B-24. Contraceptives. Flashcards
Oral contraceptive are usually administered how? Given in which phases?
Oral contraceptives are usually administered as a combination of estrogen and gestagen, given in phases. This can be done in a monophasic, biphasic or triphasic manner, or as a gestagen-only “minipill”.
The estrogen component of the pill is? The gestagen component is?
The estrogen component is always ethinylestradiol and the gestagen component varies.
Biphasic hormone doses different between which days of treatment
Biphasic hormone doses generally differ btwn days 1-10 and 11-21 of treatment
Triphasic hormone doses different between which days of treatment
Triphasic differs btwn days 1-7, 8-14 and 11-21.
How many days are skipped in the cycle?
1 week of the 28 day cycle is skipped to allow for menstruation (usually ‘sugar pills’ taken during this time to help pt remember to take pill daily)
Estrogen and gestagen combo effect on sex organs. MOA?
MOA: Inhibition of pituitary function (neg. feedback on FSH/LH); inhibition of ovulation; changes in cervical mucus, endometrium (inhibit implantation), motility (of Fallopian tube cilia) etc.
Effect on sexual organs (estrogen and gestagen combo)
● Depression of ovarian function - chronic use → ovaries shrink; discontinuation of drug can result in a long amenorrheic period
● Uterine / cervical effects - result in cervical hypertrophy (possibly w/ polyp formation) with thicker / less cervical mucus; 19-steroid preparations cause uterine glandular atrophy with reduced bleeding
● Breast effects - enlargement and lactation suppression
Advantageous side effects of estrogen and gestagen combo
Advantageous side effects:
● Cancer prevention - ↓ incidence of ovarian/endometrial cc. as well as ovarian cysts and mastopathy
● Menstrual effects - ↓ bleeding and anemia
● Also improve conditions such as endometriosis (gestagens ↓ endometrial prolif.) and dysmenorrhea
Adverse effects of gestagen and estrogen
Adverse effects:
● Mild - nausea, mastalgia, edema, HA (migraine incidence ↑) , endocrine changes, loss of “withdrawal bleeding” (aka hormonal period / fake period, monthly bleeding while on OCPs)
● Moderate - breakthrough bleeding, acne, weight gain / worsened lipid profile (gestagens), hyperpigmentation, hirsutism, ureteral dilation, vaginal infections (pH changes) and amenorrhea
● Severe:
○ Vascular - ↑ risk of venous thrombi (coag. factor changes), MCI and cerebrovascular disease
○ GI disorders - ↑ risk of cholestasis, gallbladder disease, and hepatic adenoma
○ Depression
○ May increase risk of cervical and breast cancers (unclear research on this)
Contraindication of gestagen and estrogen
Contraindications:
● Vascular disorders - such as thromboembolism or cerebrovascular disease
● Certain cancers - estrogen-dependent neoplasms, mostly breast cc. ● Vaginal bleeding of unknown origin
● Before closure of the epiphyseal plate - estrogens induce closure + thus would stunt growth
Progestin/gestagen-only therapy (minipill) drugs
Norethindrone
Norgestrel (minipill)
Indication and side effects of Norethindrone or norgestrel
Norethindrone or norgestrel - “minipill”
● Indication: pts in whom estrogens are CI, such as those w/ hepatic disease or thromboemboli
● Side Effects:
○ HA, dizziness, weight gain
○ Impaired glucose tolerance - CI in pts with family history of DM
○ Irregular bleeding
Parenteral depot injection drugs
Medroxyprogesterone acetate
Medroxyprogesterone acetate pharmacokinetics and side effects
Medroxyprogesterone acetate
● Given i.m. every 2-3 months
● Side Effects:
○ Common - HA, impaired glucose tolerance, irregular bleeding, worsens lipid profile
○ Long amenorrheic period after discontinuation (6-12 months)
Contraceptive patches drugs
Ethinylestradiol and norelgestromin combination
Ethinylestradiol and norelgestromin pharmacokinetics and side effects
Ethinylestradiol and norelgestromin combination
● Norelgestromin is an active metabolite of norgestimate
● Releases microgram-level daily doses of hormones
● Side effects are similar to oral combos, but with less liver/GB effects (lipid profile, stones, etc.)
Contraceptive implants drugs
Norgestrel or etonogestrel
Norgestrel or etonogestrel pharmacokinetics/side effects
Norgestrel or etonogestrel
● S.c. implant with DOA of 3-6 years; etonogestrel is an active metabolite of desogestrel
● Side Effects: low incidence due to low dosage
○ HA, dizziness, acne, alopecia, mood changes, breast tenderness, ↓ libido, weight gain and vasomotor issues
○ Major bleeding disturbances - irregular cycles
Local contraceptive drugs
Levonorgestrel
Nuvaring
Benzalkonium
Nonoxynol
Levonorgestrel located? DOA? Side effects?
Levonorgestrel intrauterine device
● DOA 5 years w/ daily dose of 20 ug; low systemic hormone level → low side effects
Nuvaring is? DOA?
Nuvaring combination of ethinylestradiol + etonogestrel in a vaginal ring; 3 week use with 1 week pause
Benzalkonium and nonoxynol are?
Spermicidal disinfectants benzalkonium and nonoxynol; less effective but can prevent STDs as well
Postcoital contraceptives drugs
Levonorgestrel
Ulipristal acetate
Mifepristone
Postcoital contraceptive is?
“Morning after” pills; Progestin alone or in combo with estrogen (but no advantage over monotherapy)
Levonorgestrel monotherapy dose and used within what time? Side effects?
Levonorgestrel monotherapy - high dose (0.75-1.5 mg); used within 72 hrs of sex (≤ 12 is best)
● Common side effects: nausea, vomiting, HA, dizziness, breast tenderness, abdominal / leg cramps
Ulipristal acetate MOA, used within, side effect, and indication
Ulipristal acetate
● MOA: an SPRM (lol, sperm) - “selective progesterone receptor modulator”
● use within 5 days, earlier is better
● Side effects are similar to those of other progestins
● Can also be used to treat uterine myomas
Mifepristone MOA
Mifepristone - so-called “abortion pill”
● MOA: a 19-norsteroid progesterone receptor antagonist
○ used in combination with local vaginal PGE1 or oral misoprostol
○ >95% effective in first 50 days (~7 weeks) of pregnancy
Mifepristone other potential indication
Other potential indications: endometriosis, breast cancer, meningioma
Mifepristone side effects
Side effects: of the combination of mifepristone + misoprostol
○ Vomiting, diarrhea, abdominal pain + vaginal bleeding
○ Has anti-glucocorticoid activity
