Farmakoterapi Gangguan Hormonal 1

FARMAKOTERAPI GANGGUAN   HORMONAL

dr. Domas Fitria Fak.Kedokteran UMS

Sifat-sifat umum hormon 1. 2. 3.

4. 5. 6.

Suatu chemical mesengger yang dihasilkan oleh kelenjar endokrin Disekresikan langsung ke dalam aliran darah Fungsi sebagai katalisator reaksi kimia dalam tubuh dan kontrol berbagai proses metabolisme (reproduksi; pertumbuhan dan perkembangan; mempertahankan homeostatis; pengadaan, penggunaan dan penyimpanan energi) Kadarnya dalam sirkulasi darah dapat menggambarkan aktifitas dari kel endokrin memiliki organ/jar target tertentu Berbentuk: amine, polipeptide/protein, steroid

Endokrin dan hormon Kel Endokrin

Hormon yang dihasilkan

Pituitary -Lob

anterior 

LH,FSH,, Prl, GH,ACTH,TSH LH,FSH GH,ACTH,TSH

-Lob

intermediate

MSH, α-endorphin

-Lob

posterior 

Vasopressin (ADH), oksitosin

Tiroid

Tiroksin (T4), Triiodotironin (T3) kalsitonin (T3)  kalsitonin

Paratiroid

Hormon paratiroid (PTH)

Endokrin dan hormon  Adrenal -Korteks

Kortisol,aldosteron,androstenedion

-Medulla

Norepinefrin, epinefrin

Gonad -Testis

Testoteron,estradiol,inhibin estradiol, Testoteron,estradiol,inhibin progesteron

-Ovarium

Test,estradiol Test, estradiol,inhibin, ,inhibin, prog,relaxin

Plasenta

HCG,HPL,prog, estrogen

Pankreas Insulin, glukagon, somatostatin, pancreatic polypeptide

Klasifikasi hormon (secara kimia)  



Gol amine : norepinefrin, epinefrin, T3, T4 Gol protein dan polipeptide : FSH, HCG, LH, TSH, ACTH, prolaktin, Oksitosin, Glukagon, Insulin, PTH, Somatostatin, Relaksin, sekretin, GH, Gastrin, Kalsitonin, CCK, Eritropoetin, Angiostatin, somatostatin, dan vasopressin (ADH) Gol Steroid : aldosteron, kortisol, estradiol, progesteron, testosteron,vitamin D

HORMON ADRENAL Glukokortikoid& Mineralokortikoid

Glucocorticoids & Mineralocorticoids  Therapeutic Overview 

Glucocorticoids:  Replacement therapy in adrenal insufficiencies  Antiinflammatory & immunosuppressive action  Myeloproliferative diseases  Drugs used: 

Hydrocortisone, cortisone, prednisone,prednisolone, fludrocortisone, methylprednisolone, betamethasone, triamcinolone, dexamethasone

Glukokortikoid Homon dari kortek adrenal dibentuk dizona fasciculata Fungsi:  Mempengaruhi met KH, lemak & protein  Anti inflamasi  Immunosupresive  Sekresi kelenjar ekdokrin  Osteoporosis pada tulang 

Mineralokortikoid Homon dari kortek adrenal dibentuk dizona glomerolusa Fungsi  Meningkatkan reabsorbsi Na & Cl pada tubuli ginjal  Menurunkan ekskresi Na & Cl pada kelenjar keringat, ludah dan GIT 

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Mineralocorticoid  

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Hypoalderosteronism Drug used: fludrocortisone

Steroid synthesis inhibitors  

Adrenocortical Hyperfunction Drugs used: metyrapone, ketoconazole

Ex: Methyl Prednisolon 

Dose: 4-48 mg/hari (tergantung keparahan penyakit)  tappering off (bila pemakaian > 1-2 minggu)sampai dosis pemeliharaan



Absorbsi : baik di sal pencernaan Cara kerja: menduduki reseptor spesifik dalam sitoplasma sel yang responsif  ikatan dengan DNA  mempengaruhi sintesis berbagai protein Pemakaian > 2 minggu disarankan memakai Alternate Day Therapy) pd pagi hari selang 2 hr

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Effects of Glucocorticoids 

Metabolic   

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Increased glycogenolysis & gluconeogenesis Increased Protein catabolism & decreased protein synthesis decreased Osteoclast formation & activity

Antiinflammatory 

Local & systemic effects including: 





Decreased production of prostaglandins, cytokines & interleukins Decreased proliferation & migration of lymphocytes & macrophages

Other:  

Decreased calcium absorption from gastrointestinal tract Decreased thyroid-stimulating hormone secretion

Clinical Problems 



Side effects caused mainly by high (pharmacological as compared to physiological) concentrations & for long times Most common side effects: 

Development of cushingoid habitus (trunkal obesity, moon faces, buffalo hump), salt retention & hypertention (iatrogenic Cushing”s Syndrome)

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Suppression of thr immun system (rendering the patient vulnerable to common & opportunistic infections)

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Osteoporosis (rendering the patient vulnerable to fractures)

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Peptic ulcers (resulting in gastric hemorrhagies or intestinal perforation)

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Suppression in growth in children

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Behavioral problems

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Prolonged suppression of the hypothalamic-pituitaryadrenal axis after drug discontinuation

SEX HORMONE Estrogen, Progesteron, Anti Estrogen, dll

Estrogens, Progestins, & Oral Contraceptives 

Therapeutic Overview

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Fertility control 

 

Combination oral contraception (estrogen, progestin) Progestin-only contraception Postcoital contraception

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Hormone Replacement Therapy     

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Menopause Osteoporosis Ovarian failure (estrogen, progestin) Dysfunctional uterine bleeding Luteal phase dysfunction

Ovulation Induction 

Infertility (Clomiphene citrate)

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Cancer Chemotherapy 

 

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Breast cancer (estrogens, progestins, antiestrogens, steroidogenesis inhibitors) Endometrial cancer (progestins, antiestrogens) Prostate cancer (estrogens)

Others 

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Endometriosis (danazol, progestins, gonadotrophin releasing hormone) Diagnostic (progestins)

Clinical Problems 

Estrogens:         

GI disturbance Menstrual disorders Breast discomfort Thromboembolic disorders Hypertention Endometrial cancer Decreased lactation Drug interaction Adverse effect on fetus (diethylstilbestrol)

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Progestins   

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 

GI disturbance Menstrual disorders Adverse changes in lipoprotein levels Abnormal glucose intolerance Drug interaction Adverse effect on fetus

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Clommiphene Citrate 

GI disturbance

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Vasomotor symptoms

 

Ovarian enlargement Visual disorders

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Multiple gestation

Tamoxifen 

GI disturbance Menstrual disorders

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Vasomotor Symptoms

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Mifeprestone (RU 486) 

Menstrual disturbance (rare)

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Aminoglutethimide 

GI disturbances

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CNS disturbances

Danazol 

Androgenic effect in women

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Antiestrogen-like effects

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Adverse changes in lipoprotein concentration

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Adverse effect on the fetus

Androgens & Antiandrogens 

Therapeutic Overview

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Androgens:     

Primary testicular insufficiency Hypogonadotrophic hypoganadism Constitutional delay of growth & adolescence Osteoporosis, anemia Testosterone derivatives used for replacement therapy

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Antiandrogens & Antagonists:    

Virilization in women Precocious puberty in boys Male contraceptive Drugs used to decrease androgen synthesis or block androgen action

Clinical Problems         

Masculinization in women Priapism in men Growth disturbance in children Fetal masculinization in pregnancy Jaundice Edema Acne Hypertention Weight gain

Thyroid

JARINGAN PERIFER

RAUNG EKSTRA SEL

SEL FOLIKEL TIROID

KOLOID

I I-

TRANSPOR AKTIF

I-

PEROKSIDASE I+

MIT

I-

TIROGLOB

METABOLISME

MIT

DIT

TIROGLOB SIKLUS ENTEROHEPATIK 

PEROKSIDASE

MIT T3 T4

DIT

T3

TIROGLOB

T4

T3 MIT

T3

DIT

T3

PROT T4

T4

T4

MIT

DIT

TIROGLOB T3

T4

Hypothyroidism 

Terapi - R/ Tiroksin dosis rendah 50 µg/hr per oral ditingkatkan dlm interval 6 mgg s/d T4 normal. - Dosis pemeliharaan 100-200 µg/hr per oral



Pd pasien dgn myxedema coma R/ Triiodotironin 50 µg iv pertama dilajutkan dgn 25 µg tiap 8 jam R/ dpt ditmbh Hidrokortison iv 100-300 mg/hr

obat yang berpengaruh pd  Tionamida tiroid Ct: Metimazol dan Propiltiourasil (PTU) Cara kerja: - Cegah sintesis Hormon dgn penghambatan katalisis peroksidase Tiroid - Hambat penggabungan Iodotirosin WARNING: - BUMIL: MELEWATI SAWAR PLASENTA DAN DIAKUMULASI DI JANIN - BUTEKI: DISEKRESI KE AIR SUSU PTU BETTER THAN METIMAZOL pada Bumil dan Buteki krn ikatan proteinnya kuat dan tidak disekresi dlmjml yang cukup pd air susu

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Iodida

- Hambat pelepasan T3 danT4 dari gland tiroid ke dlm

plasma - Mengurangi ukuran dan vaskularisasi kelenjar tiroid yg hiperplasi - Utk mengobati krisis tiroid



Penghambat Anion hambat pengambilan iodin oleh tiroid melalui mekanisme kompetitif transpor I. contoh:  Kalium perklorat

 Perteknetat  Tiosianat

 Kontras Media

teriodinasi

Hambat konversi T4  T3 dlm hati  I radioaktif (I 131)  Penghambat adrenoseptor

ct: propanolol

Hyperthyroidism MANAGEMEN:  Surgery  Radioactive iodine pria > 40th dan wanita menopause  Drugs: 

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Tionamida (Propylthiuracil, carbimazole, methimazole) Beta adrenergic receptor blockers iodides

Insulin

Diabetes Melitus 

IDDM:   



Insulin Diet Exercise

NIDDM:     

Oral hypoglycemic agents (sulfonylurea) Insulin Diet Weight reduction Exercise

Insulin & Oral Hypoglycemic Agents 

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

A. Insulin kerja Singkat awitan 30’ puncak 2-4 jam hilang dalam 8 jam Lisipro &aspartat kerja lebih cepat drpd insulin larut B. Insulin kerja Menengah Durasi 16-35 j Semilente: suspensi insulin zink amorf  Lente: suspensi insulin zink amorf 30% dan zink kristal 70% C. Insulin Kerja Panjang Durasi 20 j Ultralente : zink kristal Penyerapan lambat, durasi s/d 35j Insulin Starginpeakless

Obat oral antidiabetik Sulfonilurea Cara kerja:  Stimulasi sel B  Pelepasan insulin  Penurunan glukagon serum 

Ct: -glipizid, -glikazid,  t1/2 singkat -glibenklamid, t1/2 lbh pndk risiko hipoglikemia -Tolbutamid, pilihan pd orang tua, durasi singkat dll

Metabolisme : di liver  KI: - Hiperglilkemia berat - Bedah mayor 

Ef. Simpang: -weight gain Hipoglikemia Hyponatremi

Biguanida Cara kerja: di perifer  Stimulasi glikolisis lgs pd jar perifer  Mengurangi glukoneogenesis hati  Memperlambat absorbsi glukosa sal cerna  Penurunkan glukagon  Meningkatkan ikatan insulin pd reseptor 

Tdk diMetabolisme, sekresi di ginjal Ct: metformin, Dose: 500 mg 2 x sehari Cocok diberikan pada pasien DM obese

Akarbose (Inhibitor Glukosidase) 

 

Cara kerja: menghambat glukosidase di usus dan memperlambat pencernaan tepung dan sukrosa Memperbaiki Gula Darah Post Pandraia yang terganggu Dose: 25 mg 1-3 x sehari, diberikan bersama makan,

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