Repro - Pharmacology Flashcards
What effect do GnRH agonists have on the reproductive HPA axis?
GnRH agonists are stimulatory if given as pulses, inhibitory if given continuously
What effect does anastrozole have on the female HPA axis?
It is an aromatase inhibitor that prevents estrogen formation from androgens
What is the mechanism of action and result of finasteride administration?
It is an reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone
How do the clinical uses of leuprolide differ depending on the way in which it is administered?
Leuprolide is a gonadotropin-releasing hormone agonist when dosed in a pulsatile fashion and a gonadotropin-releasing hormone antagonist when dosed continuously
What adverse effects are associated with leuprolide use?
Antiandrogenic actions, nausea, and vomiting
Name three common clinical uses for leuprolide.
Infertility (pulsatile), prostate cancer (continuous, used with flutamide), and uterine fibroids
Is leuprolide dosed in a pulsatile or continuous fashion for the treatment of prostate cancer? Why?
Leuprolide is given continuously to inhibit gonadotropin-releasing hormone; this decreases circulating androgens that can stimulate prostate adenocarcinoma
How can testosterone be used to treat hormonal deficiencies?
Administration of testosterone can be used in hypogonadism and to help develop secondary sexual characteristics
What is the role of testosterone in patients who have suffered from a burn?
Testosterone stimulates anabolism, which helps promote recovery from burns or other severe injuries
What role can testosterone play in the treatment of a malignancy generally seen in women?
Testosterone can be used to treat estrogen receptor-positive breast cancer
What genital exam finding would you expect in a male using exogenous testosterone?
Testicular atrophy; because exogenous testosterone blocks the release of luteinizing hormone, intratesticular testosterone will decrease, causing testicular atrophy
How would exogenous testosterone affect the height of a child that has not completed puberty?
This child may be shorter than expected because of premature closure of the epiphyseal plates
What serum lipid panel findings would you expect in a patient who has been taking testosterone?
Elevated low-density lipoprotein and decreased high-density lipoprotein
What is the mechanism of action of finasteride?
Finasteride is a reductase inhibitor, which blocks the conversion of testosterone to the more potent dihydrotestosterone
What is the mechanism of action of flutamide?
Competitive testosterone receptor antagonist
Name two drugs that function as antiandrogens as an additional effect of their interference with steroid signaling.
Ketoconazole (an antifungal) blocks desmolase, decreasing steroid synthesis; spironolactone (a diuretic) blocks steroid binding
What are two adverse effects common to both ketoconazole and spironolactone?
Gynecomastia and amenorrhea
Flutamide is used to treat what condition?
Prostate carcinoma
What antiandrogenic drugs can be used to treat the hirsutism associated with polycystic ovarian syndrome?
Ketoconazole or spironolactone
What are the mechanisms of action of ethinyl estradiol, diethylstilbestrol, and mestranol?
Binding to estrogen receptors and acting as agonists
Name four conditions in women that are treated with estrogens.
Hypogonadism, ovarian failure, menstrual abnormalities; and as hormone replacement therapy in postmenopausal women
Name a condition in elderly men that can be treated with estrogens
Androgen-dependent prostate cancer
What are the adverse effects of treatment with exogenous estrogens?
An increased risk of endometrial carcinoma, abnormal uterine bleeding in postmenopausal women, and hypercoagulability
You diagnose a woman with clear-cell adenocarcinoma of the vagina; what should you ask about in her history?
In utero exposure to diethylstilbestrol
Name two conditions that are contraindications to estrogen therapy.
Estrogen receptor-positive breast cancer and a history of deep vein thrombosis
How does the interaction of clomiphene at the hypothalamus result in an increase in ovulation?
Clomiphene is a partial estrogen receptor agonist at the hypothalamus, blocking negative feedback on luteinizing hormone and follicle-stimulating hormone; elevated follicle-stimulating hormone and luteinizing hormone cause increased ovulation
What are two primary clinical uses for clomiphene?
The treatment of infertility and polycystic ovarian syndrome
What are four adverse effects associated with clomiphene use?
Hot flashes, ovarian enlargement, multiple simultaneous pregnancies, and visual disturbances
How is tamoxifen used in breast cancer?
Because it acts as an estrogen antagonist in the breast, it is used to treat and prevent recurrences of breast cancer in estrogen receptor-positive tumors
Which selective estrogen receptor modulator reduces the resorption of bone and is used to treat osteoporosis?
Raloxifene; it acts as an estrogen receptor agonist in bones
What are indications for hormone replacement therapy?
Menopausal symptoms (eg, hot flashes, vaginal atrophy) and osteoporosis that is caused by decreased estrogen levels
In hormone replacement therapy, unopposed estrogen can increase the risk of what disease?
Endometrial cancer; it also may increase the risk of cardiovascular events
Why is progesterone added to hormone replacement therapy?
To reduce the risk of endometrial cancer
What is the mechanism of action of anastrozole and exemestane?
Anastrozole and exemestane function by inhibiting aromatase, the enzyme that converts androgens to estrogens
In what clinical scenario are anastrozole and exemestane used?
In postmenopausal women with hormone-responsive breast cancer
What effect do progestins have on the endometrium?
Upon binding the progesterone receptor, they reduce the growth of the endometrial lining while increasing its vascularization
Name three clinical uses of progestins.
In oral contraceptive pills, to treat endometrial cancer, and to treat abnormal uterine bleeding
What is the mechanism of action of mifepristone (RU-486)?
It is a competitive inhibitor of progestins at progesterone receptors
What is the primary clinical use of mifepristone?
Termination of pregnancy in conjunction with the administration of misoprostol (PGE1)
What are the known toxicities of mifepristone?
Heavy bleeding, gastrointestinal effects (nausea, vomiting, anorexia), and abdominal pain
How reliable are oral contraceptive pills in the prevention of pregnancy?
They are very reliable (<1% failure when used correctly) but must be taken daily to be effective
What is the effect of oral contraceptive pills on malignancy?
Women taking oral contraceptive pills have lower rates of endometrial and ovarian cancer
A woman who takes oral contraceptive pills asks you about her risk for ectopic pregnancy; what is the relationship between the two?
Oral contraceptive pills decrease the risk of ectopic pregnancy (and pregnancy in general)
Name six systemic adverse effects of oral contraceptive pills.
Elevated triglycerides, hypertension, depression, weight gain, nausea, and hypercoagulability
How do oral contraceptive pills work?
They work by preventing an estrogen surge and thus the luteinizing hormone surge that causes ovulation
Dinoprostone is an analogue of what molecule?
PGE2
How is dinoprostone used in pregnancy?
Dinoprostone causes cervical dilation and uterine contractions, inducing labor
What is the role of ritodrine and terbutaline during labor?
These are β2-agonists, which relax the uterus and reduce contractions (remember: ritodrine allows the fetus to “return to dreams” by stopping premature labor)
What is the mechanism of action of tamsulosin?
Tamsulosin is an α1-receptor agonist used to treat benign prostatic hyperplasia
Why does tamsulosin relax the smooth muscles of the prostate but not the systemic vasculature?
It is selective for α1AD-receptors found on the prostate, rather than the α1B-receptors on systemic vessels
What is the primary clinical use for sildenafil and vardenafil?
The treatment of erectile dysfunction (remember: sildenafil and vardenafil fill the penis)
A patient presents with symptoms of flushing, reflux, headache, and blue-green vision; what drug has he likely ingested?
Sildenafil or vardenafil (remember: Hot and sweaty, but then Headache, Heartburn, Hypotension)
Sildenafil and vardenafil should not be used in patients taking what other class of drug?
Nitrates; the concomitant use can precipitate life-threatening hypotension
How do sildenafil and vardenafil cause the increase of penile blood flow and resultant erection?
By inhibiting cGMP phosphodiesterase, there is an increase in cGMP resulting in increased nitric oxide and smooth muscle relaxation in the corpus cavernosum
