Chemo Drugs 3 Flashcards
Doxorubicin Class: Cycle specificity: Macromolecular target: Bioactivation: MOA: Pharmacokinetics and metabolism: Side effects:
Class: antitumor antibiotic
Cycle specificity: CCNS
Macromolecular target: DNA
Bioactivation: None
MOA: Intercalation between base pairs of DNA leading to strand breaks due to inhibition of topoisomerase 2
Pharmacokinetics and metabolism: metabolized by the liver and excreted as a thiol adduct into the bile
Side effects:
1. N/V hair loss, stomatitis
2. Myelosuppression is dose limiting
2. Cardiac toxicity: congestive cardiomyopathy-determine ejection fraction prior to institution of treatment with doxorubicin
What are the special features of doxorubicin? What is doxorubicin used for?
- the drug is a vesicant
- must dose reduce in the presence of jaundice
- durg has a cumulative cardiac toxicity
- lifetime dose
Uses:
breast cancer, leukemia, sarcoma, Hodgkin’s and non hodgkin’s lymphomas
What type of toxicity does doxorubicin have? What drug is cardioprotective agent in patients receiving doxorubicin?
schedule dependent cardiac toxicity
- less toxicity if administered slowly
- schedule independent cytotoxicity
Cardioprotective= dexrazoxane-iron chelator-decrease in free radical damage
Topoisomerase 1 inhibitors
Topotecan and irinotecan
Single strand DNA breaks, relaxation of the strand and re-anneal the strands
Topoisomerase 2 inhibitors
Intercalators: daunomycin, doxorubicin, mitoxantrone, dactinomycin
Non intercalators:
etoposide
Double strand breaks in DNA, relaxation and re-anneal of strands
Intercalating and non intercalating topoisomerase 2 inhibitors and tubulin inhibitors are cross resistant to what? What can help with the resistance?
MDR-the p-glycoprotein is a membrane bound efflux pump
- giving continuously may help downregulate the glycoprotein and reverse resistance
- quinine, verapamil, cyclosporine may block the efflux pump and reverse resistance
Irinotecan Class: Cycle specificity: Macromolecular target: Bioactivation: MOA: Pharmacokinetics and metabolism: Side effects:
Class: (camptothecin, plant alkaloid)
Cycle specificity: CCNS
Macromolecular target: DNA
Bioactivation: Prodrug. Converted by carboxylesterase to 7 ethyl 10 hydroxycamptothecin (SN-38)
MOA: topoisomerase 1 inhibition leading to single stranded breaks in the DNA
Pharmacokinetics and metabolism:
hepatic metabolism is significant. Dose reduction required for jaundice. UGTIA1 is responsible for clearance by glucuronidation of drug and bilirubin (severe neutropenia in Gilbert’s syndrome-UGT1A1 polymorphism)
Side effects:
- Nausea, vomiting, stomatitis
- Myelosuppression dose limiting
- Early cholinergic diarrhea (treated with atropine)
- Late secretory diarrhea (treated with Imodium-deaths have occurred)
What are special features of Irinotecan?
Decrease dose of drug in the presence of jaundice
What are the uses of Irinotecan?
Colon cancer
Topotecan (ovarian and small cell lung cancers)
Bleomycin Class: Cycle specificity: Macromolecular target: Bioactivation: MOA: Pharmacokinetics and metabolism: Side effects:
Class: Antitumor antibiotic
Cycle specificity: CCS
Macromolecular target: DNA
Bioactivation: None
MOA: Binds to DNA, free radical production leading to single and double stranded DNA breaks. The bleomycin-iron form is the active species.
Pharmacokinetics and metabolism: 50% excreted in the urine. the liver and kidneys rapidly inactivate the drug. The lungs and the skin have very low levels of the inactivating enzyme
Side effects:
- PULMONARY TOxicity-dose limiting
- decrease in pulmonary diffusion capacity - hyperpigmentation of skin, hyperkeratosis of the palms
- stomatitis and hair loss.
- NOT myelosuppressive
- anaphylactoid reactions have been noted with first dose in patients with lymphoma
- fever chills common
Special features and dose modifications for bleomycin
- test dose is given before first dose is administered to monitor for severe reactions
- cumulative pulmonary toxicity
- baseline pulmonary function test prior to institution
- avoid administering high oxygen concentrations
- dose reductions must be made for renal insufficiency
What does bleomycin treat?
testicular cancer
Prednisone Class: Cycle specificity: Macromolecular target: Bioactivation: MOA: Pharmacokinetics and metabolism: Side effects:
Class: Steroid
Cycle specificity: N/A
Macromolecular target: steroid receptor
Bioactivation: None
MOA: unknown
Pharmacokinetics and metabolism: N/A
Side effects: Weight gain, hypertension, edema, carbohydrate intolerance. suppression of pituitary-adrenal axis, weakness, euphoria, increased appetite
What is prednisone used to treat?
Hodgkin’s disease and non-Hodgkin’s lymphoma
-also used in multiple myeloma and some forms of leukemia
Dexamethasone
used along with 5-HT3 inhibitors to prevent or ameliorate chemotherapy treatment related nausea and vomiting
- less mineralocorticoid effects than prednisone
- used to treat cerebral edema or spinal cord edema due to spinal cord compression
Tamoxifen Class: Cycle specificity: Macromolecular target: Bioactivation: MOA: Pharmacokinetics and metabolism: Side effects:
Class: hormonal agent, SERM
Cycle specificity: NA
Macromolecular target: Estrogen receptor in cancer (usually breast cancer). Mixed agonist/antagonist
Bioactivation: prodrug and is metabolized in liver to 4-hydroxytamoxifen
MOA: binds to the estrogen receptor in the cancer cell
Pharmacokinetics and metabolism: metabolized by the liver
Side effects: some weight gain, hot flashes, endometrial cancer, thrombosis
Special features of Tamoxifen
- Tamoxifen is approved as chemoprevention in women at high risk of developing breast cancer
- mildly estrogenic-favorable lipid and decreased rate of bone loss postmeno
What are the uses of tamoxifen?
breast cancer
Anastrozole Class: Cycle specificity: Macromolecular target: Bioactivation: MOA: Pharmacokinetics and metabolism: Side effects:
Class: aromatase inhibitor
Cycle specificity: NA
Macromolecular target: aromatase
Bioactivation: None
MOA: selective nonsteroidal inhibitor of aromatase produces marked lowering of plasma estrogen levels
Pharmacokinetics and metabolism: estradiol levels reduced by 70% in 24 hours and 80% after 2 weeks. metabolized extensively by live. no dose adjust for liver or renal dysfunction
Side effects: hot flashes, mood disturbances, arthritis, arthralgias, bone pain, bone loss, osteoporosis
Uses of Anastrozole
Oral administration. hormone receptor positive breast cancer (adjuvant and metastasis)
Flutamide
Class:
MOA:
Side effects:
Class: flutamide
MOA: inhibits the uptake and binding of testosterone to specific receptors in hormonally sensitive prostate cancer cells
Side effects: well tolerated. Diarrhea (20% of patients-bicalutamide-less) and elevations of liver transaminases
Uses of flutamide
Oral administration and used in the ADT (androgen deprivation treatment) therapy of metastatic prostate cancer
Leuprolide acetate
Class:
MOA:
Side effects:
Class: GnRh receptor agonist
MOA: binds to pituitary GnRH receptors and initially produces an increase in LH and FSH leading to an increase in testosterone and thus initially can stimulate tumor growth. by interruptions the pulsatile stimulation of GnRH receptors, leuprolide down regulates the secretion of gonadotropins LH and FSH leading to a reduction in testosterone levels
Side effects: hot flashes. decreased libido, loss of muscle mass, erectile dysfunction, change in body fat distribution, gynecomastia
special features of leuprolide
- patient initially treated with flutamide or bicalutamide for 2-4 weeks before starting leuprolide to avoid flare then stopped
- given intramuscularly-depot form available
