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
 Patofisiologi
1. Primary (idiopathic) OA
- the most common type, has no identifiable cause

a. Localized OA, involving one or two sites

b. Generalized OA, affecting three or more sites.
C. Erosive OA : erosion and marked proliferation in the
proximal and distal interphalangeal joints of the hands.
2. Secondary
- known cause e.g rheumatoid
- another inflammatory arthritis, trauma, metabolic
or endocrine disorders
Kombinasi proses mekanik, seluler dan
biokimia
- Perubahan komposisi dan sifat mekanis tlg rawan
(air,kolagen,proteoglycan)

- Remodelling internal brp chondrocytes utk

gantikan degradasi makromolekul yg terganggu
pd osteoarthritis
- Perubahan komposisi matriks & pe ↓ fgs
chondrocyte serta responsiveness terkait usia
pengaruhi remodelling internal, maintenance
jaringan dan hilangnya tlg rawan pe↑ resiko
degradasi permukaan tlg rawan  osteofit dan
cyste subchondral (+)
 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
■ Presence of warm, red, and tender joints suggests
inflammatory synovitis.

 Signs
■ Joint stiffness with or without joint enlargement.
■ Crepitus
 ■ Limited range of motion ( joint instability)
■ Late-stage disease( joint deformity )

 Laboratory Tests
■ No specific laboratory tests

 Other Radiologic Tests—Plain Radiographic Films

■ Joint space narrowing, appearance of osteophytes in
moderate disease
■ Abnormal alignment of joints and joint effusion in late
disease
 TERAPI

■ DESIRED OUTCOME
- to educate the patient, caregivers, and relatives
- to relieve pain and stiffness
- to maintain or improve joint mobility
- to limit functional impairment
- to maintain or improve quality of life
Terapi
a. Non farmakologi
- Exercise utk hindarkan stress pd sendi sambil
perkuat otot periartikuler
- Hindari muatan berlebihan pd sendi lutut dan
pinggul dg gunakan alat bantu (tongkat, sepatu
ortopaedi), turunkan BB, edukasi perlindungan
sendi
- Akupunktur tdk direkomendasikan
 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 therapytotal joint
replacement (arthroplasty) of the knee ,total hip
replacement
b. Farmakologi
- parasetamol, NSAIDs, analgesik opioid
 PROBLEMA MEDIK
1. Pain and inflammation
2. Underlying disease and comorbid
* CKD
* Chirrosis hepatic
* Cardiovascular disease (Hypertension, HF dll)
* Peptic ulcer disease
* Melena
* Asthma
* Anemia
* Thrombocytopenia
 Pengatasan Problema Medik
1. Pain and inflammation
- Nyeri dan inflamasi yg sering persisten disertai kekakuan
sendi
a. Knee and Hip OA
* diberikan acetaminophen up to 4 g/day (initially)
* If this is ineffective NSAIDs non selective or COX-2
selective inhibitor (celecoxib)
* Penambahan PPI/H2 blocker & misoprostol for NSAIDs
usage
* Topical NSAIDs are recommended → if acetaminophen
fails and are preferred over oral NSAIDs in patients older
than 75 years.
-Intra-articular (IA) corticosteroid injections→hip &knee OA
( if acetaminophen or NSAIDs is suboptima) with once
every 3 months

-Tramadol → in patients who have failed to full-dose

acetaminophen and topical NSAIDs
* it can be added to acetaminophen therapy or NSAIDs oral

-Opioids →in patients not responding to first-line pharmaco-

logic therapies,patients who are at high surgical risk

- Duloxetine →as adjunctive treatment in patients with partial

response to first-line analgesics
* 1 st line medication in patients with both neuropathic and
musculoskeletal OA pain.
-IA hyaluronic acid → is not routinely recommended for knee
OA pain → do not provide clinically meaningful improvement
and adverse events (eg, increased pain, joint swelling, and
stiffness).

- Glucosamine and/or chondroitin and topical rubefacients

(eg, methyl salicylate,trolamine salicylate) lack uniform
efficacy for hip and knee pain & are not preferred treatment
options.
b.Hand OA
- Topical NSAIDs→ are a first-line therapy
- Alternative first-line treatment
- Oral NSAIDs
* patients who cannot tolerate the local skin reactions
* inadequate pain relief from topical NSAIDs
- Capsaicin cream
* For patients unable to take oral NSAIDs
- Tramadol :
* patients who do not respond to topical therapy and are
not candidates for oral NSAIDs
* may be used in combination with partially effective
acetaminophen, topical therapy, or oral NSAIDs.
- Joint aspiration followed by glucocorticoid or
hyaluronate  concomitantly with oral
analgesics
-- Symptoms are intractable or there is significant
loss of function  joint replacement
a.Parasetamol
- The ACR, ELAR,OARSI →parasetamol is first-line drug
therapy for pain management in OA
- Efficacy →  aspirin, naproxen, ibuprofen, and other
NSAIDs
- Terapi awal utk nyeri ringan ( hand and knee )

- Dikombinasi dgn acetylcystein ( fixed dose) pd pasien

dgn liver disease
- Di klinik jarang digunakan , outcome klinik < bila
dibandingkan dgn NSAID
- Waspadai hepatotoksisitas (dosis > 4 g/hari ), renal
toxicity ( long term usage)
b. Terapi topikal
- Capsaicin,diclofenac gel, piroxicam gel
- Diberikan terapi tunggal atau kombinasi dgn terapi oral
( tdk boleh bersamaan )
- Utk OA hands, elbows, and wrists, and the lower
extremities (ankles, feet, and knees )
-to be considered when first-line agents fail, are contra-
indicated, or are poorly tolerated
- FDA approvel : diclofenac gel
-Topical rubefacients →methylsalicylate, trolamine salicy-
late, other salicylates →short-term efficacy in the treatment
of acute pain OA
c. NSAID
- bila tx dosis maks parasetamol(4g/hari) tdk berrespon dan
dg effusi sendi
- kombinasi pamol + NSAID  efektif
- Pilihan utk inflamasi sendi → penetrate joint fluid,
approximately 60% of blood levels
- Waspadai ESO : GI bleeding, PUD,disfungsi renal, pe↑TD
, retensi cairan, eksaserbasi HF, hyperkalemia, edema
perifer
* Pd pasien risiko tinggi : CKD,CHF, severe hepatic
disease, nephrotic syndrome, elderly,taking diuretics,ACE-I,
cyclosporine,aminoglycosides
- Diklofenak, gol oxicam, ketorolak, ketoprofen dll
d. COX-2 inhibitor
- Seefektif NSAID non selektif
- Rofecoxib withdrawn in 2004 (aritmia)
- Celecoxib is has been widely used for pain relief in OA
although some countries less often used now
(cardiovascular and GI risks )
- The newer COX-2 inh: Etoricoxib 30 mg, Lumiracoxib 100
mg/day ~ celecoxib
* are not FDA approved , but are marketed in several
other countries ( Indonesia dll )
- ESO : retensi Na dan penurunan GFR
Patients at increased risk for cardiovascular disease :
- unstable angina - myocardial infarction
- coronary artery bypass surgery - ischemic stroke
-High Framingham risk score
e. Tramadol
- Add-on therapy for patients taking concomitant NSAIDs or
COX-2–selective inhibitors
- Pada pasien yg KI dg COX inhibitor (nyeri sedang ad
berat)
- It can be used with acetaminophen
- ESO : mual, konstipasi, mengantuk, kecemasan, depresi
pernapasan ( over dosage)
- Dosage : 50-100 mg every 4-6 jam ( MD 400 mg/hari)
f. DULOXETINE
- Golongan selective serotonin and norepinephrine reuptake
inhibitor
- osteoarthritic pain of the knee
- Juga utk major depressive disorder, generalized anxiety
disorder,fibromyalgia, and diabetic peripheral neuropathic
pain
 What to monitor ...
- Efektivitas : respon nyeri dan inflamasi
- ESO :
* Kidney diseases
- Acute renal insufficiency, tubulointerstitial
nephropathy, hyperkalemia, renal papillary necrosis
- Monitor nilai Cr, BUN → 3 to 7 days of drug
initiation
-Monitor kadar K, tek darah , peripheral edema, weight
gain, nilai ALT,AST, keluhan lambung, warna faeses,
comple blood count ( 2-4 mgg setelah terapi )
g. Kortikosteroid
- Untuk aspirasi nyeri sendi ( lutut) → joint effusion (+)
- short-term benefit for pain and function

- 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
- 20 to 40 mg of methylprednisolone acetate20 to 40 mg of
methylprednisolone acetate
- methylprednisolone acetate & triamcinolone hexacetonide
→ similar efficacy
- Efektif selama 4-8 mgg
- Di klinik → pemakaian cenderung menurun :
* It is not able to change the natural history of the disease
* It may also have negative consequences on knee
structures
Nice guideline → adjunctive therapy to relive moderate to
severe pain OA
- Frekuensi : 3-5x / thn :
* Potential systemic effects of steroids
* The need for more frequent injections indicates little
response to the therapy
- Triamsinolon acetonide inj ( kenacort i.a )

- Waspadai ESO : hiperglikemi, hipertensi, retensi Na, bone

disease
h. Viscosupplement
- 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 anti inflammatory effects.
- It’s used to first to 2nd of OA

- HA products are injected once weekly for either 3 or 5

weeks
- Lbh efektif drpd intra artikuler kortikosteroid ( Cochrane
review )
- Nice guideline  tdk menawarkan ( do not offer )
i.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 bertanggung jwb kerusakan tlg rawan
- Kombinasi gluko dan chondro : moderate to severe OA

- It’s not licensed by the FDA, as health food supplements

( in Europe )
- Dari NICE guideline tdk menawarkan ( do not offer)

- Penelitian meta analysis → tdk bermakna scr klinis

j. Analgesik opioid
- Digunakan Low-dose opioid analgesic bila terapi nyeri
gagal dgn aetaminophen, NSAIDs, intraarticular
injections, or topical therapy
- For patients with underlying diseases ( renal failure,
cardiovascular disease) opioid analgesics can effectively
relieve pain
- Waktu pemberian by the clock

- Pemberian btk Sustained-release (SR) ( MST),

hydromorphone and fentanyl transdermal patch
- ESO : nausea, somnolence, constipation,dizziness
* elderly patients →more susceptible to adverse effects
k.Growth factor
→ Platelet rich plasma ( PRP)
- Autologous blood products →cellular and humo-
ral mediators to favor tissue healing based on the
activity of GF carried in blood →regulation chon-
drocytes and articular cartilage :
* Regeneration
* Induces chondrogenic differentiation of mesenchymal
stem cells
* Antagonizes the inflammatory mediator (IL-1)
- Platelets contain GFs (platelet-derived growth factor,
transforming growth factor , insulin-like growth factor 1)
→ cartilage homeostasis and cartilage regeneration
- To show more and longer efficacy than HA injections in
reducing pain and symptoms and recovering articular
function ( px with a low degree of cartilage degeneration)
- Diberikan scr intra artikular

- Dosis: 5 ml platelet konsentrat tiap 7 hari sebanyak 3 x

2. Chronic kidney disease / Acute Kidney Injury
- Pemberian NSAID berpotensial menyebabkan drug
induce kidney disease
* perubahan Cr ≥ 0,5 mg/dL pada baseline < 2 mg/dL
* peningkatan > 30% pd baseline > 2 mg/dL
* penurunan volume urine slm 24 jam
- Monitor selama 3-7 hari ( tiap 3 hari ):
* volume urine tampung selama 24 jam
* nilai Cr baseline
- Penyesuaian dosis perlu dilakukan pd NSAID yg
bisa ditolerir pd CKD
* meloxicam : - mild to moderate impaiment → no
adjustment
* Celecoxib : no adjustment in mild to moderate impairment
- Pemberian parasetamol dgn dosis maks. 4 g / hari sangat
dianjurkan
- - monitoring of serum creatinine at baseline and within 3 to 7
days of drug initiation
3.Chirrosis hepatic
- Pemberian parasetamol akan perparah penyakit
CH, perlu diberikan kombinasi asetilcystein

- Pemberian NSAID akan meretensi Na ( perberat

ascites ) dan memicu hematemesis melena

- Monitor : warna faeses , berat badan terkait dgn

perkembangan ascites
 4. Cardiovascular disease
- Pemberian NSAID berpotensi meningkatkan TD dan
eksaserbasi HF ( terutama btk injeksi)
- Pada HF : penggunaan parasetamol, tramadol,naproxen
cukup aman
- Drug induce hipertension krn NSAID dicurigai bila
selama 3x pengamatan tjd kenaikan TD
- For patients receiving antihypertensive drugs :
* blood pressure within a few weeks after initiating
NSAID/coxib therapy
* monitor appropriately
* drug doses may need adjustment
- Monitor : tekanan darah, sesak nafas ( RR)
 5.Peptic ulcer disease
- Penggunaan NSAID pd kondisi di bawah ini
akan perparah gejala PUD :
* Multiple NSAID atau dosis tinggi
* Patient > 65 years of age
* Concomitant oral corticosteroid therapy
* Terapi yg lama (risk is higher in first three
months of treatment)

- Pemberian Cox-2 inhibitor , parasetamol cukup

aman
- Pencegahan induce ulcer krn NSAID dgn
mengunakan :
 Misoprostol  a synthetic PGE E1 analog
 PPI (omeprazole, pantoprazole)  seefektif
misoprostol
H2 blockers
efektif pd pencegahan duodenal ulcer
tdk efektif pd pencegahan gastric ulcer
cimetidine jrg dipakai
● Antasida

- Monitor : keluhan nyeri lambung

6. Melena
- Pemberian NSAID akan perparah melena → life
threatening → pemakaian ditunda

- Parasetamol ,tramadol , Cox-2 inhibitor adalah

pilihan bila kondisi melena teratasi

- Monitor : warna faeses

7. Asthma
- Pemakaian NSAID akan berpotensi eksaserbasi
asthma → stop pemakaian
- Parasetamol, tramadol cukup aman

8. Anemia,thrombocytopenia
- Penggunaan NSAID berpotensi perparah anemia
dan atau trombositopenia
- Monitor kadar Hb dan trombosit
 Asessement
 Drug related problem

1. Ketidakcukupan regimen obat dlm penanganan

nyeri dan inflamasi, bisa disebabkan :
-terapi awal tdk respon
-dosis dan frekuensi subterapeutik
-lama terapi kurang
-rute terapi tdk tepat
 Rekomendasi
- Tingkatkan dosis, frekuensi serta kombinasi obat
OA
- Penggantian obat yg lbh kuat sifat analgesik/anti
inflamasinya ( mis.gol oxicam, diklofenak, COX-
2 inhibitor)
- Perubahan rute  injeksi meloksikam
 Monitoring
- Data klinik : -outcome nyeri dan inflamasi sekitar
lokasi
-ESO : nyeri lambung, perdarahan
lambung (warna BAB), Hb,
trombosit
2. Drug induce
- Bisa berupa :
gangguan hematologi (anemia, trombosito-
penia)
gastritis ( duodenal ulcer,gastric ulcer)
gastric bleeding
DILI peningkatan ALT, Bil. total > 3 x nilai
baseline
Drug induce kidney diseaseBUN dan Cr  >
30%
Drug induce hipertensi
 Rekomendasi
- Stop dan ganti obat yg dicurigai dgn obat yg lbh
aman ( diganti dgn parasetamol, tramadol, Cox-
2 inhibitor)
- Turunkan dosis obat ( dechallenge test )
- Ubah rute obat ( oral suppositoria)
 Monitoring
- Data klinik : TD, warna BAB, abdominal
discomfort
- Data lab : nilai ALT,bil. total, Cr , BUN,Hb,
trombosit
3. Ketidaktepatan dlm pemilihan obat, terkait dgn :
- Usia pasien : elderly fgs organ turun
- Penyakit komorbid ( CKD, CH, HT, HF, anemia) 
percepat progresivitas penyakit
 Rekomendasi
- Stop dan ganti obat yg aman utk elderly (ubah rute )
- Penurunan dosis obat
- Pilih obat yg tdk KI dgn penyakit komorbid, bila tdk bisa
dihindari monitoring ketat
 Monitoring
- Data klinik : ESO ( rash, erythema, SJS dll ), TD,
perdarahan lambung, keluhan lambung
- Data lab : BUN, Cr, ALT, Bil total, Hb, trombosit
 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 ( 4000-10.000/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 ( 3,5-5,5 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
4.Pasien a.n Ny S.A usia 67 thn, Tb 160 cm, BB 55 kg,
MRS tgl 30 Nopember 2014 dengan keluhan mual
selama satu minggu. Nafsu makan turun, tubuh terasa
lemas, nyeri dan bengkak pada betis kiri hingga
pergelangan kaki, sesak.Pasien memiliki riwayat
hipertensi. Pasien terdiagnosis OA + CKD std V + susp
ISK. Data klinik TD 130 / 90 mmHg, Nadi 85 x/mnt, RR
22 x / mnt, suhu 38 ○ C,inflamasi kaki. Data lab : leukosit
13.500 / mm3 , Hb 8,5 g/dL, BUN 93 g/dL, Cr. 5,7 g/dL,
K 6,3 mEq/dL. Pasien mendapat terapi infus EAS : NS
0,9% 1:1, ketosteril 3 x 2 kapsul, furosemida injeksi 1x1,
meloksikam supp. 1 x 1, ampisillin – sulbactam 3 x1,5 g
 Pertanyaan :
- Bagaimana pharm care pada pasien tsb di atas ?