B6: Pharm Exam 2

Estrogen Replacement

What drug:

MOA: E binds to intracellular receptors (ER-⍺ and ER-β) which complexes and interacts with specific DNA sequences to alter transcription rates and target genes → synthesis of specific proteins in target cell

CI: pregnancy

AE: Common: n, HA, bloating, breast tenderness

Serious: ↑ risk CHD, stroke, VTE, TGs, breast cancer, endometrial hyperplasia and subsequent endometrial cancer, and gallbladder disease

BBW: Unopposed use → ↑ endometrial cancer risk (monitor for abnormal vaginal bleeding)

AVOID use for prevention of CVD or dementia

↑ risks of MI, stroke, invasive breast cancer, PE, and DVT in post-menopausal F (50-79)

↑ risk of dementia in post-menopausal women (65+)

w/ or w/o P, prescribe @ lowest dose and for shortest duration consistent with Tx goals for specific pts

Notes: Oral, transdermal, topical, intravaginal, IM (not recommended)

Transdermal = LESS breast tenderness and VTE

Progestin replacement

What drug:

MOA: ↑ basal insulin levels and insulin response to glucose

Stimulates lipoprotein lipase activity; fat deposition

↑ body temp

Indication: Added to systemic E in F who have not undergone hysterectomy

Contraception, dysfunctional uterine bleeding

AE: Irritability, weight gain, bloating, HA, breast cancer with E, ↓ bone mineral density

Notes: Oral, transdermal, or injectable

Metabolized in liver and excreted in urine

Bazedoxifene^

Ospemifene~

Raloxifene-

Tamoxifen+

What drug:

Type: Selective estrogen receptor modulators (SERMs)

MOA: Agonist effects on bone and coagulation

Antagonist effects in breast*, uterus*, and vasomotor center

Indication: + = breast cancer

- = Tx and prevention of osteoporosis and reduction of invasive breast cancer in F at high risk

^ = Tx of vasomotor Sx and prevention of osteoporosis in combo w/ E

~ = indicated for moderate-to-severe dyspareunia from menopausal vulvar and vaginal atrophy (in F w/ intact uterus, consider w/ P)

Notes: * = Bazedoxifene + Raloxifene

Bazedoxifene

What drug:

Type: SERM

MOA: Agonist on bone and antagonist in uterus, when combined with E, it can oppose effects of E on uterus → ↓ risk of endometrial hyperplasia while allowing E to act on bone

Indication: Women <75 y/o to treat moderate-to-severe vasomotor Sx in F w/ intact uterus

Prevent osteoporosis in F w/ intact uterus

BBW: DO NOT take additional E

↑ risk endometrial cancer in F w/ uterus using unopposed E

Avoid E therapy for prevention of CVD or dementia

↑ risk of CV disorders (DVT, PE, MI, or stroke)

↑ risk of probably dementia in post-menopausal F > 65

Should be prescribed at lowest effective dose & for shortest duration consistent w/ Tx goals for individual F!!!!!!

AE: Common: dizziness, muscle spasms, GI upset, neck pain

Serious: CVA, DVT, VTE, endometrial cancer

Ospemifene

What drug:

Type: SERM

MOA: Agonist on endometrium and vaginal tissue, bone

Antagonist on breast tissue

Indication: Dyspareunia or vaginal dryness (moderate-to-severe) due to vulvar/vaginal atrophy associated w/ menopause

CI: Severe hepatic impairment, undiagnosed abnormal genital bleeding, active or Hx of DVT/PE/MI/stroke, known/suspected E-dependent neoplasia, pregnancy

AE: Common: flushing, vaginal discharge

Serious: MI, DVT, stroke, vaginal hemorrhage

BBW: ↑ risk endometrial cancer if intact uterus and use unopposed E (add P)

↑ risk CV disorders (DVT)

DI: Metabolized by CYP3A4, 2C9, 2C19 → do not use with inhibitors or inducers (↑ exposure or ↓ exposure, respectively)

Notes: Add P if pt has uterus!!!!!!!

Prasterone

What drug:

MOA: Inactive steroid (prodrug) converted to active androgens and estrogens (active = DHEA)

Indication: Moderate-to-severe dyspareunia due to vulvar/vaginal atrophy associated with menopause

CI: Undiagnosed abnormal genital bleeding

AE: Abnormal PAP smear, vaginal discharge

BBW: E is metabolite, use of exogenous E CI in F w/ known or suspected Hx breast cancer

DI: May ↑ risk hypoglycemia w/ glimepiride

Notes: Vaginal suppository used daily at bedtime

Testosterone

What drug:

Type: androgen

MOA: Acts directly on bone, skin fibroblasts, hair follicles, sebaceous glands

Acts indirectly via conversion to E in ovaries, brain, bone, and adipose tissue

Indication: Use in F controversial, lack of evidence

↑ libido and sexual function for post-menopausal F

CI: Pregnancy/lactation

Androgen-dependent neoplasia (known or suspected)

AE: PO > Transdermal: virilization, fluid retention, adverse lipid effects (↓ HDL ↑ LDL)

Notes: Menopause often results in androgen deficiency → ↓ sense well-being, ↑ fatigue, ↓ libido and pleasure (data unclear)

Paroxetine

What drug:

Type: SSRI (Non-HRT)

MOA: Inhibits reuptake serotonin by pre-synaptic nerve terminal

Indication: Moderate-to-severe abnormal vasomotor Sx (hot flashes)

CI: MAOIs within 14 days, hypersensitivity, pregnancy

AE:

Common: diaphoresis, n/v/d, fatigue, dizziness, bone fractures, abnormal bleeding, HA, insomnia

Serious: exacerbation of depression, serotonin syndrome

BBW: suicidal thoughts and behaviors

DI: Other serotonergic drugs, QT-prolonging drugs, NSAIDs, anti-coagulants, CYP2D6i, tamoxifen

Venlafaxine*

Desvenlafaxine

Citalopram

Escitalopram

What drug:

Type: SSRI (non-HRT)

MOA: Serotonin agents

Indication: * most studied – vasomotor Sx

AE: GI upset, orthostatic hypotension, insomnia, dry mouth, anxiety, weight gain, sexual dysfunction, bone loss

Gabapentin

Pregabalin

What drug:

Type: Non-HRT

MOA: ↓ frequency and severity of vasomotor Sx

AE: Dizziness, somnolence

Clonidine

What drug:

Type: Non-HRT

AE: Drowsiness, dry mouth, hypotension, bradycardia

Notes: Less effective than SSRI/SNRIs and gabapentin

Must be tapered on d/c due to rebound HTN

Black Cohosh

What drug:

Type: Non-HRT

MOA: Estrogenic effect by modifying or directly binding E receptors

Agonistic effect on serotonin receptors

↓ LH

Indication: hot flashes

AE: generally well tolerated

hepatotoxicity

Notes: Dietary supplement from herb (Actaea racemose)

Phytoestrogens

What drug:

Type: Non-HRT

MOA: Weakly bind E receptors

Indication: May ↓ hot flashes and vaginal dryness

Notes: Plant derived compounds w/ estrogenic and anti-estrogenic properties → isoflavones (soybeans), lignans (flaxseed), and coumestans (alfalfa sprouts)

Alendronate

Risedronate

Ibandronate*

Zoledronate

What drug:

Type: bisphosphonates

MOA: Inhibit osteoclast mediated bone resorption

Indication: 1st line for men and women for osteoporosis prevention and Tx

* = post-menopausal F only

AE: GI disturbances (e.g., difficulty swallowing, heartburn, esophageal ulceration)

Osteonecrosis of jaw, femur fracture

Calcitonin

What drug:

MOA: ↓ osteoclasts and prevents resorptive activity of bone

Indication: LAST LINE for F at least 5 years post-menopausal for which other Tx failed

AE: Nasal irritation

Teriparatide

Abaloparatide

What drug:

Type: PTH analogs

MOA: Synthetic recombinant human PTH; modulates Ca2+ homeostasis and stimulates osteoblast activity

Indication: 2nd line for M and F at very high fracture risk or failed bisphosphonates

AE: Nausea, muscle cramps, hypercalcemia, transient hypotension

Denosumab

What drug:

MOA: Monoclonal Ab that inhibits RANLK, thereby inhibiting formation, function, and survival of osteoclasts

Indication: 1st line therapy for post-menopausal F and M receiving androgen deprivation therapy for prostate cancer

AE: Back and MSK pain

Betamethasone*

Dexamethasone~

What drug:

Type: Ante-natal steroids

MOA: Accelerates development of type 1 and 2 pneumocytes

↑ surfactant production, induction of pulmonary β-receptors and fetal lung antioxidant enzymes, and upregulation of gene expression for ENaC

Improved lung mechanics, absorption of alveolar fluid, and gas exchange

↓ neonatal morbidity and mortality

Indication: Speed up lung development in pre-term fetus → ↓ risk respiratory distress syndrome

Off-label: ante-natal fetal maturation, 24-34 weeks where delivery anticipated within 7 days (may repeat if previous course given >14 days prior)

AE: Maternal: AMS, HTN, hyperglycemia

Fetal: hypoglycemia

Notes: * = 2 doses IM, 24h apart

~ = 4 doses IM, 12h apart

Benefits begin within 24h initiation

Terbutaline

What drug:

Type: Beta agonist

MOA: Activates β2

Myometrium relaxation via ↑ cAMP and ↓ MLCK

Indication: Off-label: pre-mature labor (1st line)

Asthma/bronchospasm

CI: Use cautiously in CV disease or DM

AE: Maternal: hypokalemia, tachyarrhythmias, hyperglycemia, HTN or paradoxical hypotension, CNS stimulation/ excitation

Fetal: tachycardia

BBW: Do not administer oral formulation

Notes: IV or SQ

Avoid prolonged use (>48h-72h)

Nifedipine

What drug:

Type: CCB

MOA: Dihydropyridine voltage gated Ca2+ channel blocker

↓ [intracellular Ca2+] → smooth m. relaxation

Indication: Off-label: tocolysis (1st line)

HTN, variant angina

CI: Avoid in CV disease, preload dependent conditions, hypotension

AE: Maternal: dizziness, flushing, hypotension

Notes: Oral IR for tocolysis

Magnesium Sulfate

What drug:

MOA: Inhibits Ca2+ channels → ↓ [intracellular Ca2+] → relax uterine smooth m.

Indication: Off-label: tocolytic → neuroprotection if birth <32 weeks to ↓ risk cerebral palsy

Pre-eclampsia/eclampsia, hypomagnesemia, constipation

CI: Myasthenia gravis

Avoid using >5-7 days due to ↓ Ca2+ and osteopenia and fractures in neonate

AE: Maternal: flushing, diaphoresis, SOB, depressed DTRs, cardiac arrest

Fetal: depression, dystonia, drowsiness, lower APGAR

DI: Nifedipine (hypotension)

Notes: IV admin

Indomethacin

What drug:

Type: NSAID

MOA: Inhibits COX → ↓ PGs

Prevents activation of uterine EP1 and FP receptors → myometrial relaxation

Indication: Off-label: tocolytic (1st line agent)

Acute pain, arthritic conditions, closure of PDA in neonates

CI: Do not use >32 weeks gestation

AE: Maternal: nausea, reflux, gastritis

Fetal: pre-mature constriction of ductus arteriosus, platelet inhibition, NEC, intracranial hemorrhage, renal dysfunction

DI: CAN be used concurrently with magnesium sulfate!

Notes: PO and rectal

Limit use 72 h

Penicillin G

Ampicillin

What drug:

Type: Beta-lactams

Indication: Prevention of GBS transmission to neonate

GBS bacteriuria

Previous birth to infant with invasive GBS

No PCN allergy

Notes: GBS screened between weeks 36-38 pregnancy via vaginal/rectal culture

If GBS screen not available, treat all pts with fever >100.4 F, membrane rupture >18h, or <37 weeks

If not at risk anaphylaxis: Cefazolin

If at risk anaphylaxis: Clindamycin or Erythromycin

Vanco if resistance

Oxytocin

What drug:

Type: Oxytocin receptor agonist

MOA: Activates oxytocin receptor

May stimulate local PG and leukotriene release

Contracts uterine smooth m. → ↑ frequency & force of contractions

Contracts myoepithelial cells surrounding mammary alveoli → milk ejection

Indication: Induce labor, post-partum hemorrhage

Bishop score >8

CI: Fetal distress, placenta previa, prolapsed umbilical cord, pelvic structure abnormalities, active herpes

AE: Bolus injections can cause hypotension

Uteroplacental hypoperfusion, fetal distress, placental abruption, uterine rupture, fluid retention, HF, seizures, hyponatremia

Notes: Labor induction: IV

Post-partum hemorrhage: IM or IV

t½ = ~5 min

Dinoprostone*

Misoprostol~

Carboprost^

What drug:

Type: PG analogs

MOA: Stimulates PGEP1 receptors → uterine contraction and softening

^ stimulates PGF2⍺ production

Indication: Cervical ripening (*, ~ off-label)

Post-partum hemorrhage (^, ~ off-label)

CI: Induction in women whom induction CI

~ = previous uterine scar due to risk of uterine rupture

^ = asthma, HTN, active hepatic/cardiac/pulm disease

AE: HA, n/v/d, abdominal pain, uterine hyperstimulation

Shivering, fever (~ & ^ when used for PPH)

Bronchospasm, HTN (^)

Notes:

* = PGE2 analog, admin endocervically and vaginally

~ = PGE1 analog, admin PO, vaginally, PR, and SL/PO

^ = PGF2⍺ analog, admin IM and intramyometrial

Fetal monitor for duration of use + 15 min following removal

Methylergonovine

What drug:

Type: Ergot alkaloid

MOA: Acts non-selectively as partial 5-HT2A agonist and ⍺1-adrenergic agonist → ↑ PLC, IP3, and Ca2+

Directly contracts uterine and vascular smooth m. (low dose = alternate periods of contraction and relaxation, high dose = powerful and prolonged contraction)

Indication: Prevention of hemorrhage

CI: Significant HTN, pre-eclampsia, CVD

AE: n/v/d, ↑ BP, flushing and chills

DI: Major CYP3A4 substrate

Notes: t½ = 0.5-2h

uterotonic effects seen within 10 min of PO admin and immediately with IV

IM, IV, and PO

Tranexamic acid

What drug:

Type: Anti-fibrinolytic

MOA: Forms a reversible complex which competitively inhibits plasminogen → inhibition of fibrinolysis

AE: Thromboembolic events, hypotension, visual defects, HA, abdominal pain, diarrhea, nasal stuffiness

Notes: IV or PO

1 dose within 3h delivery; repeat 2nd dose if bleeding continues after 30 min or stops and restarts within 24h

Reduces death from obstetric hemorrhage

Misoprostol

What drug:

Type: PG analog

MOA: Stimulates PGEP1 receptors → uterine contraction and softening

Indication: Monotherapy (less efficacy) for pregnancy termination

Dual therapy with mifepristone or methotrexate

AE: HA, n/v/d, cramping, bleeding

Notes: Vaginal or SL admin q3-12h x3 doses

Higher incidence AE, monotherapy has lower efficacy, readily available

Mifepristone

What drug:

Type: Steroid

MOA: Competitively binds and inhibits progesterone receptor activation → uterine contractions

Indication: Termination of pregnancy, terminal of tubal pregnancy, early pregnancy loss

AE: Bleeding, cramping, n/v/d, fatigue, dizziness, thermoregulatory

Notes: Takes orally on 1 day and misoprostol 24-48h later either PO, buccal, or vaginally

Alt: admin misoprostol <6 hrs after

↑ efficacy

Methotrexate

What drug:

Type: Folate antagonist

MOA: Competitively inhibits folate-dependent steps in nucleic acid synthesis (inhibits critical step in growth for rapidly dividing ectopic trophoblast)

Indication: Monotherapy for ectopic

Combined with misoprostol as abortifactant

AE: Same as mifepristone with misoprostol

Notes: IM or vaginal (allows separation of placenta from endometrium) followed by vaginal misoprostol (causes uterine contractions to pass uterine contents) 3-7 days later

Clomiphene

What drug:

Type: SERM

MOA: Selective ER modulator → competitively binds to ER as an antagonist → stimulates release of GnRH → ↑ FSH & LH → ovulation

Indication: Group 2, Ovulation induction (6 cycle limit)

Off-label: male hypogonadism, clomiphene test

CI: Current or Hx of liver disease, Ovarian cyst (not PCOS), AUB, Uncontrolled thyroid or adrenal dysfunction, endometrial carcinoma

Pregnancy

AE: Anti-Estrogen: mood swings, hot flashes, nausea, breast discomfort

Multiple pregnancy

Serious: visual disturbances, ovarian enlargement, OHSS (rare)

Notes: Resistance can occur (e.g., pts remain anovulatory) likely due to anti-E effects of ↓ endometrial thickness and ↓ cervical mucous production (↓ implantation and sperm penetration)

t1/2 = 5-7 days

Admin 50-150 mg PO on days 3-7 of cycle x 5 days

Tamoxifen

What drug:

Type: SERM

MOA: Selective ER modulator (SERM) → competitively binds ER on tumors and other tissue targets (antagonist on HPO axis)

Indication: Approved for various breast cancers

Off-label: induction of ovulation in breast cancer pts

CI: Pregnancy (cat D)

AE: Vasodilation, flushing, mood changes, edema

BBW: ↑ risk of uterine malignancies, thromboembolism

Notes: Similar ovulation & pregnancy rates compared to clomiphene

Letrozole

Anastrozole

Exemestane

What drug:

Type: Aromatase inhibitors

MOA: Inhibits aromatase → ↓ E synthesis

↓ negative feedback → ↑ GnRH, FSH, and LH

May also modestly ↑ androgen levels → ↑ follicular sensitivity to FSH stimulation

Indication: FDA approved for breast cancer

Off-label: ovulation induction in PCOS (1st line), may use in anovulatory disorders after failure of multiple clomiphene Tx or if intolerant to clomiphene

CI: Pregnancy

AE: Sweating, flushing, GI (n/v), HA, dizziness, and fatigue

Notes: Admin: 2.5-7.5 mg/day PO x5 days

More effective than clomiphene for F w/ PCOS

↓ risk multiple pregnancies

Useful in clomiphene resistance

Metformin

What drug:

Type: Biguanide

MOA: ↓ hepatic glucose production and enhanced insulin sensitivity → ↓ androgen levels → ↓ negative feedback & ↑ FSH/LH → ovulation

Indication: T2DM

Use in PCOS to treat insulin insensitivity regardless of trying to conceive or not → used in conjunction w/ clomiphene or aromatase inhibitor to help ovulation

Notes: ↑ menstrual cyclicity, improves spontaneous ovulation, does NOT improve birth rates when given alone or in combo with clomiphene

Urofollitropin

Follitropin alfa/beta*

What drug:

Type: Follitropin (FSH)

MOA: Mimics actions of FSH → stimulates follicular growth and maturation & stimulates spermatogenesis in M

Indication: Ovulation induction in anovulatory F

Hypogonadotropic hypogonadism in M*

Assisted reproductive technology (ART) for multi-follicular development

CI: Pregnancy

Abnormal vaginal bleeding, ovarian cysts (not due to PCOS)

AE: HA, muscle aches, fatigue, nausea, depression, breast tenderness/swelling

Multiple pregnancy, OHSS

Notes: * = recombinant, admin IM or SQ, shorter t½

Admin day 2-3 of cycle for up to 14 days or until adequate follicular response

Menopur

What drug:

Type: Human menopausal gonadotropin (hMG)

MOA: Stimulates follicular growth and maturation

Stimulates spermatogenesis

Indication: Ovulation induction, ART for multi-follicular development

Off-label: spermatogenesis

CI: Primary ovarian failure (high FSH), uncontrolled non-gonadal endocrinopathies (thyroid, adrenal, pituitary), pituitary or hypothalamic tumors, unknown AUB, ovarian cyst or enlargement (not PCOS), pregnancy

AE: Multiple pregnancy, OHSS

Notes: Combo of highly purified FSH And LH (menotropins) from urine from post-menopausal F

Urinary hCG

Choriogonadotropin

What drug:

Type: hCG

MOA: LH receptor agonist → stimulates ovulation by mimicking LH surge

Stimulates production of gonadal steroid hormones by causing production of androgen in testes

Indication: Hypogonadotropic hypogonadism (M)

Ovulation induction following last dose of menotropin

CI: Primary ovarian failure, uncontrolled thyroid or adrenal dysfunction, uncontrolled organic intracranial lesion, AUB, ovarian cyst or enlargement of undetermined origin, sex hormone dependent tumors

Pregnancy

AE: OHSS, thromboembolism

Mood changes, injection site rxns

BBW: Do not use for weight loss

Notes: IM admin for hypogonadism 3x weekly OR dose once after follicular maturation for ovulation induction

Bromocriptine

What drug:

Type: Non-selective dopamine agonist

MOA: Activates dopamine receptor → inhibit prolactin secretion

Indication: Fertility (hyperprolactinemia induced, in vitro fertilization protocols)

Hyperprolactinemia

AE: Lightheadedness, HA, dizziness, nervousness and fatigue

Nausea, abdominal pain, diarrhea

Notes: t½ = 6-20h

Cabergoline

What drug:

Type: Selective dopamine agonist

MOA: Activates dopamine receptor → inhibit prolactin secretion

Indication: Hyperprolactinemia

AE: Lightheadedness, HA, dizziness, nervousness and fatigue

Nausea, abdominal pain, diarrhea

Notes: Long-acting (65h), dosed twice weekly

Leuprolide

Goserelin

Nafarelin

Buserlin

What drug:

Type: GnRH agonists

MOA: GnRH agonists

GnRH receptor agonist → binds to GnRH receptor w/ initial ↑/surge in FSH/LH levels → transient ↑ in E w/ negative feedback to inhibit GnRH secretion

Indication: Precocious puberty, anemia, endometriosis, prostate cancer, breast cancer, others

Off-label: ovarian hyperstimulation to prevent endogenous GnRH release (prevents premature LH surge) → often used as a part of conventional “long” protocol for IVF initiated during luteal phase of previous cycle to inhibit LH/FSH

CI: Pregnancy, lactation

AE: Hot flashes, HA, mood wings, insomnia, vaginal dryness

Notes: Admin SQ or intranasally

Disadvantage v. GnRH antagonist – longer duration of Tx and ↑ risk ovarian cyst due to FSH and LH flare

Cetrorelix

Ganirelix

What drug:

Type: GnRH antagonists

MOA: Competitively blocks GnRH R on pituitary gland to inhibit endogenous GnRH release → prevents premature LH surge and ovulation during ovarian hyperstimulation to suppress ovulation until eggs mature

Indication: Adjunct to controlled ovarian hyperstimulation → short protocol for IVF

CI: Pregnancy

AE: OHSS, anaphylaxis (rare)

Notes: Admin SC daily

Advantage of GnRH agonists – faster onset of action (<48h) and shorter duration of therapy

Disadvantage = slightly lower rate of pregnancy with IVF

Progesterone

What drug:

MOA: Transforms proliferative endometrium into secretory endometrium

Suppresses secretion of gonadotropins

Prevents menstruation and uterine contractility

Supports luteal phase and embryo implantation (augments what is produced by corpus luteum)

Indication: Amenorrhea, endometrial hyperplasia prevention, uterine bleeding, female infertility adjunct in ART (initiated 1-3 days after oocyte retrieval and continued for 10-12 weeks)

AE: GI disturbances, psychiatric disturbances, breast tenderness

Caution: thromboembolic disorders

Notes: IVF – IM, vaginal (gel 1-2x daily or insert 2-3x daily)

Replacement = PO

Estrogen

What drug:

AE: Abnormal bleeding, nausea (take w/ food or at night), breast tenderness/fullness, bloating/weight gain, ↑ BP, ↑ TGs, migraine, hyperpigmentation (melasma, chloasma)

Rare: thrombogenic disorders (e.g., stroke, MI, DVT/PE)

- RFs = >35, smoking, DM, HTN, prolonged bed rest, overweight

**dose dependent** → low dose = better tolerated

Notes:

Estradiol = major ovarian E (PO, transdermal patch, vaginal cream, IM)

Estradiol cypionate = long-acting ester of estradiol (IM)

Premarin = mixture of conjugated E from biologic sources (e.g., mare urine – PO)

Ethinyl estradiol & mestranol = synthetic, main E used in combined OCPs

Hydroxyprogesterone

Medroxyprogesterone

Megestrol

Dimethisterone

Desogestrel^

Desonorgestrel^

Dienogest

Norgestimate^

Norethynodrel

Lynestrenol

Norethindrone*^

Ethynodiol

Norgestrel^

Levonorgestrel

Drospirenone*^

What drug:

Type: Progesterone

Indication:

HRT: progesterone, medroxyprogesterone acetate (MPA)

Progestin only pill: Norethindrone or Drospirenone

Medroxyprogesterone: q3 mos depot IM

Levonorgestrel: IUD

CI: Drospirenone: adrenal insufficiency

AE: Common: altered bleeding pattern, breast tenderness, weight gain, acne/oily skin/hirsutism, HA/fatigue, mood changes (depression), may ↑ LDL + ↓ HDL

Injectable depot medroxyprogesterone acetate (MPA): ↓ bone mineral density (ensure adequate Ca2+ and VitD, risk ↑ with >2 yrs of use)

Drospirenone (in combined OCPs): hyperkalemia, ↑ clot risk (VTE, PE – avoid in pts w/ ↑ risk)

Notes: Synthetic have different affinities and abilities to bind to P, E, and androgen receptors

^ = common in combined OCPs

* = available as P only

Drospirenone

What drug:

Type: 4th gen P

MOA: PR agonist → ↓ FSH and LH (anti-gonadotropic)

AR antagonist → ↓ T

MR antagonist → ↓ mineralocorticoids

Indication: In addition to birth control: ↓ hormone-related acne due to anti-androgen activity, ↓ pre-menstrual dysphoric disorder (PMDD) Sx, ↓ epithelial DNA synthesis in endometrial tissue

CI: Renal + hepatic impairment, liver tumors, cervical cancer, or progestin-sensitive cancers, adrenal insufficiency

AE: hyperkalemia

DI: ACEIs, ARBs, K+ sparing diuretic, K+ supplements

Combined OCPs

What drug:

Type: E and P

MOA: Ovulation prevented by: suppression of FSH-LH sequence from AP → ovulation suppression, alteration of endometrium, and production of mucus less acceptable to sperm

- E: suppress FSH and inhibits maturation of dominant follicle

- P: suppress LH surge → inhibits endometrial proliferation and thickens cervical mucus

Indication: Contraception

Also: acne in F, dysmenorrhea, anemia due to excessive menstrual loss, peri-menopausal Sx (hot flashes, night sweats), pre-menstrual syndrome (PMS), pre-menstrual migraine (w/o aura) prophylaxis, menstruation regulation

AE: Common: HA, n/v/d, dysmenorrhea, withdrawal bleeding, breast tenderness

Serious: thromboembolic disease, MI, CVA, HTN, cholecystitis, pancreatitis, ulceration of esophagus, hepatic adenomas (high doses), hormone-sensitive cancer

Combined OCPs

What drug:

CI: Pregnancy (↑ risk birth defects)

DVT/PE, CVA/CAD/IHD, DM with vascular disease, BP >160/>100 mmHg, migraine with aura, >35 & heavy smoker (>15 cigarettes daily) + migraines w/o aura, inherited hypercoagulable conditions, liver tumors, hormone dependent cancers, decompensated cirrhosis, acute or flare of viral hepatitis, SLE, <21 days post-partum, solid organ transplant, premenarchal children/teens

DI: CYP3A4 inducers → Barbs, phenytoin, carbamazepine, topiramate, corticosteroids, griseofulvin, pioglitazone, modafinil, armodafinil, rifampin, rifabutin

CI with: HIV/hepatitis C protease inhibitor (may ↑ chances of liver injury), TXA (↑ risk VTE)

Interacts with: ulipristal, tizanidine, Sugammadex, valproic acid (↑ risk seizures), prednisone (↓ efficacy of oral OCP + ↑ ADRs of prednisone), rifampin

Norethindrone

Norgestrel

Desogestrel

Drospirenone

What drug:

Type: P only pills

MOA: Thickens mucus in cervix and stops ovulation

Indication: Contraception in women who cannot take or risk > benefit of an E containing drug

CI: Known or suspected pregnancy

breast cancer (past/present), undiagnosed AUB, benign or malignant, liver tumors, acute liver disease, hypersensitivity

AE: Spotty skin and breast tenderness (clear up within a few mos)

Notes: May not have regular periods while taking (may be lighter, more frequent, or may stop completely, may have intermenstrual spotting)

Adherence is required – must take at same time DAILY with NO BREAKS: >3h (12h for Desogestrel) missed pill and opportunity for pregnancy; use backup method for 48 hrs

40% ovulate while taking → ↑ risk ectopic pregnancy

Ethinyl estradiol + norelgestromin

Ethinyl estradiol + levonorgestrel

What drug:

Type: Transdermal patch (E + P)

MOA: ovulation prevented

Indication: NOT first line for female >90 kg

CI: same as combined OCPs

AE: Common: skin rxns, mood swings, otherwise similar to OCPs

Serious: same as OCPs

BBW: No smoking >35 due to risk of serious CV ADRs, avoid if at ↑ risk of blood clots, avoid if >30 kg/m2 due to ↑ risk blood clots

DI: Similar drug interactions as OCPs

Notes: 1 patch q week for 3 weeks; week 4 patch free

Rotate application sites; apply to clean dry skin

Do not cut or damage patch, check daily, avoid heat sources on or near patch

If falls off:

- <24h = replace same or new patch

- >24 but <48 = use back up method x1 week

- >48 = start new 4 week cycle

Etonogestrel

What drug:

Type: Implant (P only – LARC)

MOA: Progestin suppresses ovulation and thickens cervical mucus

CI: Same as progestin-only pills

AE: Complication of insertion may arise, migration of implant, infection

Common: pharyngitis, implant site rxn, otherwise similar to progestin-only pills

Serious: similar to progestin-only, mainly CVD or TE

Notes: Inserted subdermally in medial, proximal portion of non-dominant arm → replace no later than 3 yrs

Easily reversible

Medroxyprogesterone acetate (MPA)

What drug:

Type: Injection (P)

MOA: Suppresses ovulation up to 14 weeks

AE: Common: injection site rxn, weight gain, amenorrhea, similar to other progestin only

Serious: anaphylaxis, ↓ bone mineral density, fracture of bones with prolonged use

Notes: Q3 mos

If initiated days 1-7 menstrual cycle w/o prior hormonal contraception, no back up method needed (otherwise back up method x7d)

Ca2+, VitD, and weight bearing exercise can help ↓ effects on BMD

Ethinyl estradiol

Etonogestrel

What drug:

Type: Intravaginal ring

MOA: Provides continuous (steady) delivery

CI: Same as other E/P containing drugs

AE: Common: mood disorder, vaginitis, vaginal discharge

Serious: vaginal ulcer, impaired fasting glucose, otherwise similar to other contraception

Most common reasons for d/c = foreign body sensation, device expulsion, vaginal Sx

BBW: >35 should not smoke

Notes: Start: insert new ring on 1st day of menstrual period but can be started anytime during cycle (may result in menstrual irregularities for first few mos) → use back up method for 7 days if no or other contraception used in last month

Keep in for 3 weeks and remove for 4th week

If ring falls out/expelled → rinse with cold or lukewarm water and re-insert. If out >3 hrs → backup method 7 days

Segesterone acetate + ethinyl estradiol

What drug:

Type: Yearly intravaginal ring

CI: Same as other E/P containing drugs

AE: HA, n/v, dysmenorrhea, abdominal pain, vulvovaginal candidiasis, vaginal discharge

Notes: Inserted q3 weeks, removed 1 week → wash with mild soap and lukewarm water, dry, and store in case until next insertion

If ring falls out or expelled → rinse with cold or lukewarm water and re-insert. If out for >2 hrs, use back up method 7 days

Copper IUD

What drug:

MOA: Cu inhibits sperm motility; sterile inflammatory rxn in endometrium leads to phagocytosis of the sperm

Prevents endometrial receptivity

Indication: Emergency contraception (most effective EC in preventing pregnancy) → insert within 5 days after unprotected sexual intercourse

CI: Known or suspected pregnancy, current STI or PID (until treated), uterine/cervical cancer

AUB w/ unknown etiology, abnormal uterine anatomy, copper allergy, Wilson’s disease

AE: Heavy bleeding and cramping can occur in the first 3-6 mos following insertion

Notes: Can be placed immediately post-partum (best if epidural is left in place during procedure, rates of expulsion may be higher)

Periods remain regular, no hormones, 10-12 yrs

↑ menstrual blood loss & dysmenorrhea, no STI protection

Levonorgestrel IUD

What drug:

Type: P only

CI: Active liver disease, uterine abnormality (structural, functional, infectious, bleeding of unknown etiology), current history of cancer

Notes: Can use for nulliparous, nulligravid, or multiparous

Paracervical block for insertion may be used for nulliparous/nulligravid women

May ↓ blood loss up to 70% at one year, amenorrhea in some, very little maintenance

Higher # bleeding days/spotting in 1st 3-6 mos, no STI protection, may cause ovarian cysts but most regress spontaneously, brief discomfort upon insertion/removal

Ulipristal acetate

What drug:

Type: Emergency Contraception

MOA: Depends on timing of administration in relation to pt menstrual cycle – primarily delays ovulation

Indication: Use as soon as possible, within 5 days of unprotected sexual intercourse

CI: Breastfeeding pt

Notes: Selective progesterone receptor modulator with mixed progesterone agonist and antagonist properties → single dose (30 mg) Rx only

More effective than LNG oral in obesity

Use barrier method for intercourse that occurs in same menstrual period this agent is taken; it affects PR and may interfere with ongoing hormonal contraception

Levonorgestrel

What drug:

Type: Emergency Contraception

Indication: Use as soon as possible, within 3 days (72h)

Less effective in obesity

Notes: Next most effective EC pill after ulipristal

Single dose (1.5 mg) or split does (0.75 mg q12h x2)

Combined E and P

What drug:

Type: Emergency Contraception

AE: Least effective, more frequent occurrence of side effects (n/v)

Menstrual irregularities may occur → pregnancy test if no menses in 3 weeks

Notes: 1 dose of 0.1 mg of ethinyl estradiol + 0.5mg of levonorgestrel followed by 2nd dose of same 12 hrs later

Bremelanotide

What drug:

MOA: Nonselective agonist to melanocortin receptors (MC1R and MC4R specifically)

Indication: Hypoactive sexual desire disorder (HSDD) in pre-menopausal women

CI: Uncontrolled HTN or known CVD

Not recommended for pregnant or breastfeeding women

AE:

Common: nausea, flushing, injection site rxn

Serious: bradycardia, transient HTN, hyperpigmentation of skin

DI: May ↓ serum concentration of naltrexone (Tx failure)

May delay gastric emptying → affecting the F oral meds

Notes: 1.75 mg SQ injection into abdomen or thigh as needed, at least 45 min before anticipated sexual activity

Limit to 1 dose in 24h; 8 doses per month due to development of HTN

d/c use if no improvement in Sx after 8 weeks

PK: caution in eGFR <30 and severe hepatic impairment

Flibanserin

What drug:

MOA: Mixed 5-HT1A agonist, 5-HT2A antagonist, ↓ norepinephrine and dopamine

Indication: Hypoactive sexual desire disorder (HSDD) in pre-menopausal women

CI: Avoid activities requiring mental alertness or coordination for 6 hrs after dose

AE: Common: dizziness, somnolence, nausea, fatigue

Serious: hypotension, syncope, CNS depression

BBW: Alcohol use → interaction (REMS program), wait >2 hrs after drinking 1-2 standard alcoholic drinks before taking drug; if >3 drinks consumed, skip the dose

Moderate or strong CYP3A4i; hepatic impairment → ↑ concentration causing severe hypotension and syncope

DI: 3A4 inhibitors, CNS depressants

Notes: 100mg QHS

Calcitonin

What is considered LAST LINE for F at least 5 years post-menopausal for which other Tx failed?

Teriparatide

Abaloparatide

What is considered 2nd line for M and F at very high fracture risk or failed bisphosphonates?

Denosumab

What is considered 1st line therapy for post-menopausal F and M receiving androgen deprivation therapy for prostate cancer?

Terbutaline

What is considered 1st line for pre-mature labor?

Nifedipine, Indomethacin

What is considered 1st line for tocolysis?

Penicillin G

Ampicillin

what is considered 1st line for prevention of GBS?

Cefazolin

what is considered 1st line for prevention of GBS in pt with penicillin allergy that is NOT at risk for anaphylaxis?

Clindamycin

Erythromycin

what is considered 1st line for prevention of GBS in pt with penicillin allergy that is at risk for anaphylaxis?

Vancomycin

what is considered 1st line for prevention of GBS in pt that is highly resistant to usual treatment metods?

Letrozole

Anastrozole

Exemestane

What is considered 1st line for ovulation induction in PCOS?

Estrogen

What drug BBW:

-Unopposed use → ↑ endometrial cancer risk (monitor for abnormal vaginal bleeding)

-AVOID use for prevention of CVD or dementia

-↑ risks of MI, stroke, invasive breast cancer, PE, and DVT in post-menopausal F (50-79)

-↑ risk of dementia in post-menopausal women (65+)

-w/ or w/o P, prescribe @ lowest dose and for shortest duration consistent with Tx goals for specific pts

Bazedoxifene

What drug BBW:

-DO NOT take additional E

-↑ risk endometrial cancer in F w/ uterus using unopposed E

-Avoid E therapy for prevention of CVD or dementia

-↑ risk of CV disorders (DVT, PE, MI, or stroke)

-↑ risk of probably dementia in post-menopausal F > 65

-Should be prescribed at lowest effective dose & for shortest duration consistent w/ Tx goals for individual F!!!!!!

Ospemifene

What drug BBW:

-↑ risk endometrial cancer if intact uterus and use unopposed E (add P)

-↑ risk CV disorders (DVT, PE, MI, stroke)

Prasterone

What drug BBW:

-E is metabolite, use of exogenous E CI in F w/ known or suspected Hx breast cancer

Paroxetine

What drug BBW:

-Suicidal thoughts and behavior

Terbutaline

What drug BBW:

-Do not admin oral formula

Tamoxifen

What drug BBW:

-↑ risk of uterine malignancies, thromboembolism

Urinary hCG

Choriogonadotropin

What drug BBW:

-Not for use as weight loss

Ethinyl estradiol + norelgestromin

Ethinyl estradiol + levonorgestrel

What drug BBW:

-No smoking >35 due to risk of serious CV ADRs, avoid if at ↑ risk of blood clots, avoid if >30 kg/m2 due to ↑ risk blood clots

Ethinyl estradiol

Etonogestrel

Segesterone acetate + ethinyl estradiol

What drug BBW:

->35 should not smoke

Flibanserin

What drug BBW:

-Alcohol use → interaction (REMS program), wait >2 hrs after drinking 1-2 standard alcoholic drinks before taking drug; if >3 drinks consumed, skip the dose

-Moderate or strong CYP3A4i; hepatic impairment → ↑ concentration causing severe hypotension and syncope

Testosterone

What drug:

CI: breast or prostate cancer, BPH, pregnancy

BBW: BP increases with oral T undecanoate and subq T enanthate

Warnings/Precautions: in HF can cause fluid retention (avoid in poorly controlled HF), in CV risk recommended to avoid in men who have experienced MI/stroke within 6 mos, may potentiate sleep apnea

AEs: sodium retention (edema, weight gain), acne, gynecomastia, hair loss/balding, infertility (azoospermia + dec. testicular size), worsened sleep apnea, elevated BP, dec. total cholesterol and HDL, hepatotoxicity (PO), polycythemia (parenteral), site rxns (topical)

DIs: warfarin, paclitaxel (inc. toxicity), bupropion

non-hormonal vaginal lubricants and moisturizers (e.g., KYjelly/astroglide, replens)

What is considered 1st line for vaginal Sx of menopause?

bisphosphonates

What is considered 1st line therapy for osteoporosis Tx and prophylaxis in men and women?

Ibandronate

What is considered 1st line therapy for osteoporosis Tx and prophylaxis in post-menopausal women only?

Denosumab

What is considered 1st line therapy for osteoporosis Tx in postmenopausal women and men receiving androgen deprivation therapy (ADT) for prostate cancer?

Teriparatide

What is considered 2nd line for osteoporosis Tx in men and women at very high fracture risk or bisphosphonate therapy has failed?

Raloxifene

What is considered 2nd line for osteoporosis Tx and prevention for men and women (general)?

Hint: SERM

Conjugated estrogens/bazedoxifene

What is considered 2nd line for osteoporosis prevention only for men and women (general)?

Hint: SERM

Calcitonin

What is considered last line in osteoporosis Tx?

Hint: treatment in women who are at least 5 years postmenopausal when alternative treatments are not suitable

teratogenic

Drugs widely accepted as _______ include:

-ACE inhibitors/ARBs: renal toxicity to fetus

-Androgens: Muscularization to female fetus

-Ethanol: Fetal alcohol syndrome

-Folate antagonists (methotrexate): spontaneous abortion, skull anomalies, facial dysmorphism, CNS, limb and cardiac abnormalities

-Isotretinoin (retinoids): CNS, face, ear malformations

-Misoprostol: birth defects, abortion, premature birth, or uterine rupture

-Statins: CNS and cardiac malformations

-Thalidomide: limb malformations, others

-Antiepileptics: NTDs, cleft palate

Warfarin: dependent upon trimester

decrease

Drugs that (increase/decrease) milk supply include:

-androgens

-bromocriptine

-ergot derivatives

-levodopa

-nicotine

-sympathomimetics

-sedating anti-histamines

-E containing birth control

a.

Drugs that (increase/decrease) milk supply include:

-anti-psychotics

-metoclopramide

-fenugreek

-methyldopa

-cimetidine

a. increase

b. decrease

pregnancy

Common types of meds to avoid during ___________ include:

-Analgesics = NSAIDs (esp. 1st trimester, 3rd trimester), opiates

-Antacids = avoid Mg-containing in 3rd trimester

-Abx = tetracyclines, fluoroquinolones, aminoglycosides?

-Anti-coagulants = warfarin

small, frequent meals; EtOH/tobacco avoidance; avoid eating before bed

What non-pharm Tx can be used for heartburn in pregnancy?

drink plenty of fluids, include more fiber in diet, physical activity

What non-pharm Tx can be used for constipation in pregnancy?

small/frequent/bland meals, acupressure, hypnosis, ginger, treat GERD

What non-pharm Tx can be used for n/v in pregnancy?

antacids (calcium carbonate but Al, Mg sucralfate are ok)

What is the preferred Tx for heartburn in pregnancy?

stool softeners (docusate sodium) and laxatives (psyllium, bisacodyl, lactulose, Mg citrate)

What is the preferred Tx for constipation in pregnancy?

vitamines + anti-histamines, phenothiazines, B6 (pyridoxine) + doxylamine, meclizine, promethazine

What is the preferred Tx for n/v in pregnancy?