Treatment of inflammatory joint disease (changed 3/4)
Objectives:
- Be able to discuss the difference between osteoarthritis and rheumatoid arthritis.
- Understand the rational for glucocorticosteroId and COX inhibitor treatment in the context of treating RA including how steroids and COX Inhibitors are used in symptom management and bridging in RA
- Understand the principles underlying the use of Disease modifying anti rheumatic drugs in RA
- Distinguish between xenobiotic and biological DMARDS
Content:
Osteoarthritis is just erosion of cartilage
RA is autoimmunity to the joint capsule
Treatment of RA Control of pain/symptoms paracetamol NSAIDS
reduce inflammation NSAIDS COX-2 inhibitors glucocorticoids (hydrocortisone)
treat disease progression DMARDS
- Xenobiotics
- Biological agents
NSAIDS
chronic use is gi problems Mechanism In cell injury the phospholipids bilayer is broken and some are converted to arachidonic acid. then Cox converts the ADA to prostaglandins which are highly inflammatory.
COX 2 is more important
Examples
- Aspirin irreversible slightly selective for COX-1
- Ketoprofen
- Ibuprofen more potent than aspirin reversible and bind cox 1and2
- Indomethacin
- Diclofenac more potent thean ibuprofen and moderate selectivity for cox-2
- Naproxen
COX-2 inhibitors (A type of NSAID)
Highly cox2 selective no gastric problem but you do get increase in CV events Examples
- Celecoxib
- Etoricoxib
Glucocorticoids
cortisol imitators Examples
- hydrocortisone
- Dexamethasone
- Prednisone used for short term control of flare ups. low dose long term therapy to help DMARDS
- Triamcinolone acetonide (inject of the joint capsule) anti inflammatory and immunosuppressive effects long term stress hormone can cause cushing syndrome is a steroid do not alter disease progression prolonged use can cause reduction in bone healing glucocorticoid can make lipocortin-1 which can inhibit phospholipase and inhibnit cox-2 which synergises well with NSAIDS
DMARDS
slow acting and cause disease profression or remission all cause immunosuppression no analgesic or direct anti-inflammatory effects
Examples
- Methotrexate (cytotoxic) common first choice DMARD fast onset many many side effects some lethal used with severe RA and some cancers folate antagonist which is required for dna production
- Cyclophosphamide (cytotoxic)
- Gold salts
- D-penicillamine
- Hydroxychroloquine
- Sulfasalazine metabolised into 5-aminosalicylic acid (5-ASA) and sulfapyridine 5-ASA helps reduce inflammation and sulfapyridine may help effects colonic bacteria metabolically process sulfasalazine
Immunosuppressants
- Cyclosporin
- Leflunomide
- Azathoioprine
Biological Agents (Fits under DMARDS)
- Infliximab anti tnf monoclonal antibodies (mouse variable region)
- Anakinra
- Abatacept
- Rituximab depletes b cells
- Onercept
- Etanercept
Treatment of RA preferred drugs
NSAIDS
- Ibuprofen
- Diclofenac COX-2 Inhibitors
- Celecoxib Glucocorticoids
- Prednisone Xenobiotics (often just kill quickly replicating cells)
- Methotrexate
- Cyclosporin Biological Agents (specific which is nice)
- TNF inhibitors
- Adalimumab anti tnf antibody with human variable region
- Etanercept (soluble tnf receptor to sponge up tnf)
- IL-6 receptor inhibitor
- Tocilizumab
- CTLA-4 inhibitor
- Abatacept blocks signal between antigen presenting cell and t cell
often drug mimic endogenous molecules often biological agent mimic endogenous signalling proteins as the immune system of depends on protein protein interactions
Tumour necrosis factor is a first line targert (REVISE)
Treatment Regime of RA
