RHEUMATOID ARTHRITIS BY PARU 2011

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arthritis, complications, treatment

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RHEUMATOID ARTHRITIS:

RHEUMATOID ARTHRITIS Presented by: PARVINDER SINGH DEPT. OF PHARMACOLOGY HSK COLLEGE OF PHARMACY, BAGALKOT .

CONTENTS:

CONTENTS INTRODUCTION TO ARTHRITIS EPIDEMIOLOGY PATHOPHYSIOLOGY SYMPTOMS CAUSES EFFECT OF INTERLEUKINS DIAGNOSIS COMPLICATIONS TREATMENT

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INTRODUCTION

Epidemiology:

Epidemiology RA affects 0.5-1.0% of population in USA Females > males 3:1 but people of any age can be affected Peak age 45-65 but onset early from age 20-45 yrs Smoking risk factor Genetic It occurs worldwide, affecting more than 6.5 million people in the U.S. alone. The disease strikes women three times more often than men. The disease may come on slowly or may appear suddenly.

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Sjogren's syndrome …is a chronic disorder of the immune system - a long-term autoimmune disease - in which the patient's white blood cells attack the saliva and tear glands, leading to dry mouth and eyes because the body's tear and saliva production is reduced. Pericarditis… is inflammation of the pericardium - the sac which surrounds the heart . It causes chest pains . Nodules … A collection of tissue appearing as a knot or knob in the skin, common in rheumatoid arthritis . Pleural effusion, sometimes referred to as “water on the lungs,” i.e. presence of excess fluid between the layers of the pleura outside the lungs. Vasculitis is a condition that involves inflammation in the blood vessels. The condition occurs if your immune system attacks your blood vessels by mistake. This may happen as the result of an infection, a medicine, or another disease or condition.

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arthritis

SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS :

SYMPTOMS AND SIGNS OF RHEUMATOID ARTHRITIS The very first joints of the hands are affected by rheumatoid arthritis. These joints are tender when squeezed, and the hand's grip strength is often reduced. Rheumatoid arthritis may lead to visible redness, swelling and pain of joints or entire hand.

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The joints of the hands are often affected by rheumatoid arthritis. These joints are swollen red and tender when squeezed. Swelling is due to synovitis

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Synovium is the smooth lining of a bone joint and Synovitis is when that lining becomes inflamed. During the inflammatory process, the synovium becomes thicker and can make the joint swollen and puffy to the touch. It is usually extremely painful; particularly when the joint is being moved and is most often characterized by swelling that is caused by fluid collection in a synovial sac.

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Rheumatoid arthritis is autoimmune disorder in which Immune system identifies the synovial membrane as "foreign" and begins attacking it. Synovial membrane shown in picture

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With long-term or intensive exposure to the antigen, normal antibodies become auto-antibodies that target self-antigens in the synovial membrane. Once the antigen or immune complex reaches the synovial membrane .The antigen presenting cell deals with it.

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First, the APC usually a macrophage in synovium engulfs the antigen. Enzymes (peroxides) inside the APC break down the antigen into smaller particles. PATHOGENESIS OF RHEMATOID ARTHRITIS

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The processed antigens are transported to the surface of the APC, where it binds with MHC ( major histocompatibility complex).

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This complex ie (part of a foreign substance and MHC) is now presented to T-cells (CD4 cells ie T-helper cell ) or CD8 (cytotoxic T cells) with which the T-cell receptor (TCR) recognizes and binds.

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Once the T-cell binds to the Antigen / MHC complex, the APC then secrete cytokines like Interleukin-1 (IL-1) Interferon-alpha (IFN-a) Interferon-gamma (IFN-g) Tumor necrosis factor (TNF) And other factors that activate lymphocytes and other immune cells to respond to the antigens .

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Matrix Metalloproteases (e.g. stromelysin ) cause activation of collagenase, which is an enzyme required for cartilage breakdown .( Anti CCP antibody stands for anti-cyclic citrullinated peptide antibody. It is a test used to confirm the diagnosis of rheumatoid arthritis .)

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APC also Secretes : Lysozymes, Elastases and Collagenases these enzymes cause cartilage breakdown. FGF (fibroblast growth factor) & Angiogenesis Factors add to pannus formation Chemokines mediates chemo attraction (chemotaxis)

Effects of IL-1:

Effects of IL-1 On exposure to IL-1, synoviocytes proliferate and produce following factors Interleukin-6 (IL-6) Prostaglandin's (e.g. , PGE2) , and platelet-activating factor, which are involved in the pain mechanism.

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IL-1 also activates endothelial cells and induce stimulation of adhesion molecule expression on endothelial cells. Enhances activity of NK cells and leads to Pyrogen (cause fever). IL-1 also causes increased production of inducible nitric oxide synthase and consequently high levels of nitric oxide kill chondrocytes, the cells responsible for cartilage remodeling. Induce osteoblast apoptosis and thereby prevent new bone formation Prevent formation of the cartilage matrix by inhibition of proteoglycan synthesis.

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The end result of IL-1 and TNF- α includes activation and migration of leukocytes and lymphocytes from the blood into inflammatory tissues as well as formation of pannus and damage to cartilage and surrounding normal cells. Pannus is a medical term for an abnormal layer of fibrovascular tissue or granulation tissue formed on the joints.

DIAGNOSIS AND TREATMENT OF RHEUMATOID ARTHRITIS:

DIAGNOSIS AND TREATMENT OF RHEUMATOID ARTHRITIS

COMPLICATIONS OF RHEUMATOID ARTHRITIS:

COMPLICATIONS OF RHEUMATOID ARTHRITIS

Rheumatoid nodules:

Rheumatoid nodules Painless firm lumps that appear beneath the skin, often single or multiple, and range in size from millimeters to centimeters in diameter occur on the underside of the forearm and on the elbow. But they can also occur on other pressure points, including the back of the head, the base of the spine, the Achilles tendon, and the tendons of the hand. These nodules may move easily when touched or they may be fixed to deeper tissues and cause pressure on surrounding nerves or can rupture, causing pain and discomfort in surrounding tissue.

Rheumatoid nodules:

Rheumatoid nodules

Skin complications of RA:

Skin complications of RA Skin and muscles becomes atrophic (thin and wrinkled), making it fragile and easy to bruise. Skin on the back of the hands may become pale or even translucent Nails may become brittle and split length-wise . The palms become reddened (palmer erythema). A rare, serious complication, usually with long-standing rheumatoid disease, is blood vessel inflammation ( Vasculitis ). It can impair blood supply to tissues and lead to tissue death (necrosis). This is most often initially visible as tiny black areas around the nail beds or as leg ulcers .

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RA VASCULITIS

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Rheumatoid Vasculitis can cause many internal symptoms, , hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), bowel ulcers, and haematuria (blood in urine). Skin ulcers (usually leg ulcers) may be extensive and painful Petechiae (purplish spots) or purpura Nail fold or edge breakdown Gangrene

TREATMENT OF RHEUMATOID ARTHRITIS:

TREATMENT OF RHEUMATOID ARTHRITIS Nonsteroidal anti inflammatory drugs (NSAIDs) are a class of drugs that reduce i nflammation, pain, fever, and swelling and are commonly prescribed for the inflammation of the joints (arthritis) and other tissues, such as in tendinitis and bursitis. Examples of NSAIDs include: Aspirin Indomethacin Ibuprofen Naproxen Piroxicam Nabumetone Diclofenac All NSAIDs should be taken with meals to prevent stomach upset.

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NSAIDs work by blocking the production of prostaglandins, chemical messengers that often are responsible for the pain and swelling of inflammatory conditions. Prostaglandins are made by two different enzymes, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 ( COX-2) & have slightly different effects on the body . COX-2 inhibitors are NSAIDs that selectively block the COX-2 enzyme and not the COX-1 enzyme. Blocking this enzyme impedes the production of prostaglandins.

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When the COX-2 enzyme is blocked, inflammation is reduced; however, since the COX-2 enzyme does not play a role in protecting the stomach or intestine, therefore do not injure the stomach or intestines as compared to COX-1 inhibitors. When the COX-1 enzyme is blocked, inflammation is reduced, but the protection of the lining of the stomach also is lost. This can cause stomach upset as well as ulceration and bleeding from the stomach and even the intestines.

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DOSE CRITERIA Aspirin………….500-1000 mg every 6 hours Indomethacin…………….50-200 mg per day Ibuprofen………200 or 400 mg every 6 hours Celecoxib ……….100 or 200 mg twice daily. While "first-line" medications (NSAIDs and corticosteroids) can relieve joint inflammation and pain, they do not necessarily prevent joint destruction or deformity.

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DMARDs For patients with an aggressively destructive form of rheumatoid arthritis, medications other than NSAIDs and corticosteroids are needed . Used for long periods of time, even years. promote remission. retards the progression of joint destruction and deformity. E.G. Hydroxychloroquine Side effects include upset stomach, skin rashes, muscle weakness, and vision changes.

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Sulfasalazine in the treatment of mild to moderately severe inflammatory bowel diseases, such as ulcerative colitis. Gold salts Gold thioglucose gold thiomalate Auranofin Side effects of gold (oral and injectable) include skin rash, mouth sores, kidney damage with leakage of protein in the urine, and bone marrow damage with anemia and low white cell count.

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Immunosuppressive Medicines These are powerful medications that suppress the body's immune system. A number of immunosuppressive drugs are used to treat rheumatoid arthritis. They include Methotrexate Azathioprine Cyclophosphamide Chlorambucil and Cyclosporine

Newer "second- line“ drugs or "biologic" medications:

Newer "second- line“ drugs or "biologic" medications Leflunomide Etanercept Infliximab Annakira Adalimumab Rituximab Abatacept Golimumab Certolizumab Tocilizumab Each of these medications can increase the risk for infections, and the development of any infections should be reported to the health-care professional when taking these newer second-line drugs.

Corticosteroid Therapy:

Corticosteroid Therapy Medications can be given orally or injected directly into tissues and joints. They are more potent than NSAIDs in reducing inflammation and in restoring joint mobility and function. Corticosteroids are useful for short periods during severe flares of disease activity or when the disease is not responding to NSAIDs. However, corticosteroids can have serious side effects, especially when given in high doses for long periods of time . Safe dose like Prenisolone is 5-10 mg daily. side effects include weight gain, facial puffiness, thinning of the skin and bone, easy bruising, cataracts, risk of infection, muscle wasting, and destruction of large joints, such as the hips.

Prosorba column Therapy:

Prosorba column Therapy The Prosorba column therapy involves pumping blood from a vein in the arm into an apheresis machine, or cell separator. This machine separates the liquid part of the blood (the plasma) from the blood cells. The Prosorba column is a plastic cylinder about the size of a coffee mug that contains a sand-like substance coated with a special material called Protein A. Protein A is unique in that it binds unwanted antibodies from the blood that promote the arthritis. The exact role of this treatment is being evaluated by doctors, and it is not commonly used currently .

CURRENT SURGERY APPROACHES:

CURRENT SURGERY APPROACHES The primary purpose is to reduce pain, improve the affected joint’s function, and improve the patient’s ability to perform daily activities Joint replacement : involves removing all or part of a damaged joint and replacing it with synthetic components. Most commonly replaced joints are the hips and knees.

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KNEE REPLACEMENT HIP REPLACEMENT

Combination DMARD therapy:

Combination DMARD therapy MTX + SSZ + OH-Chloroquine MTX + CSA MTX + Etanercept MTX + Remicade MTX + Adalimumab MTX + Leflunomide T hese combinations provides excellent safety & improved efficacy over MTX alone

REFERENCES:

REFERENCES www.google.com www.authorstream.com Pharmacology by Rang and Dale, 6 th edition. Text Book of Basic Pathology Cotran , Robbins, 6 th edition Pharmacoeconomic study of DMARDs in the management of rheumatoid arthritis, International Journal of Pharmaceutical Sciences Review and Research Volume 5, Issue 3, November – December 2010; Article-027

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Trust the physician and the teacher, and drink his remedy in silence and tranquility. For his hand though heavy and hard is guided by tender hand of unseen. And the cup he brings, though it burn your lips has been fashioned of the clay which the potter have moistened with his tears and sacred feelings . THANK YOU ALL

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