lesson 13

• Arthritis


  Painful inflammation and stiffness to the joints
• Rheumatoid Arthritis (RA)


  • Autoimmune disorder of unknown cause
  • Chronic, progressive disease causing inflammation in joints
  • Has inflammation due to the immune cells that attacks the bones

  
• Effects of joint inflammation in RA

  • Joint destruction, deformity and disability
  • Formation of PANNUS - hypervascularization of region which surrounds the damaged bone and cartilage because of the increase amount of immune cells

  
• Features of RA


  • Multiple joint arthritis and SYMMETRICAL joint involvement
  • Morning joint stiffness (pain usually lasts for an hour) - FIRST SIGN
  • Subcutaneous rheumatoid nodules presence of nodules primarily due to joint destruction & deformity
  • Characteristic upon X-ray (+) radiographic evidence of joint destruction (+) serum rheumatoid factor

  
• Osteoarthritis (OA)


  • AKA DJD (Degenerative Joint Disease)
  • Most common joint disease
  • Less severe than RA
  • Primarily affects the weight bearing joints, where in the cartilage will thin down leading to destruction, erosion, and micro fractures in the underlying bones
  • Non inflammatory type

  
• Risk factors for OA

  • Aging
  • Osteoporosis
  • Obesity
  • Smoking
  • Heredity
  • Repetitive use of joints
  • Joint Trauma

  
• Features of OA


  • Pain, stiffness, and muscle weakness around the joints
• Drugs for RA


  • NSAIDs
  • DMARDs
  • Steroids
  • Analgesic
• Drugs for OA


  • NSAIDs
  • Steroids
  • Analgesic
  • Chondroitin Sulfate
  • Glucosamine
  • Sodium Hyaluronate
• NSAIDs


  Inhibit prostaglandins that can also alter the formation of pannus
• DMARDs


  • Disease Modifying Antirheumatic Drugs
  • Alters the natural course of progression of RA
  • Cannot cure the disease itself, only slows it down
  • Require several weeks before their effects are observed (SAARDS - Slow acting antirheumatic drugs)
  • Limited use because of toxicity potential and efficacy reduces overtime
  • Can only be used for 5 years
  • Act by suppressing the activity of inflammatory and immune cells, to slow down the disease
  • As an immunosuppressant or as an immunomodulator they can increase the patients risk to acquire infections
• Progression of RA is irreversible, so the only thing that can be done is to slow it down
• Methotrexate


  • DMARD of choice for most patients with RA
  • Single, most effective DMARD up to date
  • Mechanism of action: inhibits the folate synthesis, decreasing DNA synthesis in inflammatory cells
  • Also used as an antineoplastic agent
  • Has immunoglobulin properties, reducing the activity of immune system
  • Side effects: GI, hematologic, hepatic pulmonary related reactions
• Gold compounds


  • No longer used because of toxicity and newer DMARDs are available with better efficacy and lower toxicity
  • Mechanism of action: anti-mitochondrial activity resulting to cell apoptosis
  • Examples: Auranofin, Aurothiomalate, Aurothioglucose
  • Side effects: Hematologic, dermatologic, GI, Renal hypotension and Flushing
• Leflunomide


  • Immunosuppressive drug approved by the FDA to be an alternative to Methotrexate
  • Mechanism of action: Active metabolite inhibits enzymes for pyrimidine synthesis, thereby prevents replication of DNA and synthesis of RNA and proteins in immune cells
  • Side effects: Diarrhea, Alopecia, Hepatotoxicity
  • Contraindicated in pregnancy
• Biologic agents - Immunomodulators

  • Examples: Etanercept, Adalimumab, Infliximab, Certolizumab, Golimumab
  • Mechanism of action: Tumor necrosis Factor (TNF-a) Blocking Agents
  • Side effects: Susceptibility to infectious disease
• Hydroxychloroquine


  • Also used as an antimalarial agent
  • Mechanism of action: Reduces the chemotaxis and phagocytic activity of immune cells, preventing the formation of pannus
• Sulfasalazine


  • Prodrug
  • Active metabolites: Sulfapyridine (indicated for RA) and 5-aminosalicylate (indicated for IBD)
• Penicillamine


  Mechanism of action: Reduces blood levels of inflammatory cytokines, preventing the activation of other immune cells and formation of pannus
• Drugs for RA and OA

  • Steroids (Anti-inflammatory and immunosuppressive activity, long term use has adverse effects)
  • Analgesics (NSAIDs and Narcotics)
• Chondroitin Sulfate


  • Part of a protein molecule that helps give cartilage its elastic properties and has anti-inflammatory effects
  • Can help reduce the painful swelling of the joints and slow down the breakdown of cartilage while helping restore cartilage growth
• Glucosamine


  • Thought to help with cartilage formation and repair
  • Some lab tests show it helps protect joint cartilage by limiting the breakdown and also helps to build up the levels of cartilage
  • Glucosamine Hydrochloride is another form that is considered equally effective and more easily absorbed
• Sodium Hyaluronate


  • Sodium salt of hyaluronic acid
  • Hyaluronic acid is found naturally in the fluid that bathes joints, in the vitreous human of the eye and in the skin
  • Levels of hyaluronic acid decline with age, which is why skin looks older
• Gouty Arthritis (GA)


  • AKA Tophaceous Gout
  • Accumulation of urate crystals in the synovial resulting to inflammation leading to acute arthritis

  
• Uric Acid is derived from purine compounds upon metabolism. It is actually soluble in the blood and in certain body temperature, however when it reaches relatively colder portions of the body the uric acid becomes crystals, hence the deposition in joint spaces.
• Hyperuricemia


  Abnormally elevated uric acid in the blood, the main cause of Gouty Arthritis

  
• Causes of Gouty Arthritis


  • Primary Gout (Idiopathic, familial)
  • Secondary Gout (Increased production of Uric acid, increased rate of catabolism, or renal diseases, Decreased excretion rate)
  • Use of thiazide diuretics (side effect includes increase in uric acids)

  
• Acute Gouty Attacks


  • Characterized by rapid onset with joint pain that happens at least 24 hours
  • Initial manifestation of gout or an exacerbation of chronic gout

  
• Clinical manifestations of Acute Gouty Attacks

  • Acute monoarticular arthritis
  • 1st metatarsophalangeal joint (base of big toe)

  
• Colchicine


  • Treatment of choice for Acute Gouty Attacks
  • Mechanism of action: inhibits microtubule synthesis and motility of inflammatory cells when urate crystals induced joint inflammation
  • Side effects: bloody/watery diarrhea, neuropathy

  
• Other drugs for Acute Gouty Attacks

  • NSAIDs (Naproxen, Indomethacin, Ibuprofen)
  • Glucocorticoids (Steroids)
• Chronic Tophaceous Gout


  Deposits of uric acid
• Risk factors for Chronic Tophaceous Gout

  • Renal impairment
  • Diet
  • Alcohol
  • Hypertension
  • Obesity
  • Family history
• Hypouricemic Therapy


  • Stabilizes uric acid levels; prevents acute gout attacks
  • Cannot be used for initial treatment as it may precipitate acute gout attacks
  • Given after the patient takes colchicine for 2-3 weeks

  
• Allopurinol


  • Mechanism of action: Inhibits xanthine oxidase
  • Effects: Reduces blood uric levels, Prevents the progression of gouty arthritis
  • Side effects: N&V, Hepatitis, Skin rashes

  
• Febuxostat


  • Orally administered
  • Has greater efficacy than allopurinol
  • Mechanism of action: Inhibits xanthine oxidase
• Uricosuric drugs


  • Used to prevent acute gout attacks in those who under excrete uric acids
  • Facilitate the excretion of uric acid in the urine to prevent accumulation
• Probenecid & Sulfinpyrazone


  • Mechanism of action: Competitively inhibit the reabsorption of uric acid in the kidneys, inducing loss of uric acid in the urine
  • Side effects: Formation of renal uric acid stones (increased risk), adequate hydration is recommended
• Pegloticase and Rasburicase


  Recombinant uricase enzymes which catalyze the oxidation of uric acid to allantoin, an inert, water soluble purine metabolite readily eliminated by renal excretion
• Drugs that are readily excreted do not cause toxicity or accumulate in the body, and have a better disease profile.