Pharm Flashcards
Names & Indications of estrogen
-estrols (Hexestrol & Diethylstibestrol)
Cancer therapy
HRT
Contraception
What are we trying to alter in estrogen therapy?
The estrogen response-the creation of proteins
Which pharmolocolgic agent is described as “flat and hydrophobic”?
Estrogen
Which estrogen receptor gene has a more specialized role and why?
Estrogen Receptor Gene-B: dominates in the lung and has limited tissue expression.
List the SERM corepressors
Raloxifene
Tamoxifen
Fulvestrant
What are the indications for SERMs?
They inhibit the estrogenic effects of breast cancer while maintaining bone mass.
Used in cancer therapy, HRT, and contraception
What are antihormones that inhibit activity by reducing P160 coactivator binding to estrogen receptor surfaces?
SERMs
Antagonists in breast, uterus, & CNS
Agonist in bone (bone sparing)
Unknown in liver
Raloxifeine - SERM
Antagonist in breast & CNS
Partial antagonist in uterus & liver
Agonist in bone
Tamoxifen - SERM
Largest “extra” structure of all anti-estrogens.
So large it degrades the protein
Fulvestrant - SERM
Compounds that can have estrogenic activity by binding the ER, but made in plants
Phytoestrogens
Give examples of phytoestrogens
Isoflavinoid: Soy beans, can relieve menopausal symptoms
Lignnas: High fiber foods
Coumestans: various beans. Alfalfa and clover sprouts are highest.
What are used as HRT?
Conjugated Estrogens (Premarin/Equine/Ethyinyl Estradiol)
Estradiols (Estrace and Estraderm)
Duavee
This addresses long-term issues of aging that result from loss of estrogen after menopause
HRT
Relief of menopausal symptoms is clear, but longer term benefits harder to prove
HRT
Oral Conjugated Estrogens
Premarin
Tablet/cream form of estrogen
Estrace
Dermal patch form of estrogen
Estraderm
HRT that combines SERM + E2 for those worried about endometrial cancer
Duavee
What’s the rule in dosing regarding HRT?
Use low does that works for a few years (CV benefit is greater in younger women closer to 5-7years post-menopause)
List the aromatase inhibitors
Anastorozole
Letrozole
Exemestane
In what population should aromatase inhibitors be used?
Only use in post menopausal women
MOA of aromatase inhibitors
Aromatase tissue is active in the breast, so we prevent androgens from turning into estrogens which cause growth of breast cancer
Describe the differences between the aromatase inhibitors
Anastorozole and Letrozole are competitive inhibitors (substrates) that bind to androgen.
Exemestane is a suicide substrate
List the bisphosphonates
Biphoshonates:
- Alendronate (least potent)
- Risendronate
- Ibandronate
- Zolendronic Acid (most potent)”
What’s the first line treatment of osteoporosis?
bisphosphonates
MOA of bisphosphonates
Inhibit farnesyl pyrophosphate synthase –> osteoclasts apoptose –> bone breakdown decreases
As osteoclasts die off, the messages they normally send to osteoblasts are reduced –> less osteoblast activity (which is why drug holidays are needed)
What drugs decrease vertebral and non-vertebral fx?
Bisphosphonates
Which drugs require a drug holiday and why?
Bisphosphonates - Needed to allow osteoblast activity to reset
Monitor bone mineral density and turnover markers during holiday
Re-initiate therapy if density declines or markers increase
AEs of bisphosphonates
Esophagitis (with oral forms)
Avascular necrosis/osteonecrosis of jaw
Atypical fragility fractures and delayed healing
Contraindicated in eGFR <30-35%”
Which drug is approved for women receiving aromatase inhibitors and men receiving hormone ablation for prostate cancer
Denosumab
MOA of denosumab
Humanized monoclonal antibody to RANKL put out by osteoblasts
Prevent formation of active osteoclasts and inhibit bone resorption
Does not absorb into bone matrix
Bone turnover is not suppressed after its cessation”
Things to keep in mind regarding denosumab
Shorter HL than Biphosphontes
Stopping therapy can lead to high risk of multiple vertebral fractures
Do NOT d/c without considering replacement with another anti-resorptive tx
AE of denosumab
Atypical fragility fractures
AVN of jaw
Increased risk of infections (cellulitis, endocarditis)
Suppression of bone turnover (delayed fx healing)
Contraindications of denosumab
Current hypocalcemia
Pregnancy
Hypersensitivy
Indication of teriparatide
Moderate to severe osteoporosis (ex: from GC use)
MOA of teriparatide
It’s a PTH analog.
- Increases bone formation by the same mechanism as low levels of PTH.
- Stimulates osteoclasts to release Ca2+ from bone and increase Ca2+ reabsorption from the gut and kidney.
- Low levels are anabolic and stimulate collagen synthesis
Which osteoporosis drug is administered SC
Teriparatide
AEs of teriparatide
Mild hypercalcemia
Nausea, HA, dizziness, muscle cramps
Do NOT give >2yrs
Do not use with bisphosphonates
Contraindications of teriparatide
Hypercalcemia
Multiple myeloma, bone metastasis, skeletal tumor
Children/teens with growing bones
In which tissue does Estrogen Receptor Gene A dominate?
Reproductive tissue and the liver
MOA of SERM coactivators
dimerize E2 –> less E2 affinity for DNA
–> increase transcription –> DNA relaxation
MOA of SERM corepressors
tighten up DNA and suppress gene expression
Which SERM is used for breast cancer treatment?
Tamoxifen
Which SERM is used for bone retention?
Raloxifene
Why does breast cancer best respond to this SERM drug?
Tamoxifen - due to its action on both the Estrogen-Receptor and Progesterone-Receptor
AE of Tamoxifen
- Increase in endometrial cancer in postmenopausal women
- Thromboembolic events
- Cataracts
AE of aromatase inhibitors
Osteoporosis
Indication of Trastuzumab
Breast cancer
MOA of Trastuzumab
-Acts on protein made by Her2/neu
AE of Trastuzumab
- Heart failure (cardiotoxicity)
- Respiratory problems
- Serious allergic rx
MOA of progestin
- Thins endometrium: can lead to atrophy
- Thickens cervical mucus
- Decreases tubal motility
- Several generations with varying androgen effects and bioavailability
MOA of ethinyl estradiol
- Suppress ovulation: along with progestin, negative feedback to hypothalamus and pituitary to decreased FSH/LH production
- Estrogen suppression of FSH stops folliculogenesis
- Cycle control: stabilizes endometrium
Advantages of COC
- Rapid reversibility
- Decreased ovarian and endometrial cancer risk
- Improved acne and hirsutism
- Improved dysmenorrhea and AUB
- Reduced symptoms of endometriosis
Disadvantages of COC
- Increased hypercoagulability: VTE (greatest risk in 1st year of use)
- MI, stroke: MINIMAL increased risks in adolescents/young adults
Contraindications of COC
- Smokers >35yo should discontinue OCPs
- Hx of heart disease, HTN, VTE, stroke, breast cancer, migraines with aura
Hormone in POP
Norethindrone (a progesterone)
POP indication
Use in women in whom estrogen-containing pills are contraindicated
Advantages of POP
- Safety: lower dose of hormone - greater safety than COC
- Few contraindications: estrogen-free
Disadvantages of POP
- Decreased efficacy compared to COC
- Menstrual cycle disturbances!!!
- Strict compliance necessary: use back up method of contraception (condom) for 2 days if >3hrs late taking pill.
- Increased rates of functional ovarian cysts
Hormone(s) in the transdermal contraceptive patch
Estrogen and Progestin
Which contraceptives only contain progestin?
- POP
- Depo
- Implantables (Nexplanon, IUDs - except ParaGard)
- Plan B - Levonorgestrel
Advantages of the transdermal contraceptive patch
- Increased compliance: 1 patch/week with 1 patch free week
- Forgiving: 3 day error with decreased follicular size vs. pill
- Does not cause weight gain
- Good cycle control
- Verifiable
Disadvantages of the transdermal contraceptive patch
- Possible increased risk of VTE (debatable)
- Skin reactions: in up to 50%
- Breast tenderness, headache, nausea
- Less effective in those over 90 kg
Which hormones does the Nuvaring contain?
Ethinyl estradiol and etonogestrel
Advantages of the Nuvaring
- Inhibits ovulation for at least 35 days
- Increased bioavailability through vaginal absorption, allows lower dose
- Low, steady release of hormone
- Does not cause weight gain
- No effect on bone density
Disadvantages of the Nuvaring
- Risks similar to OCPs
- Headache: most common side effect
- Vaginal symptoms: most common reason for discontinuation
- Leukorrhea
- Foreign body sensation
- Expulsion
- Comfort with insertion/removal
Which hormones does the Depo injection contain?
Medroxyprogesterone acetate
MOA of the Depo
Inhibits ovulation: eliminates LH surge
Advantages of the Depo
- *-Estrogen-free**
- Lasts 3 months
- Effective in obesity
- Decreased/absent menses
- Minimal drug interactions
- Can reduce frequency of grand mal seizures and pain associated with endometriosis
Disadvantages of the Depo
- Menstrual cycle disturbances
- *-Weight gain**
- *-Decreased bone density (BBW)**
- Depression (conflicting data)
- Delayed fertility, continued side effects after discontinuation
- Frequent visits to health care provider
Which hormones does the Nexplanon contain
Etonogestrel
Progestin only
Advantages of the Nexplanon
- Highly effective
- Lasts 3 years
- Discreet
- Decreased dysmenorrhea
- Quick return to fertility
Which hormone do the hormonal IUDs contain?
Levonorgestrel
Progestin only
MOA of hormonal IUDs
Inhibits sperm capacitation and survival
Which IUD works up to 7 years?
Mirena & Lilleta
Which IUD works up to 5 years?
Kyleena
Which IUD works up to 3 years?
Skyla
Which IUDs lead to lighter and less frequent menses?
Mirena and Lilleta
What is the most effective emergency contraceptive?
Copper IUD
It must be inserted 5-7 days post unprotected sex
How long after sex can someone use Levonorgestrel as emergency contraception?
Ideally within 72hrs post-intercourse but can be effective up to 5 days (120hrs)
Which contraceptive is a progesterone blocker?
Ulipristal Acetate (Ella)
Other than the copper IUD, what is more effective in preventing pregnancy as an emergency contraceptive than Levonorgestrel Emergency Contraception?
Ulipristal Acetate (Ella)
How long after intercourse must Ulipristal Acetate (Ella) be taken as an emergency contraceptive?
Within 5 days
After using Ulipristal Acetate (Ella), how long should someone wait before starting hormonal contraception?
They can start hormonal contraception 5 days after using Ulipristal Acetate (Ella)
