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Rheumatoid Arthritis and Osteoarthritis
Rheumatoid Arthritis and Osteoarthritis
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
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
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