Rheumatoid Arthritis Treatment 4 Flashcards
why are NSAIDS used in RA treatment
- useful as a background antiinfllamatory
- there I sinter patient variability between response to each NSAID - beware of potential side effects- consider risk vs benefit
- CV risk
- GI risk
- renal risk
describe the kinetics and mechanism of action of NSAIDS
- well absorbed
- highly protein bound
- metabolised by liver
- excreted by GF or TS
- peak plasma of 1-4hrs
- accumulate at site
- short half lives
- they lead to the inhibition of COX
- Cyclooxygenase is required to convert arachidonic acid into thromboxanes, prostaglandins, and prostacyclins
describe the efficacy between NSAIDS and COX 2 inhibition
- no difference between NSAIDS and COX 2
- particularly useful in acute inflammation
- choice varies between patients
- if no effect in 2 weeks, witch to an alternative
- no rationale for combination therapy
give an example of the GI effects that NSAIDS can cause
- serious upper GI bleeding/perforation
describe how systemic glucocorticoids are used in rheumatology
- various systemic effects that have an effect on disease modification
- they decrease proinflammatory cytokines and enzymes
- inhibit transcription factors, decrease T cell function and Fc receptor expression
- adverse events common, short courses only
describe how dose timing affects outcome
- clearance varies by time of day because of the distribution of normal cortisol production
- very early morning administration results in more profound reduction of inflammation
what are the practical recommendations of using glucocorticoids
- use the lowest dose for the shortest time
- discuss risk vs benefit
- use in combination with a DMARD
- offer adequate bone protection
describe the ACR response rates
- ACR reported as % improvement, comparing disease activity at 2 discrete time points
- usually baseline and post baseline - ACR20 is > 20% improvement
- clinically significant - ACR50 is >50% improvement
- ACR70 is >70% improvement
- ACR70 responders include ACR20 and ACR50 responders
give examples of non immunosuppressive disease modifying antirheumatic drugs
- old school drugs but still useful
- gold
- sufasalazine
- hydroxychloroquine
describe the properties of parenteral gold and how it can be used as treatment in RA
- rapidly absorbed and highly protein bound
- very slowly eliminated by kidney
- MOA unknown
- probably reduces oxidative stress and affects macrophages and cytokines - IM gold is as effective as oral methotrexate
- high ADR rate than methotrexate
give examples of adverse drug reactions of gold
- acute renal failure
- metallic taste
- diarrhoea
- rash
describe the properties of sulfasalazine and how it can be used in treatment of RA
- prodrug metabolised by bacteria to 5ASA and sulfapyridine
- MOA unclear- probably reduces oxidative damage
- effective as lower doses of methotrexate
- generally well tolerated
- can cause oligospermia
describe the properties of hydroxychloroquine and how it can be used in treatment of RA
- antimalarial found by chance to improve RA
- half life is 40 days but LDs not normally used as increases ADRs
- Cpss takes 3 months- slow acting
- often used in SLE as its anchor drug
- inhibits Toll like receptors affecting cytokine signalling
- moderate effects alone, but better in combination
- can cause retinal changes
- must have regular eye testing
- if it occurs, stop drug and switch to alternative DMARD