ASSIGNMENT ON:-

Progestins

Submitted to D. Ravi Chandra Sekhar Reddy M.Pharm

Submitted by T.V.Subba Rao B.Pharm

University College of Pharmaceutical Sciences, Acharya Nagarjuna University, Nagarjuna nagar, Guntur.

PROGESTINSDef.:- These are the substances which convert the estrogen primed endometrium to secretory and maintain pregnancy in animals after conception.

Progestin :- favoring pregnancy.

Menstrual cycle:-

Release of progesterone:-

Positive and negative feedback of progesterone:-

Hormone concentrations during menstrual cycle:-

Progesterone levels in menstrual cycle:-

Adrenal gland :-

Synthesis of progesterone:-

Functions:-

1. Preparation of uterus for maintenance of pregnancy

2.Prevention of endometrium shedding

3.Decreased uterine motility

4.Inhibition of immunological rejection of the foetus(progesterone depresses T-cell function and cell mediated

immunity)

Actions :-

1. CNS :- have sedative like effect in high concentrations during pregnancy.

2. Body temperature :- cause a slight(0.5oc) rise in body temperature

3. Respiration :- In relatively higher doses stimulates respiration

4. Metabolism :- prolonged use of oral contraceptives impairs glucose tolerance in some women. 19-

nortestosterone derivatives tend to raise LDL & lower HDL levels.

TYPES OF PROGESTERONS (BASED ON NATURE)

1. Natural progestin :-

i. progesterone a 21Carbon steroid and is derived from cholesterol.

ii. It is secreted by corpus luteum (10-20mg/day) in the later half of menstrual cycle under influence of LH.

2. Synthetic progestin's :-

These are either

i. progesterone derivatives (21C) or

ii. 19-noortestosterone derivatives (18C).

i. Progesterone derivatives :-

ex :- medroxyprogesterone acetate,

megestrol acetate,

dydrogesterone,

hydroxyprogesterone caproate,

nomegestrol acetate (newer compound).

ii. 19-nortestosterone derivatives :-

ex :- older compounds newer compounds

noerthindrone desogestrel

lynestrenol norgestimate

allylestrenol gestodene

levonorgestrel

Pharmacokinetics:-

• Progesterone, unless specially formulated, is inactive orally because of high first-pass metabolism in liver.

• It is mostly injected i.m in oily solution, has a short t1/2 (5-7 min).

• It is completely degraded in liver – major product is pregnanediol which is excreted in urine as glucoronide and

sulfate conjugates.

• A micronized formulation of progesterone has been developed for oral administration.

• Most of the synthetic progestin's are orally active and are metabolized slowly; have plasma t1/2 ranging from 8-24

hrs.

Adverse effects :-

Irregular bleeding or amenorrhea can occur if a progestin is give continuously.

The 19-nortestosteron derivatives lower plasma HDL levels may promote atherogenesis, but progesterone and its

derivatives have no such effects.

Long term use of progestin in HRT may increases the risk of breast cancer.

Blood sugar may rise and diabetes may be precipitated by long term use of potent agents like levonorgestrel.

Given in early pregnancy, progestin's can cause masculization of female foetus and other congenital abnormalities.

Uses :-

as contraceptive

Hormone replacement therapy(HRT)

Dysfunctional uterine bleeding

Endometrosis

Premenstrual syndrome/tension

Threatened/habitual abortion

Endometrial carcinoma

Anti progestin :-

Ex :- mifepristone

Þ It is a 19-norsteroid with potent competitive antiprogestational and significant antiglucocorticoid as well as

antiandrogenic activity.

Þ it is orally active, but bioavailability is only 25%.

Þ It is largely metabolized in liver by CYP3A4 and excreted in bile with t1/2 20-36hrs.

Uses of anti progestin's :-

Termination of pregnancy

Cervical ripening

Postcoital contraceptive

One month contraceptive

Induction of labour

Cushing's syndrome

Progesterone levels during pregnancy:-

Hormone levels during pregnancy:-

References:-

1. K.D. Tripathi

2. Net

Thank you