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The Role of Diacerein in the Management of OA
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Transcript of The Role of Diacerein in the Management of OA
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NAMA :Prof.DR.dr.Harry Isbagio,SpPD K-R,K-GER,FINASIM
TEMPAT/TGL.LAHIR :Magelang, 24 Desember 1948
JABATAN :Guru Besar Divisi Reumatologi Dep. Ilmu Penyakit DalamFKUI/RSUPN Ciptomangunkusumo Jakarta
PENDIDIKAN :
Tamat Dokter 1972 FKUIBrevet Spesialis Penyakit Dalam 1979 FKUIBrevet Subspesialis Reumatologi 1986 FKUIBrevet Subspesialis Geriatri 1996 FKUIDoktor 2004 FKUIGuru Besar 2005 FKUI
ORGANISASI :Ketua Umum, Ikatan Reumatologi Indonesia, 1994 2005President , Rheumatology Association of ASEAN 20012006Ketua Bidang Sp Konsultan, Kolegium Ilmu Penyakit Dalam(KIPD), 2006- 2012
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The Role Diacerein in the
Management of Osteoathrosis
Harry Isbagio
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Pathogenesis of OA
Wear and tear ? It is not necessarily age related
It is asymmetrically distribution/ localized
It is progress steadily
The sign & symptoms of inflammation
Role of inflammation in OA, what is theevidence ?
What are inflammatory factors that couldpossibly be involved in genesis of OAstructural changes?
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Osteoarthritis chondrocyte
Increase functions
Type II collagen and aggrecan synthesis (early OA)
Cell proliferation
Catabolic cytokine production
MMPs, TPA/plasmin
IL-I receptor type 1, NOS/NO, Cox-2/PGE2
Apoptosis,
Decrease functions Type II collagen and aggrecan synthesis (late OA)
IL-1 receptor antagonist
Response to IGF-1
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Chondrocyte metabolism
CatabolismAnabolism
Chondrocyte
Stimulation
IGFs, TGF-beta, PDGF, EGFBone morphogenic protein
Cartilage derived morphogenicprotein
Growth factor
Stimulation
Gamma- Interferon
TNF-alpha
Prostaglandins
Oxygen radicals, NO
IL-1, TNF-alpha, IL-17, FGFs,gamma interferon
Leukemia inhibitory factor
Glucocorticoid
Pro-collagen fragments
Inhibition
TIMP, Plasminogen activatorinhibitor
Calicrein
Inhibition
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Chondrocytes Pro-MMPs Active-MMPs
Extra-cellular
matrixdegradation
Cytokines
IL-1, TNF
+
Growth factors
IGF, TGF-b
+
PKC, NF-KB,
Kinase inhibitors
PA, plasmin
+
+
Thiol, serine proteases,
MT-MMPs
+
TIMPs
-
Heavy metal chelators (Ca,
Zn)
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Modified from Pelletier JP, Arthritis Rheum 2001;44:1237
NO
NO
+
+
+
+
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Management of Osteoarthritis
Non-pharmacological therapy
Pharmacological therapy
Surgery
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OA KNEE
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Cellmembrane
IL-1
Intracellular
signalling
COX NOSPlasmin
PGs NO Activation of MMPs
Stromelysin
Degrades cartilage
Collagenase
Degrades cartilage
TGF-B
IGF-1
Collagen II
Aggrecans
Hyaluronic acid
Mechanism of action of diacerein
Diacerein
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Conclusion
Non-pharmacological therapy is as important aspharmacological therapy, and should be used in allcases
There are some evidences that SYSADOAs, eg.diacerein is effective in osteoarthritis, and when usedfor a long term period they might be able to modifycartilage structure (disease modifying osteoarthritisdrugs: DMOADs).
Diacerein is as effective as NSAIDs in osteoarthritis,and is well tolerate.
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Thank You
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