Brainscape's Knowledge GenomeTM

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


See full index

PT 2 > Block 9 - L2-L4 > Flashcards

Block 9 - L2-L4 Flashcards

1
Q

What are the physiological effects of estrogen on female reproduction?

A

Regulation of menstrual cycle and ovulation

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

What are the physiological effects of estrogen on female puberty?

A

Development and maturation of secondary sexual characteristics

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

What are the physiological effects of estrogen on electrolyte and fluid balance?

A

Increases Na and H2O retention

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

What are the physiological effects of estrogen on the CNS?

A

Increases sense of well-being and enhances cognition

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

What are the physiological effects of estrogen on blood vessels?

A

Increases vasodilation

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

What are the physiological effects of estrogen on blood coagulation?

A

Increases coagulation and clotting factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the physiological effects of estrogen on blood lipids?

A

Increases HDL and lowers LDL

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

What are the physiological effects of estrogen on bone?

A

Decreases bone resorption, maintains BMD, helps close epiphysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the MOA of estrogen?

A
  1. Estrogen binds ER in the cytosol (unbinds from SHBG and diffuses into the cell prior to this)
  2. ER undergoes conformational changes and forms dimers
  3. ER dimers translocate into the nucleus and bind to target promoters (ERE - estrogen response element)
  4. Promoter-bound, ligand-activated ER receptors recruit transcriptional co-factors and modulate target gene expression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

List the natural endogenous estrogens in order of potency.

A

Most potent: estradiol (E2)
Middle potency: estrone (E1)
Least potent: estriol (E3)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

When are the three natural endogenous estrogens most abundant?

A

E2 - reproductive years
E1 - menopause
E3 - pregnancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where is E2 produced?

A

Ovary (most), adipose tissue, adrenal glands, liver, breast, neurons

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

Where is E1 produced?

A

Ovary, adipose tisue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Where is E3 produced?

A

Secreted from placenta and adrenal gland (not ovary), also a metabolite of E2 and E3 in the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the role of aromatase (CYP19A1) in the production of estrogens?

A

Aromatase converts Androstendione to Estrone (E1) and Testosterone to Estradiol (E2). These are converted to Estriol (E3) in the liver and placenta.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What converts E1 to E2 and E2 to E1?

A

17-beta-HSD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How is estrogen biosynthesis regulated?

A

Negative feedback via Estrogen and Inhibin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Discuss different administrations of E2.

A
  1. Significant first pass effect after oral administration (low oral bioavailability)
  2. Metabolized in liver to E1 and E3
  3. Major effect on liver (clotting factors, lipids, etc.)
  4. Transdermal preparations avoid first pass effect (lower risk of thrombosis and stroke)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How is oral bioavailability of synthetic estrogens improved?

A

Modifications - conjugated estrogens, estrogen esters, esterified estrogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Discuss CYP metabolism of estrogens.

A

Extensively metabolized by CYP 1A2, 2C9, 3A4

inducers of CYP3A4 - St. John’s Wort, carbamazepine, phenobarbital decrease estrogen levels

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

How are Phase II estrogen conjugates excreted?

A

Urine and bile (undergo enterohepatic recirculation, explaining extensive hepatic actions)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

List the 4 estrogen preparations and formulations for clinical use.

A
  1. Ethinylestradiol (EE)
  2. Conjugated equine estrogens (CEE - Premarin)
  3. Esterified estrogens (EE)
  4. Estrogen esters
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the clinical uses of estrogen?

A
  1. Hormone replaceent therapy for post-menopausal women (+/- progestin)
  2. Component of oral contraceptive pill
  3. Treatment of primary hypogonadism
  4. Primary ovarian insufficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Discuss risk of endometrial cancer in estrogen hormone replacement therapy.

A

When the uterus present, estrogen along has a 6.3x increased risk of developing endometrial cancer. This risk is removed in the presence of a progestin.

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

Discuss treatment of primary hypogonadism (Turner’s syndrome, etc.) with estrogen.

A

Used at ~11-13 years to promote development of secondary sexual characteristics, promote optimal growth and prevent osteoporosis; progestin needed to prevent endometrial hyperplasia, gonadotropin treatment required to rescue fertility

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

What is menopause?

A

Natural process of aging involving permanent cessation of the menstrual cycle (12 months after last period) due to oocyte depletion (sharp decrease in ovarian production of estrogen and progesterone)

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

What is the mean age of onset of menopause and the age range?

A

51 y/o (45-60 y/o)

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

What are other causes of menopause?

A

Gynecological surgery (hysterectomy, endometrial ablation), premature ovarian failure (idiopathic, autoimmune, PCOS)

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

When do symptoms of menopause occur?

A

~4 years prior to the final menstrual cycle

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

What are the signs and symptoms of menopause?

A 
Irregular menstrual cycles
Vasomotor responses (hot flashes) - most common
Sleep disturbances
Mood swings/depression
Vaginal dryness and atrophy
Sexual dysfunction
Cognitive decline (memory loss/ability to concentrate)
Joint pain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are long term consequences of estrogen deficiency?

A

Increased bone loss
Increased risk fo CVD
Skin changes

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

What is the goal of hormone replacement therapy for treatment of menopausal symptoms?

A

Provide relief of symptoms, especially vasomotor symptoms, vaginal dryness and atrophy, mood lability/depression, and joint pains

Treatment to prevent chronic effects of estrogen deficiency is no longer recommended due to increased risk of AE

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

What are the benefits to various routes of estrogen therapy?

A

Transdermal E2 - lower risk of VTE, stroke, hypertriglyceridemia

Oral - more favorable lipid effect (increases HDL)

Vaginal - if primary treatment is for GU symptoms

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

Why is progestin added to various treatments with estrogen?

A

Prevent endometrial hyperplasia when a uterus is present

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

Discuss the duration of estrogen therapy.

A

No more than 5 years or beyond the age of 60 y/o

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

What are the contraindications of estrogen?

A

Prior history of or high risk for (BRCA1+, etc.) breast cancer, CHD, stroke, history of endometrial cancer, liver disease, history of thromboembolic disease, history of genital bleeding, heavy smoking (increased stroke risk)

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

What are the AE of estrogen?

A
  1. Increased risk of endometrial cancer
  2. Increased risk of thromboembolic disease
  3. Increased risk of gallbladder disease (increased hepatic secretion of cholesterol)
  4. Post-menopausal uterine bleeding
  5. Fullness/tenderness of breast
  6. Severe migraines
  7. Increased risk of dementia (if taking estrogen >65 y/o)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What do estrogen do in breast cancer?

A

If ER+, increases growth of the tumor

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

What are SERMs (selective estrogen receptor modulators)?

A

ER ligands that exhibit mixed agonist/antagonist activity in a tissue-specific fashion; act as ER antagonists in some tissues and partial agonists in others

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

List the SERMs.

A
  1. Tamoxifen
  2. Raloxifene
  3. Clomiphene
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What are the sites of action for Tamoxifen?

A

Antagonist - breast tissue

Partial agonist - endometrium, bone

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

What are the sites of action for Raloxifene?

A

Antagonist - breast tissue, endometrium

Partial agonist - bone

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

What are the sites of action for Clomiphene?

A

Antagonist - hypothalamus, AP, uterus, vagina

Partial agonist - ovaries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What is the MOA of SERMs?

A

Bind directly to the ligand binding site of the ER and compete for binding with endogenous E2; induce a different conformation in the ER compared to E2; different conformations bind to distinct subsets of tissue-specific transcriptional co-factors and thereby activate distinct patterns of gene expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What are the indications of Tamoxifen?

A
  1. Primary prevention in women at high risk of breast cancer
  2. Adjuvant therapy of women ER+ early, locally-advanced, and metastatic breast cancer
  3. Treatment of male gynecomastia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

True or false - Tamoxifen resistance can occur.

A

True (both intrinsic and acquired)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What are the AE of Tamoxifen?

A
  1. Hot flashes (ER antagonism in CNS)
  2. Increased risk of thromboembolic events
  3. Increased risk of endometrial cancer (agonist effect)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What are the indications of Raloxifene?

A
  1. Treatment of osteoporosis in post-menopausal women due to E2 deficiency (activates ER in bone)
  2. Primary prevention of breast cancer in high risk patients
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Why would Raloxifene be used instead of Tamoxifen in prevention of breast cancer?

A

Raloxifene is not associated with increased risk of endometrial cancer, but it is about 75% as effective

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What are the AE of Raloxifene?

A

Hot flahses, increased risk of thromboembolic events (less than tamoxifen), leg cramps

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is the indication of Clomiphene?

A

Female infertility due to anovulation (PCOS, etc.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What is the MOA of Clomiphene?

A

Antagonizes ER in the hypothalamus and AP, prevents negative feedback, promotes increased expression of GnRH, gonadotropins, FSH, LH, increases follicular development; improves ovulatory and pregnancy rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What are the AE of Clomiphene?

A 
Hot flashes
Multiple pregnancy (only rarely leads to ovarian hyperstimulation syndrome)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What is the selective estrogen receptor degrader (SERD)?

A

Fulvestrant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What is the MOA of Fulvestrant?

A

Binds to ER, inducing an abnormal conformation that results in the subsequent degradation of the ER protein; acts as a pure anti-estrogen (no agonist activity)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What are the indications of Fulvestrant?

A

Treatment of ER+ advanced/metastatic breast cancer in post-menopausal women with disease progression following prior anti-estrogen therapy (tamoxifen, etc.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What are the AE of Fulvestrant?

A

Hot flashes, blood clots, elevated liver enzymes

58
Q

What are the contraindications of Fulvestrant?

A

Pregnant/lactating women

59
Q

List the estrogen synthesis inhibitors (aromatase inhibitors).

A
  1. Anastrozole
  2. Letrozole
  3. Exemestane
60
Q

What is the MOA of aromatase inhibitors?

A

Anastrozole and Letrozole - competitive inhibition of aromatase

Exemestane - covalent “suicide” inhibitor of aromatase

61
Q

What are the indications of aromatase inhibitors?

A

Adjuvant treatment of ER+ early or advanced breast cancers in post-menopausal women

62
Q

What are the AE of aromatase inhibitors?

A

Symptoms of estrogen deficiency (hot flashes, etc.)
Increased bone fractures
NO increase of endometrial cancer and thrombosis risk

63
Q

What are the contraindications of aromatase inhibitors and why?

A

Pre-menopausal women (little effect due to homeostatic upregulation of the HPG axis leading to increased aromatase expression and ovarian estrogen production)

64
Q

What are progestins?

A

Compounds with biological activities similar to progesterone

65
Q

What is progesterone?

A

Hormone synthesized in the ovary, testis, and adrenal cortex (and placenta during pregnancy); precursor for estrogens, androgens, and adrenocorticosteroids

66
Q

What are the key physiological effects of progesterone?

A
  1. Regulation of the luteal phase of the ovarian cycle
  2. Prepares the endometrium for implantation (antagonizes the proliferative effects of E2 on endometrial cells and promotes the secretory phase)
  3. Negatively regulates the HPG axis by reducing the frequency of GnRH pulses and reduced production of FSH and LH results in decreased ovulation
  4. Increase thickness of cervical mucus
  5. Reduction in progesterone production triggers menstruation by promoting sloughing
67
Q

What are the clinical uses of progestins?

A
  1. Hormone replacement therapy (administered in combination with estrogen to prevent endometrial hyperplasi)
  2. Hormonal contraception
68
Q

What is the MOA of progestins?

A

Potent agonists of the progesterone receptor, promoting expression of PR-dependent genes; some ALSO exhibit androgenic activity and act as weak agonists of the androgen receptor

69
Q

List the progestins in order from more androgenic activity to less.

A

More - Norgestrel and Levongestrel

Middle - Norethindrone

Low - Desogestrel, Gestodene, Norgestimate

70
Q

What are the progestin-only oral contraceptives?

A
  1. Oral pill (mini pill) - daily pill comprised of a fixed dose of norethindrone
  2. Depot administration - medroxyprogesterone acetate = 3 month protection
  3. Implant - etonogestrel rod implanted subdermally (3 years)
71
Q

What is the combined oral contraceptive?

A

Ethinyl estradiol + progestin (norgestrel or norethindrone or dosogestrel)

72
Q

What are the 2 emergency contraceptives?

A

High dose progestin (levonorgestrel) and selective progesterone modulator (ulipristal)

73
Q

What is the MOA of progestin-only contraception?

A

Decreases the frequency of GnRH pulses and decrease the responsiveness of the pituitary to GnRH - decreases release of gonadotropins and decreases ovulation; thickens cervical mucus to prevent sperm penetration; reduces endometrial growth

74
Q

What are two important therapeutic considerations for progestin-only contraception?

A
  1. Useful for women for whom estrogen-containing pill is contraindicated
  2. Pill must be taken at the same time everyday (within 3 hours)
75
Q

What are the AE of progestin-only contraception?

A
  1. Menstrual irregularities (irregular bleeding, spotting, and amenorrhea)
  2. Breast tenderness
  3. Increased prevalence of ovarian cysts
  4. Acne (androgenic effect)
76
Q

Discuss the formulations of combined oral contraceptives.

A

Monophasic - pill contains a fixed dose

Biphasic and triphasic - doses of hormones are varied to mimic physiological hormone changes during the cycle

First 21 pills contain active hormonal ingredient; last 7 pills contain placebo, which triggers menstruation by causing the endometrium and blood supply to slough off

77
Q

What are additional non-contraceptive benefits of combined OCs?

A
  1. Treatment of menstrual cycle disorders (diminishes bleeding, thins endometrium, reducing availability of arachidonic acid for PG synthesis)
  2. Treatment of hyperandrogenism (suppresses production of gonadotropins, increases expression of SHBG)
  3. Treatment of bleeding due to leiomyomas
  4. Treatment of endometriosis and pelvic pain (suppression of gonadotropin production and inhibition of endometrial proliferation)
  5. Cancer risk reduction (endometrial and ovarian cancer)
78
Q

What are the AE of combined OCs?

A
  1. Bloating, nausea, breast tenderness (subside after several months typically)
  2. Breakthrough bleeding
  3. Increased risk of venous thromboembolic disease
  4. Increased risk of MI (low in non-smokers, concern in smokers >35 y/o)
  5. Hepatic adenoma or carcinoma (rare)
79
Q

What are the contraindications of OCs?

A
  1. Age >35 y/o and smoking >15 cigarettes/day
  2. History of CAD or congenital hyperlipidemia
  3. History of venous thromboembolism
  4. History of stroke
  5. SLE
  6. History of breast cancer or other female reproductive tract cancer
  7. History of liver disease
80
Q

What are drug interactions of OCs?

A

Metabolized by CYP3A4 and other CYPs

81
Q

What is the purpose of leveonorgestrel and ulipristal (emergency contraception - “the morning after pill”)?

A

Prevention of pregnancy following unprotected sex or failure of a barrier contraceptive

82
Q

What is the MOA of leveonorgestrel?

A

High dose administration of levonorgestrel within 72 hours of sex daily for 5 days - inhibits/delays ovulation by inhibiting the LH surge; works by activating the negative feedback mechanism on pituitary production of LH; only effective if given at least 2 days prior to surge

83
Q

What are the AE of leveonorgestrel and ulipristal?

A

Nausea

Delay of menses

84
Q

What is the MOA of ulipristal?

A

Partial agonist of PR, primarily acts as an antagonist in presence of progesterone (effective when given up to 5 days after sex); inhibits or delays ovulation by inhibiting LH-induced PR-dependent genes involved in promoting follicular rupture (effective even if given during the LH surge)

85
Q

What are other clinical uses of ulipristal?

A

Treatment of uterine fibroids

Blocks progesterone-induced growth and reduces excessive bleeding

86
Q

What is the contraindication of ulipristal?

A

Pregnancy (embryotoxic)

87
Q

What is Mifepristone (RU-486)?

A

High affinity competitive antagonist of the progesterone receptor (also binds to and and antagonizes both the glucocorticoid and androgen receptors)

88
Q

What is the indication of mifepristone?

A

Medical abortion of first trimester pregnancy (<70 days) - administered once at high dose followed by misprostol (prostgalndin E1 analog)

89
Q

What is the MOA of mifepristone?

A

Impairs development of endometrium and triggers menstruation due to antagonism of PR (progesterone is required to maintain endometrium); misprostol promotes uterine contraction, leading to expulsion of the blastocyst

90
Q

What are the AE of mifepristone?

A

Excessive vaginal bleeding and abdominal cramps

91
Q

What are the contraindications of mifepristone?

A

Chronic adrenal failure, bleeding disorder, anticoagulants

92
Q

What are the physiological effects of testosterone on male sex organs?

A

Sex organ development, sperm production, prostate growth, and erectile function

93
Q

What are the physiological effects of testosterone on puberty?

A

Development and maintenance of secondary sexual characteristics

94
Q

What are the physiological effects of testosterone on the bone marrow?

A

RBC production

95
Q

What are the physiological effects of testosterone on the skin?

A

Growth of facial and body hair, collagen growth, androgenic alopecia

96
Q

What are the physiological effects of testosterone on the CNS?

A

Sex drive, sense of well-being, confidence, cognition, memory

97
Q

What are the physiological effects of testosterone on bone?

A

Bone density, maintenance, epiphyseal closure

98
Q

What are the physiological effects of testosterone on muscle?

A

Muscle mass and strength

99
Q

Testosterone is a direct agonist of the ___.

A

Androgen receptor

100
Q

What is the androgen receptor?

A

An androgen-dependent nuclear transcription factor of the steroid hormone family

101
Q

Describe the MOA of testosterone.

A
  1. Testosterone is bound to SHBG in the blood
  2. SHBG releases T, which diffuses into cells and binds AR in the cytosol
  3. AR undergoes conformational changes and forms dimers
  4. AR dimers translocate to the nucleus and bind to target promoters (HRE - hormone response element)
  5. Promoter-bound, ligand-activated AR receptors recruit transcriptional co-factors and modulate target gene expression
102
Q

Discuss the biosynthesis of testosterone.

A
  1. Testosterone is produced in the testes from cholesterol.
  2. In peripheral tissue, it can be converted to E2 via aromatase in liver/adipose/hypothalamus/skin/bone
  3. In peripheral tissue, it can be converted to DHT via 5-alpha-reductase in skin/liver/bone/UG tissue.
  4. It can be metabolized in the liver to andosterone and etiocholanolone
103
Q

What are the effects of DHT on external genitalia?

A

Differentiation and maturation during puberty, prostate size and development

104
Q

What are the effects of DHT on hair follicles?

A

Increased facial and body hair growth during puberty, male pattern baldness

105
Q

What are the effect of testosterone on internal genitalia?

A

Wolffian development during gestation, spermatogenesis

106
Q

What are the other effects of testosterone?

A

Increase mass and strength of skeletal muscle, libido, sexual function, erythropoiesis, bone growth

107
Q

What are the effects of E2 on bone?

A

Epiphyseal closure and increased density

108
Q

What are the other effects of E2?

A

Libido, sexual function, reduced body mass

109
Q

List the formulations of testosterone.

A
  1. Testosterone
  2. Methylestosterone (alkylated)
  3. Testosterone cypionate and ethanate (esterified)
110
Q

What are the features of Testosterone (formulation)?

A

Given transdermally and avoids first pass effect

111
Q

What are the features of esterified Testosterone?

A

Given parenterally, especially IM, includes a lipophilic moiety that makes the T into a prodrug requiring cleavage to be active; long-acting

112
Q

What are the features of aklyated Testosterone?

A

17-alpha alkylation inhibits hepatic catabolism; makes it orally bioavailable; also less androgenic than T with increased hepatotoxicity

113
Q

What are the indications of Testosterone?

A

Male hypogonadism

  1. Primary - disease of testes
  2. Secondary - hypothalamus/pituitary disease
114
Q

Discuss the levels of hormones seen in primary male hypogonadism.

A

Sperm and testosterone are < normal

LH and FSH > normal (no negative feedback)

115
Q

Discuss the levels of hormones seen in secondary male hypogonadism.

A

Sperm and testosterone are < normal

LH and FSH < normal

116
Q

What are the symptoms of male hypogonadism in utero?

A
  1. Ambiguous sexual organ development

2. Micropenis at birth

117
Q

What are the symptoms of male hypogonadism prior to puberty?

A

Failure to undergo complete puberty

118
Q

What are the symptoms of male hypogonadism in adults?

A

Decreased energy and libido, infertility, decreased muscle mass, bone density, and sexual hair

119
Q

Who receives treatment with testosterone?

A
  1. Adolescents at the time of puberty

2. Symptomatic adult men

120
Q

What are the AE of testosterone?

A
  1. Acne
  2. Increased risk of prostate cancer/BPH
  3. Worsening of sleep apnea
  4. Increased CVD risk (decreases HDL and increases LDL)
  5. Increased risk of venous thromboembolic disease
  6. Erythrocytosis (increases risk of VTE)
  7. Hepatic dysfunction (with alkylated form)
  8. Suppression of spermatogenesis
121
Q

Why is suppression of spermatogenesis an AE of T?

A

Inhibition of LH production results in reduction of high level endogenous local testicular T known to be required for sperm production

122
Q

What are contraindications for treatment with testosterone?

A

Pre-existing prostate cancer
High levels of PSA in men at high risk for prostate cancer
Untreated sleep apnea

123
Q

List the types of compounds used as performance enhancing drugs by athletes to boost performance and physical appearance.

A
  1. Exogenous and synthetic T
  2. Androgen precursors
  3. rhuHCG (stimulates endogenous T production)
  4. Aromatase inhibitors (prevents in vivo conversion to E2)
  5. Synthetic selective androgen receptor modulators (activate AR in muscle and bone)
124
Q

Which compound used as a performance enhancing drug is readily detected by drug testing?

A

Exogenous and synthetic testosterone

125
Q

Discuss the effects of androgen precursors in men.

A

Often present in dietary supplements - they are non androgenic in men (do not elevate T); they do increase estrogen levels

They have low affinity for AR and end up acting as partial agonists to block the effects of T in vivo

126
Q

What are the general AE of using androgens at supraphysiologic levels?

A
  1. Cardiovascular - coronary heart disease, cardiomyopathy, erythrocytosis, coagulation abnormalities, dyslipidemia, HTN
  2. Tendon rupture
  3. Neuropsychiatric - mood disorders, increased aggression/violence
  4. Liver (17-alpha derivatives) - cholestasis, hepatitis, hepatic neoplasms
127
Q

What are the AE of using androgens at supraphysiologic levels specifically in men?

A

Hypogonadism, reduced testicular volume, suppression of spermatogenesis, gynecomastia, increased risk of BPH and prostate cancer

128
Q

What are the AE of using androgens at supraphysiologic levels specifically in women?

A

Acne, hirsutism, male pattern baldness, clitoromegaly, irreversible deepening of the voice, irregular menstrual cycle

129
Q

How can androgens be used to prevent prostate cancer development?

A
  1. Androgen deprivation (level of hypothalamus)
  2. Androgen synthesis inhibitors (block conversion to T)
  3. Androgen receptor antagonists
130
Q

What is the goal of androgen deprivation therapy for the treatment of advanced prostate cancer?

A

Reduction of serum testosterone to castration levels - PALLIATIVE NOT CURATIVE

131
Q

List the GnRH agonists used in adnrogen deprivation therapy and explain the MOA.

A

Leuprolide, Goserlin, Buserelin, Triptorelin, Naferelin

Sustained GnRH signaling inhibits pituitary release of FSH and LH to decrease endogenous T production; can be an initial flare leading to a cancer flare

132
Q

What is the GnRH antagonist?

A

Degarelix

133
Q

What are the AE of ADT?

A
  1. Sexual dysfunction
  2. Osteoporosis and bone fractures
  3. Vasomotor responses (hot flashes)
  4. Loss of lean body mass and increased fat mass
  5. Fatigue
  6. Anemia (>90%)
  7. Gynecomastia
  8. Decreased penis and testicular size
  9. Emotional and cognitive changes
  10. Cardiovascular and metabolic abnormalities
134
Q

What is Abiraterone?

A

Androgen synthesis inhibitor

135
Q

What is the MOA of Abiraterone?

A

Inhibition of CYP17A1, which inhibits the synthesis of T

136
Q

What are the indications of Abiraterone?

A

Treatment of hormone-resistant prostate cancer

137
Q

What are the AE of Abiraterone?

A

Adrenocorticol insufficiency and mineralocorticoid excess (cholesterol -> pregnenolone -> progesterone -> aldosterone)

138
Q

List the first and second generation androgen receptor antagonist.

A

1st gen - flutamide, bicalutamide, nilutamide

2nd gen - enzalutamide

139
Q

What is the MOA of androgen receptor antagonists?

A

Blocks the action of T and DHT at the AR

140
Q

What is the indication of AR receptor antagonists?

A

Treatment of advanced prostate cancer in combination with either a GnRH agonist or antagonist (not used as monotherapy, which would result in an LH increase and T increase)

141
Q

What is another indication for Flutamide?

A

Treatment of hyperandrogenism in women

142
Q

What are AE of AR antagonists in men? Women? Both?

A

Men - androgen deprivation AE (sexual dysfunction, gynecomastia, etc.)

Women - generally well-tolerated

Both - first generation - serious hepatotoxicity

Enzalutamide - increased seizures (crosses BBB, inhibits GABA-A receptor)

PT 2 (15 decks)

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