Arthritis Flashcards
What is arthritis?
A common inflammatory disease, caused by a combination of genetic, environmental and hormonal factors. It decreases your quality of life.
Tell me some facts about arthritis.
40% people over 65 have arthritis
Affects 1% popn (1:3, males:females)
Expensive medical costs
What is osteoarthritis?
progressive and disabling disease
people over 60
not so painful
cartilage cells change, thins, lose elasticity and start to split…lose smooth functioning…bonce loses shape and thickens at the end producing bony spurs
What is rheumatoid arthritis?
25-50yrs, children? 1:3, M:F
Autoimmune, genetic, bacterial, viral?
Affects joints, painful and stiff and imflammed (swelling).
Primarily a synovitis (thick, inflammed synovial membrane) but leads to joint destruction and systemic lesions.
What are the principlesof managing rheumatoid arthritis?
Relieve symptoms, conserve and restore joint function, supress active pregressive disease, reduce mortality
What mediators are involved in arthritis?
TNF-alpha, IL1, IL6, IL8, IL10, IL17, and PGE2
Describe the mechanism of action of NSAIDs.
Inhibit COX and therefore inhibit PG production too (except paracetamol)
There are 2 central mechanisms…
1) time dependant irreversible inactivation
- aspirin and indomethacin
2) reversible competitive inhibition
- ibuprofen and meloxicam
Where is COX-1 found?
most cells, constitutive expressed, maintains homeostasis, Gi tract - maintains BF
TxA2 - platelet aggregation
PGI2 - inhibit platelet aggregation
Where is COX 2 found?
Induced inflammatory cells by inflammatory stimuli
Releases high levels of PG.
Name NSAIDs that are nonselective
Aspirin, Ibuprofen and Indomethacin
Name NSAIDs COX-2 selective
Celecoxib, rofecoxib, meloxicam
BUT have cardiac effects…x2 risk of MI
Disease Modifying Anti-Rheumatic Drugs:
SLow acting acnti rheumatic drugs - expain
2nd line therapies... Methotrexate - folate antag, antimetabolite in cancer chemo, most widely used, best used with NSAIDs Gold salts Antimalaria - chloroquine Suplhasalasine Penicllinamine
Disease Modifying Anti-Rheumatic Drugs:
Immunosupressives
Steroids, cyclosporins (toxic)
What are the pros and cons of using corticosteroids or glucocorticoids?
Pros: Inhibit AA release Cytokine inhibition Down reg adhesion molecules inhibit COX, iNOS induction
CONS:
osteoporosis
increase risk of infection
adrenal atrophy
Also inhibit t-lymph proliferation adn induce apoptosis.
Actions of TNF-alpha?
cytokine release (inc IL-1), decrease surface, TNF receptor, increase soluble TNF receptors, ingiogensis, MHC class 1and2, adhesion molecule expression, cehmokine release, tissue damage, metalloproetinase, PGE2 production
