Progestins - 15 Flashcards

1
Q

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
A
  • progestin
  • hormone, corticosteroids
  • ovary, testis, and adrenal glands
  • corpus luteum, luteal
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2
Q

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 ___
A
  • any route
  • 5 min
  • first pass
  • pregnanediol, glucuronic acid
  • urine
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3
Q

Physiologic effects

Menstruation cycle
* Causes the ___ and ___ changes in the endometrium following ovulation.

A

maturation and secretory

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4
Q

Physiologic effects

Metabolic effects
* ___ basal insulin levels and the insulin response to glucose.
* Promotes ___ storage in the liver.

A
  • increases
  • glycogen
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5
Q

Physiologic effects

Interference with aldosterone
* competes with ____ for the mineralocorticoid receptor.
* Causes a decrease in ___ reabsorption → Increase in ___ secretion by the ____ (in pregnancy)

A
  • aldosterone
  • Na+, aldosterone, adrenal cortex
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6
Q

T or F: progestins have depressant and hypnotic effects on the brain

A

True

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7
Q

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
A
  • estrogens
  • uterine, carcinoma
  • outside
  • inflammation
  • suppress
  • painful
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8
Q

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
A
  • ketone
  • oral
  • 18
  • acetyl, oral, 17B-OH
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9
Q

“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
A
  • 1st
  • 17
  • 19, progestenic
  • H
  • OH
  • hydrolyzed
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10
Q

Levonorgestrel
* ___ generation progestin
* ___ isomer of norgestrel, which is a racemic mixture. Only ___ form is active
* ___ oral bioavailability
* used in ___

A
  • 2nd
  • levo, levo
  • high
  • IUDs
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11
Q

Norgestimate

  • prodrug
  • Converted to levonorgestrel ___ and
    then to levonogestrel in ___.
A
  • oxime
  • vivo
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12
Q

Desogestrel

  • ___ generation
  • prodrug (no ___)
  • repidly metabolized to ___
  • ___ oral bioavailability due to extra ___ groups
A
  • 3rd
  • ketone
  • etonogestrel
  • high, methyl
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13
Q

Etonogestrel

  • The active form of ___
  • structurally analogous to ___
  • used as the subdermal implant ___ or vaginal ring ___
A
  • desogestrel
  • levonorgestrel
  • Nexplanon, Nuvaring
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14
Q

Drospirenone

  • ___ generation
  • Relatively weak progestogenic
    activity (10% of ___)
  • ___mineralocorticoid activity
  • negates side effects of ___ in combination therapy
A
  • 4th
  • levonorgestrel
  • anti
  • ethynyl estradiol
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15
Q

Medroxyprogesterone acetate

  • ___ generation
  • administered as a ___
  • ___ acting progesterone only contraceptive
A
  • 1st
  • depot injection (Depo-Provera_
  • long
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16
Q

Hormonal activities of progestins

Progestins frequently have hormonal activities other than progestonic effects
due to their interaction with ___
* Minimizing ___ and ___ activities are desirable.

A

other steroid receptors
androgenic, antiestrogenic

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17
Q

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: ___)

A
  • mestranol, ethynyl estradiol
  • 21, 7
  • estrogen, norethindrone
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18
Q

Hormonal contraception

Delivery
* mostly ___ administration
* adherence to administration schedule is more critical for ___ only therapies
* implantable; ___ , IUD; ___ , or depot injection; ___

A
  • oral
  • progestin
  • etonogestrel, levonogestrel, medroxyprogesterone acetate
19
Q

Pharmacological effects of oral contraceptives

Inhibition of ovulation
* combos of estrogens and progestins selectively inhibit ___ function
* progestin only contraceptives do not always ___ ovulation

A
  • pituitary
  • inhibit
20
Q

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

A
  • ovarian
  • 1-2 months
21
Q

Pharmacological effects of oral contraceptives

Effects on the uterus
* Change in the ___ and in the uterine endometrium → decrease in the likelihood of ___ and ___.

A
  • cervical mucus
  • conception
  • implantation
22
Q

Pharmacological effects of oral contraceptives

Effects on the breast (___ only)
* breast ___
* suppression of ___

A
  • combinations
  • enlargement
  • lactation
23
Q

Adverse effects of oral contraceptives

mild
due to estrogens: 4
due to progestins: 3

A
  • nausea, hypertension, edema, breast fullness
  • increases appetite, fatigue, breast regression
24
Q

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

A
  • irregularities, breakthrough, progestin
  • hisutism, androgen-like
25
Q

Adverse effects of oral contraceptives

Severe
* venous ___ disease due to ___
* myocardial ____ - due to androgenic activity of ___
* can be dangerous in women over 35 who ___

A
  • thromboembolic, estrogens
  • infarction, progestins
  • smoke
26
Q

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 ___.
A
  • increase, glucocorticoids
  • phenytoin, liver, decrease
  • rifampin, drug metabolizing, increases
  • tetreacyclines, enterohepatic recycling
27
Q

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
A
  • 99%, 72 hours
  • higher
  • Yuzpe, 50 mcg, 500 mcg
  • 750 mcg
  • Nausea/vomiting
28
Q

Ulipristal acetate (Ella)

  • Selective ___ receptor modulator (SPRM)
  • used as an ___ contraceptice
  • can be effective up to ___ days after unprotected sex
  • side effects: ___ and ___ pain
A
  • progesterone
  • emergency
  • 5
  • nausea, abdominal
29
Q

Mifepristone

  • Abortifacient: used in combination with ___ (a ___ derivative, oral prostaglandin)
  • side effects: nausea, vomiting, bleeding (5%)
A
  • misoprostol, PGE1
30
Q

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
A
  • weak, antiestrogen
  • endometriosis, LH, FSH, ovarian
  • atrophy
  • androgenic, breast, oily
  • hepatic
31
Q

What is this?

A

Danazol

Endometriosis treatent

32
Q

What is this?

A

Desogestrel

33
Q

What is this?

A

Drospirenone

34
Q

What is this?

A

Ethynodiol diacetate

35
Q

What is this?

A

Etonogestrel

36
Q

What is this?

A

Levonorgestrel

37
Q

What is this?

A

Medroxyprogesterone acetate

38
Q

What is this?

A

Mifepristone

Abortifacient

39
Q

What is this?

A

Norethindrone

40
Q

What is this?

A

Norgestimate

41
Q

What is this?

A

Pregnanediol (inactive)

progesterone metabolite

42
Q

What is this?

A

progesterone

43
Q

What is this?

A

Ulipristal acetate

SPRM - emergency contraception