Rheumatoid Arthritis Treatment 4

Question 1

why are NSAIDS used in RA treatment

Answer 1

1. useful as a background antiinfllamatory
   - there I sinter patient variability between response to each NSAID
2. beware of potential side effects- consider risk vs benefit
   - CV risk
   - GI risk
   - renal risk

Question 2

describe the kinetics and mechanism of action of NSAIDS

Answer 2

1. well absorbed
2. highly protein bound
3. metabolised by liver
4. excreted by GF or TS
5. peak plasma of 1-4hrs
6. accumulate at site
7. short half lives
8. they lead to the inhibition of COX
   - Cyclooxygenase is required to convert arachidonic acid into thromboxanes, prostaglandins, and prostacyclins

Question 3

describe the efficacy between NSAIDS and COX 2 inhibition

Answer 3

1. no difference between NSAIDS and COX 2
2. particularly useful in acute inflammation
3. choice varies between patients
4. if no effect in 2 weeks, witch to an alternative
5. no rationale for combination therapy

Question 4

give an example of the GI effects that NSAIDS can cause

Answer 4

• serious upper GI bleeding/perforation

Question 5

describe how systemic glucocorticoids are used in rheumatology

Answer 5

1. various systemic effects that have an effect on disease modification
2. they decrease proinflammatory cytokines and enzymes
3. inhibit transcription factors, decrease T cell function and Fc receptor expression
4. adverse events common, short courses only

Question 6

describe how dose timing affects outcome

Answer 6

1. clearance varies by time of day because of the distribution of normal cortisol production
2. very early morning administration results in more profound reduction of inflammation

Question 7

what are the practical recommendations of using glucocorticoids

Answer 7

1. use the lowest dose for the shortest time
2. discuss risk vs benefit
3. use in combination with a DMARD
4. offer adequate bone protection

Question 8

describe the ACR response rates

Answer 8

1. ACR reported as % improvement, comparing disease activity at 2 discrete time points
   - usually baseline and post baseline
2. ACR20 is > 20% improvement
   - clinically significant
3. ACR50 is >50% improvement
4. ACR70 is >70% improvement
   - ACR70 responders include ACR20 and ACR50 responders

Question 9

give examples of non immunosuppressive disease modifying antirheumatic drugs

Answer 9

1. old school drugs but still useful
2. gold
3. sufasalazine
4. hydroxychloroquine

Question 10

describe the properties of parenteral gold and how it can be used as treatment in RA

Answer 10

1. rapidly absorbed and highly protein bound
2. very slowly eliminated by kidney
3. MOA unknown
   - probably reduces oxidative stress and affects macrophages and cytokines
4. IM gold is as effective as oral methotrexate
5. high ADR rate than methotrexate

Question 11

give examples of adverse drug reactions of gold

Answer 11

• acute renal failure
• metallic taste
• diarrhoea
• rash

Question 12

describe the properties of sulfasalazine and how it can be used in treatment of RA

Answer 12

1. prodrug metabolised by bacteria to 5ASA and sulfapyridine
2. MOA unclear- probably reduces oxidative damage
3. effective as lower doses of methotrexate
4. generally well tolerated
5. can cause oligospermia

Question 13

describe the properties of hydroxychloroquine and how it can be used in treatment of RA

Answer 13

1. antimalarial found by chance to improve RA
2. half life is 40 days but LDs not normally used as increases ADRs
3. Cpss takes 3 months- slow acting
4. often used in SLE as its anchor drug
5. inhibits Toll like receptors affecting cytokine signalling
6. moderate effects alone, but better in combination
7. can cause retinal changes
   - must have regular eye testing
   - if it occurs, stop drug and switch to alternative DMARD