Flashcards
pathophysiology and drugs arthritis and gout
Cards in this deck (27)
- 1osteoarthritisnot inflammatory, degenerative joint disease
progressive loss of cartilage from the joints
progression from bone to thinning cartilage and destruction. can affect any joints.
treatment = lifestyle, analgesics, surgery, patient centred, individual - 2drugs for osteoarthritisparacetamol
NSAIDs
corticosteroids
heat/ice
capsaicin
topical formulation
hyaluronic acid
opioids
lidocaine patches
glucosamine and chondroitin may slow progression of joint disease - try for 8 weeks and determine if pain reduced. - 3rheumatoid arthritisinflammatory
cause not fully understood, but is an atypical immune response whereby immune system attacks joints leading to damage
considered chronic autoimmune disease - appears mainly in digits (poor blood supply?)(
inflammation of synovial membrane, leukocyte infiltration (macrophages, neutrophils, T&B lymphocytes, plasma cells and cytokines - IL-1, TNF alpha and IL-6) - 4pro inflammatory mediatorsfollowing cytokines
TNF-alpha (trimeric structure)
IL-1
IL-6 - 5anti-inflammatory mediatorsfollowing cytokines
TGF-Beta
IL-10 - 6Dugs for RA (analgesics)NSAIDs
Paracetamol
Codeine
(analgesics) - 7disease modifying agents (DMARDs)synthetic and biological glucocorticoids administered to control the disease rather than just manage symptoms of pain
- 8synthetic DMARDsmethotrexate
sulphasalazine
hydroxycholroquine
leflunomide - 9methotrexatesynthetic DMARD
folic acid antagonist
inhibits DNA synthesis and cell replication by competitively inhibiting conversion of folic acid to dominic acid, with cytotoxic, immunosuppressive and anti-inflammatory action.
MOA:
competitively inhibits dihydrofolate reductase (DHFR) an enzyme that precipitates synthesis to the active form of folate, needed for the synthesis of nucleotides.
methotrexate decreases circulating purine and pyrimidine, making them less available for DNA and RNA synthesis which may affect immune cell proliferation and cytokine expression. - 10sulfasalazinepro-drug
synthetic DMARD
used in churns, exact MOA unknown, local anti-inflammatory action. - 11hydroxychloroquinesynthetic DMARD
OG antimalarial
increases pH of lysosomes from 4-6
causes decreased intracellular processing, glycosylation and secretion of proteins, with many immunological and non-immunologic consequences. these effects are believed to be the cause of decreased immune cell functioning, such as reduced chemotaxis, phagocytosis and superoxide production by neutrophils. - 12leflunomidesynthetic DMARD
competitie inhibitor of dihydroorotate dehydrogenase (rate limiting enzyme in de novo synthesis of pyrimidines) hence reduces lymphocyte proliferation specific for activated T lymphocytes. - 13biological DMARDsmonoclonal antibodies to TNFalpha: infliximab, adalimumab
soluble receptor decoy for TNFalpha: (TNFalpha agonist) etanercept
receptor antagonist to IL-1
anakinra (cytokine modulator = neutralises IL-1)
monoclonal antibody to CD20
rituximab - 14infliximabbinds to TNF alpha to inhibit its activity
TNF alpha is a cytokine involved in inflammatory and immune responses and the pathogenesis of RA, psoriasis and IBD - 15adalimumabbinds to TNF alpha to inhibit its activity
TNF alpha is a cytokine involved in inflammatory and immune responses and the pathogenesis of RA, psoriasis and IBD - 16EtanerceptTNF alpha antagonist - binds to TNF alpha and inhibits its actions
- 17Anakinracytokine modulator, recombinant form of an human interleukin 1 (IL-1) receptor antagonist - neutralises activity of IL-1, which is involved in the inflammatory response
- 18rituximabdepletes B- lymphocytes, may suppress inflammatory activity by reducing B-lymphocyte induced T-Cell activation and resulting cytokine production. induces the apoptosis of B-Cells
- 19all about TNF alpha Tumor Necrosis FactorTNF alpha is a potent pro-inflammatory cytokine, mainly produced by monocytes. it is a major contributor to the inflammatory and destructive changes that occur in RA. a blockade of TNFalpha results in the reduction in a number of other pro-inflammatory cytokines, (IL-1, IL-6 and IL-8)
- 20destructive effects of TNFalpha in joints in RAbone erosion, swelling, joint space narrowing, bone resorption and cartilage degradation
- 21Receptor Antagonist to IL-1 (IL-1RA)recombinant human IL-1 is a receptor antagonist and prevents IL01 from binding to it's receptor, it decreases IL-1 mediated activity
IL-1RA is a member of the Interleukin 1 cytokine family. it is secreted by various types of cells, including immune, epithelial and adipose cells. - 22other immunomodulatory and cytotoxic agentsazathioprine and cyclosporin A
additional drugs sometimes used -> high potential for toxicity, typically these drugs are used for extra-articular, life threatening manifestations of RA, such as vasculitis
Corticosteroids
via injection for systemic effect - 23Goutgout is related to arthritis; it is peripheral resulting from deposition of sodium rate crystals in one or more joints
linked to metabolic disorder (hypercuricemia) which is an excess of uric acid that deposits in the joints, lactate builds in synovial joints and this decreases pH leading to rate crystallisation
there is an immune reaction to the crystals, activation of complement and kinin systems, accumulation of neutrophils and chemotactic mediators - 24gout treatment targetsdietary restriction of exogenous purines (meats)
xanthine oxidase inhibitors acton the endogenous purines.
recombinant uricase acts on the body's urate pool, and uricosuric agents act on renal tubules - 25acute pharmacological treatment of goutNSAIDs and paracetamol, but not aspirin, as aspirin competes with uric acid for exretion
colchicine - destabilises microtubules and hinders their polymerisation, affecting immune cell's division and movement
corticosteroids (intra-articular and short term only) - 26chronic treatment of goutallopurinol (pro-drug) alloxantlhine inhibits xanthine oxidase, reducing production of uric acid
- 27prophylactic treatment of goutprobenecid (uricosuric drug)
inhibits the tubular reabsorption of urate, increasing the urinary excretion of uric acid and decreasing soluble urate levels