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Pharmacology > Drugs To Use For Women’s Health Issues > Flashcards

Drugs To Use For Women’s Health Issues Flashcards

1
Q

Estrogens

Estradiol

A

most potent estrogen; secreted in the ovary by the premenopausal woman

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2
Q

Estrogens

Estrone

A

metabolite of estradiol; 1/3 of the potency of Estradiol; primary estrogen in the post- menopausal woman; generated from conversion of androstenedione in the peripheral and adipose tissues

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3
Q

Estrogens

Estriol

A

another metabolite of Estradiol; must less potent than Estradiol; principal estrogen produced by the placenta

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4
Q

Estrogens

Conjugated Equine Estrogen

A

sulfate esters of Estrone + Equilin is a common oral estrogen used as HRT [Premarin]

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5
Q

Estrogens

Other estrogens

A

Plant derived estrogens

Synthetic estrogens—ethinyl estradiol—undergoes less liver metabolism than naturally occurring estrogens, so can be safely used at low doses

Nonsteroidal compounds that bind to estrogen receptors [have both estrogen and anti-estrogen effects] are called SERMs [Tamoxifen, Raloxifene (Envista)]

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6
Q

Estrogens

MOA and Therapeutic Uses

A

MOA—activated steroid-receptor complex interacts with nuclear chromatin to initiate
hormone specific RNA synthesis

Used for postmenopausal hormone therapy, contraception, replacement in the
premenopausal patients who are deficient [hypogonadism, premature menopause,
surgical menopause]

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7
Q

Postmenopausal Hormone Therapy

A

Used in vasomotor instability, vaginal atrophy

If the woman has a uterus, progestogen must be included to reduce the risk of
endometrial cancer

If the woman has had a hysterectomy, unopposed estrogen is used—progestins may have negative effects on the lipid panel

ADE are less than in those using estrogens for contraception

Estradiol by patch or gel is also effective for postmenopausal symptoms

Risks of HRT—increased risk of CV events and breast cancer

Women with only GU symptoms are best treated with vaginal estrogens

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8
Q

Estrogens Androgens

Other Uses

A

Contraception

Combination of estrogen and
progestogen is used
-Orally
-Transdermal
-Vaginal

Other Entities

Primary Hypogonadism
-Estrogen that mimics natural cycle +
progestogen to stimulate development of
secondary sexual characteristics
-Must be continued until after growth has
been completed

Premature Menopause
-Estrogen + progestogen replacement is
used

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9
Q

Pharmacokinetics

Naturally Occurring Estrogens

A

Absorbed though the GI tract, skin & mucous membranes

Taken orally, estradiol is rapidly metabolized by the liver; micronized estradiol is available and has better bioavailability

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10
Q

Pharmacokinetics

Synthetic Estrogen Analogs

A

Ethinyl estradiol, mestranol & estradiol
valerate are well absorbed after oral
ingestion

These are fat soluble, they are stored in
adipose tissues, from there they are slowly
released

Synthetic estrogen analogs have prolonged action & are more potent than
natural estrogens

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11
Q

Pharmacokinetics
Estrogens

Metabolism

A

Estrogens are transported to the blood bound to albumin or SHBG; bioavailability of oral estrogen is low [because of 1st pass metabolism]; to reduce 1st pass effects—give the drug transdermally, intravaginally or by injection

They are then hydroxylated in the liver to derivatives that are then glucuronidated or sulfated

The parent drugs and the metabolites are excreted into the bile and are then reabsorbed through the enterohepatic circulation; inactive products are excreted in the urine

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12
Q

Estrogens

Adverse Effects

A

Nausea
Breast tenderness
Elevation of BP
Elevation of triglycerides
Peripheral edema
Increased risk of VTE and MI
Increased risk of breast and endometrial cancer [endometrial cancer risk reduced by
concomitant use of a progestin]

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13
Q

Selective Estrogen Receptor Modulators

A

Estrogen related compounds that display selective agonism or antagonism for estrogen receptors—depending on the target tissue

-Tamoxifen
-Toremifene [Fareston]
-Raloxifene [Evista]
-Clomiphene [Clomid]
-Ospemifene [Osphena]

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14
Q

Selective Estrogen Receptor Modulators

Mechanism of Action

A

Tamoxifen, Toremifene and Raloxifene compete with estrogen for binding to the estrogen receptor in the breast tissue
-Raloxifene also acts as an estrogen agonist in the bone, leading to decreased bone resorption, increased bone density and decreased vertebral fractures. Unlike Tamoxifen and estrogen, Raloxifene does not have appreciable estrogen receptor agonist activity in the endometrium [so no increased risk of endometrial cancer]
-Raloxifene also lowers total and LDL cholesterols

Clomiphene acts as a partial estrogen agonist and interferes with the negative feedback of estrogens on the hypothalamus
-These effects increase secretion of gonadotrophin releasing hormone and gonadotropins—stimulating ovulation

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15
Q

SERM

Uses and Pharmacokinetics

A

Tamoxifen—metastatic breast cancer; add
on therapy after mastectomy or XRT for
breast cancer; prevention of breast cancer in
those at high risk

Raloxifene—prevention of breast cancer in
those at high risk; prevention and treatment
of osteoporosis in postmenopausal women

Clomiphene—used for infertility from
anovulatory cycles

Ospemifene—treatment of dyspareunia from menopause

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16
Q

SERM

Pharmacokinetics

A

SERMs rapidly absorbed after PO
administration

Tamoxifen—metabolized by CYP450
isoenzymes

Raloxifene—rapidly converted to glucuronide conjugates through 1st pass metabolism; undergoes enterohepatic cycling—main route is excretion through the bile into the feces

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17
Q

Progestogens

A

Progesterone—natural progestogen; produced in response to LH in women & by the testes in men; also produced by adrenal cortex in both sexes

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18
Q

Progestogens

MOA

A

In women—progesterone promotes development of secretory endometrium that
accommodates implantation of newly forming embryo

High levels released during the luteal phase inhibit the production of gonadotropin and
prevent ovulation—if conception occurs, progesterone continues to be produced to
maintain the endometrium & reduce the uterine contractions

If conception does not occur, release of progesterone from corpus luteum stops—this decline causes menstruation to take place

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19
Q

Progestogens

Therapeutic Uses

A

Contraception
Treatment of hormone deficiency
Control of DUB, dysmenorrhea, endometriosis management and infertility
For contraception—they are combined with estrogens
Synthetic progestogens—progestin used in contraception are more stable to first pass
metabolism
Desogestrel, Dienogest, Drospirenone, Levonorgestrel, Norethindrone, Norethindrone acetate, Norgestimate, Norgestrel
Medroxyprogesterone acetate injection [this agent is used orally as part of HRT]

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20
Q

Progestogens

Pharmacokinetics

A

Micronized progesterone is rapidly
absorbed after oral ingestion

Metabolized by liver; glucuronidated
metabolite is excreted by the kidney

Oral medroxyprogesterone acetate has a
½ life of 30 days; when given IM or SC the
½ life is about 40-50 days and gives
contraceptive activity for approximately
90 days; other progestins have ½ lives of 1-
3 days allowing for once a day dosing

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21
Q

Progestogens

ADEs

A

Headache
Depression
Weight gain
Changes in libido

Progestins that are derived from 19-
nortestosterone possess some androgenic
activity because of their similarity to
testosterone—can cause acne and hirsutism

Those that are less androgenic—norgestimate and drospirenone, are preferred in women with acne [can raise K+]

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22
Q

Antiprogestins

A

Mifepristone [RU-486]

Progesterone antagonist with partial agonist activity
Use of this drug early in pregnancy usually in abortion due to interference with the progesterone
Often combined with the prostaglandin analog Misoprostol [PO or intravaginally] to induce contractions—uterine bleeding and the possibility of incomplete abortion

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23
Q

Contraceptives

A

Interference with ovulation—most common
pharmacologic intervention for preventing
pregnancy

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24
Q

Major Classes of Contraceptives

Combined Oral Contraceptives [COC]

A

Most common estrogen in COCs—ethinyl estradiol

Most common progestins in COCs—norethindrone, norethindrone acetate, levonorgestrel, desogestrel, norgestimate and drosperidone

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25
Q

Combined Oral Contraceptives [COC]

A

Combination on an estrogen & a progestin

Monophasic combination pills contain a constant dose of estrogen and progestin over 21-24 days

Triphasic COC attempt to mimic the natural female cycle—most contain a constant dose
of estrogen with increasing doses of progestin given over 3 successive 7 day periods

Active pills are taken for 21-24 days, followed by 4-7 days of placebo, for a total regimen of 28 days—withdrawal bleeding occurs during the hormone free period

Extended cycle contraception [84 pills followed by 7 days of placebo] results in less
frequent withdrawal bleeding

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26
Q

Patches/Rings

Estrogen Transdermal Patch

A

Ethinyl Estradiol and Norelgestromin

Patch is applied weekly for 3 weeks to
abdomen, torso or buttocks 4th week no patch is worn

Efficacy comparable to COCs in women
weighing <90 kg

Total estrogen exposure greater than with
COCs

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27
Q

Patches/Rings

Estrogen Ring

A

Vaginal ring of Ethinyl Estradiol and
Etonogestrel

Ring left in place for 3 weeks, then left out
for r1 week

Efficacy, contraindications & ADEs similar
to COCs

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28
Q

Progestins

Pills

Norethindrone—called “Mini Pill”

A

Taken daily

Less effective than COCs; they may
produce irregular menstrual cycles

Can be used while breast feeding, can
be used in those intolerant to estrogen,
those that smoke or those with
contraindications to estrogens

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29
Q

Progestins

Injections

Medroxyprogesterone acetate

A

given IM or SC every 90 days

ADE
-Weight gain
-Amenorrhea
-Bone loss/osteoporosis

Return to fertility may be delayed for
several months after discontinuation

Drug should not be used for >2 years
unless patient is unable to use other methods

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30
Q

LARCs—Progestin Based

Implants

A

Subdermal Etonogestrel

Ensures contraception for 3 years
-Effect totally reversible when surgically
removed

ADEs—irregular menses; headaches

Has not been studied in women >130% of
IBW

31
Q

LARCs—Progestin Based

IUDs

Levonorgestrel releasing IUD system

A

Levonorgestrel releasing IUD system

Lasts for 3-5 years

Suitable for those who have
contraindications to estrogens; avoid in
patients with PID or hx of ectopic pregnancy

32
Q

Emergency Contraception

A

Reduces chance of pregnancy after
an episode of unprotected or ineffectively protected intercourse

Reduces chance of pregnancy to 0.2-3%

High doses of Levonorgestrel or high
doses of Ethinyl Estradiol + Levonorgestrel

Should be taken ASAP after the
intercourse—preferably within 72°

Progestin only EC better tolerated
than estrogen/progestin
combinations

Alternative
-Progesterone agonist/antagonist— Ulipristal [Ella] can be used as EC within 5 days of unprotected intercourse

33
Q

Emergency Contraception

MOA

A

Estrogens provide a negative feedback on the release of LH and FSH by he pituitary—preventing ovulation

Progestins thicken cervical mucous,
interfering with the transport of sperm

Withdrawal of the progestin stimulated menstrual bleeding

34
Q

ADEs of Estrogens

A

Breast fullness
Fluid retention
Headache
Nausea
Elevated BP
Thromboembolism
Thrombophlebitis
MI
Stroke

35
Q

ADEs of Progestins

A

Depression
Changes in libido
Hirsutism
Acne

36
Q

Androgens

A

Steroids that have anabolic and/or masculinizing effects in both men and women

Testosterone—synthesized by Leydig cells in the testes & in smaller amounts by thecal cells in the ovaries and adrenal gland [in both sexes]

Other androgens secreted by the testes—5 alpha dihydrotestosterone [DHT]; androstenedione, dehydroepiandrosterone [DHEA]

Testosterone secretion by Leydig cells is controlled by gonadotrophin-releasing hormone from the hypothalamus, which stimulates the anterior pituitary to secrete LH and FSH

Testosterone or its active metabolite [DHT] inhibits production of these specific trophic
hormones

Androgens are needed for—normal male maturation, sperm production, increased production of muscle proteins, Hbg. and decreased bone resorption

37
Q

Androgens

MOA

A

Testosterone must be reduced to its active derivatives, such as DHT

The derivatives then diffuse into the prostate, seminal vesicles, epididymis and skin

Testosterone is converted by 5 alpha reductase to DHT

38
Q

Androgens

Therapeutic Uses

A

Used for males with primary hypogonadism or secondary hypogonadism [due to failure of the hypothalamus or pituitary]

Anabolic steroids can be used to treat chronic wasting associated with HIV or cancer

Unapproved uses—increased lean body mass, muscle strength and endurance in athletes; DHEA has been touted as an antiaging hormone

Danazol, a weak androgen, used to treat endometriosis and fibrocystic breast disease

39
Q

Androgens

ADEs

A

Weight gain
Decreased breast size
Deepening voice
Increased libido
Increased hair growth

40
Q

Pharmacokinetic

Testosterone

A

Ineffective orally

C17 esters of testosterone are given IM

Transdermal patches, topical gels and
buccal tablets are available

41
Q

Pharmacokinetics

Testosterone Derivatives

A

Alkylation of the 17 alpha position of
testosterone allows oral administration

-Fluoxymesterone [Androxy] hypogonadism or metastatic breast cancer in the male

-Oxandrolone [Oxandrin]—orally active
testosterone derivative with anabolic
activity 3-13 times that of testosterone;
used for weight gain in those with HIV or
catabolic states; used for osteoporosis
related bone pain

42
Q

Androgens

Adverse Effects

A

In females—masculization, acne, growth
of facial hair, deepening of voice, male
pattern baldness, excess muscle
development, menstrual irregularities
-Pregnant women should NOT use because
of possible virilization of the female fetus

In males—priapism, impotence,
decreased sperm production, gynecomastia, cosmetic changes [like those seen in women], stimulate growth of the prostate

In children—abnormal sexual maturation and growth disturbances from premature closing of epiphyseal plates

General effects—increased LDL,
decreased HDL, fluid retention,
edema

43
Q

Androgens

Adverse Effects

A

In athletes—using anabolic steroids can cause premature closing of epiphyses of the long bones—which will stunt the growth and
interrupt development

High doses may result in reduction of testicular volume, hepatic abnormalities, increased aggression, major mood disorders

44
Q

Antiandrogens

A

Antiandrogens counter male hormonal action by interfering with the synthesis of
androgens or by blocking their receptors

Finasteride [Proscar] and Dutasteride [Avodart] inhibit 5 alpha reductase resulting
in decreased formation of DHT—both are used to treat BPH

Flutamide [Eulexin], Bicalutamide [Casodex], Enzalutamide [Xtandi], Nilutamide
[Nilandron] act as competitive inhibitors of androgens at the target cell and
taken orally for the treatment of prostate cancer

45
Q

Writing Prescriptions for Estrogens,
Progestins, Androgens

COCs

A

In the US, most COCs contain ethinyl estradiol [one contains estradiol valerate]

Estrogens regulate endometrial proliferation and prevent ovulation and prevent estrogen
deficiency induced by progestin (important)

9 different progestins used in COCs in the US—they are the main contraceptive
component in COCs—they suppress LH, FSH and cause the endometrium to be
unfavorable for implantation

46
Q

Progestins

A

1st Generation
-Norethindrone
-Norethindrone Acetate

2nd Generation
-Levonorgestrel
-Norgestrel

3rd Generation
-Destrogestrel
-Norgestimate

Others
-Drospirenone
-Dienogest

**First choice for a woman starting COCs should be a monophasic product, preferably
with a 2nd generation progestin; cycle control may be better for some women with COCs containing 30-35 mcg ethinyl estradiol

47
Q

Other Scenarios where COCs Can be Used

A

Regulating the menstrual cycle
Reduction of heavy menstrual bleeding
Management of acne
Managing dysmenorrhea
Managing PMS
Reduce risk of ovarian, endometrial and colon cancers
During perimenopause may prevent bone loss and reduce the risk of osteoporosis

Products with Drospirenone—less like to have HTN, more likely to improve mood and lessen weight gain in those with PMS

48
Q

COCs

Contraindications/Risk Factors

A

ACOG states that COC is contraindicated for women 35 and older who smoke

Risk factors for stroke, MI and VTE are increased in patient’s that are overweight and obese

49
Q

COCs

Rings/Patches/IUDs

A

Rings
-NuvaRing

Patches
-Xulane
-Ortho Evra

IUDs 3 hormonal options-Levonorgestrel coated IUDs
-Skyla [3 years]
-Liletta [3 years]
-Mirena [5 years]

50
Q

Progestin Alternatives

A

Oral Pills—35 mcg daily
-Norethindrone
-Many brand names—Camila, Errin, Heather, Jencycla, Jolivette, Nora-BE, Ortho Micronor, Nor-QD

Injectable
-Medroxyprogesterone acetate given IM every 90 days
-Depo-Provera; Depo-subQ Provera 104

Subdermal
-Etonogegstrel 68 mg every 3 years
-Nexplanon

51
Q

Nonhormonal Contraceptive Methods

A

Vaginal spermicides [nonoxynol-9]
Male condoms
Female condoms
Diaphragm [Rx required]—must be left in place 6°
Cervical Cap [Rx required]—can be left in place 48°
Sponge—must be left in place 6°
Para-Guard Copper T380A IUD [RX required]

52
Q

Emergency Contraception

3 FDA approved options for EC

A

Progestin orally in high dose, progestin receptor modulator & Copper IUD Paraguard

High dose estrogen/progestin combinations also can be used, but are not FDA
approved—have more S/E and are not as effective as the FDA approved methods

Progestin only options are OTC and are approved for use up to 72 hours after unprotected intercourse—Plan B, One-Step, Next Choice, One Dose, My Way
-Contain 1.5 mg of Levonorgestrol

53
Q

Emergency Contraception

A

Prescription options include insertion of a copper IUD—it can be inserted up to 5 days after the unprotected intercourse [will then give long term contraception for 7 years]

Other option is Ulipristal [Ella]—nearly 3 times more effective than the OTC options, can be used up to 120 hours after the unprotected intercourse episode
-Requires a prescription

Oral forms of EC ARE affected by weight—OTC options successfully in women up to 154 pounds; Ella effective in women up tot 194 pounds

54
Q

Drugs to Manage Menopausal Symptoms

A

Bazedoxifene/Conjugated Estrogens [DuaVee]

20 mg of Bazedoxifene + .45 mg of conjugated estrogen

-SERM in combination with estrogen for treating moderate to severe vasomotor symptoms associated with menopause in women with a uterus

-Bazedoxifene acts as an antagonist for estrogen receptors in uterine tissue, so when given in combination with estrogen it opposes the effects of estrogens on the uterus

-Bazedoxifene [Viviant] is also approved for preventing postmenopausal osteoporosis in women with a uterus

Side Effects—muscle spasms, diarrhea,, nausea, indigestion, upper abdominal pain [all >10%]

55
Q

Drugs to Treat Menopausal Symptoms

Bioidentical Hormone Therapy

A

Hormone based medications that
are compounded by specialty pharmacies

FDA does not recognize this term
nor does it approve these
hormones for use

Formulas are inconsistent

Not evidenced based

56
Q

Nonhormonal Options

A

SSRIs & SNRIs—Paroxetine 7.5 mg daily [Brisdelle] is only nonhormonal FDA approved med for the treatment of menopausal vasomotor symptoms

Clonidine/Gabapentin—neither is FDA approved for vasomotor symptoms
-Clonidine—centrally acting alpha agonist thought to HC elevate threshold at which the body will develop flushing—perhaps decreasing number of hot flashes;
0.05-.15 mg BID

-Gabapentin—anticonvulsant, helps to manage hot flashes through an unknown mechanism; 900 mg daily

57
Q

Drugs to Treat Menopausal Symptoms

Phytoestrogens and Black Cohosh

A

Phytoestrogens are plant based estrogens—alternative treatments despite a LACK of evidence supporting their use; Isoflavones [one type of phytoestrogens] are derived from soy or red clover extract—not EB

58
Q

Drugs to Treat Vaginal Symptoms

A

Lack of estrogen leads to atrophy of the vaginal tissues

Before menopause, estrogen stimulated exfoliation of the vaginal cells; as the cells exfoliate, glycogen is released, which is hydrolyzed into glucose

Lactobacilli in the vaginal tissues convert this glucose to lactic acid, which maintains the vaginal pH at 3.5-4.5; without estrogens, the pH increases to 5-7.5, leading to symptoms that may include dryness, discomfort itching, burning, discharge and painful intercourse

Estrogens are the main treatment of vaginal symptoms—four local estrogens are
FDA approved—2 creams, one ring and one tablet

59
Q

Drugs to Treat Vaginal Symptoms

Ospemifene

A

Osphena is FDA approved

Oral estrogen receptor
agonist/antagonist, for the treatment of
moderate to severe dyspareunia

60 mg daily PO with food

No dosage adjustments for renal
impairment or hepatic disease

Fluconazole and Rifampin cannot be
taken while on Osphenia

Side effects—hot flashes, vaginal
discharge, muscle spasms and
hyperhidrosis

60
Q

Drugs to Treat Vaginal Symptoms

Vaginal Options

A

Lubricants—can relieve sx of dyspareunia—use immediately before intercourse
-Water based or silicone based
-Yes, Astro-Glide, Replens

Moisturizers—should be used routinely; at least every 3-4 days
-Replens moisturizer, Luvena, KY moisturizer

Women should be encouraged to continue
sexual activity—helps maintain active blood
flow to the vagina, which can help with
lubrication and prevent atrophy

61
Q

Drugs to Manage Infections of the
Genitourinary System

Bacterial Etiologies

A

Chancroid

Haemophillius ducreyi

Zithromax 1 gram PO; Rocephin 250 mg IM

62
Q

Bacterial Etiologies

A

Chlamydia

Chlamydia trachomatis

Zithromax 1 gram PO; Doxycycline 100 mg BID x 7 days

63
Q

Bacterial Etiologies

A

Donovanosis

Granuloma inguinale
Calymmatobacterium granulomatis

Zithromax 1 gram PO x 2 1 days; Doxycycline 100 mg BID x 21days

64
Q

Bacterial Etiologies

A

Gonorrhea

Neisseria gonorrhoeae

Rocephin 250 m g IM + Zithromax 1 gram PO
Suprax 400 mg PO + Zithromax 1 gram PO

65
Q

Bacterial Etiologies

A

Lymphogranuloma venereum

Chlamydia trachomatis [serotypes
L1, L2, L3]

Zithromax 1 gram PO; Doxycycline 100 mg BID x 7 days

66
Q

Bacterial Etiologies

A

Nongonococcal urethritis

Ureaplasma urealytium
Mycoplasma hominis

Zithromax 1 gram or Doxycycline 100 mg BID for 7 days OR
Clindamycin 450 mg q 6° for 7days
Levaquin 500 mg for 7 days
Ofloxacin 300 mg BID for 7 days

67
Q

Bacterial Etiologies

A

Syphilis

Treponema pallidum

Aq. Penicillin G 2.4 million units IM
Doxycycline 100 mg BID for 14 days
[both +/- Prednisone 40-60 mg daily for 3 days]

68
Q

Bacterial Etiologies

A

Bacterial vaginosis

Gardenerella vaginalis
Mobiluncus species

Flagyl 500 mg PO BID x 7 days
Flagyl gel 5 g. vaginally @ HS x 5d

69
Q

Viral Etiologies

A

CMV

Cytomegalovirus Reassurance

If treatment indicated—Foscarnet or Cidofovir [with ID consultation]

70
Q

Viral Etiologies

A

HSV

Herpes simplex

Acyclovir 400 mg TID for 7-10 days or 200 mg 5 times/day for
7-10 days
Valcyclovir 1000 mg BID for 7-10 days
Famcyclovir 250 mg TID for 7-10 days

71
Q

Viral Etiologies

A

HPV

Human papilloma Podofilox 0.5% BID for 3 days [can repeat each week for 4
cycles]

Imiquimod 5% TIW @ HS for 16 weeks
Sinecatechins [Veregen] 15% ointment TID for 16 weeks
Local therapies may be indicated

72
Q

Viral Etiologies

A

Molluscum
contagiosum

Pox virus

Curettage/Cryo +/- Cantharidin [derm specialist only]
Glycolic acid topically
Imiquimod 5% daily [leave on 6-10°]
Tretinoin topical [0.1% cream or 0.025% gel] @ HS
Salicylic acid [50-80% compounded]
K+ hydroxide topical [compounded]

73
Q

Protozoal Etiologies

A

Trichomonas

Trichomonas vaginalis

Flagyl 2 grams PO or
Tinidazole 2 grams PO with
food

Pharmacology (8 decks)

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