Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Repro II Exam I > Drugs Female Gonadal Hormones and Inhibitors (Linger) > Flashcards

Drugs Female Gonadal Hormones and Inhibitors (Linger) Flashcards

1
Q

principal function of FSH

A

direct ovarian follicle development

primary regulatory of spermatogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

in males, role of LH

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what receptors do LH, FSH, and HCG activate

A

GPCR’s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Follitropin alfa
follitropin beta
urofollitropin

A

FSH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

lutropin alpha

A

LH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Leuprolide

A

prototype GnRH analog

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q 
Goserelin
Histrelin
Nafarelin
Triptorelin
Gonadorelin
A

GnRH analogs

gonadorelin is a synthetic human GnRH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what are the contraindications for use of GnRH analogs

A

in women who are pregnant and breast-feeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Cetrorelix
Degarelix
Ganirelix

“Lix”

A

GnRH antagonists

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

clinical use of Ganirelix and Cetrorelix

A

are used to suppress LH surge during controlled ovarian hyperstimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

toxicity of GnRH antagonists

A

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 )

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what are the major estrogens produced by women

A

estradiol
estrone
estriol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is estradiol coverted by the liver into?

A

estrone and estriol (which have low affinity for the estrogen receptor)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

how do hepatic effects of estrogen occur and how can they be reduced?

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what do estrogens bind?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

continuous exposure of estrogen has what effects on the endometrium

A

(2) Continuous exposure for prolonged periods of time leads to hyperplasia of the endometrium that is usually associated with abnormal bleeding patterns

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

what are the effects of estrogen on female maturation

A

(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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What are the effects of estrogen on bone?

A

(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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

estrogen effects of fat/cholesterol levels

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what are the effects of estrogen on levels of thyroxine, estrogen and testosterone

A

(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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

effects of estrogen on blood coagulation

A

(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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

estrogen effects on progesterone receptors

A

induce synthesis of progesterone receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

estrogen effects on fluid volume

A

(2) Facilitate loss of intravascular fluid into the extracellular space, producing edema and compensatory retention of sodium and water by the kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

clinical uses of estrogens

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

what are the adverse effects of estrogens

A

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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

what are the contraindications for the use of estrogen

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

what are the differences b/w oral administrations and transdermal administration of estrogens

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

where is progesterone produced

A

ovary (corpus luteum)

testis

adrenal cortex from circulating cholesterol

placenta during pregnancy, reaching peak levels in the third trimester

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

desogestrel (inactive prodrug) and etonogestrel (active metabolite)

drospinenone

medroxyprogesterone

norethindrone

norgestimate

norgestrel

A

progestins

44
Q

what is the half life of progestins

A

plasma half life is 5 min

almost completely metabolized in one passage through the liver

45
Q

what is used as an index of progesterone secretion

A

pregnanediol

46
Q

what are the two isoforms of the progesterone receptors

A

A and B

47
Q

what are the physiological effects of progesterone

  • endometrium
  • fat
  • insulin
  • glycogen
  • sodium levels
A

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
Q

what are the therapeutic uses of progestins

A

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
Q

what does a 150 mg depot dose of medroxyprogesterone acetate given IM every 90 days do

A

produces prolonged anovulation and amenorrhea (high dose)

50
Q

what are the adverse effects of progestins

A

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
Q

how do oral contraception prevent ovulation

A

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
Q

what are the different oral preparations of hormone contraceptives

A

(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
Q

what is in the transdermal prep/patch Ortho evra

A

ethinyl estradiol

norelgestromin

54
Q

what are the ADR’s of transdermal preps / contraceptives

A

more frequent breast discomfort, dysmenorrhea, nausea, vomiting, skin irritation

55
Q

what is in the NuvaRing

A

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
Q

Injectable preparations of contraceptives include what ?

how often do you inject?

what are the adverse effects?

long term benefits?

A

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
Q

Mirena IUD contains what>

A

levonorgestrel

58
Q

IUD is effective for how long

ADR’s

A

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
Q

implantable injections contain what>

how long does it last?
ADR’s

A

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
Q

what are the emergency contraceptives made up of?

A

estrogens alone

progestins alone

estrogen + progestin

-progesterone receptor modulators

NOTE must begin within 72 hours of sex

61
Q

ADR’s of emergency contraceptives

A

iii) Adverse effects include nausea and vomiting (often administered with antiemetics), headache, dizziness, breast tenderness, abdominal and leg cramps

62
Q

Levonorgestrel emergency contraceptive

MOA?

A

(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
Q

ulipristal acetate

MOA

A

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
Q

effects of contraceptives on the ovary

A

(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
Q

effects of contraceptives on the uterus

A

(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
Q

what are the effects of contraceptives on the breast

A

(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
Q

effects of contraceptives on cortisol, renin, and aldosterone

A

(2) Increased urinary excretion of free cortisol, increased renin activity, and increased aldosterone secretion have been reported;

68
Q

effect of contraceptives on blood

A

increased blood coagulation) due to oral contraceptives are similar to those in pregnancy (a clear cause and effect relationship has yet to materialize)

69
Q

estrogen effects on serum triglyceride, phospholipids, and HDL, LDL

Progestin effects?

A

(4) Estrogens increase serum triglycerides, phospholipids, and HDL while LDL typically decreases;

progestins tend to antagonize these effects

70
Q

progestin effect on insulin

A

increase basal insulin level

71
Q

contraceptives effect on BP

A

increase blood pressure

72
Q

mild adverse effects of contraceptives

A

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
Q

Moderate adverse effects of contraceptives

A

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
Q

what are the severe vascular and mood adverse effects of contraceptives

A
  • **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
Q

what are the severe affects that can occur with the GI system with contraceptives

A

(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
Q

what are the effects of oral contraceptives on cancer

A

Decrease endometrial and ovarian cancer

77
Q

estrogen containing contraceptives are contraindicated in what pt’s

A

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
Q

progestin only contraceptives are contraindicated in what pt’s

A

contraindicated in the presence of undiagnosed vaginal bleeding, benign or malignant liver disease, and known or suspected breast cancer

79
Q

what agents should be used/avoided in pt’s with fibroid tumors

A

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
Q

what happens with contraceptive therapy when a pt is taking cytochrome P450 enzyme inducing agents (phenytoin, rifampin) or antibiotics

A

failure !

normal GI flora increase enterohepatic cycling and bioavailability of estrogens; antimicrobial drugs may reduce their efficacy by altering enterohepatic cycling of metabolites)

81
Q

what are the main non-contraceptive benefits of oral contraceptives

A

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
Q

Tamoxifen, Toremifene

What are these and what are their MOA

A

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
Q

clinical use of Tamoxifen and Toremifene

A

(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
Q

adverse effects of Tamoxifen and Toremifene

A

increase risk of thromboembolic disease (agonist of blood coagulation)

agonist of uterus- increase risk of endometrial cancer

hot flashes —> MC!

85
Q

Raloxifene

MOA

clinical uses

A

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
Q

ADR’s of Raloxifene

A

(3) Adverse effects include hot flashes, deep vein thrombosis, and leg cramps

87
Q

fulvestrant

drug type?
MOA

A

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
Q

clinical use of Fulvestrant

A

(3) Used on postmenopausal women with ER-positive breast cancer and pre- and postmenopausal women who have become resistant to tamoxifen

89
Q

adverse effects of fulvestrant

A

(4) Adverse effects include hot flashes, GI symptoms, headache, back pain, and pharyngitis

90
Q

Clomiphene MOA

A

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
Q

ADR’s of clomiphene

A

(3) Adverse effects include ovarian hyperstimulation (increased size of ovary)

, increased incidence of multiple births,

ovarian cysts

, hot flashes,

and blurred vision

92
Q

Mifepristone

A

MOA: a 19-norsteroid that acts as a progesterone receptor antagonist (also antagonizes the glucocorticoid receptor)

93
Q

major clinical use of mifepristone

A

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
Q

ADR’s of mifepristone

A

(2) Major adverse effects are nausea, vomiting, diarrhea, pelvic or abdominal pain, and prolonged bleeding;

vaginal bleeding requires intervention in 5% of patients

95
Q

Danazol

clinical use

A

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
Q

Major ADR’s of danazol

A

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
Q

what are the contraindications for use of Danazol

A

vi) Contraindicated during pregnancy and breastfeeding due to association with urogenital abnormalities

98
Q

Anastrazole
Exemestane
Letrozole

A

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
Q

clinical uses of Anastrazole
Exemestane
Letrozole (aromatase inhibitors)

A

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
Q

ADR’s of aromatase inhibitors

A

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
Q

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!

A

b/c different doses are given to different patient populations

102
Q

which progestins have more androgenic activity

A

L-norgestrel

norethindrone

  • leads to acne, hirsutism, weight gain
103
Q

which progestins have lower or anti-androgenic activity

A

Lower - norgestimate

anti-androgenic - drospirenone

actually treat acne!

Drospirenon also improves hirsutism and decreases blood pressure

104
Q

how do nuclear receptors (ER/PR) carry out their effects?

A

receptors dimerize upon binding of ligand–> Bind DNA–>

nuclear receptors act in the nucleus and initiate gene transcription

105
Q

when someone is taking combination oral contraceptives what are their levels of Hormones (LH, FSH)

A

LH and FSH are suppressed

mid cycle surge of LH is absent

endogenous steroid levels are diminished

prevent ovulation!

106
Q

if someone is taking progesterone only contraceptives, what are its mechanisms of preventing pregnancy ?

A

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

Repro II Exam I (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions