Musculoskeletal Disorders

Annotations:

• Joint cartilage degeneration (wear&tear). Non inflammatory The most common form of arthritis

1. clinical features
   1. stiffness & pain woth movement
   2. transient morning stiffness <30min
   3. deep localised ache in a joint
   4. gradual onset of pain: exercise then at night & rest
      1. increasing with disease duration
   5. gait disturbane
   6. joint swelling
   7. Crepitus

      Annotations:

      • cracks or creaks on movement
   8. hips, knees, neck & hands
2. Risk factors
   1. Age

      Annotations:

      • 50% of &gt;65 have x-ray evidence of OA
   2. Joint trauma or injury
   3. abnormality in joint shape
   4. Mechanical repetitive stress
   5. Heredity
   6. female
   7. obesity
   8. lack of exercise
3. Management
   1. Non pharmacological
      1. Patient education
      2. wight loss
      3. exercise, physiotherapy, hydrotherapy
      4. appropriate foot wear
      5. knee/ hip replacement
   2. Pharmacological
      1. Paracetamol

         Annotations:

         • first-line therapy
      2. NSAIDS

         Annotations:

         • Act on the COX enzyme system. Inhibits synthesis of prostaglandins &amp; thromboxanes. Reversibly inhibits COX1 &amp; COX2 enzymes as well as thromboxane synthase. eg ibuprofen, diclofenac, naproxen Anti-inflammatory effect mainly due to inhibition of COX2. Therapeutic effects: 1. anti-inflammatory 2. anti-pyretic 3. analgesic
      3. Corticostereoids

         Annotations:

         • intra-articular corticostereoid injections

1. Painful inflammatory monoarthritis of joints & soft tissue due to deposition of sodium urate crystals in one or more joints.
   1. raised uric acid in blood which crystallises out in joints/tendons and surrounding tissue
      1. under excretion of uric acid (90%)
      2. overproduction of uric acid (10%)
      3. Uric acid - final product of purine metabolism
   2. intermittent painful attacks
   3. men
   4. joints of the feet and ankle most commonly affected (podagra)
   5. red, hot, swollen
2. Triggers
   1. Trauma
   2. Drugs eg diuretics, cytotoxics
   3. alcohol abuse
   4. Dietary excess
   5. severe dieting
   6. obesity
   7. stress
3. Management
   1. non-pharmacological
      1. reduce alcohol intake
      2. Avoid beer, stout, port and other fortified wines
      3. avoid fructose
         1. sugary soft drinks
         2. fructose rich fruits
      4. reduce weight
      5. restrict intake of purine-rich foods
         1. red meat
         2. liver
         3. kidneys
         4. shellfish
         5. yeast extract
      6. include vegetable source of protein in diet
      7. restrict overall protein intake
      8. drink >2L of water daily
   2. acute gout
      1. NSAIDs
         1. first line
         2. diclofenac, naproxen
      2. COXIBs

         Annotations:

         • lower GI risks than NSAIDs
         1. etericoxib

            Annotations:

            • only COXIB licensed for gout
      3. Colchicine

         Annotations:

         • -factors (chemotactic) released which stimulates neutrophil migration into the joint -neutrophils engulf urate crystals &amp; release inflammatory mediators
         1. MOA: reacts with tubulin & selectively inhibits microtubule assembly: reduces neutrophil migration into affected joint & phagocytosis
         2. SE: GI (abdo pain & diarrhoea)
         3. 500 mcg 2-4 times a day until symptom resolution
            1. MAX 6mg/course
            2. not to be repeated within 3 days
         4. do not use in pregnancy!
         5. drug of choice for
            1. hypertension & HF (no fluid ret)
            2. renal impairment
            3. PUD
            4. anti coagulant patients
      4. Corticostereoids
      5. Do not use aspirin at analgesic doses - can worsen gout
   3. Chronic gout

      Annotations:

      • prophylaxis initiated 2-3 weeks after acute attack
      1. xanthine oxidase inhibitors
         1. allopurinol
            1. 1st choice
            2. co administration of colchicine or NSAIDs for 1st 6mths
         2. febuxostat
      2. uricosurics
         1. Sulfinpyrazone
         2. increases excretion of uric acid in urine by inhibiting its reabsorption

Annotations:

• pathogenesis of RA 1.antigen presenting cell 2.activate T cells - produce interleukins &amp; gamma interferon 3.stimulates B cells to differentiate into plasma cells 4. stimulate macrophages - IL1 &amp; TNF-a (stimulate osteoclasts and fibroblasts) 5.autoantibodies (RF) produced from plasma cells 6.RF binds with IgG - immune complex - joint deposition 7.fibroblasts - produce enzymes - destroy joint collagen

1. chrinic, progressive symmetrical polyarthritis of 3 or more joints
   1. small joints most likely eg hands & wrists
      1. but may also affect: hips, elbows, shoulders, knees & ankles
   2. autoimmune disease due to inflammation in the lining of membranes
      1. mostly synovial joints
   3. malaise, anorexia withs symmetrical tender & swollen joints
      1. pain, swelling and stiffness in joints
   4. diagnostic criteria: at least 4 of
      1. early morning stiffness >1hr
      2. arthritis of 3 or more joints
      3. arthritis of the hand joints
      4. rheumatoid nodules
      5. x-ray changes typical for RA
      6. serum rheumatoid factor
   5. extra-articular features of RA
      1. rheumatoid nodules
      2. anaemia
      3. peripheral neuropathy
      4. kidney disease
      5. lung disease
      6. CV disease
   6. degeneration of cartilage, bone and joint supporting structures
2. Management
   1. non pharmacoloical
      1. rest
      2. physiotherapy
      3. psychological support
      4. occupational therapy
   2. DMARDs

      Annotations:

      • -reduce inflammation and delay progression of joint damage &amp; disability -preserve joint function -no evidence of superiority of one DEMARD over another
      1. onset of effect: 4-16 weeks
         1. full therapeutic response: 4-6mths
      2. 1st line: METHOTREXATE

         Annotations:

         • more rapid onset of action than other DMARDs
         1. antifolate

            Annotations:

            • inhibits dihydrofolate reductase
         2. cytotoxic & immunosuppressant
         3. 7.5-10mg/WEEK
            1. max 20mg/week max SC 25mg/week
            2. +folic acid on diff day
         4. rapid absorption from gi
         5. teratogenic
         6. ADRs
            1. GI
            2. Liver
            3. blood dyscrasias
            4. pulmonary
         7. monitoring
            1. chest x-ray (last 6mths)
            2. FBC, LFTs, U+E, creatinine
               1. every 2 weeks until stable for 6 weeks then every 1mth
            3. some patients: pulmonary function tests
      3. sulfasalazine
      4. hydroxychloroquine
      5. leflunomide
      6. gold salts
   3. Biologicals
      1. TNF-alpha: affects cellular function via action at specific membrane bound TNF receptors
         1. anti TNF drugs neutralise the pro-inflammatory activity of TNF-alpha
            1. only use if at least 2 DMARDs tried and failed!!
            2. adalimumab
               1. MOA: binds to TNF-alpa neutralising its activity
               2. with MTX or alone
            3. etanercept
               1. MOA: competitive inhibitor of TNF-alpha at its receptor site
               2. with MTX or alone
            4. infliximab
               1. MOA: binds to TNF-alpha neutralising its activity
               2. must be given with MTX