Ppt on antifertility

ANTIFERTILITY

1. Presentation on screening model of antiaesthmatic drugs FACULTY OF PHARMACY Presented by : Guided by: Mohd Fahad Dr.Anuradha Mishra M. Pharm Ist Year (Pharmacology) INTEGRAL UNIVERSITY

2. Antifertility drugs  are chemical substances which suppress the action of hormones that promote pregnancy. These  drugs  actually reduce the chances of pregnancy and act as a protection. Antifertility drugs  are made up of derivatives of synthetic progesterone or a combination of derivatives of estrogen and progesterone.

3. CLASSIFICATIONS— GnRH antagonist: Either  Gonadotropin-releasing hormone  (GnRH) or any  Gonadotropin-releasing hormone agonist  (i.e. Lupron) may be used. GnRH stimulates the release of gonadotropins (LH and FSH) from the anterior pituitary in the body . Oestrogen antagonists: Fertility medication inhibiting the effects of  estrogen  includes  Clomiphene  and  Aromatase inhibitors . Clomiphene:- Clomiphene  (trademarked as  Clomid ) is a  selective estrogen receptor modulator  (SERM). It is the most widely used fertility drug. It is used as an  ovarian stimulator  by inhibiting the negative feedback of estrogen at the hypothalamus. As the negative feedback of estrogen is inhibited, the hypothalamus secretes GnRh which in turn stimulates the anterior pituitary to secrete LH and FSH which help in ovulation .

4. Aromatises inhibitors---- Although primarily a breast cancer treatment,  aromatase inhibitors  can also work as fertility medication, probably through a mechanism similar to clomiphene. Gonadotropins---- Gonadotropins  are the hormones in the body that normally stimulate the  gonads  (testes and ovaries). For medication, they can be extracted from urine or by genetic modification. For example, the so-called  menotropins  consist of  LH  and  FSH  extracted from human  urine  from  menopausal  women. ]  FSH and FSH analogues are mainly used for  ovarian hyperstimulation  as well as reversal of  anovulation .

5. Human chorionic gonadotropin Human chorionic gonadotropin (hCG) is normally produced during pregnancy. However, it can also replace LH as an  ovulation inducer . Other hMG is a medication containing a  follicle-stimulating hormone  (FSH) and a lutenizing hormone (LH).

6. Methods for female Female antifertility agents might be acting through following machanism:- 1.Inhibition of ovulation. 2.Prevention of fertilization. 3.Interference with transport of ova from oviduct to endometrium of the uterus. 4. Interference with the implantation of fertilized ovum. 5.Distraction of early implanted embryo.

7. In vivo methods Vaginal opening Assay for water uptake Four –day uterine weight assay Vaginal cornification Chick oviduct method Anti estrogenic activity Antagonism of physiological effect of estrogen. Aromatase inhibitor

8. CONT.... Antiovulatory Activity : HCG-induced Ovulation in Rats. Cupric Acetate-induced Ovulation In Rabbits Progestational activity Pregnancy maintenance test. Prolifration of uterine endometrium in estrogen-primed rabbit test

9. IN VIVO MODEL PREGNANCY MAINTENANCE TEST PRINCIPLE:- PROGESTERONE IS RESPONSIBLE FOR THE MAINTENANACE FOR THE PREGNANCY.THIS PRINCIPLE IS USED FOR THE SCREENING OF PROGESTATIONAL COMPOUND . PROCEDURE- Ovariectomy is done on day 5/10/15 of pregnancy in diff group of pregnant rats the animals are treated with diff test and standard drug The average of living fetuses at the end of the experiment is compared with standard and control group. NOTE-The ED50 progesterone is 5mg/day in rat and less the 0.5mg/day in mouse

10. Antiovulatory Activity HCG-induced Ovulation in Rats. Principle : Immature female albino rats do not ovulate spontaneously and do not show cyclic changes of the vaginal epithelium. Priming with human chorionic gonadotropin (HCG) induces follicular maturation, followed by spontaneous ovulation 2 days later. Injection of anti-ovulatory drugs, prior to the induction procedure will prevent ovulation. This principle is used for the screening of anti-ovulatory agents.

11. Procedure : immature female albino rats(24-26 days) Treated with various test drugs in a different dose levels After the administration of test drug HCG is given exogenously for ovulation After 2 days Animals are sacrificed Ovaries are dissected out, preserved In 10% buffered solution and subjected to histopathological evaluation Result are compared with control group

12. Carbonic Anhydrase activity in rabbits endometrium Principle:- This is linear dose response relation ship b/w dose of progestogens and carbonic anhydrase activity in rabbit endometrium. Procedure:- Immature female albino rat are used in this study. The animal are primed with estradiol and followed by the administration of test and std drug. After the drug treatment animal are sacrificed and uteri are removed. The endometrium extract of the uterus is evaluated for the carbonic anhydrase activity calorimetrically.

13. Prevention of Abortion in Oxytocin Treated Pregnant Rabbits Principle:- IV administration of oxytocin to the pregnant rabbit on 30 day of pregnancy causes abortion .prior administration of progestational compound s prevents the abortion. Procedure :- Ten units of oxytocin are administered iv to pregnant rabbits on day 30 of pregnancy . 24 h before oxytocin ,Test and std drug in oil are injected control animal are not receiving drug abort within 2-30 min after oxytocin. The drugs,which are having progestational activity,prevent abprtion.

14. In Vitro Methods Estrogenic Activity Estrogen receptor binding assay Anti-Progestational Activity Anti-progestational Activity In Immature Rabbits Anti-implantation Activity

15. Estrogenic Activity Estrogen receptor binding assay Principle : Estrogen receptor binding assay uses the principle of competitive binding of labeled and unlabeled estrogen on the estrogenic receptors. Estrogenic compounds displace the labeled estrogen in a concentration dependent manner from th eestrogen receptor.

16. Procedure: Uterus removed from Female albino mice (18 days old) Homogenized at 0 C OF Tris sucrose buffer in a conical homogenizer Human endometrium from menopausal women is frozen within two hour of hysterectomy Stored in liquid nitrogen until use

17. Cont..... Frozen endometrium homogenized in Tris- sucrose buffer Homogenates are centrifuged for 1 h Determination of specific binding in mouse uterus cytosol as a function of steroid conc. Incubation time and temp Triplicate aliquots of 125 ml of cytosol are incubated with 5 or 25 nm labeled steroid either for 2 or 24 h at 0 C for 2 or 5 hours at 25 C

18. Anti-Progestational activity in Rabbits Principle:-the anti progestational comp inhibit some/all the physiological effect of progesterone. The principle is used to screening the anti-progestational activity

19. Mc Ginty TEST Immature rabbits(700-950g) are taken direct injected progesterone into a uterine segment. Estardiol at a dose of 1 micro gram per kg per rabbit is injected by Sc route to the rabbit of positive control and test group. The rabbit of negative control group received only the vehicle (0.5 % CMC ) by subcutaneous route for 6 days. On the 7 th day, the rabbit is anesthetized by intramuscular injection of ketamine hydrochloride (Dose 35 mg/kg). The abdomen is open and the uterus is exposed by laparotomy. The upper middle segment of each horn is ligated without disturbance of blood circulation. In positive control group, 0.1 ml of progesterone was injected alone in the right uterine horn (Conc. 0.1 mg/ml).

20. Cont...... In the opposite horn,only 0.1mlof the vehicle is injected In the test group a solution of progesterone and the test drug in 0.5%C.M.C is injected into the left lumen of segment through the lower ligature,which is drawn tight after the injection . Progesterone is injected alone in the right uterine horn. In the negative control group,progesterone alone is injected in the right uterine horn

21. Cont... In the opposite horn only vehicle is injected. After the injection,the lower ligature can be tightened. 3 days later,the animal were sacrificed. The uteri was excised,weighed,fixed in buffered formaline. The section of the horn are evaluated histologically according to Mc phail score

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