Antineoplastic Drugs Flashcards
Cyclophosphamide toxicity
Cardiotoxicity
hemorrhagic cystitis - bladder burn
Hematuria
Sodium 2-mercaptoethane sulfonate role is to
MESNA’s role is to detoxify acrolein which is causes toxicity like (hemorrhagic cystitis + hematuria)
Alkylating Agents MOA
alkylating DNA guanine = cross-linking stands –> apoptosis
Platinum complexes MOA
covalent cross-linking of G-C base pairs = bend DNA
Cisplatin toxicity
Renal damage = reduced with hydration Ototoxicity Hearing loss Tinnitus Peripheral Sensory Neuropathy
Antimetabolites MOA
Block DNA formation –> abnormal DNA
Cell cycle dependent
Inhibits protein synthesis
Methotrexate MOA
competitive inhibitor of dihydrofolate reductase
blocks dTMP
stops folate-dependent enzymes of de novo purine & thymidylate synthesis
Methotrexate toxicity
nephrotoxicity
hepatic necrosis
bone marrow depression
What can reduce Methotrexate toxicity?
Leucovorin by reducing folate (5-formylretrahydrofolate)
Fluorouracil MOA
STOP DNA synthesis
converted to the fraudulent F-dUMP
F-dUMP forms a covalent complex with thymidylate synthase & methylene tetrahydrofolate (THF)
what impacts 5-FU levels
DPYD/DPD
Fluorouracil toxicity
severe ulceration of oral & GI mucosa + diarrhea
Leucovorin Calcium MOA
its folinic acid which binds & stabilizes ternary complex of 5-fdUTP & thymidylate synthase = increases fluorouracil cytotoxicity
decreases the effects of methotrexate
Leucovorin Calcium toxicity
diarrhea when given with fluorouracil
6-Mercaptopurine MOA
blocks purine (guanine) synthesis Triphosphate form incorporated into DNA --> strand breaks
6-Mercaptopurine toxicity
bone marrow depression
Xanthine oxidase inhibitors (Allopurinol) = increases effects
Xanthine oxidase & TPMT (thiopurine methyltransferase) role is to
metabolize 6-Mercaptopurine in the liver
Tumor cell lysis Syndrome is treated with
Allopurinol
Mutations in TPMT =
drug accumulation + bone marrow destruction (infection)
What is needed for 6-mercaptopurine activation
HGPRT = hypoxanthine guanine phsophoribosyl transferase
Cytarabine (Pyrimidine Analog) MOA
inhibits DNA chain elongation + base rotation
Inhibits DNA polymerase
Asparaginase MOA
Hydrolyze asparagine to aspartic acid & ammonia
Asparaginase toxicity
risk of anaphylaxis
Microtubule Inhibitors + MOA
Taxanes
- Paclitaxel (Paclitaxel)
- Docetaxel (Taxotere)
Arrest in Metaphase = blocks cell in mitosis
Taxanes toxicity =
bone marrow toxicity
peripheral sensory neuropathy (dose limiting)
Vinca Alkaloids
bind to b-tubulin & blocks polyermization with a-tubulin in the microtubules
Anthracycline Antibiotics
inhibits resealing of DNA nicks by blocking Topoisomerase 2
Anthracycline Antibiotics + Doxorubicin MOA
inhibits resealing of DNA nicks by blocking Topoisomerase 2
Anthracycline Antibiotics + Doxorubicin Toxicity
Acute cardiac = arrhythmias (ST&T waves)
chronic cardiac = (cardiomyopathy –> CHF)
Doxorubicin MOA for toxicity
free radical damage = generation of Hydroxyl radicals from peroxide
that is the role of Dexrazoxane
to protect from cardiotoxicity
Irinotecan MOA + Toxicity + Usages
Blocks Topoisomerase 1 = ssDNA break occurring
Severe GI toxicity + 1A1 & 28 polymorphism
Colon cancer
Blemycin MOA + Toxicity
OH- radicals = DNA fragmentation
No significant bone marrow toxicity but some pulmonary fibrosis
First-line drugs for tx of breast cancer in POSTmenopausal women
Anastrozole & Letrozole by being competitive nonsteroidal aromatase inhibitors
Exemestane is a
STEROIDAL IRREVERSIBLE inhibitor of aromatase
Trastuzumab MOA + toxicity
HER2 receptors
weakening heart muscles + CHF
