyrimides which mimic the structure of pyrimidines and inhibit DNA polymerase?
Fluorouracil (5-FU) gemcitabine (and its analogue cytarabine)
what are some examples of antipurines which act as fraudulent nucleotides and inhibit DNA polymerase?
mercaptopurine, thioguanin, fludarabine
what are the four different cytotoxic antibiotic classes?
anthracyclines
dactinomycin
bleomycin
mitomycin
what is the mechanism of action of anthracyclines?
bind to DNA and prevents DNA and RNA synthesis by stabilising the DNA - topoisomerase II complex
what is the most common example of an anthracycline drug?
doxorubicin
what is the mechanism of action of dactinomycin drugs?
binds in the minor groove of DNA and prevents the movement of RNA polymerase and therefore prevents transcription
what is the mechanism of action of belomycins?
these are a group of metal-chelating gycopeptide antibiotics that degrade preformed DNA, causing chain fragmentation and release of free bases (most effective at G2 stage but also active against non-dividing cells)
what is the mechanism of action of Mitomycin?
functions as a bifunctional alkylating agent, alkylating preferentially at O6 of guanine - cross links DNA and may also degrade DNA through generation of free radicals
what is the main mechanism of action of plant derivative chemotherapy drugs?
they are spindle poisons which affect microtubule function and prevent mitotic spindle formation
what are the four different classes of plant derivative chemotherapy drugs?
vinca alkaloids
taxanes
camptothecins
etoposide
what is the mechanism of action of vinca alkaloids?
bind tubular and prevent polymerisation into microtubules
what are some examples of vinca alkaloids?
vincristine and vinblastine
what is the mechanism of action of taxanes?
stabilise microtubules
what are some examples of taxanes?
paclitaxel (taxol)
docetaxel
what is the mechanism of action of camptothecins?
bind to and inhibit topoisomerase 1
what is an example of a camptothecin?
irinotecan
what is the mechanism of action of etoposide?
inhibits mitochondrial function, nucleoside transport and topoisomerase II
