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  HIS26: Rheumatoid Arthritis

Describe the manifestations and consequences of rheumatoid arthritis.

  RA –  symmetrically forming pain and swelling in small joints of hands and feet  RA can also effect other body organs: kidneys, eye, lungs, vasculitis (feet)  RA decreases lifespan by 7-10 years caused by MI/stroke –  caused by uncontrolled

inflammation.

  Gout is urate crystal deposition progressively resulting in hyperuricaemia, acute goutyarthritis, chronic tophaceous gout

   NSAIDS, steroids, Xanthine Oxidase inhibitors –  Allopurinol Symptomatic Treatments:

  NSAIDs help with function but does not change progression of disease  Low dose prednisone (may substitute NSAID)  Intra-articular/parenteral steroids –  For flares of symptoms

Outline use of DMARD’s in management of RA.

  Disease Modifying Anti-Rheumatic Drugs (Methotrexate)   Controls current inflammatory features  Effectively reduces joint damage/deformity, radiographic progression, and long term

disability

Methotrexate is the first choice drug and works by competitively inhibiting the enzymedihydrofolate reductase (DHFR). DHFR is responsible for reducing FH2 to FH4

  Decreases amount of intracellular FH4 available and affects metabolic pathways which areFH4-dependant (including purine and pyrimidine pathways)

 50% Protein bound, partially metabolized in liver, removed active renal tubular circ.

  Side Effects: Hepatotoxicity, pulmonary damage, GI problems (nausea, stomach upset, loosestools), stomatitis, soreness of mouth, infection, alopecia.

  Only given once a week, avoid pregnancy and alcohol**Dose reduction required if renal or hepatic impairment present, folic acid supplement as well

Sulfasalazine: anti-inflammatory (salicylic acid) and antibiotic (sulfapyridine)

  Reduced by a bacterial enzyme (azoreductase) to sulfapyridine and 5-ASA in bowel  Active moiety is sulfapyridine, not 5-aminosalicyclic acid (opposite for other diseases)  Side Effects: Skin reactions, hepatitis, pneumonitis, agranulocytosis, aplastic anaemia

o  Males –  Oligospermia and infertilityHydroxychloroquine –  anti malarial medication found treatable for inflammatory arthritis.

  Interferes with cell’s ability to degrade and process proteins   Side Effects: Rash, nausea, diarrhea, OCULAR RETINOPATHY, depigmentation,

myopathy

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Discuss the use of biologic therapies in RA.

  Specifically designed to treat inflammatory types of arthritis such as rheumatoid/psoriatic  Function to inhibit cytokines such as TNF (neutralize the cytokines, block the receptor or

activate the anti-inflammatory pathway) such as Infliximab 

 Some TNF is required to produce an inflammation response, when all TNF is inhibited, itmakes the patient more susceptible to infection such as tuberculosis. 

  Anti CD20 –  Rituximab binds to CD20 beneficial in RA treatment.