PROGESTRONE.pptx

PROGESTRONE.pptx

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  PROGESTRONE
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  PROGESTOGENS Progesterone is themost important progestogen in humans. It is derived from CHOLESTROL. In addition to having important hormonal effects, it serves as a precursor to the estrogens, androgens, and Adrenocortical steroids. It is synthesized in the ovary, testis, and adrenal cortex from circulating cholesterol. Large amounts are also synthesized and released by the PLACENTA during pregnancy. In the ovary, progesterone is produced primarily by the corpus luteum. Plasma levels of progesterone are further elevated and reach their peak levels in the third trimester of pregnancy. It is stable white crystalline solid with two polymorphic forms i.e. prism form and needle form . 21 C PRO-GESTARE-Meaning to carry about
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  In non-pregnant female-Regulationof menstruation. In pregnant female-Progesterone favors pregnancy by: Preventing endometrial shedding. Reducing uterine motility. Inhibits immunological reaction towards the fetus. In males its function is associated with sperm development. Increases Ca2+ mobilization in sperm.
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  Gonadotropin-releasing hormone Luitenizing hormone Progesterone
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  PROGESTRONRECEPTOR The progesterone receptor(PR) is a progestin-activated steroid receptor also known as NR3C3 Nuclear receptor subfamily 3 group C member 3.It is a INTACELLULARRECEPTOR.It has two forms PR-A and PR-B. Since the ligand-binding domains of the two PR isoforms are identical, there is no difference in ligand binding. However, the biological activities of PR-A and PR-B are distinct and depend on the target gene in question PR-B mediates the stimulatory activities of progesterone.PR-A strongly inhibits this action of PR-B - CNS UTERUS OVARY CEREBELLUM SPINAL CHORD HYPOTHALIMUS
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  MECHANISMOF ACTION The progesteronereceptors (PR) has limited distribution in the body confined mainly to the female genital tract, breast, CNS and pitutary.Upon hormone binding PR undergoes dimerization, attaches to progesterone response element (PRE) of target genes and regulate transcription through coactivators.
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  METABOLISM Reduction to pregnandiol,pregnanetriol and pregnanolone. Subsequent conjugation results in the formation of glucuronide and sulfate metabolites. EXCRETION The metabolites of pregnanediol and preganolone are excreted into urine, feces and bile, enterohepatic recycling. ABSORPTION Progesterone undergo high 1st pass metabolism, hence mostly given by I.M in oily solution. They have a short half life in the plasma, so usually prescribed for twice or thrice-daily administration. A Micronized preparation of progestrone is rapidly absorbed after its administration by any route. DISTRIBUTION Progesterone is extensively bound to plasma protein, primarily albumin (50 to 54%)and cortisol-binding protein (43 to 48%).
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  NORMAL RANGES INMALE AND FEMALE • High levels of progesterone typically don’t cause any negative health effects. Progesterone levels naturally reach high levels during pregnancy. • In fact, progesterone is present in oral contraceptives because it can trick the body into not ovulating. • A study suggests that progesterone plays a protective role against ovarian cancer. • Low levels of progesterone can also contribute to certain conditions, including: absence of menstruation miscarriage poor ovarian function STAGE PROGESTERONE LEVEL (NG/ML) pre-ovulation < 0.89 ovulation ≤ 12 post-ovulation 18–24 first trimester 11–44 second trimester 25–83 third trimester 58–214 Males 0.03 mcg/dL
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  In the middleof a person’s menstrual cycle, a rise in levels of luteinizing hormone leads to ovulation. Ovulation refers to the release of an egg from one of the two ovaries. Once the egg is released, the corpus luteum forms and begins producing progesterone. Progesterone helps to prepare the body for pregnancy by stimulating glandular development and the development of new blood vessels. This provides a good environment for implantation by a fertilized egg. Progesterone helps to prepare the body for pregnancy by stimulating glandular development and the development of new blood vessels. This provides a good environment for implantation by a fertilized egg.If the egg isn’t fertilized, the corpus luteum breaks down, leading to a drop in progesterone levels. This decrease causes the endometrium to break down, causing the beginning of a menstrual period.
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  ACTIONS  Maintenance ofpregnancy by preventing endometrial shedding, decreases uterine motility and inhibiting immunological rejection of fetus( T cell function and cell mediated immunity) SPECIFICACTIONS UTERUS- secretory changes in estrogen primed endometrium(hyperemia, tortuocity of glands and increased secretion).Continued action of progesterone cause decidual changes in endometrium (stroma enlarges, becomes spongy, glands atrophy and decreases sensitivity of myometrium to oxytocin) CERVIX-converts watery secretion (estrogen produced) to viscid, scanty and cellular which is hostile to sperm penetration VAGINA- induces pregnancy like changes in the mucosa-leukocyte infiltration of cornified epithelium
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  ACTIONS  BREAST -it causes proliferation of acini in the mammarygland. Acting along with estrogen which prepares the breast for lactation.  CNS - may have sedative effect.  BODY TEMPERATURE-causes slight (0.5 C) rise in bodytemperature.  RESPIRATION -may stimulate respiration at high doses.  METABOLISM -prolonged use of OCP impairs glucosetolerance. They also tend to raise LDL and lower HDL(ie.19-nortestoserone derivatives).  PITUTARY -progesterone is a weak inhibitor of Gonadotrophin secretion.
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  PROGESTRON DERIVATIVES-PROGESTINS • PROGESTRONDERIVATIVES (21 C) These are pure progestins.They have weaker anti- ovulatory action and are used primarily as adjutants to estrogen for HRT, threatened abortion and endometriosis • MEDROXYPROGESTERONE ACETATE • MEGESTROL ACETATE • DYDROGESTRONE • HYDROXYPROGESTRONE CAPROATE • NEWER COMPOUND • NOMEGESTROL ACETATE • 19-NORTESTOSTERONE DERVATIVES(18 C) They have weak estrogenic, androgenic and anabolic action but have potent anti-ovulatory actions. They are mainly used in combined contraceptive pills. • OLD • NORTHINDRONE • LYNESTRENOL • ALLYLESTRENOL • LEVONORGESTREL • NEW • DESOGESTREL • NORGESTIMATE • GESTODENE
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  CLINICAL USES OFPROGESTINS • Rectify hormonal deficiency and HRT • Control of dysfunctional uterine bleeding. • Contraception • Suppression of postpartum • Management of endometriosis • Treatment of endometrial carcinoma
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  ADVERSE EFFECTS Breast engorgement,head ache, rise in body temperature, edema, esophageal reflex, acne and mood swings may occur with higher doses. Irregular bleeding (amenorrhea) may occur if given continuously 19-nortestosterone derivatives lower plasma HDL level thereby may promote atherogenesis ( not seen in progesterone and its derivatives) Long term use in HRT may increase risk of breast cancer. Blood sugar may rise and diabetes may be precipitated by long term use (levonorgestrel) Intramuscular injections of progesterone are painful. If given in early pregnancy they can cause masculinization off male fetus or other congenital abnormalities.
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  ANTI-PROGESTIN • Antiprogestins havea 17-alpha substitution, which promotes higher binding affinity to both progesterone and glucocorticoid receptors, and an 11-beta substitution, which appears to be responsible for the antagonistic action. Antiprogestins also exhibit progestin agonistic and even antiestrogenic properties. Induction of a medical abortion in very early pregnancy is the most frequent clinical use of the antiprogestin MIFEPRISTONE (RU- 486). Antiprogestins may someday be used as a contraceptive since very low doses of antiprogestins cause considerable changes in endometrial morphology. At these low doses, they do not affect hormonal secretion or ovulation or bleeding patterns. At high doses, they delay ovulation but are associated with unopposed estrogen action on the endometrium. At low doses, antiprogestins do not always delay ovulation. RU-486 is a very effective and safe postcoital contraceptive. Antiprogestins may be beneficial in treating endometriosis, uterine myoma, and steroid-dependent tumors (e.g., breast cancer). They may be used to induce labor in cases of intrauterine fetal death. Antiprogestins may prove useful in treating Cushing's syndrome due to ectopic adrenocorticotropic hormone secretion, in lowering intraocular pressure in glaucoma, and in preventing the progression of viral diseases in humans. They also appear to have even more potential benefits, such as treatment of burns.