Antineoplastics Flashcards
Cyclophosphamide
Alkylating agent
MOA: forms inter strand cross linking with DNA, which acts as an intercalating agent in the grooves of DNA
ADRs: hemorrhagic cystitis. Occurs due to pre-drug metabolism that forms a toxic metabolite, know as “acrolein”. This toxic metabolite has high affinity form the bladder, and can be removed by MENSA therapy.
Uses: Considering it is a cell cycle nonspecific agent, it has wide spectrum use
ADME: prodrug that must be activated via hepatic metabolism
Carmustine
Alkylating agent
MOA: forms inter strand cross linking with DNA
ADRs: profound myelosupression
Uses: Since it has the ability to cross the BBB, it is most widely used in brain tumors
Cisplatin
Alkylating agent
MOA: forms inter strand cross linking between DNA
ADRs: nephro-/ototoxicity/ Peripheral neuropathy ‘lethal triad’
Uses: Cell cycle non-specific agent, so widely used in combination therapies for testicular and breast cancers
Methotrexate (MTX)
Antimetabolite agent
MOA: inhibits DHFR, inhibiting folic acid synthesis and dTMP synthesis
ADRs: acute toxicities. Toxicities can be managed by the “leucovorin rescue”, which acts further down the folic acid synthesis pathway to produce normal folic acid
Uses: MTX + leucovorin can be used intrathecally for treatment of meningeal leukemias
5-FU
antimetabolite
MOA: pyrimidine analog inhibitor by blocking thymidylate synthetase, thus inhibiting pyrimidine and DNA synthesis
ADRs: palmar-plantar erythrodysesthesia
Uses: first line therapy for colorectal cancer in combination with the leucovorin rescue to potentiate the actions of 5-FU
6 MP
antimetabolite
MOA: purine analog inhibitor
ADRs: hyperurecemia, acute toxicities
Uses: Pediatric ALL
ADME: 6 MP is a prodrug like cyclophosphamide that must be activated by HGPRT and TPMT in order to be an active compound. An enzyme known as XO can inactive 6 MP. Allopurinol can be administered in conjunction with 6 MP to inhibit XO and produce the active compound.
Doxorubicin
Anthracyclin and cell cycle non-specific agent
MOA: (1). acts as an alkylating agent (2). production of semiquinone and hydroxyl radicals to damage DNA (3). inhibit topoisomerase II from annealing ds breaks
ADRs: specific cardiotoxicity and vesicant abilities
Uses: potent wide spectrum agent
Bleomycin
MOA: production of semiquinone and hydroxyl radicals to damage DNA
ADRs: pulmonary fibrosis, hyper pigmentation & hyperkeratosis, and pneumonitis
Uses: BEP regimen
Vincristine
Microtubule agent
MOA: depolymerization of MTs, leading to inhibition of the mitotic spindle
ADRs: potent vesicant / dose dependent neuropathy / SIADH, leading to fluid retention and hypernaturemia
Taxol
MT agent
MOA: stabilizes MTs to cause paralysis and breaking of the mitotic spindle
ADRs: hypersensitivity rash and severe abdominal pain
Etoposide
Topo inhibitor
MOA: inhibits DNA topoisomerase II, preventing annealing of ds breaks
ADRs: metallic taste
Irinotecan
Topo inhibitor
MOA: DNA topo I inhibitor
Uses: colorectal
Imatinib
MOA: inhibits BCR-ABL tyrosine kinase affiliated with CML and the philadelphia chromosome
ADV: this dug has strong drug-drug interactions as a substrate and inhibitor, so many potent drug-drug interactions
Uses: CML
Temosirolimus
MOA: inhibits mTOR. Normally, VHL inhibits the elevation of HIF-1a. When VHL experiences a loss-of-function mutation, mTOR increases the amount of HIF-1a present in RCC
ADME: activated by CYP3A
Uses: RCC
Bortezumab
MOA: protease inhibitor, which inhibits the breakdown of IkB as a means to increase degradation of NFkB in myeloma cells
Uses: multiple myeloma
