Gynecologic Pharmacology Flashcards
1
Q
What is the primary source of circulating estrogen in premenopausal women?
A
Ovarian estradiol
Ovarian estradiol is the most active form of estrogen produced in premenopausal women.
2
Q
What is the role of progesterone during the luteal phase of the menstrual cycle?
A
Secreted by the corpus luteum; exerts negative feedback on gonadotropins
If conception occurs, progesterone maintains the endometrium; if not, its secretion ceases, leading to menstruation.
3
Q
What is the effect of estrogen and progesterone on FSH and LH secretion during most of the menstrual cycle?
A
They exert negative feedback
In midcycle, estrogen causes positive feedback, leading to an FSH and LH surge.
4
Q
Which receptors do estrogen and progesterone bind to in target cells?
A
Estrogen Receptors (ERs) and Progesterone Receptors (PRs)
These receptors are part of a superfamily that includes various steroid and thyroid hormone receptors.
5
Q
What is the primary mechanism of action for pharmacologic estrogens and progestins?
A
They mimic the actions of endogenous hormones
This provides both therapeutic effects and potential adverse effects.
6
Q
What are the common routes of administration for estrogens and progestins?
A
Oral, parenteral, and other routes
Oral bioavailability is generally low due to extensive first-pass metabolism.
7
Q
What is a significant adverse effect of estrogen use?
A
Increased risk of venous thromboembolism
Risk factors include older age, smoking, and hypertension.
8
Q
How do combined hormonal contraceptives (CHCs) prevent ovulation?
A
By preventing FSH and LH release
Progestin’s negative feedback reduces GnRH pulse frequency, inhibiting follicle development.
9
Q
What is the effect of progestin-only contraceptives on uterine bleeding?
A
They may reduce or eliminate uterine bleeding
Progestins also thicken cervical mucus and slow egg movement through fallopian tubes.
10
Q
What is the impact of hormonal contraception on menstrual bleeding patterns?
A
Phasic, extended-use, and continuous-use can affect unscheduled bleeding and spotting
Unscheduled bleeding is common at the start of therapy and often decreases over time.
11
Q
What is the primary metabolic pathway for estrogens?
A
Extensive first-pass metabolism by CYP3A4
Estrogens undergo glucuronidation and sulfation before excretion.
12
Q
What happens to the corpus luteum if conception does not occur?
A
It regresses and progesterone secretion ceases
This leads to the onset of menstruation.
13
Q
Fill in the blank: Estradiol, conjugated equine estrogens, and esterified estrogens are used in _______.
A
menopausal hormone therapy
These estrogens help in the prevention of osteoporosis and reducing fracture risk.
14
Q
True or False: Estrogen and progesterone are lipophilic compounds.
A
True
This property affects their absorption and distribution in the body.
15
Q
What is the role of inhibins and activins in the menstrual cycle?
A
Inhibins inhibit and activins activate FSH secretion
They are produced by granulosa cells in response to FSH.
16
Q
What triggers ovulation during the menstrual cycle?
A
The LH surge caused by peak estrogen levels
This occurs after the dominant follicle develops.
17
Q
What are the major estrogens produced in women?
A
- 17-β estradiol
- Estrone
- Estriol
These estrogens have different roles throughout the menstrual cycle and in various physiological states.
18
Q
What is the hypothalamic-pituitary-ovarian axis responsible for?
A
Regulating gonadotropin secretion and ovarian hormone production
This axis controls the menstrual cycle and reproductive functions.
19
Q
What is the main source of estrogen production in postmenopausal individuals?
A
Aromatase in adipose stromal tissue converts androstenedione synthesized in adrenal glands to estrone.
20
Q
What are the primary actions of estrogen at the genomic level?
A
Estrogen binds to ERs in the nucleus, dimerizes, and binds estrogen response elements, recruiting co-activators and/or co-repressors.
21
Q
What are the nongenomic actions of estrogen?
A
Activated ERs on the plasma membrane increase cyclic AMP and activate proteins like MAPK.
22
Q
What systemic effects does estrogen have?
A
Estrogen has neuroprotective effects, reduces mood fluctuations, is cardioprotective, and protects against bone loss.
23
Q
Fill in the blank: Estradiol is converted to _______ and then to estriol.
A
Estrone
24
Q
What triggers ovulation in the menstrual cycle?
A
The peak estrogen level stimulates a surge in LH and FSH release.
25
How do progestins affect hormonal contraceptive therapy?
Progestins provide negative feedback on the hypothalamus, reducing GnRH pulse frequency and preventing ovulation.
26
What are the pharmacologic estrogens used in combined hormonal contraceptives?
* Ethinyl estradiol
* Mestranol
* Estradiol
* Conjugated equine estrogens
27
What are the positive effects of estrogen therapy?
* Reduces hot flashes
* Prevents bone fractures
* Improves skin collagen
* Reduces risk of colon cancer
28
What are the negative effects of estrogen therapy?
* Breast tenderness
* Vaginal bleeding
* Nausea
* Increased risk of thromboembolic disease
29
True or False: Estrogen therapy increases the risk of myocardial infarction in nonsmokers without risk factors.
False
30
What are the absolute contraindications for estrogen therapy?
* Hypersensitivity
* ER-positive neoplasms
* Undiagnosed abnormal vaginal bleeding
* Thromboembolic disease
* heavy smokers
* pregnancy
31
What role does progesterone play in menopausal hormone therapy for individuals with a uterus?
It inhibits endometrial proliferation, reducing the risk of endometrial hyperplasia and cancer.
32
What are some common side effects of progestin therapy?
* Breakthrough bleeding
* Acne
* Hirsutism
* Hyperkalemia with drospirenone
33
What is the mechanism by which 19-nortestosterone derivatives function?
They alter testosterone structure, reducing androgenic activity and improving oral availability.
34
What is the principal method of estrogen excretion?
Renal and biliary excretion of metabolites.
35
What are two major therapeutic uses of progestins?
* Hormonal contraceptives
* Prevention of endometrial hyperplasia in menopausal hormone therapy
36
Fill in the blank: The addition of progestin to the estrogen regimen in people with a uterus reduces the risk of _______.
endometrial hyperplasia
37
What is the pharmacokinetic property of estrogens regarding metabolism?
Extensive hepatic metabolism, primarily via CYP3A4.
38
What is the role of estrogen in the liver?
It stimulates the uptake of serum lipoproteins and the production of coagulation factors.
39
What are the estrogen components commonly used in combined hormonal contraceptives?
Ethinyl estradiol*, Mestranol (prodrug of ethinyl estradiol), Estetrol (synthetic estrogen analog)
## Footnote
These components are vital for the effectiveness of combined oral contraceptives.
40
What progestin components are used in hormonal contraceptives?
Norethindrone, Norgestrel, Levonorgestrel, Segesterone acetate, Drosperinone
## Footnote
Drosperinone is a spironolactone-derivative with anti-mineralocorticoid and anti-androgenic activity.
41
What are the types of combined oral contraceptives (COCs)?
Mono-, bi-, tri-, 4-phasic
## Footnote
These differ in the hormonal dosage throughout the menstrual cycle.
42
What is the typical cycle duration for combined oral contraceptives?
28-day version with a 7-day placebo period
## Footnote
This allows for menstruation to occur.
43
What is the purpose of the 7-day progestin-free interval in hormonal contraceptives?
To allow for menstrual periods
## Footnote
This interval occurs in extended-cycle contraceptives.
44
How do combined hormonal contraceptives (CHCs) prevent ovulation?
By suppressing FSH and LH release, disrupting the mid-cycle LH surge
## Footnote
This prevents the hormonal changes that trigger ovulation.
45
What are progestin-only contraceptive pills (POPs) used for?
To prevent ovulation in women where estrogens are undesirable
## Footnote
They do not suppress lactation.
46
What is the efficacy of progestin-only contraceptives in preventing ovulation?
60-80% of cycles
## Footnote
They are slightly less efficacious than combined hormonal contraceptives.
47
What is a common side effect associated with progestin-only contraceptives?
Unscheduled (breakthrough) bleeding
## Footnote
This is more common with POPs than CHCs.
48
What are the two types of emergency contraception mentioned?
Levonorgestrel, Ulipristal (progesterone receptor modulator)
## Footnote
Both are taken after unprotected intercourse to prevent pregnancy.
49
What is a contraindication for hormonal contraceptives?
Thromboembolic disease
## Footnote
This is one of several contraindications that limit the use of hormonal contraceptives.
50
Which hormonal contraceptive methods are associated with unscheduled bleeding?
Extended-cycle and continuous-use CHCs, progestin-only contraceptives
## Footnote
Breakthrough bleeding is more common in progestin-only options.
51
What is the mechanism behind unscheduled bleeding with hormonal contraceptives?
Prolonged exposure to progestins leads to endometrial atrophy
## Footnote
This causes the endometrium to become thin and fragile, resulting in irregular bleeding.
52
What triggers ovulation in the menstrual cycle?
A peak in estrogen levels just before mid-cycle
## Footnote
This triggers a surge in LH and FSH that leads to ovulation.
53
What is the principal source of estrogen in postmenopausal individuals?
Aromatase in adipose stromal tissue
## Footnote
This converts androstenedione into estrone.
54
Why is progesterone added to menopausal hormone therapy in individuals with a uterus?
To inhibit endometrial proliferation and reduce the risk of endometrial hyperplasia and cancer
## Footnote
Estrogen alone increases these risks.
55
What are common side effects of estrogen therapy?
Nausea, breast tenderness, increased risk of thromboembolic events
## Footnote
These risks are heightened in women over 35 who smoke.
56
What are the major therapeutic uses of progestins?
Hormonal contraceptives, assisted reproduction, menopausal hormone therapy, management of abnormal uterine bleeding
## Footnote
They also help in secondary amenorrhea diagnosis.
57
What are some common side effects of progestin therapy?
Breakthrough bleeding, chloasma, androgenic effects (acne, alopecia, hirsutism)
## Footnote
Drospirenone may cause hyperkalemia.
58
What are the clinically relevant pharmacokinetic properties of SERMs, AIs, and progesterone receptor antagonists/modulators?
Selective estrogen receptor modulators (SERMs), estrogen receptor antagonists, aromatase inhibitors (AIs), and selective progesterone receptor antagonists/modulators demonstrate extensive hepatic metabolism, long half-lives, and varied receptor activity in different tissues.
## Footnote
Pharmacokinetics is crucial for optimizing patient care.
59
What is the mechanism of action of selective estrogen receptor modulators (SERMs)?
SERMs have estrogen receptor (ER) agonist effects in some tissues and partial agonist or antagonist effects in others, influenced by different regulatory proteins and receptor dimers.
60
Name some examples of selective estrogen receptor modulators (SERMs).
* Tamoxifen
Toremifene
* Raloxifene
* Bazedoxifene
Ospemifene
*Clomiphene
61
What are the therapeutic applications of SERMs?
* Treatment and prevention of hormone receptor-positive breast cancer
* Prevention and treatment of osteoporosis
* Management of dyspareunia/vaginal dryness in postmenopausal individuals
62
What is the primary use of clomiphene?
To induce ovulation in anovulatory individuals.
63
List some adverse effects associated with SERM therapy.
* Hot flashes
* Nausea/vomiting
* Skin rash
* Thromboembolic effects
64
What is the role of fulvestrant in cancer treatment?
Fulvestrant is an ER antagonist that causes estrogen receptor degradation and is used for treatment of metastatic, hormone receptor-positive, HER2-negative breast cancer.
65
What are aromatase inhibitors (AIs) and their effect?
AIs are oral drugs that suppress estrogen synthesis in postmenopausal individuals by inhibiting estrogen synthesis from adrenal androstenedione.
66
Name the first-line agents for treatment of hormone receptor-positive breast cancer in postmenopausal women.
* Anastrozole
* Letrozole
* Exemestane
67
What are common adverse effects of aromatase inhibitors?
* Hot flashes
* Dyspareunia
* Reduced libido
* Loss of bone mineral density
68
What is the primary action of mifepristone?
Mifepristone is a competitive progesterone receptor antagonist used as an abortifacient.
69
How does ulipristal function in emergency contraception?
Ulipristal is a progesterone receptor partial agonist that inhibits ovulation.
70
What is the mechanism of action of SERMs in breast tissue?
SERMs act as antagonists in breast tissue.
71
What is the action of SERMs in bone tissue?
SERMs act as agonists in bone tissue.
72
What is the adverse effect associated with ER agonists in endometrial tissue?
Increased risk of endometrial hyperplasia and endometrial cancer.
73
What is the pharmacokinetic property of tamoxifen?
Tamoxifen has a half-life of 5-7 days.
74
What are the adverse effects of fulvestrant?
* Hot flashes
* Injection site reactions
* Elevated liver enzymes
* Loss of bone mineral density
75
What is the role of aromatase inhibitors like anastrozole and letrozole?
They are used as first-line treatments for postmenopausal hormone receptor-positive breast cancer.
76
What is the significance of CYP2D6 in tamoxifen metabolism?
CYP2D6 metabolizes tamoxifen to its active metabolites, which have higher affinity for estrogen receptors.
77
What are the indications for mifepristone?
* Termination of intrauterine pregnancy through 77 days gestation
* Management of first trimester pregnancy loss
78
Fill in the blank: SERMs are categorized into _______ generations.
3
79
What is the primary use of Tamoxifen?
Adjuvant all stages of hormone-responsive breast cancer
## Footnote
Used in both post- and premenopausal adult females to reduce risk of contralateral and invasive breast cancer.
80
What is Toremifene primarily used for?
Metastatic breast cancer in postmenopausal females
## Footnote
It is also used for palliative advanced disease.
81
Which SERM is indicated for osteoporosis prevention and treatment?
Raloxifene
## Footnote
It also provides risk reduction for invasive breast cancer in postmenopausal females at high risk.
82
What is the therapeutic use of Ospemifene?
Management of dyspareunia and vaginal dryness due to vulvovaginal atrophy of menopause
83
What is Bazedoxifene combined with CEE used for?
Management of menopause vasomotor symptoms and fracture risk reduction in postmenopausal people with a uterus.
84
What are the adverse effects of SERMs?
* Vasomotor flushes
* Venous thrombo-embolism
* Endometrial hyperplasia and increased cancer risk
* QTc interval prolongation (dose-dependent)
85
Which drug interactions are associated with Tamoxifen?
* CYP2D6, 3A4 inhibitors may decrease conversion to active metabolites
* Warfarin: increases warfarin levels
* Strong CYP3A4 inducers decrease Tamoxifen efficacy
86
What is the main effect of Clomiphene?
Acts primarily as an antiestrogen in the uterus, cervix, and vagina.
87
What is Clomiphene's mechanism of action?
Binds to ERs in the pituitary and hypothalamus, reducing the number of ERs and interrupting estrogen’s negative feedback, leading to increased FSH secretion.
88
What is a potentially serious complication of Clomiphene therapy?
Ovarian hyperstimulation syndrome
## Footnote
It can cause life-threatening conditions due to fluid shifts and vascular permeability.
89
What is Fulvestrant classified as?
Selective estrogen receptor degrader (SERD)
## Footnote
It acts as a competitive antagonist for ERα and ERβ in all tissues.
90
How is Fulvestrant administered?
Once monthly intramuscular injection after loading dose (3 doses 2 weeks apart).
91
What is the mechanism of action of Fulvestrant?
Binds to ERs, forms a nuclear complex that causes downregulation of ERs, inhibiting tumor growth.
92
What are the common adverse effects of Fulvestrant?
* Hot flashes
* GI symptoms
* Headache
* Muscle pain
* Elevated liver enzymes
* Osteoporosis
* Thrombosis
* Leukopenia
93
What are Aromatase Inhibitors (AIs) used for?
* Treatment of hormone-receptor positive breast cancer
* Adjuvant or monotherapy in postmenopausal patients
* Disease progression following Tamoxifen therapy
94
What is the pharmacokinetic property of Anastrozole?
Oral, well absorbed, with a t½ of approximately 50 hours.
95
What is the mechanism of action of Exemestane?
Irreversible inhibition of aromatase (suicide inhibitor).
96
What are common adverse effects associated with Aromatase Inhibitors?
* Musculoskeletal syndrome
* Bone mineral density loss / osteoporosis
* Vasomotor flushes
* Nausea
* Fatigue
* Peripheral edema
* Sexual dysfunction
97
What does hormone-receptor positive breast cancer treatment combined with ovarian function suppression aim to achieve?
It aims to decrease estrogen levels, reduce negative feedback on FSH release, and promote follicle maturation.
## Footnote
This approach is crucial for managing hormone-sensitive breast cancer.
98
What are common side effects associated with Aromatase Inhibitors (AIs)?
* Musculoskeletal syndrome
* Bone mineral density loss / osteoporosis
* Vasomotor flushes
* Nausea
* Fatigue
* Peripheral edema
* Sexual dysfunction
## Footnote
AI-associated musculoskeletal syndrome can severely affect quality of life.
99
True or False: Pregnancy is contraindicated when using Aromatase Inhibitors.
True
## Footnote
AIs may cause fetal harm.
100
What is the mechanism of action of nonsteroidal Aromatase Inhibitors like anastrozole and letrozole?
They reversibly bind the heme site of aromatase, inhibiting estrogen production.
## Footnote
Aromatase is a key enzyme in estrogen synthesis.
101
What is the role of mifepristone as a progesterone receptor antagonist?
It leads to decidual breakdown, increased uterine prostaglandin levels, and expulsion of uterine contents.
## Footnote
Mifepristone is used for medical abortion.
102
What is ulipristal's mechanism of action for emergency contraception?
It blocks progesterone from binding to progesterone receptors, inhibiting ovulation through central and direct effects on the ovary.
## Footnote
This action prevents ovulation when taken up to 5 days after unprotected intercourse.
103
Fill in the blank: Mifepristone is contraindicated in cases of _______.
Pregnancy
## Footnote
It can lead to embryofetal loss.
104
What are the expected effects of mifepristone during its use?
* Vaginal bleeding
* Abdominal pain
* Nausea
* Vomiting
* Diarrhea
* Fever
## Footnote
Effects can be more severe with longer gestation durations.
105
What is the pharmacokinetic profile of mifepristone regarding its half-life?
Single dose: 18 hours; multiple doses: 85 hours.
## Footnote
There is a slower elimination phase where 50% is eliminated between 12-72 hours.
106
What is the action of selective estrogen receptor modulators (SERMs) like tamoxifen?
They act as agonists or competitive antagonists depending on the tissue type.
## Footnote
SERMs can reduce the risk of breast cancer and treat menopausal symptoms.
107
What are the common adverse effects of SERMs?
* Vasomotor flushes
* Headache
* Nausea
* Increased risk of venous thromboembolism
* Endometrial hypertrophy
## Footnote
Specific SERMs may also prolong the QT interval.
108
Which SERM is indicated for ovulation induction in anovulatory patients?
Clomiphene
## Footnote
It is used to treat infertility in women.
109
What is the mechanism of action for fulvestrant as a selective estrogen receptor downregulator (SERD)?
It acts as a competitive ER antagonist, leading to ER downregulation and inhibition of tumor growth.
## Footnote
Fulvestrant is used for advanced breast cancer treatment.
110
What is the risk associated with CYP2D6 polymorphism in patients taking tamoxifen?
Patients may produce less active metabolite, resulting in diminished activity of tamoxifen.
## Footnote
This can affect the efficacy of breast cancer treatment.
111
What are the pharmacokinetic properties of ulipristal?
* Oral, nearly complete absorption
* Highly bound to plasma proteins
* Primarily fecal excretion
* ~35 hours half-life
## Footnote
It is effective for emergency contraception.
112
What is the contraindication for using mifepristone in the context of ectopic pregnancy?
Pregnancy, unexplained vaginal bleeding, and undiagnosed adnexal mass.
## Footnote
These conditions can complicate treatment and pose risks.
113
What is the mechanism of action (MOA) of selective estrogen receptor modulators (SERMs) in breast tissue?
They are all antagonists.
114
What is the mechanism of action (MOA) of SERMs in bone?
They are all agonists.
115
What is the mechanism of action (MOA) of SERMs in endometrial tissue?
Tamoxifen, toremifene, and ospemifene are agonists; Raloxifene and bazedoxifene are antagonists.
116
What is the adverse effect associated with agonists in endometrial tissue?
Agonists increase risk of endometrial hyperplasia and endometrial cancer.
117
Which SERMs are used in the treatment of hormone receptor-positive breast cancer?
Tamoxifen and toremifene.
118
Which SERMs are used for risk reduction of invasive hormone-receptor positive breast cancer in high-risk patients?
Tamoxifen and raloxifene.
119
Which SERMs are indicated for reduction of fracture risk / osteoporosis?
Raloxifene and bazedoxifene-conjugated equine estrogens.
120
Which SERMs are indicated for management of vulvovaginal symptoms associated with menopause?
Ospemifene and bazedoxifene-CEE.
121
What is clomiphene’s main effect?
Clomiphene acts primarily as an antiestrogen in the uterus, cervix, and vagina.
122
What is clomiphene’s therapeutic use?
Ovulation induction.
123
What is the mechanism of action of clomiphene?
CC binds to ERs in the pituitary and hypothalamus, reducing the number of ERs in the hypothalamus, causing perceived hypoestrogenism.
124
What is a potentially serious complication of clomiphene therapy?
Ovarian hyperstimulation syndrome (OHSS).
125
What is fulvestrant’s mechanism of action that earns it the title of a selective estrogen receptor degrader (SERD)?
Fulvestrant binds ERs in tumors and all tissues, forming a nuclear complex that causes downregulation of ERs.
126
What is the therapeutic use of fulvestrant?
Used as monotherapy or in combination with a CDK4/6 inhibitor for hormone receptor-positive, HER2-negative metastatic breast cancer.
127
How is fulvestrant administered?
Once monthly intramuscular injection after loading dose.
128
What are the predictable side effects of fulvestrant related to?
Estrogen deficiency-like effects.
129
What is the effect of inhibiting aromatase?
Estrogen depletion.
130
Which aromatase inhibitor (AI) is a steroidal molecule that irreversibly binds the substrate site of the enzyme?
Exemestane.
131
What is the mechanism of action of the nonsteroidal AIs?
Anastrozole and letrozole reversibly bind the heme site of aromatase.
132
What is a common side effect of AI therapy that can be severe?
AI-associated musculoskeletal syndrome.
133
What lifestyle changes are recommended for patients taking an AI to reduce the risk of bone loss?
Increase physical activity, calcium and vitamin D supplementation, quit smoking, reduce alcohol intake.
134
What is mifepristone’s action for termination of intrauterine pregnancy?
Progesterone receptor competitive antagonist leading to decidual breakdown and uterine contractions.
135
What is the mechanism of action of high-dose mifepristone for control of hyperglycemia in Cushing syndrome?
Inhibition of glucocorticoid receptors antagonizes cortisol's effect on glucose metabolism.
136
What is the probable mechanism of action of ulipristal for emergency contraception?
Blocks progesterone from binding PRs, inhibiting LH release and ovulation.
137
what is the major source of estrogen in the postmenopausal pt.
adrenal androstenedione
138
list the neuroprotective effects of estrogen?
reduces perimenopausal mood fluctuations
139
list the cardioprotective effects of estrogen.
vasodilatory effects
protective factor for colon cancer
140
list the estrogen effects on the intenmentuary system?
increases skin turgor and collagen production
also reduces depth of wrinkles
141
what estrogens are used as menopausal hormone therapy?
estradiol
ethinyl estradiol
CEEs
142
estrogen therapy for menopause reduces development of what?
vasomotor symptoms
bone fractures
urogenital atrophy
143
what does the addition of progestin to the regimen in people with a uterus prevent?
endometrial hyperproliferation
endometrial cancer
144
use of estrogen in isolation is not assoc. with increase risk for complications with what?
total serum cholesterol
lipoprotein profiles
gallbladder disease
breast cancer (exception: menopause)
145
why is DM a Relative CI for estrogen therapy?
may impair glucose tolerance
146
T or F: MHT is assoc. w/ an increased risk for HTN
false
147
T or F: there is no CV benefit from estrogen in menopausal individulas
true
148
pts. w/ HTN and DM, as well as pts. who are smokers, are at an increased risk of what AE of estrogen
MI or Stroke
149
what effects does estrogen have on cognition?
data has not shown estrogen to have an effect on cognition
the research is still ongoing though
150
list the 19-nor derivatives of progesterone
estranes and gonanes
151
list the clinical uses of MPA.
MHT: prevention of endometriosis in women w/ a uterus
abnormal bleeding
endometriosis
Amenorrhea
152
under what circumstances should progestin use be avoided?
undiagnosed vaginal bleeding
liver disease
breast cancer
pregnancy
153
compare and contrast the AEs of estrogen and progesterone therapy
Both: increased risk of breast cancer in menopausal women
progesterone: increases LDL and risk for osteoporosis
154
what is the effect of the 84-day extended cycle version?
4 menstrual periods per year
155
what are the components of the vaginal ring?
ethinyl estradiol
segesterone acetate
156
what other effects of progestin may contribute to contraceptive actoin
formation of thick, viscous cervical mucus: hinders sperm penetration through the cervix
endometrial atrophy may deter implantation
157
what progestin-only products are oral (POPs)?
norethindrone
norgestrel
drospirenone
158
what POP is an intrauterine device with a 5-year duration?
levonorgestrel
159
what POP is an implantable rod w/ a duration of 3 yrs.?
etonogestrel
160
what emergency contraception does not require a Rx?
levonorgestrel
161
what is the MOA of Ulipristal?
inhibits Proges. from binding to PRs
this postpones follicular rupture which delays ovulation
162
make sure to review the following on estrogenpharm1 ppt
the questions
163
T or F: all SERMs are ER Antagonists in breast tissue and ER agonists in bone.
true
164
What SERM is an ER agonists in endometrial tissue?
tamoxifen
165
What SERMS is/are ER antagonist/s in endometrial tissue?
raloxifene
bazedoxifene
166
Tamoxifen is primarily used for what?
adjuvant for hormone-responsive breast cancers
167
Raloxifene is implicated in what clinical situations?
osteoporosis (prevention & treatment)
risk reduction for invasive breast cancer in postmenopausal high risk females
168
what are the clinical uses of bazedoxifene?
management of menopause vasomotor symptoms & fracture risk reduction
169
T or F: bazedoxifene is usually combined with a CEE.
true
170
T or F: raloxifene & bazedoxifene undergo extensive 1st past metabolism.
false
both drugs are metabolized through glucuronide conjugation
171
T or F: vasomotor flushes and VTEs are AEs for all SERMS
true
172
T or F: bazedoxifene is assoc. w/ increased risk for endometrial cancer.
false
173
which SERM can cause QT interval prolongation?
tamoxifen
174
what drug class decreases absorption of raloxifene?
bile acid sequestrants
175
raloxifene decreases absorption of what drug?
levothyroxine
176
by the late follicular phase, clomiphene citrate-induced central depletion of ERs leads to what?
since the ovaries cannot exhert the normal negative feedback on FSH, multiple dominant follicles erupt causing multiple ovulations
177
T or F: clomiphene is often coupled w/ a SERM to potentiate therapeutic effect
FALSE
this is a CI
also, if anything, clomiphene would decrease SERM therapeutic effects since both drugs would compete for the ER sites
178
Prolonged use of clomiphene increases the risk for what cancer?
ovarian cancer
179
Clomiphene should be cautioned for pts. w/ these preexisting conditions as clomiphene can exacerbates these conditions
uterine fibroids
pituitary tumors
thyroid disease
adrenal dysfunction
PCOS
180
T or F: clomiphene is considered saft for pregnancy
false
pregnancy is a CI
181
List the therapeutic uses of fulvestrant?
HER2 negative metastatic breast cancers
182
list the aromatase inhibitors you need to know.
exemestane
anastrozole
letrozole
183
which AI is a steroid
exemestane
184
T or F: nonsteroid imidazoles are competitive inhibitors of aromatases
true
185
what is an additional therapeutic usage of letrozole
anovulatory individuals w/ PCOS
186
what is a common AE of AIs?
reduced sexual interests and vaginal lubrication
187
T or F: estrogen derivatives reduce the effectiveness of AIs
true
188
pts. on AIs in conjunction with this drug must be monitored since AIs increases levels of it.
methadone
189
T or F: AIs are a CI for pregnancy.
true
190
list the symptoms of AI-associated msk syndrome
bone pain
joint pain
joint stiffness
focal tenosynovitis of the hands and feet
191
T or F: ulipristal is a PR partial agonist.
true
192
breakdown of the decidua leads to rapid drop in this hormone?
hCG
193
How does mifepristone cause uterus contractions?
it decreases endogenous progesterone which subsequently increases the level of uterine PGs
194
What effect does mifepristone have on the CNS?
inhibition of LH release
195
what direct effect does mifepristone have on the ovaries?
inhibition of LH-induced follicular rupture
196
T or F: mifepristone prolongs the QT interval.
true
197
T or F: in the absence of progesterone, mifepristone acts as a partial antagonist instead of a full antagonist
false
it acts as a partial agonist in the absence of progesterone
198
mifepristone is also an antagonist of what other hormone receptors
glucocorticoid Rs & androgen Rs
199
what are CIs for mifepristone?
ectopic pregnancy
active IUDs
adrenal failure
porphyrias
endometrial cancer
200
T or F: mifepristone reduces the therapeutic window of many CYP3A4 substrates
false
it is the other way around
201
make sure to review this in the estogenpharm2 ppt
the questions
202
make sure to review ........... in both the estrogen pharm ppts.
summaries at beginning and end
203
What are tocolytics?
Agents that relax the uterus and delay labor
204
What are uterotonics?
Agents that stimulate the uterus and hasten labor
205
What is the gestational age range for appropriate tocolytic therapy?
22 to 34 weeks
206
What are the goals of tocolytic therapy?
* Delay delivery by at least 48 hours for corticosteroids to enhance fetal lung maturity
* Provide time for maternal transfer to a facility with appropriate prenatal care
* Prolong pregnancy when safe to do so
207
What are examples of first-line tocolytics?
* Indomethacin (COX inhibitor)
* Nifedipine (Calcium channel blocker)
208
What are examples of second-line tocolytics?
* Terbutaline (Beta-2 agonist)
* Magnesium sulfate
* Nitroglycerin (Nitric oxide donor)
* Atosiban (Oxytocin receptor antagonist)
209
What are the potential adverse effects of tocolytics?
Risk factors and complications vary by agent, including maternal hypotension, tachycardia, and fetal concerns
210
What is the mechanism of action for calcium channel blockers like nifedipine?
Block L-type VG Ca2+ channels, reducing intracellular Ca2+ and promoting myometrial relaxation
211
What is the mechanism of action of indomethacin?
Inhibits COX, reducing synthesis of prostaglandins PGE2 and PGF2α
212
What are the pharmacokinetic properties of tocolytics?
Varies by agent; examples include route of administration and clearance rates
213
True or False: Tocolytics can reverse parturitional uterine changes.
False
214
What is the role of magnesium sulfate in tocolytic therapy?
Inhibits Ca2+ uptake, reducing uterine contractility
215
What are the effects of terbutaline on maternal and fetal health?
Maternal: hypotension, tachycardia, hyperglycemia; Fetal: tachycardia, tremors, hyperinsulinemia to neonatal hypoglycemia
216
Fill in the blank: Tocolytics do not remove the underlying stimulus that initiated _______.
preterm labor
217
What is the effect of nitric oxide donors like nitroglycerin on uterine smooth muscle?
Activates guanylyl cyclase, increasing cGMP and promoting relaxation
218
What are the common side effects associated with nifedipine?
* Nausea
* Flushing
* Headache
* Dizziness
* Palpitations
219
What complication can arise from prolonged use of indomethacin?
Constriction of ductus arteriosus in the fetus and tricuspid regurgitation
220
What is the consequence of maternal hyperglycemia caused by terbutaline?
May lead to fetal hyperinsulinemia and neonatal hypoglycemia
221
What pharmacodynamic interactions can affect drug levels in tocolytics?
Interactions vary; examples include competitive inhibition and receptor blockade
222
What is the role of oxytocin receptor antagonists like atosiban?
Prevents oxytocin-induced contractions by blocking its receptors
223
What is the primary concern when using tocolytics in patients with myasthenia gravis?
Magnesium sulfate is contraindicated
224
What is the primary action of prostaglandins in the labor process?
Induce uterine contractions
225
What are the uterine stimulants mentioned?
* Oxytocin
* Prostaglandins
* Ergot Alkaloids
226
What is the recommended gestational age for tocolytic therapy to delay labor, if appropriate?
22 to 34 weeks
## Footnote
Tocolytics are used to delay labor and allow for interventions like corticosteroid administration.
227
What are the second-line tocolytics?
Terbutaline, Magnesium sulfate, Nitroglycerin, Atosiban
## Footnote
These are used when first-line agents are not suitable.
228
What are the less effective tocolytic agents?
Magnesium sulfate, Nitroglycerin, Atosiban
## Footnote
These agents are considered less effective in delaying labor.
229
What are uterotonics used for?
Stimulate labor contractions, reduce postpartum hemorrhage
## Footnote
Uterotonics are critical in parturition and postpartum care.
230
What are the contraindications for uterotonics?
Maternal/fetal risks associated with vaginal delivery greater than cesarean delivery risks
## Footnote
Induction should not occur in such scenarios.
231
Define induction in the context of labor.
Techniques for stimulating uterine contractions before the onset of spontaneous contractions
## Footnote
Induction is necessary in some cases to ensure maternal and fetal safety.
232
What is oxytocin?
A synthetic human peptide used to induce labor, prevent postpartum bleeding
## Footnote
Oxytocin is critical in managing labor and delivery.
233
What are the clinical uses of oxytocin?
Induction and enhancement of labor, prevention/treatment of postpartum bleeding, adjunct in management of abortion
## Footnote
Oxytocin has multiple roles in obstetric care.
234
What are the potential excessive stimulation effects of oxytocin?
Fetal distress, placental abruption, uterine rupture, water intoxication
## Footnote
High doses can lead to serious complications.
235
What are the critical roles of prostaglandins in parturition?
Mediators of labor, increase in amniotic fluid and maternal plasma during labor
## Footnote
Prostaglandins are essential for cervical ripening and uterine contractions.
236
What is the role of PGE2 and PGF2α in parturition?
Promote labor by ripening the cervix
## Footnote
These prostaglandins are key in preparing the cervix for delivery.
237
What is the effect of administering COX inhibitors during labor?
Delays the onset of spontaneous labor
## Footnote
COX inhibitors can influence uterine contractions.
238
What are the therapeutic uses of misoprostol?
Promote cervical ripening, treat postpartum hemorrhage, pregnancy termination
## Footnote
Misoprostol is versatile in obstetric care.
239
What are the contraindications for carboprost tromethamine?
Asthma, active cardiac, hepatic, or renal disease
## Footnote
Carboprost can cause bronchoconstriction and is not suitable for patients with these conditions.
240
What is the pharmacological action of methylergonovine?
Sustained uterine contractions to prevent postpartum hemorrhage
## Footnote
Methylergonovine is effective in managing uterine atony.
241
What adverse effects can excessive stimulation of methylergonovine cause?
Fetal distress, placental abruption, uterine rupture, intense vasoconstriction
## Footnote
Monitoring is essential to avoid complications.
242
Fill in the blank: Tocolytics may be administered to women in preterm labor at a gestational age at which a delay in delivery for 48 hours will provide benefit to the _______.
newborn
## Footnote
Tocolytics are aimed at improving neonatal outcomes.
243
What are the first-line agents for tocolysis for women at 24 to 32 weeks of gestation?
Indomethacin
## Footnote
It is recommended unless contraindicated.
244
What side effects can terbutaline cause?
Maternal hypotension, tachycardia, arrhythmia, tremors, hyperglycemia
## Footnote
Terbutaline's side effects can affect both mother and fetus.
245
What is the role of magnesium sulfate in tocolysis?
Inhibits calcium uptake into smooth muscle, reducing uterine contractility
## Footnote
It has neuroprotective effects for the fetus.
246
What is atosiban?
An oxytocin receptor antagonist with low maternal and fetal side effects
## Footnote
Atosiban is not available in the US.
247
T or F: the goal of tocolytic therapy is to remove the underlying stimulus that initiated preterm labor.
false
248
T or F: tocolytic agents do not reverse cervical dilation
true
249
T or F: indomethacin is the first-ling tocolytic agent for gestation reaches 31-32 weeks.
true
Drug AEs for the fetus are more common after 32 weeks
250
Inhibition of PGs causes vasoconstriction. What complication can this present for the fetus?
oligohydramnios
251
What is the 1st line tocolytic agent for the 32-34 weeks gestation?
nifedipine
252
What is the MOA of terbutaline?
increases cAMP via Gs stimulation
253
Oxytocin acts on what type of receptors?
GCPRs-Gq
254
what is the name of the synthetic oxytocin human peptide?
pitocin
255
oxytocin acts on decidual tissue which promotes what?
PG release
256
What hormone receptor has a very similar structure to oxytocin receptors and can therefore be stimulated w/ high therapeutic doses of oxytocin?
ADH mediated receptors V1 & V2
257
what are CIs for oxytocin therapy?
unfavorable fetal position
fetal distress
cord prolapse
placenta previa
narrow cervix
258
What can be admin. to dilate and thin the cervix?
PGs
259
what uterotonics are used for cervical ripening?
misoprostol & dinoprostone
260
Misoprostol is an agonist of what PG?
PGE1
261
dinoprostone is an agonist of what PG?
PGE2
262
carboprost tromethamine is an agonist of what PG?
PGF2alpha
263
Which PG agonist is the cheapest?
misoprostol
the other 2 are very expensive
264
What uterotonic agent also has a therapeutic effects against benign hydatidiform moles?
dinoprostone
265
Why is asthma a CI for carboprost tromehtamine?
PGF2alpha is also a bronchoconstrictor
266
what effect does myometrial contraction have on large uterine vessles?
it compresses these vessels which yields one benefit-allows thrombosis of their lumens to prevent hemorrhage
267
T or F: ergot alkaloids are only used to treat postpartum hemorrhage b/c of their relatively long half life.
true
268
what is the MOA of ergot alkaloids on uterine SM?
partial agonists of 5-HT2a receptors
