Anticancer 3 Flashcards
MICROTUBULE INHIBITORS groups and two drugs in each?
VINCA ALKALOIDS
VINCRISTINE
VINBLASTINE
TAXANES
PACLITAXEL
DOCETAXEL
Vinca alkaloids MOA?
Vinca alkaloids bind to β-tubulin and inhibit its
ability to polymerize into microtubules.
• This results in mitotic arrest in metaphase.
• Cell division stops. Cells die by apoptosis.
AE of Vincristine?
Vincristine: Peripheral neuropathy. Bone
marrow depression is mild. Alopecia.
Ae of vinblastine?
Vinblastine: Myelosuppression is the doselimiting
adverse effect. Other adverse effects
include alopecia and peripheral neuropathy
Taxanes MOA?
Taxanes bind to the β-tubulin subunit of
microtubules and promote microtubule
polymerization.
• Stabilization of the microtubules in a polymerized
state arrests cells in mitosis and leads to apoptosis.
AE of Paclitaxel?
Hypersensitivity, myelosuppression, peripheral
neuropathy, alopecia.
• Hypersensitivity is reduced by premedication with
dexamethasone, diphenhydramine and an H2
blocker
Ae of Docetaxel?
Myelosuppression, peripheral neuropathy, fluid
retention, alopecia, mucositis.
• Pretreatment with dexamethasone is required to
prevent fluid retention.
• Docetaxel does not cause neuropathy as
frequently as paclitaxel.
• Myelosuppression is dose-limiting.
EPIPODOPHYLLOTOXINS? MOA?
ETOPOSIDE Inhibits topoisomerase II, resulting in DNA damage through strand breakage. • Blocks cell in late S-G2 phase.
What are the two Captothecans? MOA?
TOPOTECAN IRINOTECAN Inhibit topoisomerase I. Inhibition results in DNA damage.
Prednisone use?
Glucocorticoids are lympholytic and suppress
mitosis in lymphocytes.
• They are used for acute leukemia and malignant
lymphomas.
Three types of estrogen inhibitors?
SELECTIVE ESTROGEN-RECEPTOR MODULATORS (SERMs) SELECTIVE ESTROGEN-RECEPTOR DOWNREGULATORS (SERDs) AROMATASE INHIBITORS (AIs)
Which two are SELECTIVE ESTROGEN-RECEPTOR
MODULATORS(SERMs)?
RALOXIFENE
Tamoxifen
Describe Raloxifene and its uses?
Raloxifene is an antiestrogen in the uterus and
the breast, while promoting estrogenic effects in
the bone to inhibit resorption.
• Used for prevention of postmenopausal
osteoporosis and prophylaxis of breast cancer in
high risk postmenopausal women.
Describe Tamoxifen?
TAMOXIFEN
• SERMs bind to estrogen receptors and act as
agonists or antagonist depending on the tissue.
• Tamoxifen is an antagonist on breast cancer.
• Tamoxifen is an agonist in nonbreast tissues.
• Used for receptor-positive breast cancer.
• Chemopreventive agent in women at risk for
breast cancer.
Describe Fulvestrant?
SERDs are devoid of estrogen agonist activity.
• Fulvestrant binds to the estrogen receptor (ER)
inhibits its dimerization and increases its
degradation.
• ER-mediated transcription is abolished.
Describe aromatase inhibitors?
Aromatase converts androstenedione to estrone.
• In postmenopausal women, this conversion is
the primary source of circulating estrogens.
• Aromatase inhibitors are the standard of care for
adjuvant treatment of postmenopausal women
with hormone receptor–positive breast cancer.
Nonsteroidal and Reversible competitive inhibitors of aromatase?
ANASTROZOLE & LETROZOLE
Steroidal and Irreversible inhibitor of aromatase?
EXEMESTANE
ANDROGEN INHIBITORS subgroups?
GONADOTROPIN-RELEASING
HORMONE AGONISTS
ANDROGEN RECEPTOR BLOCKERS
Preferred approach to prostate cancer?
use of GnRH agonists,
alone or in combination with an androgen
receptor blocker.
Which two are gonadotropin releasing hormone agonists?
GOSERELIN
LEUPROLIDE
Describe gonadotropin releasing hormone agonists?
When given continuously or as a depot, GnRH
agonists cause an initial surge in LH and FSH
levels, followed by inhibition of gonadotropin
release.
• Testosterone levels fall to 10% of their initial
values after a month.
• The initial surge can be counteracted by
concurrent administration of flutamide for 2-4
weeks.
Describe Flutamide?
Synthetic, nonsteroidal antiandrogen.
• Metabolized to an active metabolite that acts as a
competitive antagonist at the androgen receptor,
preventing its translocation to the nucleus.
Inhibitor of EDFR tyrosine kinase solely?
Gefitnib and Erlotinib
Inhibitor of trysosine kinase BCr-abl
Imatinib
Lapatinib inhibits?
Inhibitor of EGFR and ErbB2 tyrosine kinases.
Trastuzumab acts against?
Monoclonal antibody against ErbB2.
Asparginase MOA?
Most normal tissues synthesize L-asparagine in amounts sufficient for protein synthesis. • Certain neoplastic tissues, however, require exogenous source. • Asparaginase hydrolyzes serum asparagine, depriving these cells of the asparagine necessary for protein synthesis, leading to cell death.
Ae of Asparaginase?
• Hypersensitivity. • Decrease in clotting factors. • Liver abnormalities. • Pancreatitis, seizures, coma due to ammonia toxicity.
Describe Hydroxyurea?
Inhibits ribonucleotide reductase. • This leads to depletion of deoxynucleoside trisphosphate pools. • DNA synthesis is thereby inhibited. • Kills cells in S phase. • Given orally.
What is interferon gamma used for?
Approved for hairy cell leukemia, chronic
myelogenous leukemia (CML), malignant
melanoma and Kaposi’s sarcoma.
AE of Interferon Gamma?
Depression.
• Fever with chills.
• Leukopenia, thrombocytopenia. Fatigue, malaise, anorexia, weight loss, alopecia,
transient elevation of liver enzymes.
Uses for Hydroxyurea?
Used for melanoma, chronic myelocytic leukemia, and carcinoma of the ovary.
• Hydroxyurea used concomitantly with irradiation therapy is used for carcinomas of the
head and neck.
• Hydroxyurea is also approved for use in the treatment of adult sickle cell disease.
