medicamentos atuantes no sistema reprodutivo feminino - anticoncepcionais gilberto de nucci...
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Medicamentos atuantes no sistema reprodutivo feminino - Anticoncepcionais
Gilberto De [email protected] http://gilbertodenucci.com
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Dúvidas
Arquivo
Medicamentos atuantes no sistema reprodutivo feminino - Anticoncepcionais
Link
Dúvidas
Arquivo
Medicamentos atuantes no sistema reprodutivo feminino - Anticoncepcionais
Linkhttp://www.gilbertodenucci.com/medicamentos_contraceptivos.ppt
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In the United Statesaccording to a study published in 2011
In 2006, 49% of pregnancies were unintended—a slight increase from 48% in 2001.
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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Walter F. Boron/ Emile L. Boulpaep – Medical Physiology – Fig 54-1
The anatomy of the female internal genitalia and accessory sex organs
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Walter F. Boron/ Emile L. Boulpaep – Medical Physiology – Fig 54-1
The anatomy of the female internal genitalia and accessory sex organs
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Ovarian cycle
Rupture of mature follice and release of
ovum (ovulatory phase)
Corpus luteum formation
(luteal phase)
Growth and development of the
follice (follicular 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.
(1) an egg matures inside the ovary,
(2) which then releases the egg ,
(3) allowing it to travel through the fallopian
tube, where it rests awaiting fertilization
(4) If the egg is not fertilized, it is flushed out
with the menstrual flow
www.healthofchildren.com/images/gech_0001_000...
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800
600
400
200
0800
600
400
200
0
8
6
4
2
0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Est
radi
ol (
pg/m
l)F
SH
and
LH
(n
g/m
l)
Days of female sexual cycle
FSH
LHEs
trad
iol
Ovu
lati
onO
vula
tion
Progesterone
Pro
gest
eron
e (n
g/m
l)
Men
stru
atio
n
Approximate plasma concentrations of the gonadotropins and ovarian hormones during the normal 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
www.jillstanek.com
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Pu
ber
ty
Men
opau
se400
300
200
100
00-----12 13------40 50 60
Age (yr)
Est
roge
ns
excr
eted
in u
rin
e(µ
g/24
hr)
Estrogen secretion throughout the sexual life of the female human being
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 – 9.85 mg norethynodrel + 150 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 sinfulEssential 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
A clinical Guide For Contraception - Fifth edition - pag 37
Ethisterone
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Norethindrone
A clinical Guide For Contraception - Fifth edition - pag 37
Ethisterone
Progestagional derivatives of testosterone
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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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s
Nomegestrel
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s
Dienogest
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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).
Hormonal Contraceptives for Acne Management – CUTANEOUS MEDICINE FOR THE PRACTITIONER - VOL. 81 NO. 1S JANUARY 2008
DRSP, drospirenone; EE, ethinyl estradiol;COC, indicates combined oral contraceptive;
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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.
Essential of Reproductive Medicine – Fig. 26.2
26%24%
19%
7% 6%
3%1% 1% 1%
30
25
20
15
10
5
0
Percentage of Women Ages 15-50
Pill Sterilization Condom Withdrawa/ Rhythm
Hysterectomy/ Menopause
Injectable Spermicide IUD Implants
Method
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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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250
200
150
100
50
020-24 25-29 30-34 35-39 40-44
0 0 0
Age group (years)
Dea
ths
/ 100
,000
wom
en nonuser, nonsmokeruser, nonsmokernonuser, heavy smokeruser, heavy smoker
Number of deaths from cardiovascular diseases per 100,000 women by smoking status or nonuse of oral contraceptives.
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 1 4-5 per 100,000 per year
Pregnant women 12 48-60
High-dose oral contraceptives 6-10 24-50
Low dose oral contraceptives 3-4 12-20
Leiden mutation carrier 6-8 24-40
Leiden carrier and oral contraceptives 10-15 40-75
Leiden mutation – homozygous 80 320-400
A Clinical Guide for Contraception – tab. Pag 53
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Noncontraceptive Health Benefits of Oral Contraceptives
Percent Reduction/ Protection
(%)Minium Use
RequiredDuration of
EffectOCP
Formulation CommentsDefinitive evidence
Ovarian cancer 40 3-6 months At least 15 >20 µg EE Also protective against years hereditary ovarian cancer
Endometrial cancer 50 12-months 15 years All monophasic No data on multiphasic or progestin-only forms
Benign breast disease 30 12-24 months 1 year >20 µg EE Effect consistent across all age groups
Pelvic inflamatory 50 12 months Current use >20 µg EE ? Effect on outpatient disease cases of PID
Ectopic pregnancy 90 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
(%)Minium Use
RequiredDuration of
EffectOCP
Formulation CommentsConflicting evidence, favor beneficial effect
Bone mineral density 60 Unknown Unknown >35 µg EE Decreased incidence of hip fractures with higher doses
Colorectal cancer 40 96 months Unknown >50 µg EE Increasing protection with increased duration
Uterine leiomyomas 30, 50 10 years; Unknown Unclear If used in setting of fibroids no 7 years clinically significant uterine growth
Toxic shock syndrome 50 Current use Current use Unclear May be influenced by change in tampon composition/absorbency
Essential of Reproductive Medicine – Tab. 26.2
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Noncontraceptive Health Benefits of Oral Contraceptives
Percent Reduction/ Protection
(%)Minium Use
RequiredDuration of
EffectOCP
Formulation CommentsConflicting 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 40 Current use Current use Unclear May alter severity and clinical course rather development
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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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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Anticonvulsants
Anti-infective agents
Barbiturates
Carbamazepine
Phenytoin
Rifampin
Topiramate
Vigabatrin
Medications That Decrease Serum Concentrations of Hormonal Contraception
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 0.180 mg of norgestimate and 0.035 mg of ethinyl estradiol
• 7 light blue tablet contains 0.215 mg of norgestimate and 0.035 mg of ethinyl estradiol
• 7 dark blue tablet contains 0.250 mg of norgestimate and 0.035 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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Pressione o anel
Retire do SachêEscolha uma posição confortável
para inserir o anel
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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)
Figura A Figura B
Figura C
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40 mm
2 mm
Rate-controlling membrane: (.06 mm) 100% EVA
Core: 40% Ethylene vinyl acetate (EVA)
60% Etogestrel (68 mg)
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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 0.1–0.2(1995) (PMW)
Lahteenmaki et al. 0.250 mg oral ~ 1.7(1995)
Kives et al. (2005) 1.5 mg oral 15.21.5 mg vaginal 5.4
Sivin et al. (1997) Implant 1.4–1.0Rod 0.77
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)