E2 RA treatment

Question 1

delays in treatment result in what

early, intensive treatment increases chances of..

Answer 1

1. long term joint damage

2. halting or slowing disease progression

Question 2

Name some DMARDs

Answer 2

Glucocorticoids
Classical DMARDs
Biologics
JAK inhibitors

Question 3

Name phases of treatment

Answer 3

Phase I –conventional synthetic DMARDs and glucocorticoids
Phase II – change to a 2nd csDMARD and add in biologics
Phase III - Replace bDMARD with an alternative, or a JAK inhibitor

Question 4

Non-steroidal anti-inflammatory (NSAIDs) drugs

Answer 4

aspirin
indomethacin
ibuprofen
diclofenac
fenbufen
sulindac
Piroxicam

Question 5

Describe the two major isoforms COX exists in

Answer 5

COX-1
constitutive
involved in normal physiology e.g. early stages of inflammation in the endothelium
Found in blood vessels, Ca dependent enzyme & makes moderate amount of ProsE2 - following activation of endothelial cells

COX-2
inducible
Induced/upregulated in chronically inflamed tissue
regulated by cytokines such as TNFa & IL-1 in cells such as macrophages

Question 6

Describe NSAIDs

1. which drugs have moderate preference for COX1
2. marker preference for COX1
3. Name COX2 selective inhibitors
4. Other than COX which actions contribute to NSAIDS anti-inflammatory action

Answer 6

‘Classical’ NSAIDs are non-selective inhibiting both COX-1 and COX-2

1. most show some moderate preference: e.g. naproxen, indomethacin
2. marked: flurbiprofen
3. celecoxib, rofecoxib, eterocoxib.
4. Lots of macrophages in joints producing COX2

Question 7

(~ Name aspirin mechanisms NSAIDS)

• what does aspirin trigger
• what does aspirin mediate

Additionally, what do Indomethacin and diclofenac do

Answer 7

Triggers formation of lipoxins: aspirin-triggered lipoxin (ATL) & resolvins via COX-2 (further provide anti-inflammatory effects.)
- mediates acetylates COX-2 & acetylated COX-2 –> converts eicosapentanoic acid (EPA) to 18R-HEPE which is then converted by 5-LOX to resolvin E1, = mediate the resolution of inflammation

Inhibit degradation of resovlins/ lipoxins

Question 8

Name threapeutic effects of NSAIDS

Answer 8

Reduce pain – very effective analgesics
Reduce inflammation – pain, vasodilatation, increased vascular permeability + swelling of joint
Reduce morning joint stiffness
(anti-piretic: reduce fever)
- Effectively reduce symptoms but do not modify underlying disease process

Question 9

Name the Adverse effects of NSAIDs

Answer 9

G.I tract (peptic ulcer disease)
Kidney (PGs contribute to renal blood flow, reduced PGs – reduced blood flow – renal insufficiency in susceptible patients)
involved in vasodilation - inhibiting PG = enhanced constriction)
Lung (Aspirin induced Asthma – 20% of population, severe bronchospasm)
cardiovascular system (increased risk of MI & stroke)