Chemo Drugs II: Hormonal Agents and Intercalating Agents Flashcards
Doxorubicin and Daunomycin
MOA
Topoisomerase II blockers – introduce double stranded DNA breaks
Intercalates between base pairs in the DNA helix
Function of Topoisomerase enzymes
Resolves conformational and topological changes (supercoils) in DNA
Cuts out the knot, then resynthesizes the part that is missing
What drugs block topoisomerase II enzymes?
Doxorubicin
Daunomycin
Etoposide
What drugs block topoisomerase I enzymes?
Ininotecan
Topotecan
What is MDR? How does it work?
“Hydrophobic vacuum cleanser”
Pumps drugs out of the cytoplasm
MDR is found in many chemo-resistant cells
Doxorubicin
MOA
Metabolism
Intercalates into DNA and inhibits topoisomerase II (introduces double stranded breaks into DNA)
Cell cycle nonspecific
Hepatically metabolized; reduce dose if patient has jaundice
Doxorubicin
Indications
Lymphoma (Hodgkin or non)
Leukemia
Breast CA
Doxorubicin
Major Toxicity
Dose for that toxicity?
Cardiotoxic!
Schedule-dependent toxicity
Max lifetime cumulative dose = 400 mg/m2
Cumulative toxicity that may result in dilated cardiomyopathy
Avoid doxorubicin if baseline ejection fraction is abnormal
Irinotecan
MOA
Metabolism
Topoisomerase I inhibitor
-Introduces single stranded breaks into DNA
Hepatic metabolism; reduce dose in jaundice
Irinotecan
AEs
Early diarrhea (cholinergic) – use atropine to prevent
Late (7-10days) diarrhea (secretory) – use imodium and hydration
Myelosuppression
Ppl with Gilbert’s disease may have inc risk of severe diarrhea and myelosuppression
Irinotecan
Indications
Colon cancer treatment
Bleomycin
MOA
Free radical damage to DNA
Cell cycle specific
Bleomycin
Excretion and Metabolism
50% renal excretion
Liver and kidney rapidly inactivate bleomycin. Lungs and skin cannot inactivate bleomycin
Bleomycin
AEs
Cumulative Pulmonary Toxicity – Rapidly fatal IPF
-Monitor baseline PFTs before tx
May cause vein hyperpigmentation
Bleomycin
Indications
Testicular cancer
When is prednisone used in cancer?
May be used in myeloproliferative or lymphoproliferative disorders
Dexamethasone
Indications in cancer
Used with Ondansetron to lower chemo-related N/V
May also resolve cerebral or spinal cord edema
Tamoxifen
MOA
SERM
Antagonist at breast ER
Agonist at bone and uterus ER
Tamoxifen
Indications
ER positive breast cancer
Also prevents breast cancer in women at higher risk
Tamoxifen
AEs
Hot flashes, thrombosis, endometrial hyperplasia and carcinoma
List the Aromatase Inhibitors
Anastrozole
Exemestane
Letrozole
Flutamide
MOA and Indication
AR receptor antagonist used in prostate cancer
Inhibits growth of prostate CA
Leuprolide
MOA and Indication
Long acting GnRH agonist used to shut down the gonadal axis
Decreases testosterone production in long-term, which helps halt prostate cancer growth
Leuprolide
What happens short-term and long-term with this drug? How can this be addressed?
GnRH agonist
During the first 7-10 days, leuprolide has an AGONIST effect to increase androgen production
-Initial stimulation of prostate CA cells
May cause increased bone pain (if prostate CA has metastasized to bone) and compression of tumor in epidural space
Before giving leuprolide, give pt flutamide to block AR and prevent this
