KG - Pharm 2 Exam 3, Sex Hormones Flashcards
(132 cards)
1
Q
Which groups of sex hormones are needed for secondary sex characteristics & functions?
(how do you know HOW to treat with these drugs?)
A
steroids
- multiple levels for tx
- determined by WHAT is needed
2
Q
how does GnRH work?
A
- release is pulsatile for stimulating FSH & LH release
- tonic GnRH admin leads to suppressed gonadotropin release
3
Q
which drugs are GnRH LONG ACTING AGONISTS?
A
Leuprolide
Goserelin
4
Q
Action of Leuprolide & Goserelin?
A
- CONTINUOUS ADMIN SUPPRESSES RELEASE OF LH & FSH (after initial surge)
5
Q
When are leuprolide/Goserelin used?
A
- IVF
- steroid dependent CAs
- endometriosis
- precocious puberty (will stop pre-pubertal development)
6
Q
which drugs are GnRH ANTAGONISTS?
A
Cetrorelix
Ganirelix
7
Q
Action of Cetrorelix & Ganirelix?
A
- suppress LH and FSH
8
Q
When are Cetrorelix & Ganirelix used?
A
- IVF
- steroid dependent CAs
- endometriosis
- precocious puberty (will stop pre-pubertal development)
9
Q
How are GnRH agonists different from antagonists?
A
- 4-5 tx w/ ANTAGONISTS, 3 wks tx w/ AGONIST to suppress gonadotropins
- no initial surge of gonadotropins w/ ANTAGONIST
10
Q
Which class of drugs demonstrates challenges during the start of tx when the pt has metastatic prostate cancer? (And what do you add to the tx plan?)
A
GnRD AGONISTS
- ADD ANTIANDROGEN
11
Q
Side effects long acting GnRH agonists/antagonists?
A
- menopausal symptoms
- testicular atrophy
12
Q
Which hormone drives folliculogenesis during the menstrual cycle?
A
FSH
13
Q
Which hormone, in high levels, causes a POSITIVE FEEDBACK on LH release?
A
estrogen
14
Q
stages of menstruation?
A
- follicular/proliferative phase
- ovulation
- luteal/secretory phase
- menstruation
15
Q
describe follicular/proliferative stage of the menstrual cycle
A
FSH DRIVES FOLLICULOGENESIS
- get increased estrogen
- get endometrial development and thickening
16
Q
describe ovulation stage of the menstrual cycle
A
high, sustained levels of estrogen cause POSITIVE FEEDBACK on LH release
- LH surge
- ovulation
- luteinization
17
Q
describe luteal/secretory phase of the menstrual cycle
A
LH maintains corpus luteum
- progesterone and estrogen = MAINTENANCE OF ENDOMETRIUM
18
Q
which hormones MAINTAIN the ENDOMETRIUM?
A
progesterone, estrogen
19
Q
describe menstruation stage of the menstrual cycle?
A
loss of LH –> loss of CL –> loss of P&E
20
Q
effects of FSH in women?
A
develop ovarian follicles & supports estrogen synthesis
21
Q
effects of FSH in men?
A
stimulates spermatogenesis
22
Q
which drug contains both FSH & LH?
A
human menopausal gonadotropins (hMG)
aka menotropins
23
Q
for what are hMGs used for?
A
for FSH PROPERTIES ONLY
24
Q
for what is Urofollitropin (uFSH) used?
A
PURIFIED FSH
with only FSH
25
what does LH do?
- stimulates ovulation
- stimulates luteinization of follicles
- steroid production
(women = progesterone synthesis, men = testosterone synthesis)
26
for what is hCG used?
LH AGONIST, USED INSTEAD OF LH
| - BINDS TO LH RECEPTOR
27
pharmacokinetics of hCG?
longer half life than LH
28
why use gonadotropins?
- reverse infertility
(men = INDUCE SPERMATOGENESIS, LH increases testosterone --> FSH induces spermatogenesis)
(women = IVF, FSH stimulates ovaries & estrogen production, single dose of LH given to induce ovulation)
29
how are FSH and LH usually used?
IN SEQUENCE
- FSH for 9-12 days until estradiol levels normal
- then SINGLE DOSE hCG (LH) to induce ovulation
30
side effects gonadotropins?
- uncomplicated ovarian enlargement
- OVARIAN HYPERSTIMULATION SYNDROME (life threatening)
- MULTIPLE BIRTHS - 20%
- GYNECOMASTIA
- HA, depression, edema, precocious puberty
31
contraindications gonadotropins?
sex steroid dependent cancers
32
which are the major endogenous estrogens?
ESTRADIOL
ESTRIOL
ESTRONE
33
mechanism - estrogens?
NUCLEAR RECEPTORS
| - interact w/ DNA
34
metabolism - estrogens?
- conjugated by liver (excreted in bile)
| - ENTEROHEPATIC CIRCULATION (reverses conjugation, increases bioavailability)
35
estrogen function - ovary?
prepare for ovulation
36
estrogen function - uterus?
ENDOMETRIAL GROWTH
37
estrogen function - vaginal epithelium?
proliferation, maintenance
38
estrogen function - endocervical glands
mucous
39
estrogen function - breasts
growth - pregnancy & puberty
40
estrogen function - puberty
- growth & maturation
| - CLOSES EPIPHYSES
41
estrogen function - bone
MAINTENANCE
42
estrogen function - blood clotting
- SYNTHESIS OF CLOTTING PROTEINS
| - INCREASED PLATELET ADHESIVENESS
43
estrogen function - metabolic
Liver
- clotting factors
- HORMONE BINDING PROTEINS: SHBG, CBG, TBG
INCREASED HDL, DECREASED LDL
Na+, H2O retention
44
why are there synthetic oral forms of estrogens?
naturally occurring not orally active
45
what forms are EXOGENOUS ESTROGENS?
synthetic --> oral contraceptives
conjugated --> HRT
estradiol --> creams/patches
46
uses - exogenous estrogens?
- ORAL CONTRACEPTIVES
- postmenopausal HRT
- STIMULATING PUBERTAL DEVELOPMENT in hypogonadic girls
- decrease uterine bleeding
- suppressing ovulation in dysmenorrhea
47
adverse effects - estrogens
- endometrial hyperplasia
- nausea
- breast tenderness
- MIGRAINES
- gallbladder dz
- HTN
- THROMBOEMBOLISM, thrombophlebitis, incr platelet aggregation, ACCELERATED BLOOD CLOTTING
48
contraindications - estrogens
- ESTROGEN DEPENDENT NEOPLASMS (ie: breast CA)
- undiagnosed genital bleeding
- uncontrolled HTN
- liver dz
- THROMBOEMBOLIC DISORDERS
- smoking & > 35 yo
- pregnancy
49
tamoxifen - MOA
selective estrogen receptor modulator (SERM)
50
when is Tamoxifen an agonist?
BONE - limits bone loss
| UTERUS - may increase risk uterine CA
51
when is Tamoxifen an antagonist?
BREAST - used as PALLIATIVE & PROPHYLACTIC TX IN BREAST
| CANCER - reduces risk of further breast cancer
52
why would you use Raloxifene instead of Tamoxifene?
prevention better for osteoporosis
53
why would you use Toremifene instead of Tamoxifene?
similar to Tamoxifene but it will probably increase HDL
54
clomiphene - MOA
Selective estrogen receptor modulator (SERM)
| - ANTAGONIZES NEGATIVE FEEDBACK OF ESTROGEN IN HYPOTHALAMUS
55
clomiphene - "adverse" effect?
multiple pregnancies (5-10%)
56
fulvestrant - MOA?
full estrogen receptor antagonist
57
list of aromatase inhibitors?
anastrozole
letrozole
exemastane
58
aromatase inhibitors - MOA
do not inhibit adrenal steroid synthesis
59
which aromatase inhibitor is irreversible?
Exemastane
60
aromatase inhibitors - indications?
- DOC - BREAST CANCER TREATMENT IN POSTMENOPAUSAL WOMEN
| - ADVANCED BREAST CANCER AFTER TAMOXIFEN FAILURE IN POSTMENOPAUSAL WOMEN
61
aromatase inhibitors - adverse effects?
- diarrhea
- abd pain
- n/v
- hot flashes
- joint pain
62
aromatase inhibitors - contraindications?
- premenopausal women
| - PREGNANCY = CAT X
63
how is progesterone made?
- produced by CORPUS LUTEUM
| - produced by fetal/placental unit in pregnant women
64
progesterone - MOA
NUCLEAR RECEPTOR
| - interact w/ DNA
65
progesterone - physiological effects, uterus?
converts endometrium to SECRETORY STATE
- MAINTAINS PREGNANCY
- suppresses contractility during pregnancy
66
progesterone - physiological effects, endocervical glands?
regulates cervical mucous
67
progesterone - physiological effects, breasts?
lobuloalveolar development at the end of the mammary ducts during pregnancy and puberty
68
progesterone - physiological effects - thermogenic action?
increases body temperature
69
why are there synthetic forms of progesterone?
progesterone is not orally active, so different formulations
70
classes of progesterones?
```
19-nortestosterones (progestin + androgenic activity)
progesterone derivatives (varying levels androgen activity)
```
71
progestins - uses?
- CONTRACEPTION
- prevent ENDOMETRIAL HYPERPLASIA in HRT
- tx of other problems when estrogens are contraindicated
72
progestins - side effects?
- possibly increased BP
- high doses may reduce plasma HDL levels
- depression, drowsiness
73
list antiprogestins?
Mifepristone
| Danazol
74
Mifepristone - MOA?
- PROGESTERONE/GLUCORTICOID receptor antagonist
75
mifepristone - uses?
- TERMINATE PREGNANCY (w/ prostaglandins)
| - prevent implantation
76
mifepristone - side effects?
- vomiting
- diarrhea
- abd or pelvic pain
- vaginal bleeding
77
danazol - MOA?
weak progestin/androgen that suppresses ovarian function
78
danazol - uses?
used to TREAT ENDOMETRIOSIS
79
danazol - side effects?
- weight gain
- edema
- acne/oily skin
- hirsutism
- deepening voice
- headache
- flush
- libido changes
- cramps
80
what is the most common contraception option?
combination pill - estrogen + progestin
| 99.9% effective
81
which combo contraception pill MUST YOU KNOW?
Drospirenone/ethinyl estradiol
82
oral contraceptives - MOA?
- INHIBIT OVULATION - no LH surge
- change cervical mucous (block sperm)
- change endometrium (DECREASE IMPLANTATION)
- progestin withdrawal initiates bleeding at end of cycle
83
what estrogens are usu in combo oral contraceptives?
ethinyl estradiol or mestranol
84
what progestins are usu in combo oral contraceptives?
levonorgestrel or norethindrone
85
what is most important when combining estrogens and progestins in a combo pill?
E:P ratio - MINIMAL AMTS desired
86
how do combo contraceptives work?
21 days
- estrogen stays the same = incr progestin content at each stage
- 1 stage = mono phasic
- 2 stages = biphasic
- 3 stages = triphasic
87
combo oral contraceptives mimic normal hormonal cycle... why?
MINIMIZE SIDE EFFECTS
88
how are new oral contraceptives different from other combo oral contraceptives?
new pills provide longer cycle times or no cycle at all
- Seasonale = 84 on, 7 off
- Seasonique = 84 on, 7 estrogen only
- Lybrel = always on pill
89
new combo oral contraceptives - adverse effects
- increased breakthrough bleeding (esp during first year)
| - hard to tell if you're pregnant
90
Ethinyl estradiol/Drospirenone combo oral contraceptive - MOA
mineralcorticoid antagonist
91
Ethinyl estradiol/Drospirenone combo oral contraceptive - advantages?
- LESS WATER RETENTION - FDA APPROVED FOR PMDD
| - very little androgenic properties
92
newest combo pill (Natazia) - MOA
- takes advantage of estradiol valerate to produce E2 in vivo
- BIOIDENTICAL HORMONES
- uses dienogest as progestin, weird 4 cycle regimen
93
NuvaRing - how does it work?
vaginal ring containing 3 week supply of etongesterel & ethinyl estradiol
94
progestin only - mini pills?
- 87-98% EFFECTIVE FOR BIRTH CONTROL
| - used for ADOLESCENTS & BREAST FEEDING
95
progestin only - depo-provera?
3 month depot injection of medroxyprogesterone
96
progestin only - implanon?
- single silastic tube implanted in arm
| - > 99% effective - 3 yrs
97
progestin only - Mirena?
- IUC w/ levonorgesterel
| - 99.9% effective - up to 5 years
98
emergency contraception - Plan-B?
- lenonorgesterel only pill
| - taken w/in 72 hrs after intercourse (better sooner, available w/out prescription to age 18+)
99
emergency contraception - preven?
similar to plan B, but w/ ethyinyl estradiol
100
emergency contraception - mifepristone (RU-486)?
can also be used to prevent implantation if w/in 72 hrs after intercourse
101
combo oral contraceptives - adverse effects (common)?
common
- WEIGHT GAIN
- NAUSEA
- EDEMA
- DEPRESSION
breakthrough bleeding (progestin alone or too little estrogen)
TRY DIFFERENT COMBOS!
102
combo oral contraceptives - adverse effects (CV + less common)?
CV PROBLEMS
- CLOTTING (women 35+, SMOKING)
- MILD HTN
- MIGRAINE
- MI/STROKE
cholestatic juice/gallbladder dz
TERATOGENESIS
FERTILITY - can be suppressed 3+ months
103
combo oral contraceptives - benefits?
- EFFECTIVE CONTRACEPTION
- reduced risk for OVARIAN & ENDOMETRIAL CANCER (50% reduction even after 2 yrs, protection lasts 15 years after stopping), ovarian cysts, benign breast dz, ectopic pregnancy, iron def, RA, PMS, etc)
- CONSENSUS = SAVES 1000s OF LIVES, DZ EPISODES & HOSPITALIZATION EVERY YEAR
104
combo oral contraceptives - absolute contraindications?
- thrombophlebitis
- THROMBOEMBOLIC PHENOMENA
- CV disorders
- ESTROGEN-DEPENDENT NEOPLASMS
- pregnancy
105
combo oral contraceptives - relative contraindications?
- LIVER DISEASE
- teens prior to epiphyseal closure
- asthma, eczema
- migraine, HTN
- DM
- optic neuritis, retrobulbar neuritis
- seizure disorders
- smoking & > 35 yo
106
combo oral contraceptives - drug interactions?
- P450 inducers reduce effectiveness (phenytoin, rifampin, carbamazepine)
- ANTIBIOTICS REDUCE EFFECTIVENESS (stop enterohepatic circulation)
- decrease effectiveness of anticoags, anticonvulsants, tricyclic antidepressants, guanethidine, oral hypoglycemics
107
what happens in menopause (general)?
reduced ovarian response to gonadotropins
- decreased ovarian steroids
- increased gonadotropins
108
menopause - VASOMOTOR problems?
- HA
- palpitations
- night sweats
- insomnia
- HOT FLASHES
109
menopause - GENITOURINARY problems?
- vaginal dryness
- atrophy
- pain
- loss of trophic effects of estrogen
110
menopause - OSTEOPOROSIS problems?
- decrease in bone mass = serious problem
(50% spinal compression fractures by 75)
(20% hip fractures by 90)
111
menopause - HEART DZ problems?
- increased cholesterol & LDL
| - decreased HDL
112
Who should consider HRT?
- younger pts tend not to have as many side effects(w/in ten yrs)
- HYSTERECTOMIES - ESTROGEN ONLY
- girls w/out ovarian development
113
How is Raloxifene different?
- does not affect CHD
- DOES prevent osteoporosis & breast cancer
- NO effect on hot flashes
114
what might reduce adverse effects of HRT?
different routes of administration
- creams for urogenital tract
- transdermal good for osteoporosis w/ less CHD effects
115
HRT - adverse effects?
- endometrial cancer (progestins reduce)
- BREAST CANCER - SMALL RISK (1.25 fold)
- -> 8 cases per 10,000 women/yr
- gallbladder dz
- CARDIOVASCULAR
116
HRT - advantages?
- menopausal symptoms
- osteoporosis
- heart dz
117
HRT - concerns?
- breast cancer
| - strokes
118
when do the concerns outweigh the risks of HRT?
> 10 yrs after menopause
119
androgens - physiological effects
VIRILIZING
- spermatogenesis
- sexual devleopment
ANABOLIC
- incr bone density
- incr amino acid incorporation into muscle
- incr RBC mass
- antagonize catabolic effects of glucocorticoids
PUBERTY
- development of secondary sexual characteristics, males
120
androgens - uses (male)
TESTICULAR DEFICIENCY
121
androgens - uses (women)
FEMALE HYPOPITUITARISM
| - estrogens and androgens
122
androgens - uses (both sexes)
- hypoproteinemia of NEPHROSIS
| - NEGATIVE NITROGEN BALANCE PATIENTS (ie: burn patients)
123
androgens - side effects (men)
- DECREASED SPERMATOGENESIS
| - may exacerbate prostate cancer
124
androgens - side effects (women)
- MASCULINIZATION
| - PSEUDOHERMAPHRODITISM of fetus in pregnant women
125
androgens - side effects (both sexes)
- baldness
- fluid retention, edema
- OILY SKIN (ACNE)
- DECREASED HDL, increased LDL
- PSYCHOLOGICAL CHANGES
126
list androgen receptor antagonists
- flutamide
| - spironolactone
127
flutamide - info
- USED IN PROSTATE CANCER w/ LONG ACTING GnRH AGONIST
| - hepatotoxic (reversible)
128
spironolactone - info
- mineralcorticoid antagonist
- high doses anti androgen
- uses = HIRSUTISM & PMS in women, PRECOCIOUS PUBERTY
129
list 5 alpha reductase inhibitors
finasteride
| dutasteride
130
5 alpha reductase inhibitors - MOA
- INHIBITS 5 alpha reductase (no DHT)
| - suppresses male sex accessory organs w/out affecting libido
131
5 alpha reductase inhibitors - uses
- BENIGN PROSTATIC HYPERPLASIA
| - MALE PATTERN BALDNESS
132
5 alpha reductase inhibitors - warnings
- teratogenic (even handling crushed pills!
