Progestins - 15 Flashcards
(43 cards)
Progesterone
- most important ___
- functions as a ___ and a precursor to estrogens, androgens, and ___
- syntheiseized in the ___, ___, and ___
- large amount of progesterone is synthesized by the ___ in the ovary in the ___ phase and by the placenta during pregnancy
- progestin
- hormone, corticosteroids
- ovary, testis, and adrenal glands
- corpus luteum, luteal
Progesterone metabolism
- Rapidly absorbed following administration by ___
- half life in the plasma: ___
- Almost completely metabolized through ___ (liver)
- converted to ___ and conjugated with ___
- excreted into the ___
- any route
- 5 min
- first pass
- pregnanediol, glucuronic acid
- urine
Physiologic effects
Menstruation cycle
* Causes the ___ and ___ changes in the endometrium following ovulation.
maturation and secretory
Physiologic effects
Metabolic effects
* ___ basal insulin levels and the insulin response to glucose.
* Promotes ___ storage in the liver.
- increases
- glycogen
Physiologic effects
Interference with aldosterone
* competes with ____ for the mineralocorticoid receptor.
* Causes a decrease in ___ reabsorption → Increase in ___ secretion by the ____ (in pregnancy)
- aldosterone
- Na+, aldosterone, adrenal cortex
T or F: progestins have depressant and hypnotic effects on the brain
True
Clinical uses
- hormonal contraception
- hormonal replacement therapy in combination with ___
- prevents some adverse effects of estrogens (___ bleeding and endometrial ___)
- Endometriosis - growth of endometrial cells ___ the uterine cavity
- cells respond to the hormonal changes and cause severe pain from ___ during menstruation
- progestins ___ growth of endometrial cells
- also used for dysmenorrhea (___ menses) and bleeding disorders
- estrogens
- uterine, carcinoma
- outside
- inflammation
- suppress
- painful
Structure-activity relationship in progestins
- ___ at the 3 position is essential for activity; can be introduced by in vivo oxidation
- 17α-ethynyl moiety leads to ___ activity.
- C-___ Me group (or Et group) required for activity
- native ___ moiety has highest activity, but poor ___ bioavailability; ___ or esters are used is oral preparations
- ketone
- oral
- 18
- acetyl, oral, 17B-OH
“19-nor, 17-ethynyl” steroids (oral contraceptives)
- ___ generation progestins
- ___ ethynyl group increases oral bioavailability
- ___ methyl group is not necessary for ___ activity
- replacement of 19-methyl with ___ enhances the activity
- Replacement of 17-acetyl with __ increases oral bioavailability.
- ester groups are rapidly ___ in vivo
- 1st
- 17
- 19, progestenic
- H
- OH
- hydrolyzed
Levonorgestrel
* ___ generation progestin
* ___ isomer of norgestrel, which is a racemic mixture. Only ___ form is active
* ___ oral bioavailability
* used in ___
- 2nd
- levo, levo
- high
- IUDs
Norgestimate
- prodrug
- Converted to levonorgestrel ___ and
then to levonogestrel in ___.
- oxime
- vivo
Desogestrel
- ___ generation
- prodrug (no ___)
- repidly metabolized to ___
- ___ oral bioavailability due to extra ___ groups
- 3rd
- ketone
- etonogestrel
- high, methyl
Etonogestrel
- The active form of ___
- structurally analogous to ___
- used as the subdermal implant ___ or vaginal ring ___
- desogestrel
- levonorgestrel
- Nexplanon, Nuvaring
Drospirenone
- ___ generation
- Relatively weak progestogenic
activity (10% of ___) - ___mineralocorticoid activity
- negates side effects of ___ in combination therapy
- 4th
- levonorgestrel
- anti
- ethynyl estradiol
Medroxyprogesterone acetate
- ___ generation
- administered as a ___
- ___ acting progesterone only contraceptive
- 1st
- depot injection (Depo-Provera_
- long
Hormonal activities of progestins
Progestins frequently have hormonal activities other than progestonic effects
due to their interaction with ___
* Minimizing ___ and ___ activities are desirable.
other steroid receptors
androgenic, antiestrogenic
Hormonal contraception
Types
* combinations of estrogens (___ or ___) and progestins
* typically __ days of active compounds and ___ days of placebo
* mono, bi, and or triphasic
* continuous progestin therapy without ___ (example: ___)
- mestranol, ethynyl estradiol
- 21, 7
- estrogen, norethindrone
Hormonal contraception
Delivery
* mostly ___ administration
* adherence to administration schedule is more critical for ___ only therapies
* implantable; ___ , IUD; ___ , or depot injection; ___
- oral
- progestin
- etonogestrel, levonogestrel, medroxyprogesterone acetate
Pharmacological effects of oral contraceptives
Inhibition of ovulation
* combos of estrogens and progestins selectively inhibit ___ function
* progestin only contraceptives do not always ___ ovulation
- pituitary
- inhibit
Pharmacological effects of oral contraceptives
Effects on the ovary
* Suppression of ___ function
* When discontinued, a majority of patients return to the normal cycle in ___ months
- ovarian
- 1-2 months
Pharmacological effects of oral contraceptives
Effects on the uterus
* Change in the ___ and in the uterine endometrium → decrease in the likelihood of ___ and ___.
- cervical mucus
- conception
- implantation
Pharmacological effects of oral contraceptives
Effects on the breast (___ only)
* breast ___
* suppression of ___
- combinations
- enlargement
- lactation
Adverse effects of oral contraceptives
mild
due to estrogens: 4
due to progestins: 3
- nausea, hypertension, edema, breast fullness
- increases appetite, fatigue, breast regression
Adverse effects of oral contraceptives
Moderate
* ____ in menstruation, ___ bleeding– more common in ___-only contraceptives
* Weight gain, acne, and ___– more common with the combos containing ___ progestins
* Amenorrhea
- irregularities, breakthrough, progestin
- hisutism, androgen-like
