NOTE FOR DOCTOR OF PHARMACY (PHARM D) - YEAR III PHARMACOTHERAPEUTICS II

1. OSTEOARTHRITIS
Dr.Namitha Cheriyan
Assistant Professor
KK College of Pharmacy

2. What is osteoarthritis?
Osteoarthritis is a form of arthritis that features
the breakdown and eventual loss of the cartilage
of one or more joints. Cartilage is a protein
substance that serves as a "cushion" between
the bones of the joints

3. INTRODUCTION
• Most common chronic disease
• Primarily affect the weight bearing joints like knee, hip
joint etc.(elbow,shoulder joint-rare)
• Cause-pain ,limitation in motion,deformity,progressive
disability and decrease in quality of life
• Other names – degenerative joint disease or
hypertrophic arthritis
• Characterized by increased destruction of cartilage and
subsequent proliferation of adjacent bones

4. Epidemiology
• Affects 50% of those over the age of 65
• Not always symptomatic
• Most people over the age of 55 may have the high
chance for the disease
• Until 55-affect men more frequently
• After 55 –women have more chance to get OA
• OA is not a normal part of aging process- but age
related changes contributes to OA

5. Etiology
• Increased age
• Gender
• Genetic predisposition
• Obesity
• Previous injury either due to sport occupation
• Previous history of RA or gout
• Acromegaly

6. Clinical presentation
• PAIN:
i. Deep aching
ii. Pain in motion-early cases
iii. Pain in rest-late in disease
• Stiffness in affected joints
• Instability of weight-bearing joints

7. Classification
1. Primary OA
Most common and has no identifiable cause
• Localized OA -involving 1 or 2 sites
• Generalized OA - affecting 3 or more sites
2. Secondary OA
Associated with a known cause such as RA or
other inflammatory arthritis ,trauma,metablic disorders
etc.

8. Synovial joint

9. Synovial joint Notes:
• Synovial joint enable
frictionless movement of
bones
• Cartilage-made of
chondrocytes and water-to
maintain integrity of the matrix
in healthy cartilage
• Chondrocytes-control the
synthesis and degradation of
matrix
• Synovial fluid-composed of
hyaluronic acid-to maintain
functional and structural
characteristics of extracellular
matrix

10. • Cartilage is made up of – chondrocytes
• Chondrocytes produce large amount of extra
cellular matrix
• This extra cellular matrix is composed of -
collagen fibers,proteoglycan and elastin fibers

11. Pathophysiology
advancing age or other risk factors
Strength of tendons /ligaments and muscles decline
The no: of chondrocytes decreases due to apoptosis
and decreased proliferation
The synthesis of normal proteoglycan reduces
Chondrocytes loses the ability to promote healing &
cartilage remodelling

12. Cont..
Cartilage matrix degradation
Pro-inflamatory cytokines and ILs promote cartilage
degradation
PAIN

13. Diagnosis
• Primarily diagnosed by clinical presentation
• Confirmation and progression can be achieved by –
Radiography
Joint space narrowing and bone deformity can be
assessed
• Arthroscopy –normal cartilage seems smooth white
and glistering ,while osteoarthritic cartilage will be
yellowed and irregular.
• Synovial fluid analysis
• Erythrocyte sedimentation rate

14. Management
Goal of treatment
• To reduce /alleviate pain and other symptoms
• To improve the quality of life
Non pharmacological management
• Reduce weight if obese
• Strengthening exercise to improve muscle strength
• Use of assistive devices and joint protection

15. Pharmacologic Management of OA
• Non-opioid analgesics : Acetaminophen,NSAIDs,COX2
inhibitors
• Opioid analgesics
• Tramadol
• Topical agents
• Intra-articular agents
• Surgery

16. Non-opioid Analgesic Therapy
1. First-line—Acetaminophen
• Pain relief and less toxicity compared to NSAIDs
• But no anti inflammatory effect
• Beware of toxicity from use of multiple
acetaminophen-containing products
• Maximum safe dose = 4 grams/day

17. • NSAIDs and COX2 inhibitors are indicated
in OA treatment, when the response to
Acetaminophen is inadequate

18. 2. NSAIDs
NSADIs are the nonselective inhibitors of COX 1 ,COX 2
as well as thrmboxane synthetase .
• Lower doses may be effective
• Do not retard disease progression
Analgesia – in a short duration
Anti inflammatory effect – with high doses and require
several days of therapy
ADR: GI,hepatic and renal toxicity,confusion,urticaria
etc.

19. • Aspirin 650mg every 4 hr
• Diclofinac 75mg BD
• Ibuprofen 400 mg TID
• Naproxen 500 mg BD

20. 3. Cyclooxygenase-2 (COX-2) inhibitors
• Pain relief equivalent to NSAIDs
• Probably less GI toxicity
• No effect on platelet aggregation or bleeding time
• ADR: Renal toxicity, edema
• Eg:celecoxib 100 g BD

21. Opioid Analgesics for OA
• Usually reserved for patients who fail single-or
multiple analgesic therapy
• Codeine, oxycodone, Propoxyphene
ADRS
• Long-acting oxycodone may have fewer CNS side
effects
• Constipation,sedation,respiratory depression
• Morphine and fentanyl patches for severe pain
interfering with daily activity and sleep
• Propoxyphene should be avoided in elderly

22. Tramadol
• Centrally acting analgesic - Affects opioid and
serotonin pathways
• Tramadol is a good choice when the patients pain is
unrelieved by NSAIDs/patient cannot take NSAIDs
• Non ulcerogenic
• May be added to NSAIDs, acetaminophen
• ADR: Nausea, vomiting, lowered seizure threshold,
rash, constipation, drowsiness, dizziness
• Dose :50-100 every 4-6 hr (not exceed 400 mg/day)

23. Topical Agents
• Local cold or heat: Hot packs, hydrotherapy
• Capsaicin-containing topicals
• Avoid contact with eyes
• Use as monotherapy or with oral therapy
• Effective in reliving pain in some OA patients

24. OA: Intra-articular Therapy
1. Intra-articular steroids
• Corticosteroids
• Good pain relief
• Most often used in knees and not usually recommended for
hip owing to administration difficulties
• With frequent injections- risk of infection, worsening
diabetes etc.
• Duration of action -4 weeks

25. 2. Hyaluronate injections*
• Hyaluronic acid derivatives
• Intended to improve elasticity and viscosity of
synovial fluid
• Symptomatic relief
• Expensive
• Require series of injections
• No evidence of long- term benefit
• Limited to knees
• Eg: Sodium hyaluronate 2ml weekly for 5 weeks
Hylan polymers 2ml weelky for 3 weeks

26. Surgical Therapy for OA
Surgery will be preferred when the patient shows:
I. Very bad pain
II. Lost a lot of cartilage
III. Unresponsive to conservative therapies

27. Arthroscopy (it’s a keyhole surgery)
• May reveal unsuspected focal abnormalities
• Expensive, complications possible
Osteotomy
. Done to correct certain defects in hip and knee
. Prefer in patients <60 years with mild arthritis
. To delay total joint replacement
Total joint replacement
• When pain severe and function significantly limited
• Replace the end of the bones in a damaged joint
• Create new joint surface

28. Osteotomy
One of the most common surgeries for
osteoarthritis
Displacement osteotomy:
A bone is “redesigned surgically to alter
the alignment or weight-bearing stress
areas

29. Arthrodesis
•Fusion of bones in a joint
•Bones are held together by
plates, screws, pins, wires, or rods
•New bone begins to grow
•Limited joint motion
•Pain reduction

30. Arthroplasty(Total knee replacement)
• The surgeon removes damaged cartilage and bone from
the surface of your knee joint and replaces them with a
man-made surface of metal and plastic

31. Treatment protocol