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Medicamentos atuantes no sistema reprodutivo feminino - Anticoncepcionais
Gilberto De Nucci
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Dúvidas denucci@gilbertodenucci.com Arquivo
Medicamentos atuantes no sistema reprodutivo feminino - Anticoncepcionais Link
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In the United States according to a study published in 2011
In 2006, 49% of pregnancies were unintended—a slight increase from 48% in Among women aged 19 years and younger, more than 4 out of 5 pregnancies were unintended. The proportion of pregnancies that were unintended was highest among teens younger than age 15 years, at 98%.
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The anatomy of the female internal genitalia and accessory sex organs
Walter F. Boron/ Emile L. Boulpaep – Medical Physiology – Fig 54-1
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The anatomy of the female internal genitalia and accessory sex organs
Walter F. Boron/ Emile L. Boulpaep – Medical Physiology – Fig 54-1
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Ovarian cycle Rupture of mature follice and release of ovum (ovulatory phase) Growth and development of the follice (follicular phase) Corpus luteum formation (luteal phase) Corpus luteum degeneration Foyes Principles of Medicinal Chemistry – Fig. 29.2
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In this illustration, the menstrual cycle is divided into four stages.
an egg matures inside the ovary, which then releases the egg , allowing it to travel through the fallopian tube, where it rests awaiting fertilization If the egg is not fertilized, it is flushed out with the menstrual flow
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Approximate plasma concentrations of the gonadotropins and ovarian hormones during the normal female sexual cycle 800 600 400 200 Progesterone 8 6 4 2 Ovulation Estradiol Menstruation Progesterone (ng/ml) Estradiol (pg/ml) 800 600 400 200 LH Ovulation FSH and LH (ng/ml) FSH Days of female sexual cycle Guyton & Hall – Textbook of Medical Physiology – fig 81.3
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Mechanism of Action of Estrogen/Progestin Contraceptives
Inhibition of ovulation by suppression of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Alteration of cervical mucus to inhibit sperm transport Interference with ovum transport Inhibition of implantation by suppression of normal endometrial development Essential of Reproductive Medicine – Tab. 26.1
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Fertilization process
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Estrogens excreted in urine
Estrogen secretion throughout the sexual life of the female human being 400 300 200 100 Puberty Menopause Estrogens excreted in urine (µg/24 hr) Age (yr) Guyton & Hall – Textbook of Medical Physiology – fig 81.10
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MÉTODOS ANTICONCEPCIONAIS
Tabela – Natural Barreira – impede o encontro - Diafragma - Preservativo - DIU normal Medicamentoso DIU – cobre ou progestogênico Skin patch Anel vaginal Implante Pílula
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A clinical guide for contraception – fifth Ed – pg 191
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CONTRACEPTIVOS HORMONAIS
Forma eficaz, segura e reversível. - Puros: somente progestágeno - Combinados: associação de estrogênio e progestágeno
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Historical Landmarks Animal experiments in the late 1930s demonstrated that high- dose progesterone could arrest ovulation Carl Djerassi synthetized progestin from an extract of Mexican wild yam root in late 1940 First pill marketed for cycle control (1960) - Enovid 10 – mg norethynodrel microg mestranol Not legal to discuss contraception or prescribe the pill for the indication of contraception until 1969 Pope Paul VI Humanae Vitae (1968) – pill sinful Essential of Reproductive Medicine – Tab. 26.1
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ESTROGÊNIO Década de 60 - Pró-Hormônio – Mestranol 150 mcg
Etinil Estradiol - Alta dose (> ou = 50 mcg) - Baixa dose (35, 30, 20, 15 mcg) - Tendência – Ultrabaixa (sem consenso)
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Mestranol (pró-droga)
A clinical Guide For Contraception - Fifth edition - pag 36
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Ethinyl estradiol A clinical Guide For Contraception - Fifth edition - pag 36
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Estradiol Valerate a
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Low – Dose Oral Contraceptives
Products containing less than 50 mcg of ethinylestradiol
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Classification of oral contraceptives
Into generation according to the type of progestogens associated with estrogen Combined (estrogen + progestin) or progesting only
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First-Generation Oral Contraceptives
Products containing either norethisterone acetate, lynestrenol, ethynodiol acetate or norethynodrel.
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Testosterone Ethisterone
A clinical Guide For Contraception - Fifth edition - pag 37
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Progestagional derivatives of testosterone
Ethisterone Norethindrone A clinical Guide For Contraception - Fifth edition - pag 37
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A clinical Guide For Contraception - Fifth edition - pag 38
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A clinical Guide For Contraception - Fifth edition - pag 38
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Second-Generation Oral Contraceptives
Products containing levonorgestrel or norgestimate
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A clinical Guide For Contraception - Fifth edition - pag 38
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A clinical Guide For Contraception - Fifth edition - pag 41
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Dienogest A clinical Guide For Contraception - Fifth edition - pag 42
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Third-generation Oral Contraceptives
Products containing desogestrel, norgestimate or gestodene
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A clinical Guide For Contraception - Fifth edition - pag 39
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Fourth-Generation Oral Contraceptives
Products containing drospirenone, dienogest or nomegestrol acetate
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Drospirenone A clinical Guide For Contraception - Fifth edition - pag 42
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Nomegestrel s
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Dienogest s
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Change in adjusted mean number of lesions (papules, pustules, open and closed comedones) from baseline to end point (full analysis set). DRSP, drospirenone; EE, ethinyl estradiol; COC, indicates combined oral contraceptive; Hormonal Contraceptives for Acne Management – CUTANEOUS MEDICINE FOR THE PRACTITIONER - VOL. 81 NO. 1S JANUARY 2008
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Oral Contraceptives With Acne Benefits
Pharmacology of Hormonal Contraceptives and Acne – CUTANEOUS MEDICINE FOR THE PRACTITIONER - VOL. 81 NO. 1S JANUARY 2008
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Progestin only Low daily doses of progestin (norethindrone, levonorgestrel or desogestrel) Injectable 3-month contraceptives (depot medroxyprogesterone acetate) IM Levenorgestrel implant or etonogestrel single-rod implant – 3 years Intrauterine device containing levonorgestrel – 5 years
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Contraceptive use in the United States, 1995. Hysterectomy/ Menopause
Percentage of Women Ages 15-50 30 25 20 15 10 5 26% 24% 19% 7% 6% 3% 1% 1% 1% Pill Sterilization Condom Withdrawa/ Rhythm Hysterectomy/ Menopause Injectable Spermicide IUD Implants Method Essential of Reproductive Medicine – Fig. 26.2
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A clinical Guide For Contraception - Fifth edition - pag 63
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A clinical Guide For Contraception - Fifth edition - pag 66
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Number of deaths from cardiovascular diseases per 100,000 women by smoking status or nonuse of oral contraceptives. 250 200 150 100 50 nonuser, nonsmoker user, nonsmoker nonuser, heavy smoker user, heavy smoker Deaths / 100,000 women 0 0 20-24 25-29 30-34 35-39 40-44 Age group (years) Essential of Reproductive Medicine – Fig. 26.4
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Relative Risk and Actual Incidence of Venous Thromboembolism
Population Relative Risk Incidence Young women-general population per 100,000 per year Pregnant women High-dose oral contraceptives Low dose oral contraceptives Leiden mutation carrier Leiden carrier and oral contraceptives Leiden mutation – homozygous A Clinical Guide for Contraception – tab. Pag 53
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Noncontraceptive Health Benefits of Oral Contraceptives
Percent Reduction/ Protection (%) Minium Use Required Duration of Effect OCP Formulation Comments Definitive evidence Ovarian cancer months At least >20 µg EE Also protective against years hereditary ovarian cancer Endometrial cancer months years All monophasic No data on multiphasic or progestin-only forms Benign breast disease months year >20 µg EE Effect consistent across all age groups Pelvic inflamatory months Current use >20 µg EE ? Effect on outpatient disease cases of PID Ectopic pregnancy Current use Current use >20 µg EE No increased risk for ectopic pregnancy in women who become pregnant with OCP use Essential of Reproductive Medicine – Tab. 26.2
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Noncontraceptive Health Benefits of Oral Contraceptives
Percent Reduction/ Protection (%) Conflicting evidence, favor beneficial effect Bone mineral density Unknown Unknown >35 µg EE Decreased incidence of hip fractures with higher doses Colorectal cancer months Unknown >50 µg EE Increasing protection with increased duration Uterine leiomyomas , years; Unknown Unclear If used in setting of fibroids no 7 years clinically significant uterine growth Toxic shock syndrome Current use Current use Unclear May be influenced by change in tampon composition/absorbency Minium Use Required Duration of Effect OCP Formulation Comments Essential of Reproductive Medicine – Tab. 26.2
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Noncontraceptive Health Benefits of Oral Contraceptives
Percent Reduction/ Protection (%) Conflicting evidence, favor no effect Functional ovarian cysts 80, 48, 8 Current use Current use Monophasic No statistically significant effect >35 µg EE; Monophasic <35 mcg EE triphasic all types Rheumatoid arthritis Current use Current use Unclear May alter severity and clinical course rather development Minium Use Required Duration of Effect OCP Formulation Comments Essential of Reproductive Medicine – Tab. 26.2
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Benefícios dos AOC Menor risco de câncer endometrial e ovariano.
Menor risco de prenhez ectópica Menstruaçãoo mais regular (menor fluxo, menor dismenorréia, menor anemia) Menor incidência de salpingite Aumento da densidade óssea
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AOC e câncer Redução de 50% do risco de câncer de endométrico
Redução de 40% do risco de câncer de ovário Sem efeito no câncer de cérvix uterina ou no câncer de mama.
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Possible Contradications to Use of Combined Oral Contraceptive Pills
Absolute Contraindications 1. Thrombophlebitis or Thromboembolic disorders 2. Past history of deep vein thrombophlebitis or thromboembolic disorders 3. Cerebrovascular or coronary artery disease 4. Known or suspected breast carcinoma 5. Known or suspected estrogen-dependent neoplasia 6. Pregnancy 7. Benign or malignant liver tumor 8. Known impaired liver function 9. Previous cholestasis during pregnancy or with prior pill use Essential of Reproductive Medicine – Tab. 26.6
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Possible Contradications to Used of Combined Oral Contraceptive Pills (cont)
Strong Relative Contraindications 10. Severe headaches, particularly vascular or migraine headaches, that start after initiation of oral contraceptives 11. Hypertension with resting diastolic BP of 140 mmHg or greater on three or more separate visits or an accurate measurement of 110 mmHg diastolic or more on single visit 12. Mononucleosis, acute phase 13. Elective major surgery or major surgery requiring immobilization planned in next 4 week 14. Long-leg cast or major injury to lower leg 15. Over 40 years old, accompanied by a second risk factor for the development of cardiovascular disease (such as diabetes or hypertension) 16. Over 35 years old and currently a heavy smoker (15 or more cigarettes/day) 17. Abnormal genital bleeding Essential of Reproductive Medicine – Tab. 26.6
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Contraindicado formalmente em doença colestática aguda ou crônica
AOC e Fígado Transporte ativo de componentes biliares é inibido por estrógenos e progestágenos. Contraindicado formalmente em doença colestática aguda ou crônica
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Importante Não há evidências de aumento de incidência de doença hepática séria causado por uso de ACO
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Contraceptivo Oral e Trombose
Estrógenos, mas não progestágenos, aumentam a produção de fatores de coagulação. Tabagismo e uso de estrógenos apresentam efeito aditivo no risco de trombose arterial. Contraceptivos de dose baixa de estrógeno (< 50 microg EE) não aumentam o risco de IM ou AVC em mulheres saudáveis, não fumantes, independente da idade. IM e AVC podem ocorrer em mulheres que usam contraceptivos de alta dose, ou que apresentam fatores de risco cardiovascular acima da idade de 35 anos.
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Medications That Decrease Serum Concentrations of Hormonal Contraception
Anticonvulsants Anti-infective agents Barbiturates Carbamazepine Phenytoin Rifampin Topiramate Vigabatrin Oral Contraceptives: Mechanism of Action, Dosing, Safety, and Efficacy – CUTANEOUS MEDICINE FOR THE PRACTITIONER - VOL. 81 NO. 1S JANUARY 2008
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Monophasic pill Contains a fixed combination of a estrogen (generally ethinyl estradiol) and a progestogen
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Biphasic Pill - Kariva 21 white tablets contains 0.15 mg desogestrel and 0.02 mg ethinyl estradiol. 2 light-green tablets contains inert ingredients 5 light-blue tablet contains 0.01 mg ethinyl estradiol.
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Triphasic pill - Ortho Tri-Cyclen 28
7 tablet contains mg of norgestimate and mg of ethinyl estradiol 7 light blue tablet contains mg of norgestimate and mg of ethinyl estradiol 7 dark blue tablet contains mg of norgestimate and mg of ethinyl estradiol 7 green tablet contains only inert ingredients
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Quadraphasic pill - Natazia
2 dark yellow tablets containing 3 mg estradiol valerate 5 red tablets containing 2 mg estradiol valerate and 2 mg dienogest 17 light yellow tablets containing 2 mg estradiol valerate and 3 mg dienogest 2 dark red tablets each containing 1 mg estradiol valerate 2 white tablets (inert)
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Return of fertility after stopping contraception (Doll et al., 2001)
(with permission). Intrauterine devices and intrauterine systems - Human Reproduction Update, Vol.14, No.3 pp. 197–208, 2008
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Escolha uma posição confortável para inserir o anel
Retire do Sachê Pressione o anel
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Figura A Figura B Figura C Coloque o anel na vagina com uma das mãos (fig. A). Se necessário o lábio pode ser afastado com a outra mão. Empurre o anel para dentro da vagina até senti-lo confortável (fig. B) Deixe o anel no lugar durante 3 semanas (fig. C)
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40 mm 2 mm Core: 40% Ethylene vinyl acetate (EVA)
60% Etogestrel (68 mg) Rate-controlling membrane: (.06 mm) 100% EVA
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Required Equipment for Implanon Insertion
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Implantation technique
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Contraindication for Implanon
Known or suspected pregnancy Current or past history of thrombotic disease Hepatic tumors or active liver disease Undiagnosed abnormal genital bleeding Known, suspected or history of breast cancer Hypersensitivity to any of the components in Implanon™ A New Implantable Contraceptive - Nursing for Women’s Health - Volume 11 - Issue 6
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Technique for the Tcu-380A
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Níveis de levonorgestrel
A Clinical Guide for Contraception - Pag. 169
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Serum levels of LNG according to delivery.
Author Route of delivery Serum levels (ng/ml) Raudaskoski et al. IUS –0.2 (1995) (PMW) Lahteenmaki et al mg oral ~ 1.7 (1995) Kives et al. (2005) mg oral 1.5 mg vaginal 5.4 Sivin et al. (1997) Implant 1.4–1.0 Rod Intrauterine devices and intrauterine systems - Human Reproduction Update, Vol.14, No.3 pp. 197–208, 2008
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HORMONIOS EM TRATAMENTOS
Correção de ciclos irregulares Reposição em caso de perdas de orgão produtores Complementos (Climatério)
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