Progestins - 15 Flashcards
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
Adverse effects of oral contraceptives
Severe
* venous ___ disease due to ___
* myocardial ____ - due to androgenic activity of ___
* can be dangerous in women over 35 who ___
- thromboembolic, estrogens
- infarction, progestins
- smoke
Drug interactions
- Oral contraceptives may ___ blood levels of other steroids by interfereing with their metabolism. Example: ___
- Anticonvulsants such as ____, induce drug-metabolizing enzymes in the ___. Effectiveness of oral contraception will ___ due to increased breakdown.
- Antibiotics such as ___ also induce ___ enzymes in the liver. This ___ the rate of metabolism of many other drugs.
- Antibiotics such as ___, suppress gut flora that participate in ___.
- increase, glucocorticoids
- phenytoin, liver, decrease
- rifampin, drug metabolizing, increases
- tetreacyclines, enterohepatic recycling
Emergency contraceptives
- “morning after” pill is effective ___ of the time when treatment is begun in ___ hours
- similar to oral contraceptives, but with a ___ dose
- Combo (originated from ___ regimen): Ovral, Preven, (ethinyl estradiol ___ mcg + norgestrel ___ mcg)
- Progestin only: Plan B (levonorgestrel ___ mcg)
- side effects: ___ - more common in combo products
- 99%, 72 hours
- higher
- Yuzpe, 50 mcg, 500 mcg
- 750 mcg
- Nausea/vomiting
Ulipristal acetate (Ella)
- Selective ___ receptor modulator (SPRM)
- used as an ___ contraceptice
- can be effective up to ___ days after unprotected sex
- side effects: ___ and ___ pain
- progesterone
- emergency
- 5
- nausea, abdominal
Mifepristone
- Abortifacient: used in combination with ___ (a ___ derivative, oral prostaglandin)
- side effects: nausea, vomiting, bleeding (5%)
- misoprostol, PGE1
Danazol
- Weak androgen, ___ progestin, and ___estrogen
- effective for ___ : inhibits ___ and ___ surge and suppresses ___ function
- causes ___ of the endometrium
- adverse effects: mostly from weak ___ activity. Weight gain, decreased ___ size, acne, ___ skin, hisutism
- contraindications: ___ dysfunction, pregnancy/breast feeding
- weak, antiestrogen
- endometriosis, LH, FSH, ovarian
- atrophy
- androgenic, breast, oily
- hepatic
What is this?
Danazol
Endometriosis treatent
What is this?
Desogestrel
What is this?
Drospirenone
What is this?
Ethynodiol diacetate
What is this?
Etonogestrel
What is this?
Levonorgestrel
What is this?
Medroxyprogesterone acetate
What is this?
Mifepristone
Abortifacient
What is this?
Norethindrone
What is this?
Norgestimate
What is this?
Pregnanediol (inactive)
progesterone metabolite
What is this?
progesterone
What is this?
Ulipristal acetate
SPRM - emergency contraception
