Drugs affecting fertility and reproduction 1 Flashcards
Estrogens - MoA
Hypertensive effect by increased angiotensinogen synthesis.
Thromboembolic effect by increased hepatic synthesis of clotting factors.
Gallbladder disease by increased cholesterol excretion in bile.
Estrogens - Clinical use
Primary hypogonadism, including cases caused by surgical oophorectomy, menopause
Estrogens - Contraindications and Special consideration
CONTRAINDICATED: pregnancy, uterine fibroids.
Use with caution if hepatic diseases, endometriosis, thromboembolic diseases, hypercalcemia
Estrogens - Adverse effects
Breast tenderness, headache, edema, nausea, vomiting, anorexia, change in libido
HT, thromboembolic disorders, gallbladder disease
Conjugated equine estrogens - Clinical use
HRT in postmenopausal women
Estrone can be adm IM
Conjugated equine estrogens - Special consideration
Hydrolyzed to estrone and equilin before absorption from the gut.
Converted in the liver to sulfate and glucuronide conjugates
Ethinyl estradiol and Mestranol - Clinical use
Oral estrogen-progestin contraceptives
Acne vulgaris
Dysmenorrhea
Micronized estradiol and Trandermal estradiol - Clinical use
HRT in postmenopausal women
Long-lasting ester of estradiol + Route of adm
Estradiol cypionate and Estradiol valerate
IM: both Oral: estradiol valerate
Estradiol valerate - Clinical use
Contraceptive, Heavy or prolonged menstrual bleeding
Estrogens
Conjugated eqine estrogens Ethinyl estradiol Mestranol Micronized estradiol Vaginal estradiol tablets Estradiol cypionate Estradiol valerate Transdermal estradiol
Progesterone esters
Suppress ovarian function in the treatment of dysmenorrhea, endometriosis, and uterine bleeding.
In HRT, the progesterone esters are used in combination with estrogens to decrease the incidence of estrogen-induced irregular bleeding and to prevent uterine hyperplasia and endometrial cancer.
Progesterone esters - Special consideration
Extend oral bioavailability and half-life of progesterone
Esters of progesterone + Route of dam
Megestrol - Oral
Hydroxyprogesterone caproate - IM
Medroxyprogesterone acetate - IM + oral
Hydroxyprogesterone caproate - Clinical use
Reduce the risk of preterm delivery in women with a history of at least one spontaneous preterm birth.
What is the progestin- only contraceptive?
Medroxyprogesterone acetate
Synthetic progestins
Norgestrel Desogestrel Norgestimate Norethindrone Drospirenone
Which synthetic progestin is a spironolactone derivative?
Drospirenone
Synthetic progestins - are mostly derivatives of?
nortestosterone
Synthetic progestins - MoA
Estrogenic, antiestrogenic and androgenic activities
Synthetic progestins - Clinical use
Oral contraceptives
Dysmenorrhea, endometriosis, uterine bleeding
Which synthetic progestin has more androgenic activity than other progestins?
Norgestrel
Which synthetic progestins has less androgenic and more pro gestational activity?
Desogestrel and Norgestimate
Which synthetic progestin has an intermediate androgenic potency?
Norethindrone
Which synthetic progestin is an aldosterone antagonist?
Drospirenone
Drospirenone - Special considerations
Antiandrogenic effect
Less incidence of weight gain, mood changes and acne
Norgrestrel - Adverse effects
Increased incidence of acne, hirsutism, increased libido, oily skin.
Drospirenone - Adverse effects
Decreased BP (decreased salt and water retention). In contraceptive: 2-3X increased risk of VTE compared to levonorgestrel (but still low risk)
Estrogen - Progestin contraceptives - MoA
Synergistic suppression of ovulation, by feedback inhibition of GnRH secretion.
Estrogen component: Decreased FSH secretion (no maturation of follicle).
Progestin component: inhibit LH surge (no ovulation).
Delayed maturation of endometrium, development of viscous cervical mucus
Estrogen - Progestin contraceptives - Clinical use
Contraceptives
Acne vulgaris
Dysmenorrhea
Estrogen - Progestin contraceptives - Special consideration and Contraindication
For dysmenorrhea: treatment is started some days before menstruation. NSAIDs are alternative treatment for dysmenorrhea.
Smokers over 35 years should use other contraceptive methods.
Caution if gall bladder disease.
CONTRAIND: thromboembolic disease, history of MI, CAD, active liver disease, breast cancer, carcinoma of reproductive tract
Reduce incidence of endometrial and ovarian cancer. Does not increase the risk of breast cancer. Low risk of hepatic adenoma
Estrogen - Progestin contraceptives - Adverse effects
Hypertension, thromboembolic disorders, gallstones
High dose: breast cancer
Increases Risk of stroke, MI, DVT
Increased Estrogen: breast enlargement, dizziness, dysmenorrhea, edema, headache, irritability, nausea, vomiting, weight gain (cyclic)
Decreased Estrogen: Atrophic vaginitis, continuous bleeding, early bleeding, hypomenorrhea, vasomotor symptoms
Increased Progestin: Acne, depression, fatigue, hirsutism, libido change, oily skin, weight gain (noncyclic)
Decreased Progestin: Dysmenorrhea, hypermenorrhea, late-cycle bleeding
Estrogen - Progestin contraceptives - Interactions
Carbemazepine, phenytoin: increased hepatic metabolism of oral contraceptives (may cause contraceptive failure).
Antibiotics (penicillins, tetracyclines): Decreased enterohepatic cycling of contraceptives and decreased contraceptive effect.
Estrogen cause increased potency of cyclosporine, antidepressants, glucocorticoids + increase antagonize warfarin effect + increased hepatotoxicity of dantrolene
Difference between Monophasic and Triphasic estrogen- progestin contraceptives
Monophasic: Same amount of progestin throughout cycle.
Triphasic: Increased amount of progestin after 7-14 days
Monophasic estrogen-progestin contraceptives + Special considerations
Ethinyl estradiol + levonorgestrel: 84 days continuous use, then 7 inactive tablets.
Drospirenone + ethinylestradiol: Available for 21-day and 24-day regimens (latter less rates of contraceptive failure)
Ethinyl estradiol + levonorgestrel - Clinical use
Menstrual suppression
Extended-cycle preparations contain
Ethinyl estradiol + levonorgestrel
Norelgestromin/ethinylestradiol (ortho evra) - Special considerations and Adverse effects
4 week adm cycl. New patch same day each week for 3 weeks, week 4 is patch-free.
Less effective in women weighting >198 pounds.
Greater incidence of venous thromboembolism than oral contraceptives
Progestin-only contraceptives - MoA
Decrease Frequency of GnRH pulse (Decrease LH surge).
Thicken & decrease cervical mucus, create a thin, atrophic endometrium that is hostile to implantation of the blastocyst
IUD: produces localized effects on the endometrium
Progestin-only contraceptives - Clinical use
Suited as contraceptive for smokers, older women, or with contraindication for estrogen
Progestin-only contraceptives - Special consideration
Increased Contraceptive failure risk compared to estrogen-progestin contraceptives.
Must be taken daily without interruption
Progestin-only contraceptives - Adverse effects
Frequent spotting, amenorrhea, increased risk of ectopic pregnancy.
Irregular and unpredictable menstrual cycle
Progestin-only contraceptives
Norethindrone
Medroxyprogesterone
Levonorgestrel
Ulipristal acetate
Medroxyprogesterone acetate - Clinical use
Castration agent in men convicted of pedophilia, serial rape, sex crimes.
Emergency contraceptives
Levonorgestrel and Ulipristal acetate
Levonorgestrel - Adverse effects
Usually nausea and vomiting (reduced by eg promethazine).
Headache, dizziness, leg cramps, abdominal cramps
