Pharm 34 Objectives Flashcards
What is the primary reason why women with a uterus also need progestin therapy if they are receiving pharmacologic therapy with an estrogen?
- To oppose estrogen mediated stimulation of the endometrium.
What are the physiologic estrogens?
- Estrone (EI)
- Estradiol (E2)
- Estriol (E3)
What are the physiologic progestin?
Progesterone
What are the physiologic hormones that could be prescribed?
Estradiol and Progesterone
What is the primary ovarian estrogen, and the most abundant estrogen in a woman of reproductive age
Estradiol
What are the synthetic estrogens?
Ethinyl estradiol (EE) and diethystilbestril (DES)
The structural alteration of the estradiol to ethinyl estradiol causes what?
Greatly enhances the potency
What is the primary use of Ethinyl estradiol?
Contraceptives and by adding EE you confer the estrogen risks/adverse effects.
What are the synthetic progestins?
Medroxyprogesterone acetate (MPA) and Megestrol acetate
The injectable route of Medroxyprogesterone acetate (MPA) is used for what?
Progestin-only contraceptives
The oral route of Medroxyprogesterone acetate (MPA) is used for what?
Counter balance the effects of pharmacologic estrogen supplementation on the uterus.
What is the clinical use of Megestrol acetate?
Cachexia associated with AIDS and other wasting syndromes: breast, prostate and endometrium carcinoma
What are the non-physiologic sources of estrogenic substances?
- Conjugated estrogens
- Selective estrogen receptor modulators
- Delestrogens
- Some phenols
- Estrogen mimic compounds (soybeans)
- BPA in plastic bottles
Why is Premarin considered “natural” even though its estrogen content is different from the body’s physiologic estrogens?
Conjugated equine estrogens, contain estrogens that are not physiologic for humans but are most similar to estrone.
(come from pregnant horse urine.)
What does SERM mean?
Selective estrogen receptor modulator
What are the two classes of antiestrogens that may be used for secondary prevention of breast cancer?
SERMs and Aromatase inhibitors
What is the maximum accepted durations of Tamoxifen when using it for secondary prevention of breast cancer?
5 yrs
Why should Tamoxifen only be used for 5 yrs?
It is an estrogen receptor agonist at the uterus which results in proliferation of endometrial cells which can lead to endometrial, uterine and GI cancers.
Aside from cancer risks from Tamoxifen what other potential severe ASEs can occur if used for greater than 5 yrs?
- Stroke
- PE
- QT prolongation
- Cataracts
What are some common ASEs of Tamoxifen?
- Hot flashes
- Vaginal dischage
- Amenorrhea or menstrual changes
Describe the paradigm shift in the medical community regarding the use of “hormone replacement therapy” after the publication of the Women’s Health Initiative study.
- Women received conjugated equine estrogen plus medroxyprogesterone acetate or a placebo
- Study was halted after 5.6 years due to increased coronary artery disease, stroke, and pulmonary embolism
- May have reduced risk of colorectal cancer and hip fractures
- WHI criticized for the older age of participants
75% of women age 60 and above
What are the effects of administration of exogenous gonadotropin (or an antagonist) on circulating testosterone and estrogen levels?
- Suppress gonadotropin production = decreased production of gonadal hormones
- Clomiphene (SERM, partial agonism of central estrogen receptor) prevents estrogen’s negative feedback = increases gonadotropin levels
Why is testosterone best administered by non-enteral route?
- High first-pass effect with oral dosage forms
- Liver toxicity occurs with oral testosterone
What are the benefits of transdermal testosterone?
High transdermal bioavailability and can be administered by gel patches, and injectable.
What are the appropriate techniques to reduce the risk for harmful accidental exposure of gonadal hormones?
Apply to axillary areas or use a patch
Prior to initiating testosterone to treat hypogonadism what must be done?
Obtain 2 morning testosterone labs obtained on separate days and if these serum [ ] are below the normal range then you can diagnose with hypogonadism.
- if not than tx is not necessary and may in fact be risky.
What hormone antagonist are useful for different hormone responsive cancers?
- Raloxifene
- Ospemifene
- Tamoxifen
- Anastrozole
Raloxifene is FDA approved to do what?
- Increase bone density
- Reduce risk for vertebral fractures
- decrease risk for uterine and breast cancer
(used in menopausal women)
Raloxifene is contraindicated in patients with what?
- Hx of VTE/stroke
- Pregnancy
Tamoxifen is the primary hormonal option for treating what?
ER positive breast cancer in post menopausal women and men
Tamoxifen and SSRIs are commonly co-administered but what do you need to consider when these are taken together?
Consider strong CYPT2D6 inhibitor = can reduce production of the active metabolite.
Ospemifene is both an ER antagonist and ER agonist, what does the antagonist aspect prevent?
Breast cancer
Ospemifene is both an ER antagonist and ER agonist, what does the agonist aspect prevent?
Loss of bone density and vaginal atrophy
Ospemifene is useful in what type of patients?
Pts who have difficulty apply vaginal estrogen therapy products due to dexterity or pain.
All SERMs except for Bazedoxifene can increase what?
Increase menopausal symptoms
What are the short term effects of GnRH agonist on gonadal hormones? (pulsatile administration)
Mimic the natural secretion of GNRH and is used to stimulate the release of FSH and LH from the anterior pituitary
What are the long term effects of GnRH agonist on gonadal hormones? (sustained administration)
Leads to down regulation of the GnRH receptors and decreases secretion of FSH and LH, leading to decrease testosterone and estrogen secretion.
What are the effects of GnRH antagonist on gonadal hormones?
Rapid reduction in gonadal hormone production, avoding the initial “flare-up” seen with the agonist.
Sustained administration with GnRH in men with prostate cancer results in?
Synergistic anti-androgen therapeutic effect to simultaneously administered androgen receptor inhibitors
What is the current most accepted clinical use of estrogens (and progestins) for “HRT” that is a temporary (months to a couple years) treatment of menopasusal symptom with the lowest effective dose/exposure?
Oral conjugated equine estrogens + medroxyprogesterone acetate
What is the major use of topical vaginal estrogens?
Vulvar-vaginal atrophy sxs (dryness, irritation, soreness, and dyspareunia)
Why would a pt want a systemic estrogen for menopause sxs over a topical?
If they are having hot flashes and other associated sxs
What is the MOA of Tamsulosin?
Provides fairly rapid relief of urinary symptoms
What is the MOA of Dutasteride?
Inhibits both type 1 and type 2, 5a-reductase
What is the MOA of Finasteride?
Selectively inhibits type 2, 5a-reductase
What timeline do you want to be sure to tell the patient when starting them on tx fro BPH?
Can take weeks to months to notice improvement in urinary symptoms and six months for the full effect
What gonadal hormone agonist drug is not relatively or absolutely contraindicated during pregnancy? and why?
Progesterone and hydroxyprogesterone caproate can be supplemented in women who have experience miscarriages due to deficient physiologic progesterone production during pregnancy
What are the ASEs of SERMS and aromatase inhibitors?
MSK pain and muscle cramps
What are the ASEs of SERMS and clomiphene?
Thromboembolism
What drug class has a lower risk for VTE?
Aromatase inhibitor
5a-reductase inhibitor is what pregnancy category?
- Cat. X
- women of childbearing age should avoid all contact, and not even touch any dosage forms of 5a-reductase inhibitors
What should you counsel all pts on who are taking Tamsulosin?
- Orthostatic Hypotension
- take 30 min after the same meal every day
What are some drug classes that worsen urinary sxs in pts with BPH?
- Alpha 1 agonist
- Androgens
- Antimuscarinic and anticholinergics
Estrogen only tx should only be given to women who have had what?
Complete hysterectomy
What are BBWs for oral progestins?
- Breast cancer
- Cardiovascular
- Dementia
