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    Farmakoterapi Osteoporosis: Suharti K Suherman Dept. Farmakologi & Terapeutik Fkui

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    This document summarizes drug therapies for osteoporosis, including hormonal replacement therapy, selective estrogen receptor modulators, bisphosphonates, calcitonin, and recombinant parathyroid hormone. It discusses the mechanisms of action, indications, studies supporting efficacy and safety, dosing, and potential side effects of each class of drugs. The document provides an overview of pharmacological management options for treating and preventing osteoporosis.

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    Farmakoterapi Osteoporosis: Suharti K Suherman Dept. Farmakologi & Terapeutik Fkui

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    meldrewb
    60 views23 pages
    This document summarizes drug therapies for osteoporosis, including hormonal replacement therapy, selective estrogen receptor modulators, bisphosphonates, calcitonin, and recombinant parathyroid hormone. It discusses the mechanisms of action, indications, studies supporting efficacy and safety, dosing, and potential side effects of each class of drugs. The document provides an overview of pharmacological management options for treating and preventing osteoporosis.

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    This document summarizes drug therapies for osteoporosis, including hormonal replacement therapy, selective estrogen receptor modulators, bisphosphonates, calcitonin, and recombinant parathyroid hormone. It discusses the mechanisms of action, indications, studies supporting efficacy and safety, dosing, and potential side effects of each class of drugs. The document provides an overview of pharmacological management options for treating and preventing osteoporosis.

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    60 views23 pages

    Farmakoterapi Osteoporosis: Suharti K Suherman Dept. Farmakologi & Terapeutik Fkui

    Uploaded by

    meldrewb
    This document summarizes drug therapies for osteoporosis, including hormonal replacement therapy, selective estrogen receptor modulators, bisphosphonates, calcitonin, and recombinant parathyroid hormone. It discusses the mechanisms of action, indications, studies supporting efficacy and safety, dosing, and potential side effects of each class of drugs. The document provides an overview of pharmacological management options for treating and preventing osteoporosis.

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    of 23

    FARMAKOTERAPI OSTEOPOROSIS

    Suharti K Suherman
    Dept. Farmakologi & Terapeutik
    FKUI
    TERAPI OSTEOPOROSIS
    • Nonfarmakologi : perubahan life-style +
    suplemen , dll.
    • FARMAKOTERAPI 
    *Hormonal Replacement Therapy(HRT)
    *Selective Estrogen Receptor Modulator
    *Bisphosphonate
    *Calcitonin
    *Recombinant Paratiroid : Teriparatide
    Bone remodeling sequence in healthy subjects
    HRT  al. Estrogen (ERT)
    • tulang estrogen
    # meregulasi aktivitas osteoblast ;
    # me ⇓ Σ & activitas osteoclasts.
    # WPM  aktivitas osteoblast ⇓
     osteoclast >> active  OP

    • ERT menstimulasi aktivitas osteoblast


    Indikasi

    • u/ WPM  mencegah & terapi OP


    • Kegunaan telah banyak dibuktikan 
    tetapi mengingat ESO yg serius
    apalagi, jangka lama 
    Estrogen replacement therapy
    • Women Health Initiative study (WHI)
    randomized controlled trial,first
    proved HT ⇓ incidenc of all OP-
    related fractures in PMW
    • later study concludedserius SEs >
    benefits on bone  a significant ⇓
    in HT use for PMW with OP
    •  HT was not used as 1st-line th/ for
    OP & fracture
    Levin V .A, et.al.. Estrogen th/ for osteoporosis in the modern era. Osteoporosis
    International (2018) 29:1049–1055
    . Later studies  challenged these &
    have shown significant efficacy of
    HT in various doses, durations,
    regimens, & routes of administratn
    These studies support that HT improves
    BMD & ⇓ fracture risk in ♀ with &
    without OP

    & suggest that low-dose transdermal


    HT are less likely associated with
    the SEs of breast -Ca,
    endometrial hyperplasia, CAD &
    VTE previously observed in
    standard-dose oral HT regimens.
    • Given the need for Estr in PMW & evidenc
    supporting the cost effectiveness,
    safety, efficacy , we propose that
    HT should be considered for the
    primary prevention & Th/ of OP
    in appropriate candidates.
    • lower-dose & transdermal that have
    been shown to be safer than oral
    standard-dose HT.
    •
    • low dose transd 17β Est (14μg/day) mono
    th/for 2 yrs  a significant ⇑ in BMD &
    prevention of bone loss without ⇑ risk
    of endometr hyperpl &vaginal bleeding
    compared to placebo
    • 17β- estradiol transdermal patch  slow,
    sustained release of the hormone,syste
    matic distribution, & more constant
    blood levels than oral dose
    •  + vit D + Calcium + physical exercise
    • Levin ER,et al. Estrogen, Progestin, & the Female Reprod Tract. In: GG, 13th
    ed. 2018.McGraw-Hill, 803–830.
    SELECTIVE ESTROGEN RECEPTOR
    MODULATOR = SERM
    • senyawa dg : tissue-selevtive activity
    • SERM yg telah disetujui FDA
    • Generasi - 1 : tamoxifen
    - 2 : raloxifen (RLX)
    - 3 : bazodoxifen

    Nolin TD & Friedman PA. Agents affecting mineral ion homeostatis & bone turnover.
    GG,13th ed, 2018.887.
    SERM  raloxifen : menghambat
    resorpsi tulang , tanpa stimulasi
    mammae
    Indikasi : th/ & pencegahan osteoporosis
    pd WPM
    & ternyata ⇓ resiko invasive
    breast-Ca (in high risk PMW)

    Bikle DD. Agent that affect bone mineral homeostasis. In ; Bestram G


    Katzung,editor. Basic & Clinical Pharmacology, 14th ed. McGrawHill,, 14th
    ed.2018, 772-791.
    Seung S K, et.al. Treatment of osteoporosis & ⇓ in risk of invasive breast-Ca in
    PMW with raloxifene Expert Opin Pharmacother. 2011 March; 12(4):
    Studi RLX
    • 3 studi besar :
    1.Multiple Outcomes of Raloxifene Evaluation
    (MORE, 1999, 2002),
    2. Continuing Outcomes Relevant to Evista
    (CORE, 2004, 2005)
    3. Raloxifene Use for The Heart (RUTH, 2006)
     RLX tdk hanya atasi osteo- penia / porosis
    WPM, tetapi juga ⇓ kejadian fraktur
    vertebra / nonvertebra & insidens Ca-
    mammae
    • Kemudian 2 studi lain
    a. Study of Tamoxifen & Raloxifene
    (STAR, 2006)  terbukti efektivitas RLX
    = tamoxifen dlm cegah Ca-mammae
    b. Evista Versus Alendronate (EVA trial,
    2007) : efektivitas RLX = alendronat
    dlm me ⇓ insidens fraktur osteoporosis
    Studi-2 tsb memberikan highlight  RLX
    berguna u/ pencegahan & th/osteoporo
    sis WPM & u/ pencegahan estrogen-
    related breast cancer
    • Penggunaan dimonitor, mungkin timbul
    ESO al. thromboemboli;
    hasil meta-analisis  resiko deep
    vein thrombosis (DVT),
    pulmonary embolism (PE);
     karenanya kontra-indikasi u/ WPM
    dgn/pernah alami thromboemboli,
    meski rx tsb > banyak terjadi pd
    WPM di US & Eropa;
    di Asia >sering terjadi gangguan GI
    BISFOSFONAT
    Potensi anti resorpsi 3 generasi
    Chemical Antiresorptive
    Generation Examples potency
    modification
    First Short alkyl or halide Etidronate 1
    side chain Clodronate 10

    Second Cyclic side chain Tiludronate 10


    Amino-terminal Pamidronate 100
    group Alendronate 100-1,000

    Third Cyclic side chain Risedronate 1,000-10,000


    Ibandronate 1,000-10,000
    Zoledronate 10,000+

    Reprinted with permission from WattsEndocrinol


    NB. Metab Clin
    North. Am
    1998;27:419-439.
    Farmakologi Bisfosfonat
    • Bone-seeking
    • Efektif pd pemberian oral
    atau IV
    OH R1 OH
    • Absorpsi oral  buruk
    O = P— C— P = O • Tidak dimetabolisme,
    ekskresi melalui ginjal
    OH R2 OH
    • Retensi ditulang cukup
    lama
    • Side chain determines
    potency & side effects
    Mekanisme kerja
    • Hambat aktivitas osteoclast progenitors
    • Hambat Osteoclast recruitment
    • Merangsang apoptosis mature osteoclast
    • Efek antiapoptotic pd osteoblast &
    osteocytes
    • Indikasi : osteoporosis  PMW atau
    andropause
    • Efek samping : gangguan sal cerna ;
    arthralgia, myalgia, flu-like syndr ;
    rx lokal pd tempat infus, rx alergi
    umum (jarang)
    • Efek samping yg serius : ONJ (jarang);
    BP th/  subtrochanteric femur
    fracture in longterm recommend a
    “drug holiday” after 5 yrs of th/
    and 3 yrs for zolendronic acid
    Preparat :

    • Risedronat  5mg/h atau 35mg/mggu


    Alendronat  10mg/h atau 70mg/mggu
    Ibandronat  150mg/bln  oral
    3mg/3ml IV bolus/3month
    Zolendronic acid  ; 5mg /100ml/ thn
    Calcitonin

    • hormone produced by parafollicular C


    cells
    • A single chain peptide hormone  IM /
    nasal spray
    • Postmenopausal oeteoporosis 
    calcitonin inhibit osteoclast activity
    in bone resorption osteoclast
    ↑ BMD = Bone Mineral Density)
     enough intake Calcium & vit D
    • Preparations : synthetic salmon
    calcitonin  nasal spray 50 IU
    2x/ day or injection ampul 50 IU
     1 x / 2 days

    • Adverse reactions : nausea, flushing,


    dose-dependent
    • Hati-hati efek samping kanker hepar

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