Flashcards in Misc Repro Drugs Deck (45):
Estradiol (valerate & cypionate) / Estrone sulfate/ Equilin sulfate / Quinestrol
Class: Estradiol esters (steroidal)
Mech: Absorbed through skin, mucus membranes, GI Tract; body-wide distribution via sex-hormone binding globulin
Thera: Contraception, primary hypogonadism, postmenopausal hormone therapy
Important SE's: Weight gain, HTN; less commonly, may cause breast cancer, DVT, cervical and endometrial cancer
Other SE's: Nausea, breast tension/pain, vaginal bleeding, headache
Misc: Strongly contraindicated in breast or endometrial cancers, endometriosis, undiagnosed vaginal bleeds; relatively contradinicated in pregnancy, thromboembolic disease, HTN, hepatic disease, family history of breast or uterine cancer
Ethinyl estradiol / Mestranol
Class: Alkyl estrogens
Everything else is the same as the estradiol esters!!!
Class: Non-steroidal synthetic estrogen
Important SE's: Increased risk of clear cell adenocarcinoma of vagina & cervix
Tamoxifen citrate (Nolvadex)
Class: Non-steroidal anti-estrogen; selective estrogen receptor modifier
Mech: Blocks estrogen from binding ER and causing growth in ER(+) breast cancer
Thera: ER(+) breast cancer
Important SE's: Pro-estrogenic effect on uterine epithelium (increase risk of endometrial cancer); partial estrogen agonist in bone and endometrium
Misc: Anti-estrogenic effect on mammary epithelium; must be used in very high doses
Clomiphene citrate (Clomid)
Class: Non-steroidal anti-estrogen
Mech: Blocks estrogen binding to hypothalamic receptors (no estradiol negative feedback on gonadotropins) --> increased secretion of gonadotropins & LH --> ovulation
Thera: Stimulate ovulation in patients who want to get pregnant
Important SE's: Hot flashes, multiple pregnancy
Other SE's: Stomach pain, headache, upset stomach, vomit
Misc: Cis-isomer (zuclomiphene) is a weak estrogen agonist; trans-isomer (enclomiphene) is a potent estrogen antagonist
Class: Combination pill
Mech: Constant level of estrogen suppresses FSH, LH surge; progesterone suppresses LH surge, thickens cervical mucus, leads to endometrial atrophy
Important SE's: As with synthetic estrogen and progesterones
Misc: Consistent dose of estrogen and progestin (only take 21 days)
How are Biphasic Ortho-Novum and Triphasic Ortho-Novum different from monophasic ortho-novum?
Thera: Fixed estrogen, progestin increased for days 11-21; and Fixed or variable estrogen, while progestin increases in 3 phases (1-7, 8-14, 15-21), respectively
Class: Progestin only
Mech: As progestin
Thera: Less effective than combination pill for contraception; use when patient has estrogen contraindication; good in lactating women (estrogen reduces milk production)
Important SE's: More likely to produce irregular menstrual cycle (estrogen required to provide stability to endometrium)
Other SE's: Suppresses endometrial cancer
Levonorgestrel (Plan B)
Class: Synthetic progestogen
Mech: Not known
Thera: Prevent implantation
Important SE's: Likely the same as combination oral contraceptives
Misc: Must be taken within 72 hours of coitus
Mifepristone (RU-486, Korlym)
Class: Anti-progestin; glucocorticoid receptor antagonist
Mech: Competitively binds to progesterone receptor (leading to detachment of fetus); glucocorticoid recepter antagonist
Thera: Abortion; Cushing's Syndrome
Misc: Must take early in pregnancy (by day 49); oral administration; must be given by doctor in medical facility prepared for surgery if abortion incomplete
Sildenafil citrate (Viagra) / Vardenafil HCl (Levitra)
Class: PDE5 inhibitor
Mech: Bind catalytic site of PDE5; inhibits PDE5 breakdown of cGMP --> decreased Ca --> smooth muscle relaxation --> erection
Thera: Erectile dysfunction; does not trigger an automatic erection, but improves response to sexual stimulation;
Important SE's: Headache, dizziness, change in vision (NAION)
Other SE's: Flushing, upset stomach, stuffy or runny nose, UTI, diarrhea
Misc: Oral (once/day max); half-life of 4 hours, peak plasma concentration in 1-2 hours; contraindicated if on nitrates or α-blockers (unsafe drop in BP)
How does Tadalafil (Cialis) differ from sildenafil citrate / Vardenafil HCl (Levitra)?
Misc: Oral (once/day max); half-life of 17.5 hours, peak plasma concentration in 1-2 hours; contraindicate if on nitrates or α-blockers (unsafe drop in BP)
In the follicular phase of the menstrual cycle, what are the two roles of estrogen and what days they occur?
1. Negative feedback on FSH release early on (days 1-10ish)
2. Positive feedback on LH (triggers LH surge); about 24-48 hours before ovulation
What is the follicle converted to after ovulation? What does this product make primarily? Write out the gonadotropin secretion pathway and the negative feedback loop
Corpus luteum; progesterone;
GnRH released from hypothalamus --> FSH and LH released from hypothalamus --> estrogen and progesterone release from ovaries that can usually serve as negative feedback on the AP and hypo
List the natural estrogens; list the synthetic (steroidal and non-steroidal) estrogens; which of the synthetics is used in the kidney?
1. Estradiol (E2), estrone (E1), estriol (E3)
2. Ethinyl estradiol, mestranol, quinestrol
3. DES, chorotrianisene, methallenestril;
Use the STEROIDAL synthetic estrogens in the kidneys (the non-steroidals are too toxic)
What is the main difference between the steroidal estrogen derivatives? What do they share?
All share 18 carbons with 4 rings; different substitutions at carbons 3 and 17
What are the three major estrogens made by women? In ______ women, what is the source of one of these estrogens? What cells make estrogen? Where is one of these estrogens converted to the other two? How do you get estrogens in the first place (ie what are they converted from)?
E1, E2, E3;
premenopausal; the ovary;
granulosa cells; estradiol converted in liver to estrone and estriol;
estrogens converted from androstenedione and testosterone in other tissues (adipose, bones, brain; adrenal gland in postmeno women and men)
During pregnancy, large quantities of _____ are produced by the what? What is the major circulating estrogen in premenopausal women? In men and postmenopausal women?
What enzyme is involved in estrogen production? What androgens are converted to estradiol and estrone? What cells have this enzyme expressed?
Aromatase; androstenedione and testosterone;
ovaries, placenta, adrenal gland, adipose tissue, testes, brain
Which of the synthetic estrogens is used more therapeutically? List these (3 categories)
1. estradiol esters (estradiol valerate, estradiol cypionate)
2. conjugated estrogens (estrone sulfate, equilin sulfate)
3. alkyl estrogens (ethinyl estradiol, mestranol)
What does estrogen bind to in the blood before it goes to the granulosa cells? Where does it then head to in the cell?
SHBG; binds to estrogen receptor in the nucleus upstream of estrogen responsive element (ERE)
How are estrogens absorbed in therapy? What can estrogen also bind to in circulation, but with ____ affinity?
Skin, mucous membranes, GI tract;
albumin with LOWER affinity than SHBG
Where is estradiol mainly metabolized? Significant amounts of estrogens and their active metabolites are excreted in _____ and reabsorbed from the ____; why is estradiol not used orally frequently? What is a solution to this problem? How do we excrete the inactive metabolites?
Liver (to E1 and E3); bile; liver;
first pass effect;
use micronization to increase half life and reduce destruction in GI tract;
Life effects of estrogen on female maturation and the repro system
1. development of secondary sex characteristics and sexual organs
2. stimulate endo and follicular growth, breast cell growth, synthesis of progesterone receptors
_____ and ____ are responsible for ovulation at high levels?
Estrogen and LH surge!!
With a constant level of estrogen applied therapeutically, you can prevent ____ _____ and ______, providing a contraceptive effect
follicle maturation (negative feedback on GnRH and FSH) and ovulation (not triggering the LH surge)
List the side effects of estrogen therapy; what are a couple beneficial effects?
1. Increased risk of stroke (postmeno women)
2. Risk of DVT (postmeno women)
3. Increased body fat, salt, and fluid retention
1. Increased HDL, decreased LDL
2. Decreased bone resorption (treat osteoporosis)
List three ways that estrogens can be used therapeutically?
1. Contraception (e.g. ethinyl estradiol used with progestin to prevent pregnancy)
2. Primary hypogonadism (use as replacement therapy if patient is estrogen-deficient)
3. Postmeno hormone thearpy (deal with hot flashes and atrophic vaginitis; prevent osteoporosis)
Some common adverse effects of estrogens? Less common adverse effects? When is estrogen contraindicated?
Nausea, breast tension/pain, vag bleeding, headache, weight gain, HYPERTENSION!!;
Breast cancer? increased incidence of DVT and PE, heart attack, stroke, gallbladder disease, maybe risk of endometrial and cervical cancers;
breast/endo cancer, endometriosis, undiagnosed vag bleeding, pregnancy
What are two examples of antiestrogen therapeutics?
2. Clomiphene citrate
What is tamoxifen and where does it act?
Nonsteroidal agent; 1. antiestrogenic on mammary epi (partial estrogen competitive antagonist) 2. pro-estrogenic on uterine endomet and bone
Which binds better to estrogen receptors, tamoxifen or estrogen? What could prolonged use of tamoxifen lead to?
Estrogen, so you need a lot of tamoxifen;
prolonged use could lead to endometrial carcinoma
What is clomiphene citrate? What are the two isomers? Which of the isomers is the potent antagonist? What is the mechanism of action of the antag?
Cis-clomiphine and trans-clomiphine;
block estrogen binding to receptors in hypo and estradiol's neg feedback on gonadotropins is inhibited
What are some adverse effects of clomiphene citrate?
Symptoms of menopause, stomach pain, headache, upset stomach, vomiting, multpile preg
In females, what makes progesterone during pregnancy? How do males make it? How do both sexes make it? How do you stimulate its production?
Corpus luteum, and during pregnancy the placenta;
Testis; adrenal cortex;
Use GnRH and LH
Progesterone stimulates the _____ to develop _____ glands and support ___ ____ implantation. What could low levels of progest in first few weeks of preg lead to? What does long-term use of progest have on endomet? What do high levels of progest trigger?
endometrium; secretory; fertilized egg; miscarriage;
growth suppressing effect on endometrial cancers (atrophic effect on endometrium);
negative feedback on hypothalamus to stop releasing gonadotropin, suppressing ovulation
What are the two uses of progestin? How can progesterone be given?
1. Contraception (used with estrogens or progestin-only methods)
2. HR therapy (especially for postmeno women to reduce risk of endometrial cancer);
Micronized progesterone (increase half life, decrease first-pass metabolism) and transvaginal progesterone (produce uterine effects with minimal systemic side effects)
What could the synthetic progestins cause as side effects? Adverse effects of natural progestins?
Strong androgenic activity and cause hirsutism and acne, along with edema, abdo bloating, anxiety, irritability, depression, muscular pain, with less common risks of DVT and thrombosis; minimal side effects (fatigue and drowsiness)
For progestins, what are the contraindications and cautions?
Thromboembolic disorders, increased risk of thrombosis, liver disease or dysfunction, undiagnosed vag bleeding, pregnancy (atrophic effect on endomet)
What are three forms of contraceptives?
Estrogen-progestin combinations, progestin-only, postcoital
For the E-P combination, describe its characteristics; what do the estrogenic and progestational agents do?
Reversible contraceptives and 99.9% effective in preventing pregnancy, with low failure rate due to poor patient compliance; suppress FSH, and at constant levels the estrogen can prevent LH surge, while progestin suppresses LH secretion and prevents ovulation, thickens cervical mucus, and leads to endomet atrophy
Why would you use progestin-only oral contraceptives? Why do women tend to stop this method?
Although less effective than combos, there is a growth suppressing effect on endomet cancers and lactating women are good candidates for this method of contraception; irregular menstrual cycle more so than combo products
What is an example of postcoital contraceptives (emergency contraception)? When should you take this pill?
Think of minepristone (abortion pill), a progestin antagonist that competitively binds to progesterone receptor and blocks progesterone binding to its receptor, leading to breakdown of uterine lining; early on with physician with surgery on hand in cause there is heavy bleeding
List the three drugs approved for erectile dysfunction; what do they do? Where do the PDE5 inhibitors work?
Cialis, levitra, viagra (inhibit phosphodiesterase type 5 ); bind to the catalytic site of PDE5 to inhibit its enzymatic activity