Term
| Estradiol (17-β-estradiol) |
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Definition
Most potent estrogen produced; secreted by the ovary
Principle estrogen in pre-menopausal women |
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Term
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Definition
Metabolite of estradiol with 1/3 estrogenic potency of estradiol
Principle estrogen of menopausal women |
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Term
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Definition
Metabolite of estradiol
Present in significant amounts during pregnancy
- Produced by the placenta |
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Term
| 5α-dihydrotestosterone (DHT) |
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Definition
Active metabolite of testosterone
Inhibits testosterone production through a negative feedback loop |
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Term
| Actions of Bisphosphonates, like Fosamax® |
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Definition
| • ↓ osteoclastic bone resorption, resulting in an increase in bone mineral density
• Kinetics – absorption: orally active but very poor absorption (must be sure to educate the patient on this)
o Decreased by food: must be taken at least 30 minutes before breakfast with 8 oz. of plain water
o Distribution: into bones
o Elimination: kidney |
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Term
| Examples of Bisphosphonates |
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Definition
| • Alendronate (Fosamax®)
• Ibandronate (Boniva®)
• Zoledronic Acid (Zometa® -- injection)
• Risedronate (Actonel ®) |
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Term
| Adverse effects of Bisphosphonates, like Fosamax® |
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Definition
• GI upset, esophagitis, or esophageal ulceration
• Musculoskeletal pain, osteonecrosis of the mandible |
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Term
| Actions of osteoporosis treating SERMs, like Evista® |
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Definition
• ↑ bone density by ↓ resorption of bone & ↓ bone turnover
• Little to no effect on the endometrium; may ↓ the risk of breast cancer |
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Term
| Adverse effects of osteoporosis SERMs, like Evista® |
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Definition
| Hot flashes, leg cramps, DVT/PE |
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Term
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Definition
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Term
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Definition
| Nasal spray used to reduce bone resorption |
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Term
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Definition
| Recombinant parathyroid hormone for osteoporosis treatment |
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Term
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Definition
• Steroid hormones diffuse across cell membranes & bind with high affinity to specific nuclear receptors
• 2 subtypes: α & β
• Metabolism:
o High 1st pass effect
o Multiple mechanisms hydroxylated (then glucuronidated or sulfated)
• Excretion:
o Excretion & reabsorbed into the enterohepatic circulation
o Urinary excretion |
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Term
| Characteristics of naturally occurring estrogens |
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Definition
o Absorbed through the GI tract, skin, & mucous membrane
o Estradiol PO is rapidly metabolized & partially inactivated by the liver |
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Term
| Characteristics of synthetic estrogen analogs, such as Ethinyl estradiol (EE) |
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Definition
| Well absorbed when taken PO, also absorbed from topical administration: transdermal patch, topical gel, intravaginally, injection |
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Term
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Definition
• Contraception
• Post-menopausal hormone replacement therapy (HRT)
o Vasometer instability (hot flashes) & vaginal atrophy; also help with maintenance of bone mass
o Lower doses are required for HRT (compared with contraceptives)
• Primary hypogonadism
o Estrogen therapy to mimic the natural cyclic pattern
o Stimulates the development of secondary sexual characteristics |
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Term
| Adverse effects of estrogens |
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Definition
| • Most common: nausea & breast tenderness
• Other AEs:
o Thromboembolic events
o MI
o Peripheral edema (Na/water retention)
o HTN
o ↑ BG
o ↑ cholesterol
o Hepatic dysfunction |
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Term
| Actions of Progesterone (natural progestin) |
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Definition
o Produced in response to luteinizing hormone (LH)
o Promotes the development of a secretory endometrium
High levels of progesterone released during the 2nd half of the menstrual cycle (inhibiting additional ovulation)
If contraception occurs, progesterone continues to be secreted maintaining the lining of the endometrium
If conception does not occur, progesterone secretions stops abruptly, thus stimulating menstruation |
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Term
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Definition
• Hormone deficiencies
• Dysfunctional uterine bleeding
• Dysmenorrhea
• Endometriosis
• Contraception (generally combined with estrogens, may be used alone) |
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Term
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Definition
| Synthetic progestin used in combination oral contraceptive pills (OCP) |
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Term
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Definition
o Headache, depression, weight gain, changes in libido
o Structurally similar to testosterone & may cause androgenic effects |
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Term
| Selective Estrogen Receptor Modulators(SERMs) |
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Definition
Interacts at estrogen receptors
Have different effects on different tissues |
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Term
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Definition
| Compete with estrogen for receptors in breast tissue |
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Term
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Definition
Breast cancer
o Adjuvant therapy
o Palliative tx of metastatic breast cancer
o Adjuvant therapy after mastectomy or radiation |
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Term
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Definition
• Hot flashes, nausea, menstrual irregularities
• Other: Endometrial hyperplasia/malignancies, DVT/PE |
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Term
| Actions of Estrogen Contraceptives |
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Definition
• Suppress production of FSH
o Preventing the selection & emergence of a dominant follicle
• Potentiates the contraceptive effects of progestins |
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Term
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Definition
| Ethinyl estradiol
Mestranol -- converted to EE in the liver |
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Term
| Characteristics of Transdermal patch |
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Definition
• Alternative to OCPs
• Total estrogen exposure is greater than OCPs – Probably due to lack of 1st pass effect
• May not be as effective in patients weighing over 90 kg |
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Term
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Definition
| • Continual absorption of estrogen/progestin |
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Term
| Characteristics of progestin-only "mini pills" |
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Definition
• Norethindrone or norgestrel
• Low continuous dose of progestin
• Less effective than combined OCPs
o Greater risk of pregnancy & more menstrual cycle irregularities
o More dependent on patient compliance |
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Term
| Uses of Progestin-only "mini-pills" |
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Definition
o Contraindications to estrogen
o Breastfeeding |
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Term
| MoA of Progestin contraceptives |
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Definition
• Inhibit ovulation by suppressing LH surge
• Thickening of cervical mucus
• Alters fallopian tube peristalsis |
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Term
| Antiprogestin: Mifepristone |
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Definition
• Progesterone antagonist/partial agonist
• Used for abortion; followed by a dose of misoprostol |
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Term
| Synthetic estrogen + synthetic progestin |
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Definition
• Highly effective at preventing contraception
• More predictable cycles; less pain & blood loss associated with cycles
• Most commonly used type of contraception |
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Term
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Definition
| Same tablet taken every day (same strength of estrogen/progestin in each tablet) |
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Term
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Definition
| Tablets alter the strength of progestin to more closely mimic the natural hormone cycle |
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Term
| Combined OCPs help decrease... |
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Definition
• Endometrial cancer
• Ovarian cancer
• Benign breast disease
• Pelvic infections
• Ectopic pregnancies
• Iron deficiency anemia |
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Term
| Characteristics of menstrual periods with use of combined OCPs |
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Definition
Menstrual periods are...
• Predictable
• Shorter
• Less painful |
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Term
| Contraindications for use of combined OCPs |
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Definition
• Thromboembolic disease, Cerebral vascular disease, Coronary artery disease
• Smokers > 35 years of age
• Hepatic: liver dysfunction or hepatic disorders
• Breast cancer
• Undiagnosed abnormal vaginal bleeding
• Pregnancy |
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Term
| Cautions for use of combined OCPs |
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Definition
| • HTN (age)
• Diabetes Mellitus
• Gallbladder disease
• Epilepsy (drug interactions & TERATOGENIC effects of anticonvulsants) |
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Term
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Definition
• Antibiotics
• Barbituates
• Benzodiazepines
• Phenytoin (Dilantin®)
• Sulfonamides |
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Term
| Meds that may be affected by use of combined OCPs |
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Definition
• Anticoagulants
• Hypoglycemics |
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Term
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Definition
• Testosterone binds to a specific receptor in the target head
o Must be metabolized to be active
o Testosterone is converted to DHT by 5α-reductase
o May also be converted to estradiol |
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Term
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Definition
o Testosterone: ineffective orally (inactivated by 1st pass metabolism), administered IM
o Also available in transdermal patches, topical gels, and buccal tablets
o Some synthetic testosterone derivatives can be given orally |
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Term
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Definition
| • Androgenic effects: used in males with inadequate androgen secretion
• Anabolic effects: used for wasting associated with HIV or cancer
• Danazol: mild androgen used for endometriosis & fibrocystic breast disease
• Unapproved use: anabolic steroids are used to increase lean body mass, muscle strength, and endurance |
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Term
| Adverse effects of Androgens |
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Definition
Females
o Masculinization effects
Males
o Priapism or impotence, decreased spermatogenesis, gynecomastia, growth of the prostate
General effects
o Increased LDL, decreased HDL
o Fluid retention (edema) |
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Term
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Definition
o Interfering with androgen synthesis
o Blocking androgen receptors |
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Term
| Uses/example of 5α-reductase inhibitors |
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Definition
| • Used for BPH (↓ in DHT formation leads to ↓ prostate size)
• Finasteride (Proscar®) |
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Term
| Uses of androgen receptor blockers |
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Definition
| • Used in carcinoma of the prostate
• Flutamide (Eulexin®) |
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Term
| Actions of PDE-5 Inhibitors |
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Definition
• Nitric oxide (NO) mediates the smooth muscle relaxation that allows increased blood flow to the corpus cavernosum
• NO activates cGMP to maintain smooth muscle relaxation
• PDE-5 is responsible for the degradation of cGMP
o If cGMP is destroyed, the smooth muscle relaxation is not maintained
o Allows cGMP to persist |
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Term
| Kinetics of PDE-5 Inhibitors |
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Definition
o Shorter-acting: take 1 hour prior to sexual activity (half-life is a few hours)
o Longer-acting: slower onset but effects for up to 36 hours
o All PDE-5 inhibitors are metabolized by CYP 450 |
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Term
| Adverse effects of PDE-5 Inhibitors |
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Definition
• Headaches, flushing, dyspepsia, nasal congestion
• Drug interactions:
o NITRATES: may cause extreme hypotension
o Other CYP450 drugs |
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