Rheumatoid Arthritis and Osteoarthritis

 Two primary pathologic conditions affecting the joints and periarticular

structures
 Can cause severe pain and deformity

Rheumatoid Arthritis
 A chronic systemic disorder that affects many different tissues in the body
but is characterized primarily by synovitis and destruction of articular
cartilage
 Progressive
 Associated with pain, stiffness and inflammation

Criteria for the classification of Rheumatoid Arthritis:

1. Morning stiffness
2. Arthritis of 3 or more joint areas
3. Arthritis of hand joints
4. Symmetric arthritis
5. Rheumatoid nodules
6. Serum rheumatoid factor
7. Radiographic changes

Overview of drug therapy in RA goals:

1.  Joint inflammation
2. Arrest progression of the disease

NSAID’s
o Primary line of defense in treating RA
o Not as powerful in reducing inflammation as corticosteroids but have
fewer side effects and has added advantage of analgesia
o MOA:
 Inhibition of synthesis of prostaglandin by inhibiting the
cyclooxygenase enzyme that initiates their synthesis
 Prostaglandins participate in inflammatory response by increasing
local blood flow and vascular permeability and exerting
chemotactic effect on leukocytes
 Also they sensitize pain receptors to the nociceptive effects of
other pain mediators (bradykinin)
o Adverse effects:
 Stomach irritation  gastric ulceration  hemorrhage
 Liver toxicity
 Impaired renal function
Corticosteroids
o  Inflammatory symptoms but does not halt progression of disease
o Reserved for Pt. whose disease is uncontrolled by NSAID’s
o May be injected directed to the joint
o MOA:
  Synthesis of prostaglandins and leukotrienes

 Glucocorticoid
 Promote synthesis of protein that inhibits function of
phospholipase A2 enzyme  liberates fatty acid precursors for
prostaglandin and leukotriene biosynthesis

 Immunosupressive properties
 Inhibit migration of monocytes and neutrophils to injury site

o Adverse effects:
1. Catabolic effect on tissues
2. Osteoporosis
3. Muscle wasting and weakness
4. Hypertension
5. Aggravation of DM
6. Glaucoma
7. Cataract

DMARD’s
o Eclectic group of agents identified as being able to arrest or even reverse
the pathologic changes in some Pt.’s with RA
o Also referred to as slow acting anti-rheumatic drugs (SAARD’s)
o Induce remission by modifying pathologic process in RA
o Inhibit immune response (monocytes, T, B lymphocytes)
o Controls synovitis and erosive changes
o Sample drugs:
 Antimalarials
 Chloroquine (Aralen)
 Hydroxychloroquine (Plaquelin)
 Azathioprine (Imuran)
 Gold compounds
 Auranofin (Ridaura)
 Aurothioglucose (Solganal)
 Gold sodium thiomalate (Myochrysine)
 Methotrexate (Rheumatrex)
 Penicillamine (Cuprimine, Depen)
Antimalarials
o Chloroquine, Hydroxychloroquine
o MOA:
 Known to  PH within certain intracellular vacuoles in
macrophages and other immune system cells
 Effect disrupts the ability of cells to process antigenic proteins and
presents antigen to T cells
  T cell stimulation results in immunosuppression and attenuation
of arthritic response
 Also they stabilize lysosomal membranes and impair DNA and RNA
synthesis
o Adverse effects:
 Retinal damage (high doses)
 Advisable:
 <3.5 – 4.0 mg/kg chloroquine
 <6 – 6.5 mg/kg/day hydroxychloroquine
 Headache
 GI distress

Azathioprine
o Imuran
o Immunosuppressant drug used to prevent tissue rejection following
organ transplants
o Severe cases
o MOA:
 Impair synthesis of DNA and RNA precursors
 Inhibit immune responses mediated by T cells and other
immunocompetent cells
o Adverse effects:
 Fever
 Chills
 Sore throat
 Fatigue
 Loss of appetite
 Nausea
 Vomiting
Gold Therapy
o Primary drugs identified as DMARD’s
o Aurothioglucose (Solganal), Gold sodium thiomalate (Myochrysine) 
injected
o Auronofin (Ridaura)  oral, better tolerated
o May arrest further progression of RA but does not reverse the damage
o MOA:
 Inhibits maturation and function of mononuclear phagocytes
 Accumulate in the lysosome of macrophages and other synovial
cells thereby suppressing the action of key components in the
cellular immune reaction
  Lysosomal enzyme release
  Responsiveness of prostaglandins
o Adverse effects:
 GI distress (diarrhea, indigestion)
 Irritation of oral mucosa
 Rashes/itching of the skin
 Proteinuria
 Conjunctivitis
 Blood dyscrasias (thrombocytopenia, leukopenia)

Methotrexate
o Folex, Mexate, Rheumatrex
o Antimetabolite used frequently in treating CA
o One of the most effective DMARD’s
o  Synovitis,  bony erosion, less narrowing of joint space
o MOA:
 Impair DNA and RNA synthesis
 Inhibits synthesis of folic acid thus inhibiting formation of
nucleoproteins that serves as DNA precursors
 Inhibits proliferation of rapidly replicating cells (monocytes,
lymphocytes)
o Adverse effects:
 Loss of appetite
 Nausea
 GI distress
 Intra GI hemorrhage
 Pulmonary problems
 Hematologic d/o
 Liver dysfunction
 Hair loss
Penicillamine
o Cuprimine
o Derivative of penicillin
o Chelating agent used in treatment of heavy metal intoxication (lead
poisoning)
o MOA:
 Reduce serum immunoglobulin M rheumatoid factor
 Depress T cell function
o Adverse effects:
 Fever
 Joint pain
 Rashes/itching
 Swelling of lymph nodes
 Bloody/cloudy urine
 Swelling of feet and legs
 Unusual weight gain
 Sore throat
 Excessive fatigue

DMARD combinations in RA
o Gold + Penicillamine
o Gold + Hydroxychloroquine

Newer nontraditional therapies for RA

o Drugs that affect immune response
 Cyclosporine (Sandimmune)
- Immunosupressant used in prevention of rejection of organ
transplants
 Sulfasalazine (Azulfidine)
- For IBD
- Immunosuppressant effects
o Dietary manipulation  enhance synthesis of certain endogenous anti-
inflammatory and immunosuppressant compounds
 Fish oil
 Fatty acids (gammalinoleic acid)
Osteoarthritis
o OA>RA
o 75% of 75 y/o, 90% of 80 y/o
o Associated with intrinsic defect in joint cartilage
o Low progressive deterioration of articular cartilage that is accompanied
by degenerative bony changes
o MC in knees/hips, hands/feet
o Obesity and genetics  predisposing factors
o Non-pharmacologic treatment:
 PT
 Weight loss
 Joint replacement

NSAID’s and Acetaminophen

o NSAID
 1st choice
 Analgesic properties
 Anti-inflammatory
o Acetaminophen
 Pain control
 For Pt.’s of  risk for gastric ulcer or NSAID induced effects

Viscosupplementation
o Attenuate progressive changes in the joint structure
 HYALURONAN
- Substance that restores lubricating properties of synovial fluid
- Polysaccharide that helps restore normal viscosity of synovial
fluid
o 2-10 weekly injections
o Rehab concerns
 By  pain and inflammation  facilitate more active and vigorous
program of exercise
 PT must be aware of side effects
 Catabolic effects  careful ROM and strengthening to
prevent fracture
 Headache and nausea