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Dúvidas
Arquivo
Medicamentos atuantes no sistema reprodutivo feminino
Site
www.gdenucci.com
Dúvidas
Arquivo
Medicamentos atuantes no sistema reprodutivo feminino
Site
www.gdenucci.com
Walter F. Boron/ Emile L. Boulpaep – Medical Physiology – Fig 54-1
The anatomy of the female internal genitalia and accessory sex organs
Walter F. Boron/ Emile L. Boulpaep – Medical Physiology – Fig 54-1
The anatomy of the female internal genitalia and accessory sex organs
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
Hypothalamus GnRH
(pulses /hr)
PituitaryLH-FSH
Ovary Estrogen
Progesterone
Correlation of serum gonadotrophic and ovarian hormone levels and feedback mechanisms
Follicular phaseFSH-LH
(pulses/hr)
2 4 6 8 10 12 14 16 18 20 22 24 26 28Days
500
400
300
200
100
50
40
30
20
10
Menses
Serum levels
LHmlUml
pgml
ngml
Progesterone
10987654321
EstrogenFSH
Combined oral contraceptives (COs; all doses in µg except where noted)
Agent Estrogen Progestogen Pharmacological features
Monophasic Continuous administration may be extended up to 12 weeks to minimize inconvinience/symptoms of breakthrough
Available in 21- or 28 day dose packs
ME 50 NE 1 mg
EE 50 NE 1 mg
EE 50 NG 500
EE 35 NE 1 mg
EE 35 NE 500
EE 35 NE 400
EE 35 LNG 150
EE35 LNG 100
EE 30 DRG 150 Less androgenic effects
EE 30 NG 300 Less androgenic effects
EE 30 LNG 150
EE 20 LNG 100 Less nausea and bloatingIncrease breakthrough bleeding
Integrated Pharmacology – Fig 15.47
Combined oral contraceptives (COs; all doses in µg except where noted)
Agent Estrogen Progestogen Pharmacological features
Multiphasic Reduced overall progestogen dose minimizesweight gain, fluid retention, dysmenorrhea
EE 30, 40, 30 LNG 50, 75, 125
EE 35 MGM 180, 215, 250 Less androgenic effects
EE 35 NE 50, 100, 50
EE 35 NE 0.5, 0.75, 1 mg
EE 35 NE 0.5, 1 mg
Low Dose Minimizes headache, menorrhagia
EE 20 NE 1 mg
EE 20, 0 , 10 DEG 150 Less androgenic effects
Antiandrogenic EE 50 CYP 2 mg Reduces androgenic effects in polycystic ovarysyndrome (not registered in US)
Integrated Pharmacology – Fig 15.47
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
Walter F. Boron/ Emile L. Boulpaep – Medical Physiology – Fig 54-1
Secreção de GnRH aumentada (tanto frequência como amplitude)
Aumento dos níveis de FSH e LH (até 4x)
Diminuição dos níveis de estradiol (< 20 pg/mL)
Hormônios na menopausa
Sintomas da Menopausa
• Ondas de calor (60-82%)
• Calafrios
• Ansiedade
Falência ovariana prematura
•Amenorréia por 6 meses <40 anos
•FSH > 40 IU/mL
Effect of SERMs on estrogen tissues
Integrated Pharmacology – fig 20.8
Osteoporose
Deterioração da microarquitetura do esqueleto causando aumento da fragilidade dos ossos
Bone mass wich age
Integrated Pharmacology – fig 20.2
Densitometria
• Mulheres acima de 65 anos • Mulheres menopausadas que apresentaram fratura• Candidatas a tratamento de osteoporose• Mulheres utilizando reposição hormonal• Mulheres menopausadas abaixo de 65 anos mas que apresentam fatores de risco para osteoporose
Prevenção farmacológica
Suplementação de cálcio - 1200mg/diaVitamina D - 400-800 IU/dia
Approximate body stores of vitamins
Vitamin Body’s storage capacity
Vitamina B12 3-6years
Vitamina A 6-10 months
Vitamina D 2-4 months
Folic acid 1-3 months
Vitamin C 2-4 weeks
Vitamin B3 2-4 weeks
Vitamin K 1-2 weeks
Vitamin B1 1-2 weeks
Vitamin B2 1-2 weeks
Vitamin B6 1-2 weeks
Integrated Pharmacology – fig 27.6
Mode of action of vitamins
Co-enzymes Antioxidants Hormones
Vitamin B1 Vitamin C Vitamin A
Vitamin B2 Vitamin E Vitamin D
Vitamin B3
Vitamin B6
Vitamina B12
Vitamin K
Biotin
Folic acid
Pantothenic acid
Integrated Pharmacology – fig 27.7
Approximate body stores of vitamins
Vitamin Body’s storage capacity
Vitamina A 5000 IU
Vitamin B1 1.5 mg
Vitamin B2 1.7 mg
Vitamin B3 20 mg
Vitamin B6 2 mg
Vitamina B12 0.003 mg
Vitamin C 60 mg
Vitamina D 400 IU
Vitamin E 30 IU
Vitamin K 0.08 mg
Pantothenic acid 10 mg
Biotin 0.3 mg
Folic acid 0.4 mgIntegrated Pharmacology – fig 27.9
Therapy for osteoporosis
Medication Type Dose Indications
Alendronate Bisphosphonate 10 mg qd Prevention and treatment
Calcitonin Salmon calcitonin 200 IU/ spray qd Treatment
hPTH(1-34) Parathyroid hormone 400 U Treatment
Raloxifene SERM 60 mg qd Prevention and treatment
Residronate Bisphosphonate 5 mg qd Prevention and treatment
Tibolone Synthetic steroid 2.5 mg qd Prevention (not FDA approved)
Essential of Reproductive Medicine – Tab. 28-2
Hypothalamus GnRH
(pulses /hr)
PituitaryLH-FSH
Ovary Estrogen
Progesterone
Correlation of serum gonadotrophic and ovarian hormone levels and feedback mechanisms
Follicular phaseFSH-LH
(pulses/hr)
2 4 6 8 10 12 14 16 18 20 22 24 26 28Days
500
400
300
200
100
50
40
30
20
10
Menses
Serum levels
LHmlUml
pgml
ngml
Progesterone
10987654321
EstrogenFSH
Serum levels of estrogens, pro-gestins, and hCG in women during the first trimester of pregnancy
Essential Reproductive Medicine – Fig 6-2
Gonadotrofina coriônica humana (hCG)
• Produzido pelo embrião logo após a fertilização
• Previne a desintegração do corpo lúteo
• Mantem a produção de progesterona
• Utilizado como marcador de gravidez
• Indutor de ovulação
Serum levels of estrone (E1) estradiol (E2), estriol (E3), and progesterone (P) in women during the second and third trimester of normal pregnancy
Essential Reproductive Medicine – Fig 6-3
0 10 20 30 40
Weeks of Gestation
E1,
E2 a
nd
E3,
ng/
ml 24
16
8
0
180
120
60
0
PE2
E3
E1
HO
O O
O
RO
RO
EquilinEquilin sodium sulfate
EstroneEstrone sodium sulfate
Piperazine estrone sulfate
R = HR = SO3 –Na+
R = HR = SO3 –Na+
R = SO3 + N NHH
H
Conjugated and esterified estrogens
Foyes Principles of Medicinal Chemistry – fig. 29.7
http://www.eset.com – Clinical Endocrinology & Metabolism
Disfunção Ovulatória
I - hipofunção hipotalâmica-hipofisária
II - Disregulação hipotalâmica-hipofisária-ovariana (ovário policístico)
III - falência ovariana prematura
Hipofunção hipotalâmica-hipofisária (prolactina aumentada)
Agonistas de dopamina
Clomifen/gonadotrofinas
Disfunção hipotalâmica-hipofisária IICitrato de clomifeno
Gonadotrofinas contendo FSH
Com pico precoce de LH em cada ciclo:Agonista de GnRH
Antagonista de GnRH
Com resistência a insulinaMetformina
Com hiperandrogenismoGlicocorticóides (prednisona ou dexametasona)
Citrato de clomifeno
• Agonista/antagonista dos receptores de estrógeno no hipotálamo/hipófise
• Inibe o feedback negativo dos estrógenos
• Estimula a liberação de gonadotrofinas
• Promove crescimento folicular
• Promove aumento da frequência de pulso de LH
Clomifeno - contra-indicações
• Cistos ovarianos
• Gravidez
• Doença hepática
• Problemas visuais (2%)
• Outros eventos adversos: ondas de calor
Agonista de Dopamina
• Bromocriptina (Parlodel)
• Inibe a liberação de prolactina (receptores D1/D2)
The hypothalamic-Pituitary-Ovarian Axis and the Role of Insulin
Glicocorticóides
• Bloqueia a liberação de andrógenos (abole pico circadiano de ACTH)
• Atua tanto na adrenal como no ovário
• Prednisona/Dexametasona
Gonadotrofinas
• Purificadas de urina
• Utilizado na falha de clomifeno
Gonadotrofinas
• Menotrofinas
• Urofolitrofinas
• Preparações purificadas de FSH
• FSH/LH recombinante
Gonadotrofina coriônica humana (hCG)
• Produzido pelo embrião logo após a fertilização
• Previne a desintegração do corpo lúteo
• Mantem a produção de progesterona
• Utilizado como marcador de gravidez
• Indutor de ovulação
Endometriose
Presença e proliferação de tecido endometrial fora do útero
Walter F. Boron/ Emile L. Boulpaep – Medical Physiology – Fig 54-1
The anatomy of the female internal genitalia and accessory sex organs
Endometriose
• Mais frequente no ovário
• Ligamento útero-sacro
• Parede pélvica
• Fundo de saco posterior
Endometriose
• Dismenorréia
• Dispaurenia
• Infertilidade
Endometriose
• Doença dependente de estrógeno
• Raro portanto na menopausa
Endometriose
• ACO monofásico baixa dose
• Danazol - teratogênico
• Progestágenos
• Agonistas de GnRH com terapia de reposição
Gonadotropin-Releasing Hormone (GnRH) Agonists
Drug
Gonadorelin
Gorserelin
Histrelin
Leuprolide
Nafarelin
Drug Summary Table – Pharmacology of Reproduction
Principles of pharmacology – the Pathophysiologyc Basis of Drug Therapy – pag.454
Generic name Brand name Form Dosage
Buserelin
Suprecur Nasal sprayBuserelin comes in a nasal spray pump. The recommended dosage is two sprays into each nostril every 8 hours (3 times a day).
Suprefact injectable Daily injectionDaily injections of buserelin start with a dosage of 200 micrograms, and increase up to a maximum of 500 micrograms. The final dose is the minimum needed to alleviate pain symptoms.
Goserelin ZoladexMonthly or three-monthly injection
Goserelin is embedded in a small biodegradable implant about the size of a grain of rice. The implant is injected under the skin in the lower half of the abdomen once a month.
LeuprorelinLeuprolide
Lupron Depot
Monthly injection Leuprorelin comes as a monthly or, three-monthly, injection that is injected under the skin of the abdomen or arm, or sometimes into the buttock or thigh muscles.
Prostap SR
Enantone
Lucrin Depot
Trenantone-Gyn Three-monthly injection
Naferelin
Synarel
Nasal spray
Nafarelin comes in a nasal spray pump. The recommended dosage is one spray of the pump into one nostril in the morning, and one spray into the other nostril in the evening every day. In a few women, the recommended dosage does not stop menstruation. If symptoms persist in these women, the dosage may be increased to one spray in both nostrils morning and night.
Synarella
TriptorelinDecapeptyl SR
Monthly and three monthly injection Triptorelin comes as an injection that is injected under the skin or into
the buttock muscle once a month or once every three months.Gonapeptyl Monthly injection
http://www.eset.com - GnRH-agonists as a treatment for endometriosis - by Ros Wood (Australia)
GnRH agonistas/antagonistas para endometriose