Progestin drugs

Question 1

Progestins

Answer 1

Progesterone
Norethindrone
Ethynodiol diacetate
Levonorgestrel
Noregestimate
Desogestrel
Etonogestrel
Drospirenone
Medroxyprogesterone acetate

Question 2

1st generation progestin names

Answer 2

Progesterone
Norethindrone
Ethynediol diacetate

Question 3

1st gen progestin properties

Answer 3

19-nor, 17 ethynyl steroids (oral contraceptives)
17-ethnyl group increases oral bioavailability
19-methyl group not necessary
Replacement of 19 methyl with H enhances activity
Replacement of 17 acetyl with OH increases oral bioavailability
Ester groups are rapidly hydrolyzed in vivo

Question 4

Levonorgestrel

Answer 4

2nd gen progestin
Levo isomer of norgestrel, which is a racemic mix
Only levo form is active
High oral bioavailability
Used in IUDs

Question 5

Norgestimate

Answer 5

Prodrug
Converted to levonorgestrel oxime and then to levonogestrel in vivo

Question 6

Desogestrel

Answer 6

3rd generation progestin
Prodrug
Rapidly metabolized to etonogestrel
High bio availability

Question 7

Etonogestrel

Answer 7

Active form of Desogestrel
Structurally analogous to levonorgestrel
Used in the subdermal implant (Nexplanon) or the vaginal ring

Question 8

Drospirenone

Answer 8

4th gen progestin
Relatively weak progestogenic activity (10% of levonorgestrel)
Anti mineralocorticoid activity
Negates Side effects of ethynyl estradiol in combination therapy

Question 9

Medroxyprogesterone acetate

Answer 9

1st gen progestin
Used for depot injection
as a long acting progesterone-only contraceptive

Question 10

Drug interactions

Answer 10

Other steroids
OCs may increase the blood levels of other steroids by interfering with their metabolism (i.e glucocorticoids)
Anticonvulsants
Phenytoin - induces drug-metabolizing enzymes in the liver
Antibiotics
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 11

Ulipristal acetate

Answer 11

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

Question 12

Mifepristone

Answer 12

RU-486
Progesterone antagonist
Abortificant
used in combo with misoprostol (PGEI derivative, oral prostaglandin) up to 70 days
SE: Nausea, vomiting, bleeding (5%) requires intervention admin only by physicians

Question 13

Danazol

Answer 13

Weak androgen, weak progestin, and antiestrogen
Effective for endometriosis
inhibits the surge of LH and FSH and suppress ovarian function; causes atrophy of the endometrium
Adverse effects: mostly from weak androgenic activity
Weight gain, decreased breast size, acne, oily skin, hirsutism
Contraindication
Hepatic dysfunction
Pregnancy and breast feeding