chemotherapy medication

Name 3 antimetabolite: what phase do they act on

act on S phase

1. methotrexate, trimethroprim, pyrimethamine

2. 5-fluorouracil

3. cytosine arabinoside

how does methotrexate, trimethroprim and pyrimethamine work

competitive folate inhibitor which is taken into the cell and reduced by dihydrofolate reductase produces tetrahydromethotrexate

THM inhibits thymidylate synthase production of deoxythymidine monophosphate

Name 3 antimetabolite: what phase do they act on

act on S phase

1. methotrexate, trimethroprim, pyrimethamine

2. 5-fluorouracil

3. cytosine arabinoside

how does methotrexate, trimethroprim and pyrimethamine work

competitive folate inhibitor which is taken into the cell and reduced by dihydrofolate reductase produces tetrahydromethotrexate

THM inhibits thymidylate synthase production of deoxythymidine monophosphate

how does 5-fluorouracil works

forms a complex with uracil → fluorouracil-deoxy uridine via thymidine phosphorylase

forms a complex with tetrahydrofolate inhibiting thymidylate synthase

how does cytosine arabinoside work

is an adenine analogue that prevents chain elongation

what are the drugs acting on G2 phase (3)

1. bleomycin

2. dactinomycin

3. topoisomerase II inhibitors: actinomycin, doxorubicin

how does bleomycin mork +~ side effects

only drug that works on cell in Go

1. iron chelator that binds to the major groove of DNA

2. produces hydroxyl free radicals that destroy DNA

causes pulmonary fibrosis

how does dactinomycin work

1. binds to the minor groove of DNA and disrupts RNA polymerase binding

how do topoisomerase II inhibitors work, ex?

actinomycin, doxorubicin

1. stabilise topoisomerase II and DNA in its unstable unwound formation

2. DNA is vulnerable to dmg

drugs acting on M phase

1. vinca alkaloids: vincristine, vinblastin, vindesine

2. taxol

how do vinca alkaloids work? ex?

vincristine, vinblastine, vindesine

1. bind to B tubulin and inhibit tubulin dimer addition

2. microtubules get progressively shorter until cell dies

how does taxol work

binds to B tubulin and stabilises it allowing addition of tubulin dimers until the cell dies

non-specific alkylating agents?

1. cisplatin

2. cyclophosphamides

produce immonium and carbonium ions that are e- hungry and form cross-links between nitrogenous bases causing them to apoptose

how does cisplatin work

square planar molecule with 2NH3 and 2Cl- that form cross-links between nitrogenous bases causing them to apoptose

how does cyclophosphamides work

produces phosphamide mustard and acrobin

how do cells become immune to alkylating agents

1. increased drug efflux pump

2. increased expression of glutathione

3. up regulated drug metabolism enzymes

anti-neoplastic drug?

asparaginase

1. in normal cells it is no-essential but in cancer cells it is essential

2. asparaginase breaks down asparagine

PARP inhibitor

olaparib

1. inhibits poly-ADP ribose polymerase that repairs single stranded DNA breaks → double stranded DNA breaks

2. normal cells are unaffected as they have BRCA2 genes which can repair the break

vascular disrupting agents

colchicine derivative: combrostating A1 diphosphate

1. disrupts tubulin cytoskeleton causing cells to be stuck is a misshapen configuration

2. cells fall off and occlude vessels

3. exposed collagen also activates platelets

anti-angiogenesis

avastin

1. inhibits VEGFR

tyrosine kinase inhibitors (3)

1. imatinib: prevents EGFR

2. sorafenib, sunitinib: inhibits PDGF

3. calbiochem: inhibits FGF

vascualr normalising medication

1. verapamil: inhibits Ca2+ in causing vasodilation

2. cilengitide: AVB3 integrin inhibitor

higherarchie of immunogenicity

omab>ximab>zumab>umab

anti-CTLA4

ipilimumabipil

ipilimumab

anti-CTLA4

rituximab

chimeric anti-CD20 (B cell lymphoma)an

anti-CD20

rituximab

herceptin

inhibits HER2 to decrease cell growth (humanised Ab)

her2 inhibitor

herceptin

blinatumomab

anti CD19 on B cells (bispecific)

anti-TNF-a

etanercept, infliximab

immunosuppresion

tacrolimus, cyclosporin (calcineurin inhibitor)