PMC 4 Final Exam New Material

what structure is this?

aziridinium ion

what is aziridinium?

the active electrophile for nitrogen mustards

what structure is this?

acrolein

what is important to know about acrolein?

it is highly urotoxic and nephrotoxic

what structure is this?

chloroacetaldehyde

what is important to know about chloroacetaldehyde?

it is nephrotoxic and neurotoxic

what structure is this?

mesna

what does mesna do?

inactivates acrolein and protects the bladder

what structure is this?

mechlorethamine hydrochloride

what is important to know about mechlorethamine hydrochloride?

it activates rapidly, causing nonspecific alkylation

what structure is this?

chlorambucil

what is important to know about chlorambucil?

it is stabilized by the aromatic ring, allowing oral delivery

what structure is this?

estramustine phosphate sodium

what is important to know about estramsutine phosphate sodium?

when it is metabolized, it releases estradiol, so it is contraindicated with estrogen-dependent tumors.

what structure is this?

cyclophosphamide

what is important to know about cyclophosphamide?

it is a prodrug which yields lower GI toxicity and less non-specific toxicity

what structure is this?

ifosfamide

what is important to know about ifosfamide?

it is toxic to the bladder, nephrons, and neurons, commonly exhibiting CNS toxicity

what structure is this?

thiotepa

what is important to know about thiotepa?

common AEs include dizziness, blurred vision, headaches, and myelosuppression

what structure is this?

what is important to know about streptozocin?

it treats metastatic pancreatic islet cell carcinoma

what structure is this?

2-chloroethyl carbocation

what is 2-chloroethyl carbocation?

a cytotoxic electrophile generated by nitrosoureas

patients with elevated O6-alkylguanine-DNA-alkyltransferase often are resistant to ____ ?

DNA methylators

what structure is this?

dacarbazine

what structure is this?

methyl carbocation

what does dacarbazine generate?

a methyl carbocation as its active electrophile

what structure is this?

altretamine

what does altretamine generate?

a reactive iminium ion

what structure is this?

reactive iminium ion

what structure is this?

busulfan

what is important to know about busulfan?

it can induce 2 year long pancytopenia

what structure is this?

sodium thiosulfate

what is important to know about sodium thiosulfate?

it concentrates in renal tubules and protects kidneys from cisplatin

what structure is this?

carboplatin

what is important to know about carboplatin?

it is an organoplatinum antineoplastic agent

what structure is this?

oxaliplatin

what is important to know about oxaliplatin?

it is often active when resistance to cisplatin and carboplatin has developed

what structure is this?

cisplatin

what is important to know about cisplatin?

it can produce ototoxicity and irreversible hearing loss

what is the major limiting side effect of anthracyclines?

cardiotoxicity

what is a unique side effect of anthracyclines?

it can make the urine a reddish color

what is special about the liposomal formulation of doxorubicin?

it is taken up by the tumor cells about 3 fold more than the hydrochloride formulation

what structure is this?

valrubicin

what is important to know about valrubicin?

it is an anthracycline which converts most slowly to the toxic C13-ol form

what structure is this?

mitoxantrone

what is a special side effect of mitoxantrone?

may turn urine, whites of eyes, and skin a slightly blue-green color

what structure is this?

dactinomycin

what is dactinomycin’s MOA?

includes inhibiting topoisomerase II, causing double strand DNA breaks

what structure is this?

mitomycin

what is mitomycin’s MOA?

it is a prodrug activated by NADPH/CYP450 reductase,

its MOA includes hydroxy radicals inducing single strand DNA breaks and also cross-linking DNA

what structure is this?

bleomycin

what is important to know about bleomycin?

it does NOT suppress bone marrow

the enzyme bleomycin hydrase cleaves bleomycin so it can no longer interact with DNA.

what structure is this?

fluorouracil, a pyrimidine antagonist

what structure is this?

capecitabine, it is activated by thymidine phosphorylase

what structure is this?

methotrexate, an analog of 7,8-dihydrofolate and it inhibits the enzyme dihydrofolate reductase

what is an important thing to know about methotrexate?

it can precipitate in renal tubules, causing crystalluria

what structure is this?

leucovorin, it is a 5-formyltetrahydrofolate which can generate folate cofactors required for pyrimidine and purine biosynthesis

what structure is this?

pemetrexed

what structure is this?

6-mercaptopurine, it is a purine antagonist antineoplastic prodrug

what structure is this?

thioguanine, it is a purine antagonist antineoplastic prodrug

both mercaptopurine and thioguanine prodrugs must be activated by what?

hypoxanthine guanine phosphoribosyl transferase

what is the primary MOA for activated thioguanine?

incorporation into DNA and RNA, halting elongation and promoting apoptosis

what is the primary MOA for activated mercaptopurine?

inhibition of glutamine phosphoribosylpyrophosphate amidotransferase

what do we do to the dose of mercaptopurine when given with allopurinol?

HALVE the dose of mercaptopurine

allopurinol does ___ block the elimination of thioguanine?

does NOT block

thiopurine methyl transferase (TPMT) is involved in what?

inactivating both mercaptopurine and thioguanine,

AND
activating ONLY mercaptopurine

what does decreased patient thiopurine methyl transferase expression require?

decreasing both mercaptopurine and thioguanine doses

what does increased patient thiopurine methyl transferase (TPMT) expression require?

decreasing mercaptopurine dose, but INCREASing the thioguanine dose (IT-IT)

what structure is this?

cytarabine, it is an antineoplastic DNA polymerase inhibitor

the triphosphate form of all the DNA polymerase inhibitors is what?

active

what do the deaminase enzymes work to do?

inactive DNA polymerase inhibitors

what structure is this?

gemcitabine, an antineoplastic DNA polymerase inhibitor

what structure is this?

fludarabine, an antineoplastic DNA polymerase inhibitor

what structure is this?

cladribine, an antineoplastic DNA polymerase inhibitor

what structure is this?

clofarabine, an antineoplastic DNA polymerase inhibitor

what structure is this?

pentostatin, a purine analog with MOA of inhibiting adenosine deaminase

what structure is this?

hydroxyurea, MOA is inhibiting ribonucleotide reductase