Anti Fertility Agents Final

8/10/2019 Anti Fertility Agents Final

http://slidepdf.com/reader/full/anti-fertility-agents-final 1/24

Anti Fertility Agents andOvulation Inducing Drugs

Submitted By

P.Poongothai



Physiology of Human Reproduction

The reproductive cycle in the human in whenOvulation is a key event. is the result of theinterplay of the hypothalamus the pituitary and theovaries. With respect to ovulation, the mammalianfemales can be divided into two groups

I.Relfex ovulators

E.G.Rabbits, Cats, ferrets and rinks, in when thesensory stimulus of mating or electrical stimulationof cervix induces ovulation.

II.Spantaneous ovulators

like cows, monkeys and women in whom tofollicular rupture occurs in the absence of anyimmediate sensory stimulus.



Fertility Control

The Fertility control can be achieved by

Controlling the central mechanism

Modifying other physiological mechanism ofreproduction

Preventing the union of sperm with ovum

Fertility Controlled by using drugs which can act by Inhibiting ovulation

Modifying the cervical mucus

Interfering with the implantation

Slowing down the rate of egg transfer Preventing the ovum maturation and sperm

capacitation

Immunological methods : and

Inhibiting spermatogenesis in males



Estrogen – progestin combination pill

Since the first clinical demonstration of use3fulness

of such an oral combination for contraception bypincus (1955) Several commercial preparationshave been available. The pills are

Remarkable efficacy

Relative safety; and

Ease of administration

Combination oral contraceptive (COC) pills :

It contain

a) Ethinylestradial or its 3-methyl either mestranolas the estrogen; and

b) A progestin belonging to 19-nortesterone group(nonethisterone, norgestral or ethynodiol

acetate) or a derivative of norgestrel(desogestrel)



Methods of Administration

Fixed dose combination pills (Monophasic pills)

The commonest procedure is to administerone pill containing both an estrogen and progestindaily, orally at bed time, for 21 days, from 5th to

25th day of 28 day cycle. The next coarse is started7 days after the last dose.

The pill should be avoided in breast feeding

women as if interfers with lactation

When used properly the ‘Pill’ is the most effective(99% to 100%) contraceptive available.



Biophasic and Triphasic combination pills :

These are combination oral contraceptive pillscontaining varying proportions of an estrogen

and a progestin and are designed to stimulatethe hormonal profile of the normal menstrualcycle.

Extended cycle COC :

a) A COC pill containing 30 mcg of ethinyl estradioland 150 mcg of levonorgestrel (seasonable) iftaken daily for 84 days. The major advantage is

it reduces the number of menses.b) Another pill available (Lybrel) contains EE 20mcg

and levonorgestrel 90 mcg. It causeamenorrhaea within an year.



Mechanism of action

The mechanism of the contraceptive action of theseagents in complete, The combination type suppresses bothFSH rise (due to the estrogen component) and LH peak (due

to the progestin component) observed during the normalmenstrual cycle by inhibiting the release of GnRH. Thusfollicular growth is not initiated and ovulation does notoccur.

Pharmacological actions of COC pills

EndometriumPituitary – ovarian axis

Metabolic effects

Hyperglycemia

Glycosuria

Mildly impaired glucose tolerance Abnormal GTC related to dose to progestin

Desogestrel affect carbohydrate metabolism

Cholesterol increase

LOL Increase

HDL Decrease



General

Nausea

AncrexiaVomiting

Bleeding irregularities

Thromboembolic phenomena Hypertension

Uterine fibroids

Carcinogenicity



Therapeutic use

An oral contraceptives

These pills safe, lighty effective and acceptable Postcoital contraception

Polycystic contraception

Dysfunctional uterine bleeding

Premature menopause Turner syndrome



Progestins Alone as contraceptives

Levonorgestral

This 19, nortestosterone compound possessvery potent progestational activity. In the daily anddose of 30mcg (Microval) continuously. If preventsconception. The drug probably acts by severalmechanisms. It reduces the sperm penetrability ofthe cervical mucus and impairs luteal function. Itcauses irregular and generally start bleedingintervals.

‘Progestin-only’ pills are currently used anonly in patients with a specific contraindication toestrogen, in breast-feeding mother. The pill shouldbe started by a breast-feeding mother 6 weeks

after childbirth.



Antiestrogenic Agents

Levormeloxifene

This chroman derivative, shows weakestrogenicity, potent anti-estrogenicity and isdevoid of progestogenic or androgenic activity.

The main side effect is prolonged menstrualcycle, and enlarged ovaries. It should be avoided inpolycystic ovarian disease, renal and hepaticdisorders, tuberculosis and lactating mothers.



Injectable contraceptives

Injectable progestational preparations,depotmedrooxy progestrone acetate andnorestisterone enanthate are highly effective, longactive. They enter circulation directly with outpassing through liver. They don’t cause birth defectand not affect sex drive.

Medroxyprogestrone Acetate

MPA is a progestational compound which iseffective both orally and parenterally. It is notmetabolized into estrogen in body. The long acting

DPMA is given by IM and inhibit LH, lead tosuppression of valuation. It act on endometriumfallopian tube and cervical mucus and excrete inbreast milk but does not suppress lactation.Repeated injections cause prolonged ovulationinhibition for several months after discontinuation.



Adverse Reactions

Bleeding irregularities, spotting, prolongedamenorrhea, weight gain and adrenal suppression.

Levonorgestral Implant

It consists six, flexible, silastic rods,containing levonogestral in crystalline form. The

machanism of action of this is an antiestrogenicon endometrium and cervical mucus which becomethick and adverse to sperm penetration. LH peakand ovulation are suppressed.



Adverse Reactions

Local injection, irregular bleeding,amenorrhoea, headache, nervousness, nausea,skin rash, aone, hirustism, brest tenderness,weight gain and enlarged ovarian follicles.

Progestin IUCD

progestasert consists of progesterone micro-crystals in a silicon fluid, surrounded by a release-rate-limiting membrane. It release minutequantities of drug over a period of one year.Menstrual pattern is not disturbed, ovulation is not

suppressed and it used to treat menorrhagia.



Mifepristone (Ru 486):

This derivative of norethisterone has antiprogestin activity.

Pharmacological actions:

Administered to women in early and late luteal phases of themenstrual cycle. It inhibit glandular secretary activity and accelaratedegenarative vascular changes lead to menstrual bleeding within 72-hours. It acts as progesterone antagonist in the presence of.

Progesterone and act as an agonist in the absence of progesterone.

Absorption, Fate, Excretion

It administered :orally or parenterally and metabolized slowlyby liver and excreted in bile.

Adverse reactions:Single dose cause nausea vomitting, abdominal pain, and

heavy prolonged bleeding. Long term administration cause fatigue,anemia, weight loss, thining of hair, menstrual disturbance, decreasein libido and gyneco mastia.



Therapeutic uses:

Post – coital containing IUCDS inserted within 5

days from the day of sexual inter course is alsoeffective as post. coital contraceptive agents.

Induction of abortion.

Cervical dilatation.



Male contraception:

In males androgen, estrogen, progestin and also

steroid combination inhibit spermatogenesis.Gossypol:

It is a polyphenolic compound obtained from cottonseed. In rat, it cause dose dependent germinal celldamage of testes, long term treatment lead tosterility. It does not damage leyding cell and nogenetic damage. Adverse effects are GIdisturbances, fatigue, dizziness, decreas3ed libido,hypokalemic paralysis.



Ovulation Inducing Drugs:

The problem of infertility is a joint one and bothpartners need detailed examination.

Deficiency of the thyroid hormone is anuncommon cash cause responsible for anovulatorycycles. Estrogen administration cause LH release inrodents, monkey and women. Low dose estrogenuse in some follicular activity is present but

midcycle LH peak is lacking or corpus luteum isinadequate.

Progestins are useful in inadequate corpuslueteum and endometriosis.

Dexamethasone in small doses (0.25 – 0.5daily) induces ovulation in some PCOs patient bysuppressing androgen



Classification of ovulation inducing drugs

I. Synthetic GnRHII. Human manopausal and chorionic

gonadotrophins

III.Bromergocriptine

IV.Anti estrogenic compound clomiphene citrate



Clomiphene Citrate

It is a triphenylesthylene compound resembleto stilbestrol and chlorotrianisene. In rat, it

stop estrous cycle, decrease secretion of

gonadotropins and reduce the size of ovaries. It

induce ovulation. It available in ‘Cis’ and ‘trans’ form and ‘cis’ form structurally resembles to

estrogen



Pharmacological actions

Antiestrogenic action

It bind to estrogen receptor result inestrogen antagonist action.

Miscellaneous actionIt has a weak estrogenic action, on boneand endometrium.





Cylclofenil

It structure similar to clomiphene and

used to similar purpose. It given 200mgtwice a day for 10 days, it induceovulation.

Letrozol

This aromatase inhibitor used forovulation induction in PCO patients. Itreduce estrogen. It promote thedevelopment of healthy ovarian folliclesand ovulation.



Thankyou

Documents

Anti Fertility Agents Final