Progestins

What is the most important progestin in hunmans?

Progesterone

What is progesterone a precursor for?

Estrogen, androgens, and corticosteroids

Where is progesterone synthesized in?

Ovaries, testis, and adrenal glands

Where is a large quantity of progesterone synthesized?

Corpus luteum in the ovary

Where is progesterone metabolized almost completely in one passage?

The liver

What is progesterone converted to andc conjugated with what?

Preganendiol with glucuronic acid

What does progesterone affect in terms of insulin and response to glucose?

Increases basal insulin and insulin response to glucose

What does progesterone promomte in the liver?

Glycogen storage

What does progesterone compete with for mineralocorticoid receptors?

Aldosterone

What effects does progesterone have on the brain?

Depressant and hypnotic effects

List the clinical uses of progesterone

Hormone contraception, hormone replacement therapy, endometriosis, dysmenorrhea, and bleeding disorders

What suppresses the growth of endometrial cells?

progestins

What part of progestins increases oral bioavailability?

17-ethynyl group

What part of progestins is not necessary for progestenic activity?

19-methyl group

How do you enhance the activity of progestins?

Replace 19-methyl with H

How do you increase further oral bioavailability of progestins?

Replace 17-acetyl with OH

What in progestins is rapidly hydrolyzed and where?

Ester groups in vivo

In what form is levonorgestrel active in?

Levo form

What is levonorgestrel used in?

IUDs

What is a prodrug of levonorgestrel?

Norgestimate

What is norgestimate converted to

Levonorgestrel oxime

What is desogestrel rapidly metabolized to?

Etonogestrel

What is etonogestrel structurally analogous to?

Levonorgestrel

What is etonogestrel used in??

Subdermal implant or vaginal ring

What is Drospirenone’s relative strength compared to levonorgestrel?

10% weaker

What does drospirenone do in combination therapy with ethynyl estradiol?

Negates it

What is the most desirable activity of progestins?

Minimize andorgenic and antiestrogenic activites

What are the two types of hormonal contraception?

Combination therapy of estrogen and progestins and continuous progestin therapy without estrogen

What are the methods of delivery for hormonal contraceptives?

Oral, implantable, IUD, or depot injection

What is crucial for oral administration of hormonal contraception with progestin-only therapies?

Adherence to administration schedule

The combination of estrogens and progestins selectively inhibit what?

Pituitary function

(T or F) Progestin-only contraceptives don’t always inhibity ovulation

True

What pharmacological effects do oral contraceptives have on the ovary?

Suppresion of ovarian function

How long does it take for a majority of pateints to return ot normal cycle after discontinuing oral contraceptives>?

1-2 months

What effect do oral contraceptives have on the uterus

Changes the cervical mucus and in the uterine endometrium

What does the change of cerivical mucus and in the uterine endometrium affect?

Decrease the likelihood of conception and implantation

What effect do oral contraceptives have on the breast in combinations only?

Breast enlargement and suppression of lactation

Nausea, hypertension, edema, and breast fullness are mild adverse effects of oral contraceptives due to what?

Estrogens

Increased appetite, fatigue, and breast regression are adverside effects of oral contraceptives due to what?

Progestins

Irregular mensturation is more common in what oral contraceptives?

Progestin-only contraceptives

Weight gain, acne, and hirsuitsim is more common in what oral contraceptives

Combinations containing androgen-like progestins

Venous thromboembolic disease is a severe adverse effect of oral contraceptives due to what?

Estrogens

Myocardial infarction is a severe adverse effect of oral contraceptives due to what?

Androgenic activtiy of progestins

Oral contraceptives with orther steriods may cause what and by what action?

Increased blood levels of other steroids by interfering their metabolism

Anticonvulsants like Phenytoin with oral contraceptives causes what in the liver?

Induces drug metabolizing enzymes which increases the rate of metabolism

Tetracyclines with oral contraceptives causes the suppression of what?

Gut flora

What does gut flora particpate in

enterohepatice recycling

What is an example of a selective progesterone receptor modulator

Ulipristal acetate

What is ulipristal acetate used as?

Emergency contraceptive

How long can ulipristal acetate effective for?

5 days after unprotected sex

Mifrepristone is an example of what?

Progesterone antagonist

Mifepristone does what in combination with what

Induces abortion in combination with misoprostol

What is Danazol effective for?

Endometriosis

What does Danazol do that makes it effective for endometriosis?

Inhibits the surges of LH and FSH and suppresses ovarian function, causes atrophy of endometrium

What are the adverse effects of Danazol caused fromed?

From weak androgenic activity

What are the contraindications of Danazol?

Hepatic dysfunction, pregnancy, and breast-feeding