Treatment of Prostate Cancer Flashcards
MOA of bicalutamide
androgen receptor blocker. mostly in prostate (less central). Has some slight agonist activity in other tissues but mainly antagonist.
ADE of bicalutamide
GI toxicity, hot flashes, aches/pains
Hepatotoxicity
Teratogen
MOA of flutamide
androgen receptor Antagonist. Exclusively in prostate. (FLUTE-amide works only on your flute)
GI toxicity, hot flashes, aches/pains
hepato
ADE of flutamide
black box warning for hepatotoxicity/failure
blood dysacria
GI toxicity, hot flashes, aches/pains
Teratogen
MOA of nicalutamide (nilutamide)
androgen receptor blocker of prostate AND central
ADE of nicalutamide (nilutamide)
Black box warning for respiratory insufficiency and interstitial penumonitis. HF and HTN Blood dysacria Increased light to dark transition time. GI toxicity, hot flashes, aches/pains Hepatotoxicity NOT A TERATOGEN - NULL-utamide
MOA of estramustine
Estrogen+nitrogen mustard that alkylates.
binds EBP on prostate CA.
inhibits microtubules, promoting disassembly and G2/M arrest.
Produces DNA strand breakage.
Has estrogenic effects.
Depressess testosterone levels via negative feedback on HP axis
ADE of estramustine
Has estrogenic effects similar to estradiol -> Edema, thromboembolism, MI, PE, and stroke.
GI, gynecomastia, mastalgia, impotence
elevated hepatic enzymes and hyperbilirubinemia
MOA of goserelin
GnRH agonist. SubCu.
down regulation of GnRH receptor on pituitary decreases FSH and LH. Serum levels of testosterone drop to castrate levels within 2-4 weeks.
ADE of goserelin
transient disease flare (give androgen receptor blocker)
CV effects - edema, HTN, MI
CNS - headache, fatigue, depression, seizures
Elevated TGs, weight gain
Reduced libido
gynecomastia
hepatotoxicity rarely
MOA of histrelin
GnRH agonist, SC injection.
down regulation of GnRH receptor on pituitary decreases FSH and LH. Serum levels of testosterone drop to castrate levels within 2-4 weeks.
ADE of histrelin
transient disease flare (give androgen receptor blocker) CV effects - edema, HTN, MI CNS - headache, fatigue, depression, seizures, suicide (HYSTERIA-lin) Elevated TGs, weight gain Reduced libido gynecomastia hepatotoxicity rarely CATEGORY X TERATOGEN
MOA of leuprolide
GnRH agonist. IM/SC injections.
down regulation of GnRH receptor on pituitary decreases FSH and LH. Serum levels of testosterone drop to castrate levels within 2-4 weeks.
ADE of leuprolide
transient disease flare (give androgen receptor blocker) CV effects - edema, HTN, MI CNS - headache, fatigue, depression, seizures Elevated TGs, weight gain Reduced libido gynecomastia hepatotoxicity rarely CATEGORY X TERATOGEN
MOA of triptorelin
GnRH agonist. IM injection.
down regulation of GnRH receptor on pituitary decreases FSH and LH. Serum levels of testosterone drop to castrate levels within 2-4 weeks.
ADE of tripttorelin
transient disease flare (give androgen receptor blocker) CV effects - edema, HTN, MI CNS - headache, fatigue, depression, seizures Elevated TGs, weight gain Reduced libido gynecomastia hepatotoxicity rarely CATEGORY X TERATOGEN
MOA of degarelix
reversible GnRH receptor antagonist. SC injection. reduces LH and FSH secretion and drops testosterone to castrate levels within 3 days.
ADE of degarelix
hot sweats HTN Elevated hepatic enzymes QT prolongation wiegh tgain, arthralgia, chills, fatigue impotence
MOA of abiraterone
CYP17 inhibitor (17a-hydroxylase inhibitor) prevents testosterone production and shunts towards mineralocorticoids.
ADE of abiraterone
Increases mineralocorticoids causing HTN and fluid retention.
Contraindicated with preexisting CV issues.
Give with corticosteroids to suppress ACTH drive.
Elevated hepatic enzymes.
Category X teratogen (female partner precautions required)
MOA of sipuleucel-T
Autologous (from-self) immunotherapy that stimulates T-cell immunity against prostatic acid phosphatase (PAP).
Made of pateint APCs cultured with recombinant PAP-GM-CSF. Product is reinfused with T, B and NK cells.
ADE of sipuleucel-T
paresthesias, citrate toxicity and fatigue.
infusion reactions, fever/chills/dispnea, GI effects like N/V
Where are the two sources of androgens acting in the prostate?
testicular testosterone
and
Locally produced DHT from adrenal produced dehydroepiandrosterone (DHEAS)
What are the effects of ERa on prostate? ERb?
ERa mediates abberant proliferation, inflammation and malignancy.
ERb promotes antiproliferative, anti-inflammatory, and anticarcinogenic effects.
