1 FARMACOLOGIA de la SECRECION OVARICAESTROGENOS PROGESTAGENOS ANTAGONISTAS de PROGESTERONA
2 LH MSH, POMC
3 ESTROGENOS Fuente: - Ovarios (teca interna y granulosa de foliculo ovarico). - Suprarrenales, Placenta y testiculos. - Conversión andrógenos estrógenos en: hígado, tejido graso, m. esquelético, folículos pilosos. - Alimentación (remolacha, lúpulo, papas, trébol).
4 ESTROGENOS CLASIFICACION: a) Estrogenos con estructura esteroide:Naturales: estradiol, estrona2, estriol3, equilina, equilenina. Sinteticos: etinilestradiol, mestranol, quinestrol b) Estrogenos sin estructura esteroide: Sinteticos: potencia, tolerancia y absorcion: dietilestilbestrol=Cancer, benzestrol, dienestrol.
5 ESTROGENOS Caracteres sexuales 2rios femeninos
6 ESTROGENOS EFECTOS FISIOFARMACOLOGICOSORGANOS SEXUALES FEMENINOS A) Utero Crecimiento uterino (txhipoplasico, aghipotrofico). Ciclo menstrual: fase proliferativa (crecimiento y reconstruccion endometrio, dia 4-14). Fase Secretoria (caen d28=hemorragias deprivacion hormonal) pildora postcoital.
7 ESTROGENOS EFECTOS FISIOFARMACOLOGICOSUtero Intensidad contraccion uterinat +oxitocina. Trompas de falopio. peristalsis, proliferacion y diferenciacion del endosalpinx. Cervix. cantidad, fluidez y cristalizacion del moco penetracion espermatozoides. Vagina. Estimula la queratinizacion epitelio mucoso de revestimiento vaginal.
8 ESTROGENOS Mamas. Crecimiento, volumen y # conductos galactoforos, depósito de grasa. Embarazo: pigmentacion areolar. Deficit=hipoplasia, Exceso=ginecomastia-hombre e inh lactacion en mujer. Ovarios Maduracion ovocito, sensibiliza accion de Gonadotrofin.
9 ESTROGENOS EFECTOS FISIOFARMACOLOGICOS2. En hipotalamo-hipofisis. Estrogenos ejercen autorregulacion cibernetica (feedback negativo) en Hipot e Hipof xa liberacion de GnRH, +LH y -FSH (ejm. CO). 3. Proteccion Embarazo. E2+progesterona: implantacion huevo fecundado y curso de la gestacion. Determinacion estriol urinario = estado y condición del feto.
10 - Estimulan matriz proteica (impiden perdida).ESTROGENOS Huesos - Estimulan matriz proteica (impiden perdida). - deposito de Ca (contenido mineral). - x eso uso en Tx restitución estrogenica2a en menopausicas evita osteoporosis y perdida piezas dentales, densidad mineral osea=T2.
11 - glicemia (= a GH, corticoides) ESTROGENOS 5. Acciones Metabólicas - glicemia (= a GH, corticoides) - Accion anabolica (=GH y Testosterona) - LDL, HDL (contrario a Testosterona ). - Retencion de agua y Na (= a Testoste, corticoides) - Distribucion de grasa en Mujer (=Corticoides?) - Higado: alteran el metabolismo y sintesis de proteinas (transcortina, glob fijadora de T4, transferrina, etc).
12 - Estimulan libido?. día 13. (=testosterona). 7. Piel y pelo ESTROGENOS 6. SNC, Libido y Siquismo: - Estimulante SNC: Ejm:+convulsiones en fase preovulatoria, ñas con disgenesia gonadal=desarrollo psiquicotx. Psicosis postparto Tx progesterona. =testosterona y corticoides. - Estimulan libido?. día 13. (=testosterona). 7. Piel y pelo elementos elasticos piel, acne. Embarazo: pigmentacion linea blanca, cloasma. Caida cabelloE2. (anti-androgeno: finasterida y dutasteridab)
13 adhesividad plaquetaria. factores II, VII, IX y X,ESTROGENOS 8. Tejido sanguineo adhesividad plaquetaria. factores II, VII, IX y X, plasminogeno coagulacion! (Testoster efecto estimulante eritropoyetina). MEC ACCION En R intrac de c blanco: Er alfa (mamas, vagina, utero, ovarios, hipotalamo y vasos) y Er beta (prostata, encefalo, pulmones y vasos).
14 ABSORCION, DESTINO y EXCRECIONESTROGENOS ABSORCION, DESTINO y EXCRECION vo, im, mucosas y piel naturales degradacion hepatica. Sangre 80% liga a betaglobulina organos sexuales. Metabolizados en Higado (cirrosis=hiperestrog H=ginecomastia). Naturales a estriol. Sinteticos conjugados con Ac glucoronico y sulfurico orina,
15 ESTROGENOS USOS CLINICOSGINECOLOGIA: Terapia de Reemplazo Hormonal: hipoplasia o insuf gonadal, agenesia ovarica. Dismenorrea, Hemorragia uterina disfuncional, Pre y postmenopausea. Evitar osteoporosis: +Ca, Vit D3 y fluoruros. Sintomas vasomotores. This low-dose estrogen transdermal patch, Estraderm (Estradiol Transdermal System), is transparent and about the size of a silver dollar. It releases small amounts of estrogen directly into the bloodstream at a constant and controlled rate to a female requiring estrogen replacement therapy for postmenopausal symptoms.
16 ESTROGENOS USOS CLINICOSContraceptivos (solos o combinados)
17 ESTROGENOS USOS CLINICOSVaginitis atrofica
18 ESTROGENOS USOS CLINICOSCardioproteccion? En enf coronaria arterioesclerotica. Enfermedad de Alzheimer? Inhibidor de lactancia, Dg embarazo, Tx Ca prostata (ya no). Acne Diagnostico de amenorrea (ovarica o endometrial?)
19 ESTROGENOS FCOPATOLOGIASinteticos+, n-v, anorexia. Cefalea, peso, hemorragias uterinas, induracion senos, trastornos sicologicos, estimulacion de neoplasias genitales y trastornos tromboembolicos. AdenoCa de endometrio. Ca de mama?. Cutaneas: cloasma, urticaria, eritema multiforme Coagulopatias, ictericia, HTA.
20 ESTROGENOS PRECAUCIONES Y CONTRAINDICACIONESHistoria personal o fliar de Ca genital o de mama, trastornos tromboembolicos, epilepticas o con tratornos cardiovasculares y diabeticas. Di-etil-estil-bestrol NO en embarazo x adenoCa vaginal y cervical o adenosis vaginal en hijas de madres q tomaron.
21 2. PROGESTERONA y COMPUESTOS GESTAGENOSSustancias naturales o sinteticas q` producen transformacion secretoria del endometrio (2da fase ciclo menstrual). Favorece el proceso de nidacion del blastocisto. Mantenimiento del embarazo.
22 PROGESTERONA y COMPUESTOS GESTAGENOSCLASIFICACION Deriv Progesterona: Clormadinona, megestrol, medroxiPg, dehidroxiPg. B) Deriv de 19-nortestosterona: 1. Estranos: etinodiol, linestrenol, norgestrienona, noretinodrel, noretisterona, tibolona. 2. Gonanos: desogestrel, gestodeno, Levonorgestrel, norgestimato, nomegestrol.
23 PROGESTERONA y COMPUESTOS GESTAGENOSORIGEN Pg y 17-hidroxiPg de: - Ovario (c. luteo) y - Capsulas suprarrenales colesterol
24 PROGESTERONA y COMPUESTOS GESTAGENOS ACC FISIOFARMACOLOGICAS1.Endometrio. Actividad secretora glandulares, llenan de glucogeno (xa blastocisto). 2. Cervix. Mucus espeso e impenetrable.
25 PROGESTERONA y COMPUESTOS GESTAGENOS3. Musculo uterino. Accion depresora (px o tx del aborto). (contrario E2). 4. Hemorragia por deprivacion +E2 xa diagnostico hormonal del embarazo (lutogynestryl).
26 PROGESTERONA y COMPUESTOS GESTAGENOS5. Favorece el proceso de nidacion del blastocisto (x la transformacion decidual y proceso mecanico de la nidacion). 6. Inhibe la capacitancia del espermatozoide en la cavidad uterina. 7. Mama +E2=proliferacion de los acinos glandulares. Lactancia i por E2-P2.
27 PROGESTERONA Y COMPUESTOS GESTAGENOS8. Accion termogena. oT dia x progester y otros progestagenos (excepto etisterona y dihidrogesterona). 9. Retrocontrol negativo a hipotalamo (CO). 10. Acciones metabolicas (contrarias a E2): secrecion insulina, almacenamiento glucogeno higado, secrecion urinaria de Na y nitrogeno, estimula la respiracion.
28 PROGESTERONA y COMPUESTOS GESTAGENOSABSORCION, DESTINO y EXCRECION Todas vias (Prog v.o. efecto 1er pasoT2yE2 pregnandiol (inactivo, dosificar en orina xa ver influencia progestacional) proteinas todos tejidos, aparato genital, hipotalamo e hipofisis orina (glucoronatos y sulfatos).
29 PROGESTERONA Y COMPUESTOS GESTAGENOSFARMACOPATOLOGIA Acne, edema, peso, molestias digestivas, Cefalea y depresion. Urticaria, prurito, candidiasis?, hemorragias uterinas, ictericia, libido, atrofia de la mucosa vaginal.
30 FARMACOPATOLOGÍA: AUMENTO DE LA MICCION N-V constipación diarreaDolor mamario cefalea Caída del cabello DOLOR ABDOMINAL ↑peso
31 PROGESTERONA y COMPUESTOS GESTAGENOSUSOS CLINICOS: Amenaza aborto y aborto habitual. Tx hemorragia uterina funcional, dismenorrea, tension premenstrual, endometriosis. Tx Ca mama y endometrio (megestrol).
32 FDA approves drug to reduce risk of preterm birth in at-risk pregnant womenFor Immediate Release: February 4, 2011 The U.S. Food and Drug Administration today approved Makena (Hydroxyprogesterone caproate) injection to reduce the risk of preterm delivery before 37 weeks of pregnancy, in pregnant women with a history of at least one spontaneous preterm birth. The drug is not intended for use in women with a multiple pregnancy, such as a twin pregnancy, or other risk factors for preterm birth. The FDA approved Makena under the agency’s accelerated approval regulations that allow promising drugs to be approved based on a surrogate endpoint benefit (here, reducing the risk of delivery before 37 weeks of pregnancy) that is reasonably likely to predict a clinical benefit. Under these regulations, the manufacturer must conduct additional studies after the product is approved to demonstrate that the drug does, in fact, have a clinical benefit. An international trial is ongoing to learn if there is also improvement in the outcome of babies born to women given Makena. Such outcomes include reducing the number of babies who do not survive or who suffer serious health problems shortly after birth. “Preterm birth is a significant public health issue in the United States,” said Sandra Kweder, M.D., deputy director of the Office of New Drugs in the FDA’s Center for Drug Evaluation and Research. “This is the first drug approved by the FDA that is indicated to specifically reduce this risk.” A health care provider would give Makena once a week by injection into the hip. Treatment should begin at 16 weeks and no later than 21 weeks of pregnancy. The FDA reviewed data on the safety and effectiveness of Makena in a multicenter randomized double-blind clinical trial. The study included 463 women 16 to 43 years of age who were pregnant with a single fetus and had a history of a prior spontaneous preterm birth. Among women treated with Makena, 37 percent delivered early (before 37 weeks) as compared with 55 percent of women in the control group. A separate study evaluated the development of children born to mothers enrolled in the controlled trial. In this study, children ages 2.5 years to 5 years reached similar developmental targets, regardless of the mother’s treatment. The confirmatory study that is ongoing will be followed by a similar infant follow-up study, to be completed about That study is expected to include infants, depending on the number of study sites and mothers willing to participate. The most common side effects reported with Makena included pain, swelling, or itching at the injection site; hives, nausea and diarrhea. Serious adverse reactions were rare; there was a single report each of blood clot in the lungs (pulmonary embolism) and an infection at the injection site. The FDA originally approved hydroxyprogesterone caproate under the trade name Delalutin in 1956 for use in pregnant women. The approved indications include threatened miscarriage. The original manufacturer requested the withdrawal of Delalutin from the market in 2000 for reasons unrelated to safety.
33 PROGESTERONA Y COMPUESTOS GESTAGENOS USOS CLINICOS:-solos/combinacion con Estrog. -Pildora postcoital o de emergencia (PAE)
34
35 PROGESTERONA Y COMPUESTOS GESTAGENOSPRECAUCIONES Virilizacion en el feto. (x Dg hormonal del embarazo).
36 3. ANTAGONISTAS DE PROGESTERONA MIFEPRISTONADerivado 19-noresteroide. Antagonista competitivo en Rec de Prog y cortisol. En hipotalamo es agonista x eso LH. No actividad antiEstrog y debil antiAndrog.
37 ANTAGONISTAS DE PROGESTERONA MIFEPRISTONA1. Abortiva: luteolisis, desprendimiento de decidua, contractibilidad uterina, dilatacion cervix, Favorece desprendimiento del embrion. Eficacia +temprano <9sem y + adm prostaglandinas E2 (Misoprostol, cytotec). 95%.
38 Anticonceptivo de emergenciaLa mifepristona también puede ser usada a menores dosis como un anticonceptivo de emergencia; si es que es tomada después del coito pero antes de la ovulación, la mifepristona puede prevenir la ovulación y por ende el embarazo. En este rol, una dosis de 10 mg no es tan efectiva como una de 600 mg, pero tiene menos efectos secundarios. El uso de mifepristona en una dosis de 25 mg a 50 mg (considerada una dosis media) como anticonceptivo de emergencia viene avalado por estudios clínicos del año 2008 que consideran a la mifepristona junto con el levonorgestrel y el DIU, pero por delante de éstos, como métodos anticonceptivos de emergencia más efectivos que el método de Yuzpe, el danazol y anordrin, estando asociados a menos efectos secundarios. El Mifeprex y Mifegyne están disponibles sólo en tabletas de 200 mg38
39 ANTAGONISTAS DE LA PROGESTERONA MIFEPRISTONAAbortiva: dosis unica 600 mg (90% eficaz) (myfegyne) 48 hoo x Pg E2 (misoprostol-Cytotec). 2. Util too CO postcoital = impide la implantacion. 3. Tx endometriosis (Danazol-ladogal, androgeno debil q` antagoniza accion de E2 )./
40 Método de Yuzpe Es un método anticonceptivo de emergencia que consiste en administrar 2 pastillas o tabletas de anticonceptivo oral de macrodosis que incluya 50 ug deEtinilestradiol y 250 ug de Levonorgestrel (Noral ®, Neogynon ®), durante las primeras 72 horas después del coito sin protección y repetir la ingesta 12 horas más tarde. En caso de no estar disponibleas las pastillas o tabletas de macrodosis se administran 4 tabletas de microdosis que incluyan 30 ug de Etinil-Estradiol y 150 ug de Levonorgestrel (Nordette ®, Microgynon ®) en las primeras 72 horas después del coito sin protección y tomar otras 4 píldoras 12 horas más tarde. Se considera un método seguro, económico, accesible y con efectos secundarios que implican en muy pocos casos náuseas.
41 Oral misoprostol for the management of incomplete abortion in EcuadorOral misoprostol for the management of incomplete abortion in Ecuador. CLINICAL ARTICLE Rolando Montesinos a, Jill Durocher b,⁎, Wilfrido León a, Mónica Arellano c, Melanie Peña b, Ernesto Pinto b, Beverly Winikoff b a Hospital Gineco-Obstétrico Isidro Ayora, Quito, Ecuador International Journal of Gynecology and Obstetrics Journal homepage: © 2011 International Federation of Gynecology and Obstetrics. Accepted 27 July 2011 Objective: To assess the feasibility of introducing misoprostol for the treatment of incomplete abortion in Quito, Ecuador. Methods: In a randomized prospective study conducted at a large tertiary-level maternity hospital and a private secondary-level clinic between November 2006 and November 2007, women with incomplete abortion were treated with either 600 μg of oral misoprostol (n=122) or manual vacuum aspiration (MVA) (n=120). All participants were requested to return for follow-up care on day 7 to determine the success of the treatment and to document their satisfaction with the method and the adverse effects experienced. Results: Sixteen percent of women (39/242) did not return for their follow-up visit and their outcomes are unknown. Among those who did return, 94% (100/106) of women showed successful completion of abortion after treatment with misoprostol, as compared with 100% (97/97) of women treated with MVA. Most women described their adverse effects after treatment as tolerable (misoprostol, 95%; MVA, 91%). Nearly all women reported being satisfied with their treatment (196/203); there were no differences among the women's reports of satisfaction according to treatment received. Conclusion: An oral dose of 600 μg of misoprostol was found to be an acceptable and effective non-surgical option for treating incomplete abortion. Discussion: Misoprostol is widely available in Latin America but, before the present study, its safety and efficacy as a treatment for incomplete abortion had not been systematically documented in the region. Studies conducted elsewhere have established the high efficacy of misoprostol relative to standard surgical options for uterine evacuation. In the present study, 600 μg of oral misoprostol effectively evacuated the uterus in nearly 95% of women. This rate mirrors the efficacy reported in an earlier trial conducted in Burkina Faso, West Africa, comparing the same 2 treatment methods (misoprostol versus MVA) in twice as many women with fewer cases lost to follow-up. The present study conducted in Ecuador, although small, provides confirmatory evidence that supports the use of a non-surgical treatment for incomplete abortion. The adverse effects profile of both treatments was consistent with those described elsewhere. Reported rates of heavy bleeding and pain after 600 μg of oral misoprostol range from 24% to 35% and from 56% to 99%, respectively. These adverse effects occurred at a similar rate among Ecuadorian women treated with misoprostol: one-third had heavy bleeding, and two-thirds had pain. The occurrence of fever and chills was infrequent (4%) and comparable to previously reported rates among other populations for this indication. There were no reports of women returning after discharge from the study with bleeding problems or infection. Although treatment with misoprostol alone and MVA worked well, there were some notable differences in the provision of care between the 2 sites. Providers were trained to use ultrasound at follow-up only for those cases in which there was doubt of complete uterine evacuation; however, among women who received misoprostol, ultrasound was used more frequently at the private clinic than at the public hospital (96% versus 29%). Unlike the public hospital, ultrasound use at follow-up at the private clinic did not decrease over time. The smaller case load of women seeking post-abortion care at the private clinic may not have enabled providers to gain significant experience and confidence with the new method. It is likely that as misoprostol treatment is increasingly offered, ultrasound use at follow up— in addition to unnecessary surgical evacuation in the misoprostol group—will decline. This would improve the success rate and dissipate any significant difference in the effectiveness of misoprostol versus MVA, such as that detected in the present study (94% versus 100%; P=0.018). In fact, several studies have shown that high success rates (96%–99%) in the misoprostol group can be achieved without the systematic use of ultrasound at follow-up. The present study had some limitations. Sixteen percent of women did not return for their follow-up visits. Most women lost to follow-up attended the public hospital, as compared with only 1 woman attending the private clinic. Study staff attempted to contact women who did not return to confirm their health status and to encourage them to return for follow-up care. Many women confirmed via telephone that they believed their abortion to be complete owing to a cessation of symptoms. Nevertheless, their outcomes could not be clinically confirmed and their data were thus excluded from the analysis. Importantly, follow-up visits are not routine for women seeking post-abortion care at the public hospital; at the private clinic, by contrast, follow-up visits are integral to the service. These differences between the 2 service delivery contexts may explain why more women from the public hospital did not return. It also raises the question of whether follow-up visits should be routine for post-abortion care in all contexts. Most women who did return for their follow-up visit correctly determined their abortion status (before being examined) on the basis of a cessation of symptoms, suggesting that with adequate counseling women can determine when to return for follow-up care. Alternatives to routine follow-up deserve further attention because strategies will probably differ between public and private healthcare settings, where caseload, patient flow, and costs to the women and healthcare systems vary. The results from the present study confirm that misoprostol is an effective, safe, and acceptable non-surgical method for the treatment of incomplete abortion. Misoprostol would be yet another step away from the once highly medicalized procedure for the treatment of incomplete abortion towards an option that can be provided more easily at all levels of the healthcare system. Future research should explore the cost effectiveness of offering misoprostol for post-abortion care, particularly in low-resource settings where this simple technology may have the greatest impact on expanding access to services.