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Drugs Female Gonadal Hormones and Inhibitors (Linger) Flashcards

(106 cards)

1
Q

principal function of FSH

A

direct ovarian follicle development

primary regulatory of spermatogenesis

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2
Q

in males, role of LH

A

main stimulus for the synthesis of testosterone from cholesterol by Leydig cells

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3
Q

what are the clinical uses of FSH, LH and HCG

A

used in states of infertility to stimulate spermatogenesis in men and to induce ovulation in women

ii) Most common use is for controlled ovulation hyperstimulation, a key step of assisted reproductive technologies (ART) such as in vitro fertilization (IVF)

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4
Q

what receptors do LH, FSH, and HCG activate

A

GPCR’s

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5
Q

clincal use of menotropins (human menopausal gonadotropins or hMG)

A

(a) Used in conjunction with hCG to induce ovulation and pregnancy in infertile females experiencing anovulation not caused by primary ovarian failure
(b) Stimulation of multiple follicle development in ovulatory patients as part of an ART
(c) Unlabeled: Stimulation of spermatogenesis in hypogonadotropic hypogonadism

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6
Q

Follitropin alfa
follitropin beta
urofollitropin

A

FSH

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7
Q

clinical use of rFSH, uFSH

A

(a) Ovulation induction in patients who previously received pituitary suppression (uFSH)
(b) Ovulation induction in patients in whom the cause of infertility is functional and not caused by primary ovarian failure (rFSH alfa and beta)
(c) Spermatogenesis induction in men with hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure (rFSH alfa and beta)
(d) Development of multiple follicles with ART (uFSH, rFSH alfa and beta)

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8
Q

lutropin alpha

A

LH

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9
Q

clinical use of lutropin alfa

A

only used in combination with rFSH alfa for stimulation of follicular development in infertile women with profound LH deficiency

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10
Q

what is the clinical use of extracted hCG

A

(a) Extracted hCG is used to induce ovulation and pregnancy in anovulatory, infertile females; treatment of hypogonadotropic hypogonadism, spermatogenesis induction with rFSH

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11
Q

what is the clinical use of rhCG

A

(b) rhCG induces ovulation in infertile females who have been pretreated with follicle stimulating hormones; induces ovulation and pregnancy in infertile females when the cause of infertility is functional

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12
Q

what are the adverse effects of gonadotropins (LH and FSH ) and HCG

A

(1) Multiple pregnancies
(a) Risk of multiple pregnancy is 15-20% in ART patients (1% in the general population)
(b) Multiple pregnancies increase the risk for gestational diabetes, preeclampsia, and preterm labor

(2) Overstimulation of the ovary during ovulation induction often leads to uncomplicated ovarian enlargement that usually resolves spontaneously

(3) Ovarian hyperstimulation syndrome
(a) Occurs in 0.5-4% of patients
(b) Characterized by ovarian enlargement, ascites, hydrothorax, and hypovolemia, sometimes resulting in shock

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13
Q

Leuprolide

A

prototype GnRH analog

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14
Q
Goserelin
Histrelin
Nafarelin
Triptorelin
Gonadorelin
A

GnRH analogs

gonadorelin is a synthetic human GnRH

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15
Q

what is the outcome of continuous administration of gonadorelin and leuprolide or other analogs

A

biphasic response!

first 7-10 days—> agonist effect with increased concentrations of gonadal hormones (flare)

after first 7-10 days–> inhibitory action that manifests as a drop in the concentration of gonadotropins and gonadal steroids (due to receptor down -regulation and changes in the signaling pathways activated by GnRH)

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16
Q

what are the clinical uses of GnRH analogs where stimulation of gonadotropin production is useful ?

A

female and male infertility

diagnosis of LH responsiveness –> determines whether delayed puberty in a hypogonadotropic adolescent is due to constitutional delay or to hypogonadotropic hypogonadism

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17
Q

what are the clinical uses of GnRH analogs where suppression of gonadotropin production is useful

A

Controlled ovarian hyperstimulation

endometriosis

uterine leiomyomata (benign estrogen sensitive uterine fibroids) (treatment may reduce size

prostate cancer

central precocious puberty

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18
Q

continuous treatment of women with GnRH analog can cause what typical symptoms

A

menopausal symptoms- hot flashes, sweats, headaches

  • depression, diminished libido, generalized pain, vaginal dryness and breast atrophy
  • decreased bone density and osteoporosis (long-term use)

ovarian cysts may develop in the first 2 months!

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19
Q

what are the contraindications for use of GnRH analogs

A

in women who are pregnant and breast-feeding

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20
Q

what does continuous GnRH agonist administration in men cause

A
hot flushes 
sweats
edema
gynecomastia
decreased libido
decreased hematocrit
reduced bone density 
asthenia
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21
Q

Cetrorelix
Degarelix
Ganirelix

“Lix”

A

GnRH antagonists

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22
Q

MOA of GnRH antagonist

A

synthetic competitive antagonists of GnRH receptors inhibit the secretion of FSH and LH in a dose-dependent manner

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23
Q

clinical use of Ganirelix and Cetrorelix

A

are used to suppress LH surge during controlled ovarian hyperstimulation

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24
Q

clinical use of degarelix

A

(4) Degarelix is used to treat advanced prostate cancer (GnRH antagonists reduce concentrations of gonadotropins and androgens significantly more rapidly than GnRH agonists and avoids the initial testosterone surge)

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25
toxicity of GnRH antagonists
short term use for controlled ovarian hyperstimulation is generally well tolerated hypersensitivity reactions including anaphylaxis can occur iii) Adverse effects of long-term use for prostate cancer are similar to GnRH agonists (hot flushes, sweats, edema, gynecomastia, decreased libido, decreased hematocrit, reduced bone density, and asthenia )
26
what are the major estrogens produced by women
estradiol estrone estriol
27
what is estradiol coverted by the liver into?
estrone and estriol (which have low affinity for the estrogen receptor)
28
how do hepatic effects of estrogen occur and how can they be reduced?
iv) The combined first-pass effect and reabsorption of active compounds by the intestine (with enterohepatic circulation) causes significant hepatic effects in comparison to the periphery (see below); hepatic effects of estrogen can be minimized by routes that avoid first-pass liver exposure (e.g., vaginal, transdermal, injection/depot)
29
what do estrogens bind?
estradiol binds to SHBG (strongly) and with lower affinity to albumin act as agonists on the estrogen receptor (ER) - member of the superfamily of nuclear receptors and activate gene transcription
30
continuous exposure of estrogen has what effects on the endometrium
(2) Continuous exposure for prolonged periods of time leads to hyperplasia of the endometrium that is usually associated with abnormal bleeding patterns
31
what are the effects of estrogen on female maturation
(1) Required for the normal sexual maturation and growth of the female (2) Stimulate development of vagina, uterus, and uterine tubes as well as secondary sex characteristics (3) Stimulate stromal development and ductal growth in the breast (4) Responsible for the accelerated growth phase and the closing of epiphyses of long bones that occur at puberty (5) Contribute to the growth of axillary and pubic hair (6) Alter the distribution of body fat to produce typical female body contours
32
What are the effects of estrogen on bone?
(4) Responsible for the accelerated growth phase and the closing of epiphyses of long bones that occur at puberty (1) Decrease the rate of bone resorption by promoting the apoptosis of osteoclasts and by antagonizing the osteoclastogenic and pro-osteoclastic effects of IL-6 and other cytokines
33
estrogen effects of fat/cholesterol levels
stimulate adipose tissue production of leptin (4) Increase high-density lipoproteins (HDL) and triglycerides, slightly reduce low-density lipoproteins (LDL), and reduce total plasma cholesterol levels
34
what are the effects of estrogen on levels of thyroxine, estrogen and testosterone
(3) Stimulate the production of metabolic proteins (e.g., cortisol-binding globulin, thyroxine-binding globulin, sex hormone-binding globulin) that lead to increased circulating levels of thyroxine, estrogen, testosterone
35
effects of estrogen on blood coagulation
(1) Enhance the coagulability of blood (2) Increase circulating levels of factors II, VII, IX, and X and decrease antithrombin III (3) Increase plasminogen levels and decrease platelet adhesiveness
36
estrogen effects on progesterone receptors
induce synthesis of progesterone receptors
37
estrogen effects on fluid volume
(2) Facilitate loss of intravascular fluid into the extracellular space, producing edema and compensatory retention of sodium and water by the kidney
38
clinical uses of estrogens
primary hypogonadism postmenopausal hormone replacement - reduces the hot flashes and other vasomotor symptoms - prevents bone fractures and urogenital atrophy -suppress ovulation in pt's with intractable dysmenorrhea or to suppress ovarian function for the treatment of hirsutism and amenorrhea due to excessive ovary androgen secretion
39
what are the adverse effects of estrogens
uterine bleeding (especially postmenopausal uterine bleeding) cancer - breast cancer - recent studies show that combined estrogen + progestin may increase breast cancer risk significantly than just estrogen alone endometrial carcinoma - up to 15x greater in pt's taking estrogen doses for 5 or more years - concomitant use of progestins and estrogens prevents the increased risk due to estrogen alone ***protective - nausea - breast tenderness - hyperpigmentation - migraines- increased risk of stroke - cholestasis - gallbladder disease - HTN
40
what are the contraindications for the use of estrogen
i) Patients with estrogen-dependent neoplasms (e.g., endometrial carcinoma, breast cancer) or at high risk for breast carcinoma ii) Patients with undiagnosed genital bleeding liver disease a history of thromboembolic *** (absolute) disorder and heavy smokers (not absolute) cardiovascular disease
41
what are the differences b/w oral administrations and transdermal administration of estrogens
i) Due to a greater concentration of estrogens that reach the liver, oral estrogen preparations have more effect on the circulating levels of proteins produced in the liver (e.g., sex-hormone binding globulin, angiotensinogen) compared to transdermal preparations for the same level of gonadotropin suppression ii) Transdermal estrogen preparations do not significantly increase the concentrations of renin substrate, corticosteroid-binding substrate, and thyroxine-binding substrate and do not produce the characteristic changes in serum lipids
42
where is progesterone produced
ovary (corpus luteum) testis adrenal cortex from circulating cholesterol placenta during pregnancy, reaching peak levels in the third trimester
43
desogestrel (inactive prodrug) and etonogestrel (active metabolite) drospinenone medroxyprogesterone norethindrone norgestimate norgestrel
progestins
44
what is the half life of progestins
plasma half life is 5 min | almost completely metabolized in one passage through the liver
45
what is used as an index of progesterone secretion
pregnanediol
46
what are the two isoforms of the progesterone receptors
A and B
47
what are the physiological effects of progesterone - endometrium - fat - insulin - glycogen - sodium levels
endometrium - ii) Decreases estrogen-driven endometrial proliferation iii) Abrupt decline at the end of the cycle is the main determinant of the onset of menstruation ix) Causes maturation and secretory changes in the endometrium that are seen following ovulation maintains pregnancy and mammary gland development (with estrogen) stimulates lipoprotein lipase and favors fat deposition increases basal insulin levels and the insulin response to glucose promotes glycogen storage and ketogenesis viii) Can compete with aldosterone for the mineralocorticoid receptor, causing a decrease in sodium reabsorption (leads to increased secretion of aldosterone)
48
what are the therapeutic uses of progestins
HRT and hormone contraception long term ovarian suppression -used to treat dysmenorrhea, endometriosis, bleeding disorders, hot flushes (menopausal women when estrogens are contraindicated) and contraception diagnostic uses -estrogen-progesterone combination can be given to test the responsiveness of the endometrium in pt's with amenorrhea
49
what does a 150 mg depot dose of medroxyprogesterone acetate given IM every 90 days do
produces prolonged anovulation and amenorrhea (high dose)
50
what are the adverse effects of progestins
i) Breakthrough bleeding ***(most common when progestins alone are used for contraception) ii) Progestins may increase blood pressure in some patients (typically a minor effect) iii) The more androgenic progestins reduce plasma HDL levels in women iv) HRT with an estrogen and progestin may increase the risks for cardiovascular problems and breast cancer compared to the risk in women taking estrogen alone***
51
how do oral contraception prevent ovulation
estrogen and progestins inhibit LH/FSH (through negative feedback) and thus prevent estrogen surge no estrogen surge --> no LH surge--> no ovulation ! estrogen and progestin also decrease the likelihood of conception and implantation through changes in cervical mucus, the uterine endometrium, and in the motility and secretion in the uterine tubes
52
what are the different oral preparations of hormone contraceptives
(1) Combinations of estrogens and progestins (2) Continuous progestin therapy without estrogens (b) Useful in patients for whom estrogen administration is undesirable (e.g., cardiovascular disease, estrogen-dependent neoplasms, etc.) (c) Higher incidence of abnormal bleeding
53
what is in the transdermal prep/patch Ortho evra
ethinyl estradiol norelgestromin
54
what are the ADR's of transdermal preps / contraceptives
more frequent breast discomfort, dysmenorrhea, nausea, vomiting, skin irritation
55
what is in the NuvaRing
ethinyl estradiol and etonogestrel iii) Rapid return to fertility after removal (back-up contraception should be used if removed for more than 3 hours)
56
Injectable preparations of contraceptives include what ? how often do you inject? what are the adverse effects? long term benefits?
medroxyprogesterone acetate inhibits ovulation for 14 weeks!! inject every 3 months iii) Unpredictable spotting and bleeding, particularly during the first year of use iv) The return of fertility can be delayed as long as 18 months after the last injection in some patients (undesirable in women planning a pregnancy soon after cessation) vi) Suppression of endogenous estrogen secretion may be associated with a reduction in bone density (reversible) and increased risk of atherosclerosis v) Long-term use reduces menstrual blood loss and may reduce risk of endometrial cancer
57
Mirena IUD contains what>
levonorgestrel
58
IUD is effective for how long ADR's
ii) Effective for 5 years iii) Increased irregular bleeding for 3-6 months after placement; reduced total bleeding after that and 20% of users report amenorrhea after 1 year of use iv) May increase risk of ovarian cysts v) Rapid return to fertility following removal
59
implantable injections contain what> how long does it last? ADR's
etonogestrel ii) Surgically inserted under the skin of the upper arm and is effective for three years; removal also requires surgery iii) Bleeding abnormalities are common iv) Fertility returns rapidly after removal in most patients v) Release 20-33% as much steroid as oral agents, little effect on lipoprotein and carbohydrate metabolism or blood pressure
60
what are the emergency contraceptives made up of?
estrogens alone progestins alone estrogen + progestin -progesterone receptor modulators NOTE must begin within 72 hours of sex
61
ADR's of emergency contraceptives
iii) Adverse effects include nausea and vomiting (often administered with antiemetics), headache, dizziness, breast tenderness, abdominal and leg cramps
62
Levonorgestrel emergency contraceptive MOA?
(2) Precise mechanism in emergency contraception is unknown (proposed mechanisms include inhibited or delayed ovulation, alterations in endometrial receptivity for implantation, interference with functions of the corpus luteum that maintains pregnancy, production of a cervical mucus that decreases sperm penetration, alterations in tubular transport of sperm, egg, or embryo, or disruption of the fertilization process) (3) Does not reverse a pregnancy that has already occurred (i.e., if the fertilized egg has already implanted in the uterus)
63
ulipristal acetate MOA
Plan B (Ella) (1) MOA: partial agonist at progesterone receptors; inhibits ovulation when taken up to five days after intercourse, may also block implantation of the fertilized egg (so interfere with pregnancy that has begun to develop in the uterus) requires a prescription (3) As effective as levonorgestrel when used within 3 days and may be more effective 3-5 days after unprotected intercourse ADR's include headache and abd pain
64
effects of contraceptives on the ovary
(1) Chronic use depresses ovarian function (ovaries usually become smaller) (2) The majority of patients return to normal menstrual patterns upon discontinuation (75% ovulation rate in first posttreatment cycle and 97% by the third; 2% remain amenorrheic for up to several years after discontinuation)
65
effects of contraceptives on the uterus
(1) Prolonged use may cause hypertrophy of the cervix and polyp formation (2) Glandular atrophy and decreased bleeding are common depending on the preparation
66
what are the effects of contraceptives on the breast
(1) Estrogen-containing agents can stimulate breast enlargement and tend to suppress lactation in lactating females (the effects of low estrogen doses are not appreciable on breast-feeding) (2) Small amounts of oral contraceptives have been shown to cross into the milk (without clinical importance)
67
effects of contraceptives on cortisol, renin, and aldosterone
(2) Increased urinary excretion of free cortisol, increased renin activity, and increased aldosterone secretion have been reported;
68
effect of contraceptives on blood
increased blood coagulation) due to oral contraceptives are similar to those in pregnancy (a clear cause and effect relationship has yet to materialize)
69
estrogen effects on serum triglyceride, phospholipids, and HDL, LDL Progestin effects?
(4) Estrogens increase serum triglycerides, phospholipids, and HDL while LDL typically decreases; progestins tend to antagonize these effects
70
progestin effect on insulin
increase basal insulin level
71
contraceptives effect on BP
increase blood pressure
72
mild adverse effects of contraceptives
often alleviated by change in pill formulation (1) Nausea, mastalgia, and edema are all related to the amount of estrogen in the preparation (can often be alleviated by a preparation containing smaller amounts of estrogen or progestins with more androgenic effects) (2) Transient and mild headache (3) Migraines are often made worse or are new onset with therapy (due to association with an increased frequency of cerebrovascular accidents, treatment should be discontinued) (4) Withdrawal bleeding sometimes fails to occur and may cause confusion with regard to pregnancy (more common with combination preparations)
73
Moderate adverse effects of contraceptives
breakthrough bleeding (more common with progestins alone) weight gain (combination agents more commonly cause this) increased skin pigmentation acne (improved with large estrogen amounts, made worse with androgen-like progestins) hirsutism (aggravated by norethindron, levonorgestrel) vaginal infections amenorrhea
74
what are the severe vascular and mood adverse effects of contraceptives
* **vascular! --> 1) -venous thromboembolic disease (associated with estrogen) 2) Myocardial infarction - increased risk when obese, history of preeclampsia, or HTN, hyperlipoproteinemia, or DM, smokers 3) -Cerebrovascular disease (mostly in women over age 35 who are heavy smokers) Depression!
75
what are the severe affects that can occur with the GI system with contraceptives
(a) Cholestatic jaundice is increased in patients taking progestin-containing drugs (b) Increased incidence of symptomatic gallbladder disease, including cholecystitis and cholangitis (c) Increased incidence of hepatic adenomas
76
what are the effects of oral contraceptives on cancer
Decrease endometrial and ovarian cancer
77
estrogen containing contraceptives are contraindicated in what pt's
i) Estrogen-containing contraceptives are not recommended for: smokers ≥ 35 years old patients with hypertension, coronary artery disease, cardiovascular and cerebrovascular disorders (or past history of these disorders), diabetes with end-organ damage, migraine headaches with focal neurological symptoms, vaginal bleeding of unknown cause patients with known or suspected tumors of the breast or other estrogen-dependent neoplasms adolescents in whom epiphysial closure has not yet been completed (progestin-only agents or non-hormonal methods are more appropriate)
78
progestin only contraceptives are contraindicated in what pt's
contraindicated in the presence of undiagnosed vaginal bleeding, benign or malignant liver disease, and known or suspected breast cancer
79
what agents should be used/avoided in pt's with fibroid tumors
v) For women with fibroid tumors, agents with the smallest amounts of estrogen and the most androgenic progestins should be used (estrogens increase fibroid growth rate)
80
what happens with contraceptive therapy when a pt is taking cytochrome P450 enzyme inducing agents (phenytoin, rifampin) or antibiotics
failure ! normal GI flora increase enterohepatic cycling and bioavailability of estrogens; antimicrobial drugs may reduce their efficacy by altering enterohepatic cycling of metabolites)
81
what are the main non-contraceptive benefits of oral contraceptives
i) Combination (estrogen + progestin) oral contraceptives confer: (1) reduced risk of epithelial ovarian and endometrial cancer, (2) lower incidence of ectopic pregnancy and benign breast disease, (3) reduction in dysfunctional uterine bleeding and dysmenorrhea, (4) improvement in premenstrual symptoms, hirsutism, and acne
82
Tamoxifen, Toremifene What are these and what are their MOA
Selective Estrogen Receptor Modulators (2) MOA: Competitive partial agonist inhibitors of estradiol at the estrogen receptor Antagonists on breast, agonist on uterus - may increase risk of endometrial cancer (possible b/c certain tissues have higher concentrations of corepressors)
83
clinical use of Tamoxifen and Toremifene
(3) Used to treat breast cancer (estrogen receptor positive or status unknown) and for chemoprevention of breast cancer in high-risk individuals Lower incidence of MSK disorder or fx plasma lipids --> reduction in atherosclerosis
84
adverse effects of Tamoxifen and Toremifene
increase risk of thromboembolic disease (agonist of blood coagulation) agonist of uterus- increase risk of endometrial cancer hot flashes ---> MC!
85
Raloxifene MOA clinical uses
selective estrogen receptor modulator Agonist effects on lipids and bone; antagonist on endometrium and breast (2) Used for the prevention of postmenopausal osteoporosis and chemoprevention of breast cancer in at-risk individuals
86
ADR's of Raloxifene
(3) Adverse effects include hot flashes, deep vein thrombosis, and leg cramps
87
fulvestrant drug type? MOA
selective estrogen receptor downregulator (1) MOA: bind to ERs and inhibit dimerization while increasing protein degradation (2) Thought to completely abolish the expression of estrogen-dependent genes
88
clinical use of Fulvestrant
(3) Used on postmenopausal women with ER-positive breast cancer and pre- and postmenopausal women who have become resistant to tamoxifen
89
adverse effects of fulvestrant
(4) Adverse effects include hot flashes, GI symptoms, headache, back pain, and pharyngitis
90
Clomiphene MOA
Selective estrogen receptor downregulator MOA: weak estrogen. acts as a competitive partial agonist inhibitor of endogenous estrogens (occupies hypothalamic ER's) -selectively blocks estrogen receptors in the pituitary , reducing negatively feedback mechanism, thereby increasing FSH and LH and stimulation of ovulation
91
ADR's of clomiphene
(3) Adverse effects include ovarian hyperstimulation (increased size of ovary) , increased incidence of multiple births, ovarian cysts , hot flashes, and blurred vision
92
Mifepristone
MOA: a 19-norsteroid that acts as a progesterone receptor antagonist (also antagonizes the glucocorticoid receptor)
93
major clinical use of mifepristone
iii) Major use is to terminate early pregnancies (1) Standard dosing regimen will terminate 85% of pregnancies; combination with synthetic prostaglandin E1 (misoprostol) terminates pregnancy in over 95% of patients treated during the first 7 weeks after conception
94
ADR's of mifepristone
(2) Major adverse effects are nausea, vomiting, diarrhea, pelvic or abdominal pain, and prolonged bleeding; vaginal bleeding requires intervention in 5% of patients
95
Danazol clinical use
Inhibits ovarian steroid synthesis. Synthetic androgen that acts as a partial agonist at androgen receptors. Weak glucocorticoid activity Use: endometriosis and fibrocystic disease of the breast iii) Suppresses pituitary output of FSH and LH and decreases rate of growth of abnormal breast tissue
96
Major ADR's of danazol
v) Major adverse effects include weight gain, edema, decreased breast size, acne and oily skin, increased hair growth, deepening of the voice, headache, hot flushes, changes in libido, and muscle cramps (androgenic, progestational, and glucocorticoid effects)
97
what are the contraindications for use of Danazol
vi) Contraindicated during pregnancy and breastfeeding due to association with urogenital abnormalities
98
Anastrazole Exemestane Letrozole
Aromatase inhibitors - decrease estrogen synthesis i) MOA: inhibit the function of aromatase (CYP19, responsible for the conversion of androstenedione and testosterone to the estrogens estrone and estradiol, respectively)
99
clinical uses of Anastrazole Exemestane Letrozole (aromatase inhibitors)
in postmenopausal women, conversion of androstenedione to estrogens occurs in the peripheral tissues AIs are only recommended for women who are postmenopausal, where their use can lead to profound estrogen deprivation used in breast cancer in postmenopausal women (not pre-menopausal b/c in these women estrogen is made in the ovary and if you block production in the ovary, less estrogen will increase FSH and LH--> enhance fertility)
100
ADR's of aromatase inhibitors
v) Associated with a significantly lower incidence of vaginal bleeding, vaginal discharge, hot flashes, endometrial cancer, and deep vein thrombosis compared to SERMs and SERDs
101
why is there no increased risk when you use progestins as contraceptives in pre-menopausal but there IS increased risk if used as HRT in post-menopausal For breast cancer!
b/c different doses are given to different patient populations
102
which progestins have more androgenic activity
L-norgestrel norethindrone - leads to acne, hirsutism, weight gain
103
which progestins have lower or anti-androgenic activity
Lower - norgestimate anti-androgenic - drospirenone actually treat acne! Drospirenon also improves hirsutism and decreases blood pressure
104
how do nuclear receptors (ER/PR) carry out their effects?
receptors dimerize upon binding of ligand--> Bind DNA--> nuclear receptors act in the nucleus and initiate gene transcription
105
when someone is taking combination oral contraceptives what are their levels of Hormones (LH, FSH)
LH and FSH are suppressed mid cycle surge of LH is absent endogenous steroid levels are diminished prevent ovulation!
106
if someone is taking progesterone only contraceptives, what are its mechanisms of preventing pregnancy ?
Highly efficacious but block ovulation in only 60-80% of cycles Effectiveness thought to be due largely to a thickening of cervical mucus (decreases sperm penetration) and to endometrial alterations that impair implantation Depot injections are thought to exert similar effects, but also yield plasma levels of drug high enough to prevent ovulation in virtually all patients Thought to be due to decreases in GnRH pulse frequency