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ARTHRITIS. • Family of diseases that affect the mechanical function of the articular cartilage • chronic , degradation of articular cartilage • Arthritis or chronic joint pain currently affects 70 million Americans - most common disease. ARTHRITIS.
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ARTHRITIS • Family of diseases that affect the mechanical function of the articular cartilage • chronic, degradation of articular cartilage • Arthritis or chronic joint pain currently affects 70 million Americans - most common disease
ARTHRITIS • each year - 44 million outpatient visits • $22 billion in medical costs • $82 billion total in medical costs and los productivity
ARTHRITIS - Classes 1. Rheumatoid Arthritis • Inflammatory condition • Initially affects synovial membrane • Autoimmune disease – The body’s immune system produces inflammation and tissue damage. • Inflammatory cytokines, free radicals, prostaglandins (important in growth and repair - here too much) • Pannus ---> articular cartilage • Increases “stickiness” and reduces lubrication
Pannus • Synovial membrane produces pannus >> adheres to articular cartilage • Contains abnormal proteins, blood vessels, scar tissue, collagen. • Causes articular degradation
ARTHRITIS - Classes • Rheumatoid Arthritis • Late stages • Cartilage wears away • High friction • Bone may be exposed on bone • Disruption of periosteum and bone • Increased bone formation in joint • AND/OR • Bone degeneration
ARTHRITIS - treatment 1. Rheumatoid Arthritis • Treatment - traditional • NSAIDS (aspirin - anti-inflammatory) • COX1 inhibitors (cycloxygenase 1 --> prostaglandins) • Cortisone (anti-inflammatory and catabolic steroid) • Gold (anti-inflammatory) • Immunosupressants (side effects) • Cyclosporin: side effects - bad for mitochondria • **Methotrexate (MTX) (used in chemotherapy) pregnancy contraindicated • Hydroxychloroquine (HCQ) - pregnancy contraindicated
ARTHRITIS - treatment • Rheumatoid Arthritis • Treatments - NEW • TNF-a inhibitors (inflammatory cytokines - regulate immune system activity; local growth at low levels) • Infliximab (antibody for TNF-a) [Remicade] • Etanercept (TNF-a inhibitor) [Enbrel] • Anakinra (IL-1ß blocker) [Kineret] • COX-2 inhibitors (Vioxx, Celebrex) • Inducible nitric oxide synthase (iNOS) inhibitors (experimental) • iNOS involved in the inflammatory response
ARTHRITIS - treatment TNF-a inhibitors • Infliximab (antibody for TNF-a) [Remicade] • Etanercept (TNF-a inhibitor) [Enbrel] Hamilton & St. Clair, 2000
ARTHRITIS - treatment • Rheumatoid Arthritis • Treatment - New • Exercise Training! • Patients with rheumatoid arthritis can tolerate exercise if combined with new anti-inflammatories (ex. Infliximab) • Exercise can reduced joint pain, morning stiffness, fatigue • Aids against loss of muscle strength
ARTHRITIS - classes 2. Osteoarthritis • The most common form of joint disease • Degeneration of the articular cartilage; joint surfaces • Long term effects of injury, wear and tear, overtraining • Related to the aging process • Abrasions • Without smooth articular cartilage surfaces: lubrication • Increased friction • Secondary inflammation increases and injury, wear and tear increase
ARTHRITIS - classes 2. Osteoarthritis • Late stages • Cartilage wears away
ARTHRITIS - classes 2. Osteoarthritis • Late stages • Cartilage wears away • Bone may be exposed on bone • High friction • Disruption of periosteum and bone • Increased bone formation in joint • AND/OR • Bone degeneration
ARTHRITIS - treatment 2. Osteoarthritis • NSAIDS • Aspirin • Naproxen sodium • COX-2 inhibitors (Vioxx, Celebrex) • TNF-a blockers • Infliximab [Remicade] • Etanercept [Enbrel]
ARTHRITIS - classes 3. Gouty arthritis (Gout) Causes: • heredity and diet (ex. Henry VIII) • elevated uric acid levels form crystals on articular cartilage Treatment: Allopurinol - Inhibits enzyme (xanthine oxidase) which produces uric acid allopurinol - XO uric acid