L 14 progestins

Question 1

progesterone

Answer 1

-Most important progestin in human
-Functions as a hormone and also a precursor to the estrogens, androgens, and corticosteroids.
-Binds to the progesterone receptor and alters rate of transcription
-Synthesized in the ovary, testis, and the adrenal glands.
-A large quantity of progesterone is synthesized by the corpus luteum in the ovary in the luteal phase and by the placenta during pregnancy

Question 2

metabolism

Answer 2

-Rapidly absorbed following administration by any route.
-Half-life in the plasma ~5 min
-Synthetic progestins are used clinically.
-Almost completely metabolized in one passage through the liver.
-Converted to pregnanediol and conjugated with glucuronic acid.
-Excreted into the urine

Question 3

physiological effects

Answer 3

menstruation cycle,
metabolic effect
interference with aldosterone
depressant and hypnotic effets on the brain

Question 4

menstruation cycle physiological effects

Answer 4

causes the maturation and secretory changes in the endometrium following ovulation

Question 5

metabolic effect physiological effects

Answer 5

-increases basal insulin levels and the insulin response to gluscose
-promotes glycogen storage in the liver

Question 6

interference with aldosterone physiological effects

Answer 6

-completes with aldosterone for the mineralocorticoid receptor
-causes a decrease in Na+ reabsorption –> increase in aldosterone secretion by the adrenal cortex (in pregnancy)

Question 7

clinical uses

Answer 7

-hormonal contraception
-hormone replacement therapy in combination with estrogens
-endometriosis
-dysmenorrhea
-bleeding disorders

Question 8

hormonal replacement therapy in combination with estrogen

Answer 8

Prevents some adverse effects of estrogens (uterine bleeding and endometrial carcinoma).

Question 9

endometriosis

Answer 9

-Growth of endometrial cells outside the uterine cavity
-The cells respond to the hormonal changes and cause severe pain from inflammation during menstruation.
-Progestins suppress the growth of endometrial cells

Question 10

19 nor, 17 ethynyl steroids (oral contraceptives)

Answer 10

-1 st generation progestins
-17-ethynyl group increases oral bioavailability.
-19-methyl group is not necessary for progestenic activity.
-Replacement of 19-methyl with H enhances the activity.
-Replacement of 17-acetyl with OH increases oral bioavailability.
-Ester groups are rapidly hydrolyzed in vivo.

Question 11

levonorgestrel

Answer 11

-2 nd generation progestin
-Levo isomer of norgestrel, which is a racemic mixture.
-Only levo form is active.
-High oral bioavailability
-Used in intrauterine devices (IUDs) also (Mirena ®)

Question 12

etonogestel

Answer 12

-The active form of desogestrel
-Structurally analogous to levonorgestrel
-Used in the subdermal implant (Nexplanon ®) or the vaginal ring (Nuvaring ®).

Question 13

drospirenone

Answer 13

-4 th generation progestin
-Relatively weak progestogenic activity (10% of levonorgestrel)
-Antimineralocorticoid activity
-Negates side effects of ethynyl estradiol in combination therapy.

Question 14

medroxyprogesterone acetate

Answer 14

-1 st generation progestin
-Used for depot injection (Depo- Provera ®) as a long-acting progesterone-only contraceptive.

Question 15

hormonal activites of progestins

Answer 15

-Progestins frequently have hormonal activities other than progestonic effects due to their interaction with other steroid receptors.
-Minimizing androgenic and antiestrogenic activities are desirable

Question 16

types of hormonal contrception

Answer 16

-Combinations of estrogens (ex. ethynyl estradiol or mestranol) and progestins
=Typically 21 days on active compounds and 7 days on placebo (à withdrawal bleeding)
=Monophasic, biphasic, or triphasic according to the dose variation
-Continuous progestin therapy without estrogen (“minipill”, ex. norethindrone)

Question 17

delivery of hormonal contraception

Answer 17

-Mostly oral administration
=Adherence to the administration schedule is more critical for progestin-only therapies.
-Implantable (etonogestrel), IUD (levonogestrel), or depot injection (medroxyprogesterone acetate)

Question 18

pharmacologial effects of oral contraceptives: inhibition of ovulation

Answer 18

-Combinations of estrogens and progestins selectively inhibit pituitary function.
-Progestin-only contraceptives do not always inhibit ovulation

Question 19

pharmacologial effects of oral contraceptives: effects of ovarian functions

Answer 19

-Suppression of ovarian function
-When discontinued, a majority of patients return to the normal cycle in 1-2 months

Question 20

pharmacologial effects of oral contraceptives: effect on the uterus

Answer 20

Change in the cervical mucus and in the uterine endometrium à decrease in the likelihood of conception and implantation

Question 21

pharacological effects of oral contraceptives: effects on the breasts

Answer 21

-combination only
-Stimulation of the breasts à enlargement
-Suppression of lactation

Question 22

mild adverse effects of oral contraceptives

Answer 22

-Nausea, hypertension, edema, breast fullness – due to estrogens
-Increased appetite, fatigue, breast regression – due to progestins

Question 23

moderate adverse effects of oral contraceptives

Answer 23

-Irregularities in menstruation (breakthrough bleeding) – more common in progestin-only contraceptives
-Weight gain, acne, hirsutism – more common with the combinations containing androgen-like progestins
-Amenorrhea

Question 24

severe adverse effects of oral contraceptives

Answer 24

-Venous thromboembolic disease – due to estrogens
-Myocardial infarction – due to androgenic activity of progestins
-Can be dangerous in women over 35 who smoke

Question 25

drug interactions: other steroids

Answer 25

-Oral contraceptives may increase the blood levels of other steroids by interfering their metabolism.
-Ex. glucocorticoids

Question 26

drug interactions: anticonvulsants

Answer 26

Phenytoin; Induces drug-metabolizing enzymes in the liver

Question 27

drug interactions: antibiotics

Answer 27

-Rifampin
-Induces drug metabolizing enzymes in the liver.
-Increases the rate of metabolism of many other drugs.
-Tetracyclines
-Suppresses gut flora that participate in enterohepatic recycling.

Question 28

emergency contraceptives

Answer 28

-Postcoital (“morning-after”) contraception
-Effective 99% of the time, when the treatment is begun in 72 hrs.
-Similar to oral contraceptives, but with much higher doses.
-Types
=Combination (originated from the Yuzpe regimen)
=Ex. Ovral ®, Preven ® (ethinyl estradiol 50 μg + norgestrel 500 μg)
=Progestin only
=Ex. Plan B ® (levonorgestrel 750 μg)
-Side effects
=Nausea, vomiting – more common in combinations

Question 29

ulipristal acetate

Answer 29

-Selective progesterone receptor modulator (SPRM)
-Used as an emergency contraceptive
-Can be effective up to 5 days after an unprotected sex
-Side effects: Nausea, Abdominal pain

Question 30

mifepristone

Answer 30

-RU-486
-Progesterone antagonist
-Abortifacient: Used in combination with misoprostol (PGE 1derivative, oral prostaglandin) up to 70 days.
-Side effects:
=Nausea, vomiting,
=Bleeding (5%) (Requires intervention, Administered only by physicians)

Question 31

danazol

Answer 31

-weak androgen, weak progestin, and antiestrogen
-effective for endometriosis

Question 32

danazol: effective for endometriosis

Answer 32

-Inhibits the surges of LH and FSH and suppress
ovarian function.
-Causes atrophy of the endometrium.

Question 33

adverse effects of danazol

Answer 33

-Mostly from weak androgenic activity
-Weight gain, decreased breast size, acne, oily skin,
hirsutism

Question 34

danazol contraindications

Answer 34

-hepatic dysfunction
-pregnancy and breast feeding

Question 35

progestins

Answer 35

-Norethindrone
-Ethynodiol diacetate
-Levonorgestrel
-Norgestimate
-Desogestrel
- Etonogestrel
-Drospirenone
-Medroxyprogesterone acetate

Question 36

selective progesterone receptor modulators

Answer 36

Ulipristal acetate (Ella ®)

Question 37

progesterone antagonist

Answer 37

Mifepristone (Mifeprex)

Question 38

atypical drugs

Answer 38

Danazol (Danocrine ®)