FARMAKOTERAPI OSTEOARTHRITIS
DEWI RAHMAWATI
PEMERIKSAAN MUSKULOSKELETAL 3 MENIT Gaits (Cara Berjalan) Arms (Tangan) Legs (Kaki) Spine (Tulang Belakang)
PERTANYAAN KUNCI • APAKAH ANDA MERASA NYERI ATAU KEKAKUAN DI SENDISENDI ATAU TULANG BELAKANG? • APAKAH ANDA MENGALAMI KESULITAN BERJALAN, MENAIKI TANGGA ATAU BANGUN DARI TEMPAT TIDUR? • APAKAH ANDA MENGALAMI KESULITAN BERPAKAIAN?
PENYAKIT REUMATIK YANG LAZIM DITEMUI DALAM PRAKTEK UMUM
REUMATISME JARINGAN LUNAK OSTEOARTRITIS ARTRITIS REUMATOID GOUT SYSTEMIC LUPUS ERYTHEMATOSUS ARTRITIS SEPTIK REUMATOID ARTRITIS JUVENIL SPONDILITIS ANKILOSA ARTRITIS PSORIATIK SKLERODERMA PURPURA HENOCH-SCHONLEIN
PENYAKIT REUMATIK RAWAT JALAN
• REUMATISME JARINGAN LUNAK • OSTEOARTRITIS • GOUT
BONE REMODELLING
PEMBENTUKAN TULANG DAN KARTILAGO • BONE REMODELLING SEPANJANG HIDUP TERGANTUNG KEBUTUHAN PERTUMBUHAN DAN PERUBAHAN BEBAN TUBUH (WEIGHT-BEARING) • PEMBENTUKAN TULANG BARU & MATRIX MINERALIZATION (OLEH OSTEOBLAST) RESORPSI TULANG & RELEASE MINERAL (OLEH OSTEOCLAST)
• RESERVOIR UNTUK MINERAL (CA, PO4, DLL)
PEMBENTUKAN TULANG & KARTILAGO SEL PROGENITOR
SEL IMMATURE SEL IMMATURE (OSTEOBLAST) (CHONDROBLAST) PEMBELAHAN SEL & SEKRESI MATRIX OSTEOCYTE (UTK TULANG)
CHONDROCYTE (UTK KARTILAGO)
Sejumlah osteoblast & fibroblast disimpan di periosteum dan chondrocyte disimpan di perichondrium, untuk pembentukan kembali tulang & kartilago
MINERAL HOMEOSTASIS
• PENYIMPANAN & PELEPASAN MINERAL DI TULANG KADAR MINERAL (CA, PO4) DI DLM DARAH
• SEX HORMON (ESTROGEN
& TESTOSTERON) DAN GROWTH FACTOR TERUTAMA MEMPENGARUHI SAAT USIA MUDA
• DIPENGARUHI OLEH PARATHYROID HORMON (PTH), HORMON THYROID CALCITONIN, DAN 1,25 DIHYDROXYCHOLECALCIFER OL (CALCITRIOL) + SUMBER MINERAL DARI MAKANAN
• DIPENGARUHI JUGA OLEH SITOKIN DAN GROWTH FACTOR
MINERAL HOMEOSTASIS (LANJUTAN…) • OSTEOCYTE BERPERAN MELEPASKAN MINERAL DARI TULANG • OSTEOCLAST TERUTAMA BERPERAN DALAM RESORPSI TULANG • PTH MENINGKATKAN JUMLAH DAN AKTIVITAS OSTEOCLAST, TETAPI DIDUGA HAL INI KARENA PENGARUH PTH-ACTIVATED OSTEOBLAST YANG PADA KONDISI NORMAL SELALU BERADA DI DALAM KESEIMBANGAN
MINERAL HOMEOSTASIS
SENDI NORMAL VS. OA Lutut Normal kapsul
Lutut Osteoartritik penebalan kapsul Pembentukan kista
kartilago sinovium tulang
sklerosis tulang subkondral fibrillated cartilage hipertrofi sinovial pembentukan osteofit ACRFP
OSTEOARTHRITIS • DIAWALI DENGAN JARINGAN KARTILAGO AUS / TERCABIK • LALU TERJADI KERUSAKAN JARINGAN DI SEKITARNYA (RUANG ANTAR SENDI MENYEMPIT), TERBENTUK SUBCHONDRAL CYST • TIMBUL NYERI • USAHA UNTUK MEMPERBAIKI / REGENERASI (SCLEROSIS, OSTEOPHYTE LIHAT GAMBAR SENDI NORMAL VS OA)
OSTEOARTHRITIS -DEGENERATIVE JOINT DISEASE. -PREVALENSI MENINGKAT SEIRING DG USIA, MENINGKAT 2-10X DR USIA 30-65 TH
RISK FACTORS FOR OSTEOARTHRITIS
• • • • • • • • •
AGE OLDER THAN 50 CRYSTALS IN JOINT FLUID OR CARTILAGE HIGH BONE MINERAL DENSITY HISTORY OF IMMOBILIZATION INJURY TO THE JOINT JOINT HYPERMOBILITY OR INSTABILITY OBESITY (WEIGHT-BEARING JOINTS) PERIPHERAL NEUROPATHY PROLONGED OCCUPATIONAL OR SPORTS STRESS
ETIOLOGY
• CALCIUM DEPOSITION • CONGENITAL OR DEVELOPMENTAL • ENDOCRINE • GENETIC DEFECTS :INTERLEUKIN-1 FAMILY,INTERLEUKIN-4 RECEPTOR • INFECTIOUS • METABOLIC
• NEUROPATHIC • POST-TRAUMATIC • RHEUMATOLOGIC DISEASES (OTHER THAN PRIMARY OSTEOARTHRITIS) • OBESITY • OCCUPATION :CARPENTERS, AGRICULTURAL WORKERS • SPORT : BOXING, BASEBALL PITCHING, CYCLING, FOOTBALL
TINJAUAN UMUM OSTEOARTHRITIS DEGRADASI KARTILAGO: HILANGNYA INTEGRITAS MATRIKS PERAN BERBAGAI SITOKIN, ENZIM DAN OKSIDA NITRAT UMUR ADALAH FAKTOR RISIKO PALING KUAT FAKTOR RISIKO LAIN: OBESITAS, CEDERA, KELEMAHAN OTOT LUTUT DAN PANGGUL MERUPAKAN TEMPAT YANG PALING SERING TERKENA NODUS HEBERDEN DAN BOUCHARD NYERI MEKANIK, TIDAK ADA GEJALA SISTEMIK
DEGRADASI TULANG KARTILAGO
HERBEDEN’S NODES
OSTEOARTHRITIS PADA LUTUT
PERUBAHAN STRUKTUR TULANG
CLINICAL PRESENTATION GENERAL
■ MILD SYMPTOMS FOR MONTHS TO YEARS ■ TYPICAL AGE :USUALLY >50 YEARS. SYMPTOMS
■ PAIN IN THE AFFECTED JOINTS (HANDS, KNEES,HIPS ) ■ PAIN IS MOST COMMONLY ASSOCIATED WITH MOTION,PAIN IN LATE DISEASE CAN OCCUR WITH REST ■ JOINT STIFFNESS IN THE MORNING < 20-30’ THAT RESOLVES WITH MOTION; RECURS WITH REST SIGNS
■ JOINT STIFFNESS WITH OR WITHOUT JOINT ENLARGEMENT. ■ CREPITUS A CRACKLING OR GRATING SOUND HEARD WITH JOINT MOVEMENT THAT IS CAUSED BY IRREGULARITY OF JOINT SURFACES
■ LIMITED RANGE OF MOTION THAT MAY BE ACCOMPANIED BY JOINT INSTABILITY. ■ LATE-STAGE DISEASE IS ASSOCIATED WITH JOINT DEFORMITY (FIGURE 95-3 )
LABORATORY TESTS ■ NO SPECIFIC LABORATORY TESTS USEFUL IN THE DIAGNOSIS.
OTHER RADIOLOGIC TESTS—PLAIN RADIOGRAPHIC FILMS ■ JOINT SPACE NARROWING, APPEARANCE OF OSTEOPHYTES IN MODERATE DISEASE (GAMBAR 95-4) ■ ABNORMAL ALIGNMENT OF JOINTS AND JOINT EFFUSION IN LATE DISEASE.
DIAGNOSIS HIP OA • PAIN IN THE HIP, ESR <20 MM/H, FEMORAL OR ACETABULAR (TWO OF THE THREE) • OSTEOPHYTES ON RADIOGRAPHY, OR JOINT SPACE NARROWING ON RADIOGRAPHY. KNEE OA PAIN AT THE KNEE,OSTEOPHYTES ON RADIOGRAPHY AGE > 50 YEARS, • MORNING STIFFNESS ≤ 30 ‘, CREPITUS ON MOTION,BONY ENLARGEMENT, BONY TENDERNESS, OR PALPABLE WARMTH
Characteristics of osteoarthritis in the diarthrodial joint.
PENATALAKSANAAN OA NON-FARMAKOLOGI • TERAPI PEMANASAN ATAU DINGIN • PROTEKSI SENDI MISALNYA PENURUNAN BERAT BADAN ORTOTIK, ALAT-ALAT BANTU • LATIHAN, MISALNYA ISOMETRIK, SEPEDA STATIS FARMAKOLOGI • ANALGESIK - SISTEMIK AND TOPIKAL • OBAT ANTIINFLAMASI NON-STEROID (TERUTAMA COX-2 • SPECIFIK INHIBITORS) • STEROID INTRA-ARTIKULER • HYALURONAT INTRA-ARTIKULAR • ?DISEASE-MODIFYING DRUGS OPERASI
PERTIMBANGAN LATIHAN PADA OSTEOARTHRITIS PANGGUL DAN LUTUT
• PERTAHANKAN BERAT YANG SESUAI
• PERTAHANKAN RANGE OF MOTION DAN FLEKSIBILITAS • LATIHAN DALAM AIR, DENGAN SEPEDA ATAU DAYUNG • LAKUKAN AKTIVITAS WEIGHT-BEARING DAN WEIGHT- BEARING SECARA BERGANTIAN
• GUNAKAN TARUK PADA SISI KONTRALATERAL
MESIN
NON-
PERTIMBANGAN LATIHAN PADA OSTEOARTHRITIS PANGGUL DAN LUTUT
• JANGAN MEMBAWA BEBAN LEBIH DARI 10% BERAT TUBUH • SESEDIKIT MUNGKIN MENAIKI TANGGA, BERDIRI SATU KAKI ATAU DUDUK DI KURSI RENDAH • KECEPATAN BERJALAN JANGAN MEMBUAT GEJALAGEJALA SENDI KAMBUH • PILIH SEPATU DAN SOL YANG MENAHAN GONCANGAN • PEMANASAN SEBELUM MELAKUKAN LATIHAN JALAN
SENDI NORMAL VS OA VS RA
TERAPI ■ DESIRED OUTCOME (a) TO EDUCATE THE PATIENT, CAREGIVERS, AND RELATIVES (b) TO RELIEVE PAIN AND STIFFNESS (C) TO MAINTAIN OR IMPROVE JOINT MOBILITY (D) TO LIMIT FUNCTIONAL IMPAIRMENT (E) TO MAINTAIN OR IMPROVE QUALITY OF LIFE
GENERAL APPROACH TO TREATMENT • THE PRIMARY OBJECTIVE TO ALLEVIATE PAIN • ACETAMINOPHEN UP TO 4 G/DAY (INITIALLY) • IF THIS IS INEFFECTIVE NSAIDS OR COX-2 SELECTIVE INHIBITOR (CELECOXIB) • APPLICATION OF CAPSAICIN OR METHYLSALICYLATE TOPICAL CREAMS ADJUNCTS FOR PAIN CONTROL • GLUCOSAMINE AND CHONDROITIN IN COMBINATION MODERATE TO SEVERE ARTHRITIS
• JOINT ASPIRATION FOLLOWED BY GLUCOCORTICOID OR HYALURONATE CONCOMITANTLY WITH ORAL ANALGESICS OR AFTER THEIR LACK OF EFFICACY • OPIOID ANALGESICS FINAL MEDICATION IF OTHER THERAPIES ARE UNSUCCESSFUL • SYMPTOMS ARE INTRACTABLE OR THERE IS SIGNIFICANT LOSS OF FUNCTION JOINT REPLACEMENT
TERAPI
A. NON FARMAKOLOGI - EXERCISE UTK HINDARKAN STRESS PD SENDI SAMBIL PERKUAT OTOT PERIARTIKULER - HINDARI MUATAN BERLEB PD SENDI LUTUT DAN PINGGUL DG GUNAKAN ALAT BANTU (TONGKAT, SEPATU ORTO-PAEDI), TURUNKAN BB, EDUKASI PERLINDUNGAN SENDI
PHYSICAL AND OCCUPATIONAL THERAPY
• PHYSICAL THERAPY—WITH HEAT OR COLD TREATMENTS AND AN EXERCISE PROGRAM — TO MAINTAIN AND RESTORE JOINT RANGE OF MOTION AND TO REDUCE PAIN AND MUSCLE SPASMS. • WARM BATHS OR WARM WATER SOAKS (RENDAM AIR HANGAT) DECREASE PAIN AND STIFFNESS
SURGERY
• OA WITH FUNCTIONAL DISABILITY AND/OR SEVERE PAIN UNRESPONSIVE TO CONSERVATIVE THERAPYTOTAL JOINT REPLACEMENT (ARTHROPLASTY) OF THE KNEE ,TOTAL HIP REPLACEMENT
B. FARMAKOLOGI - PARASETAMOL UTK NYERI RINGAN (PILIHAN PERTAMA) , SEDANGKAN NSAID LBH EFEKTIF UTK NYERI SEDANG AD BERAT. * ESO : HEPATOTOXICITY, RENAL TOXICITY (LONG-TERM USE) - TOPIKAL NSAID, CAPSAICIN KRIM SEKUAT NSAID LOKAL. - INJEKSI KORTIKO INTRA-ARTIKULER SGT EFEKTIF TX NYERI & INFLAMASI ISOLATED JOINT
NSAID DAN COX-2 INHIBITOR - DIGUNAKAN BILA TX DOSIS MAKS PARACETAMOL(4G/HARI) TDK BERRESPON DAN DG EFFUSI SENDI. - KOMBINASI PAMOL + NSAID EFEKTIF - PX DG INFLAMASI SENDI : PILIHANNYA NSAID - EFEK SERIUS : GI BLEEDING, DISFUNGSI RENAL, PE↑TD , RETENSI CAIRAN, EKSASERBASI HF. - COX-2 INHIBITOR SEEFEKTIF NSAID NON SELEKTIF, DG ESO RETENSI NA DAN PENURUNAN GFR. - TRAMADOL PD PX YG KI DG COX INHIBITORNYERI SEDANG AD BERAT. ESO : MUAL, KONSTIPASI, DROWSINNES
• ROFECOXIB WITHDRAWN IN 2004 BECAUSE OF INCREASED CARDIOVASCULAR EVENTS (ARITMIA) ANALYSIS OF THE ADENOMATOUS POLYP PREVENTION ON VIOXX (APPROVE) TRIAL • CELECOXIB IS LESS OFTEN USED NOW AND CARRIES A BLACK BOX WARNING FOR CARDIOVASCULAR AND GI RISKS • THE NEWER COX-2 INH: ETORICOXIB 30 MG, LUMIRACOXIB 100 MG/DAY ~ CELECOXIB
Other
Toxicities with NSAIDs
- Kidney diseases ~Acute renal insufficiency, tubulointerstitial nephropathy, hyperkalemia, renal papillary necrosis Clinical features :Cr ↑ and BUN ↑, hyperkalemia,TD ↑, peripheral edema, weight gain - Monitoring : Cr (3 to 7 days of drug initiation)
RISK FACTORS FOR ULCER COMPLICATIONS INDUCED BY NSAIDS
DEFINITE RISK FACTORS -PATIENT > 65 YEARS OF AGE -PREVIOUS ULCER DISEASE OR UPPER GASTROINTESTINAL TRACT BLEEDING -USE OF MULTIPLE NSAIDS OR USE OF A HIGH DOSAGE OF ONE OF THESE DRUGS -CONCOMITANT ORAL CORTICOSTEROID THERAPY -CONCOMITANT ANTICOAGULANT THERAPY -DURATION OF THERAPY (RISK IS HIGHER IN FIRST THREE MONTHS OF TREATMENT)
POSSIBLE RISK FACTORS -FEMALE GENDER -SMOKING -ALCOHOL CONSUMPTION -HELICOBACTER PYLORI INFECTION
KORTIKOSTEROID
- KORTIKO SISTEMIK TDK DIREKOMENDASIKAN OK INFLAMASI BKN KOMPONEN PRIMER PATOFIS OA. - INJEKSI INTRAARTIKULER (TRIAMCINOLONE HEXACETONIDE 40 MG) EFEKTIF UTK ASPIRASI EFUSI SENDI YG NYERI DAN BENGKAK, - FREKUENSI :3-5X / YEAR : * POTENTIAL SYSTEMIC EFFECTS OF STEROIDS * THE NEED FOR MORE FREQUENT INJECTIONS INDICATES LITTLE RESPONSE TO THE THERAPY).
VISCOSUPPLEMENT - MEDICAL DEVICES SBG PENGGANTI AS HYALURONAT DI SENDI YG RUSAK PD OA - NA HYALURONAT, HYLAN ( ALAMI DI CAIRAN SENDI) BUAT LINGK VISCOUS, BANTALAN SENDI, JAGA FGS NORMAL SENDI - SBG LUBRIKAN & SHOCK ABSORBER PD SENDI, SHG LINDUNGI TLG RAWAN DR KERUSAKAN - DIPAKAI BILA ANALGESIK GAGAL UTK OA LUTUT ( DI-BERIKAN ONCE WEEKLY DG 3-5 X INJEKSI SERI) RELIEF NYERI BERTAHAN AD ≥6 BLN
HYALURONATE INJECTIONS • CONTAINING HYALURONIC ACID (HA; SODIUM HYALU-RONATE) • AVAILABLE FOR INTRAARTICULAR INJECTION FOR TREATMENT OF KNEE OA DECREASE PAIN • HA IS AN IMPORTANT CONSTITUENT OF SYNOVIAL FLUID AND ENDOGENOUS HA HAVE ANTIINFLAMMATORY EFFECTS. • HA PRODUCTS ARE INJECTED ONCE WEEKLY FOR EITHER 3 OR 5 WEEKS
GLUKOSAMIN DAN CHONDROITIN - GLUKOSAMIN ENDOGEN (MONOSAKARIDA AMIN) *DISINTESIS DR GLUCOSA, BAGIAN INTEGRAL PD BIO-SINTESIS PROTEOGLIKANS & GLIKOSAMINOGLIKAN (SUBSTRAT HYALURONIC ACID), YG BENTUK BLOK TLG RAWAN - CHONDROITIN SULFAT, SUBTRAT UTK PEMBENTUKAN MATRIK SENDI & MEMBLOK ENZYM YG BERTANGUNG JWB KERUSAKAN TLG RAWAN - KOMBINASI GLUKO DAN CHONDRO : MODERATE TO SEVERE OA
PROBLEM MEDIK - PERSISTENT PAIN AND INFLAMMATION - HEMATOLOGIC DISORDER (ANEMIA, TROMBOSITOPENIA DLL) - GI DISORDER HEMATEMESIS MELENA, GI BLEEDING - UNDERLYING DISEASE AND COMORBID * CKD * CIRRHOSIS HEPATIC * CARDIOVASCULAR DISEASE (HYPERTENSION, HF DLL) * GASTRITIS * HEPATITIS
DRUG RELATED PROBLEM - INAPPROPRIATE DRUG LESS OPTIMAL DOSAGE - DRUG INDUCE - ADVERSE DRUG REACTION - FAILURE TO RECEIVE A DRUG MONITOR - KONDISI NYERI DAN INFLAMASI - DATA HEMATOLOGI, RFT,LFT - SIDE EFFECT : GASTRIC BLEEDING ( MELENA ) - TEK DARAH, ELEKTROLIT
Algoritme OA
STUDI KASUS 1. PASIEN A.N NY. SH USIA 67 TH, MRS TGL 11 SEPTEMBER 2010 DGN KELUHAN MUAL, MUNTAH DAN BAB WARNA HITAM,PANAS SELAMA TIGA HARI . PASIEN GEMUK,SERING ALAMI KEKAKUAN DAN NYERI SENDI TERUTAMA PAGI HARI. RIWAYAT OBAT JAMU PEGAL LINU DAN PUYER 16. DATA VITAL SIGN ( NADI : 90 X/MNT ; RR 22X/MNT;SUHU 38ºC). DATA LAB, LEUKOSIT 12.000 / MM3,HB.12,0 G/DL, K 2,5 MEQ/L. PASIEN DIDIAGNOSIS OBS. FEBRIS + GASTRITIS + MELENA. DARI FOTO GENUE PASIEN MENGALAMI OATEOARTHRITIS. DOKTER YANG MERAWAT MEMBERI ANTASIDA SIR 3X CII, OMEPRAZOLE 20 MG 2X1, PARASETAMOL 4X1, CEFTRIAXONE INJ 2X1, PIROKSIKAM 10 MG 2X1
2. TN. STR UMUR 60 THN, DATANG KE POLI REUMATOLOGI DGN KELUHAN NYERI BERAT DAN INFLAMASI PADA LUTUT KIRI HINGGA BETIS.PASIEN SUDAH MENDAPAT NA DIKLOFENAK 3X50 MG, RANITIDIN 150 MG 2X1, NEUROBION TAB 3X1 SAAT KONTROL 1 BULAN YANG LALU. DATA LAB MENUNJUKKAN LEUKOSIT 5000 / MM3 ( 400010.000/MM3), LED 30 MM/JAM ( 0 – 20 MM/JAM), TROMBOSIT 60.000 (150.000-400.000/MM3). PASIEN TERDIAGNOSIS OA
3. PASIEN A.N. TN SPD UMUR 50 TH, MRS DGN KELUHAN PERUT MEMBESAR ± 1 BLN,OEDEMA PADA KAKI, BICARA NGLANTUR, SOMNOLENCE, NYERI PADA TANGAN YANG DIGERAKKAN TERASA SAKIT.DATA KLINIK ,TD 130/100, SUHU 36ºC, NADI 88X / MNT, DATA LAB,LEUKOSIT 7500 / MM3, TROMBOSIT 90.000 / MM3, ALBUMIN 2,5 ( 4-6 G/DL), GLOBULIN 4,5 G/DL ( 4-6 G/DL). PASIEN TERDIAGNOSIS SIROSIS HEPATIKA DENGAN PENYAKIT PENYERTA OSTEOARTHRITIS. PASIEN PUNYA RIWAYAT HEMATEMESIS MELENA.DI BANGSAL, PASIEN MENDAPAT TERAPI FUROSEMIDA INJ 1-1-0, SPIRONOLAKTON 100 MG 1-1-0, KANAMYCIN KAPS 4 X 2, LAKTULOSE SIR 3 X CII, MELOXICAM 7,5 MG 2X1
• PERTANYAAN : - BAGAIMANA PHARM CARE PADA PASIEN TSB DI ATAS ?
