E2.1 RA Drugs

Question 1

Name drugs for treating RA

- are NSAIDS a good drug for treating RA

Answer 1

Disease modifying anti-rheumatic drugs (DMARDs) such as
Glucocorticoids
Conventional synthetic DMARDs (classical)
Biological DMARDs (anti-TNF etc.)
Targeted synthetic DMARDs (JAK inhibitors)
- good drug choice for treating pain in RA however they don’t alter disease progression….

Question 2

What factors dictate what combinations of drugs are used to treat RA

Answer 2

Disease progression (severity and rate of joint damage),
How well the patient responds to a chosen DMARD,
Patient becomes refractory to a DMARD,
Other underlying health conditions and the severity of side effects.
The cost of treatment

Question 3

1. Name some DMARS
2. Describe efficacy in trials
3. Describe drug onset

Answer 3

1. infliximab, cyclosporin, sulphasalazine, leflunomide, methotrexate, corticosteroids and IL-1 receptor antagonists
2. These were all superior to placebo in reducing erosions in RA
   Anti-malarials appear to be less effective
3. The drugs are slow in onset and NSAIDs are needed to control pain

Question 4

GC suppress what actions of inflammatory response

Answer 4

All actions
Reduce vascular permeability
Inhibit adhesion molecule expression
- (required to get WBC into inflamed joint
Inhibit fibroblast activity
- slow fibroblast proliferation/ release of MMP
Inhibit WBC accumulation/activity
Inhibit COX-2 and cytokine production (e.g. Il-1, IL-6)
Used less frequently due to side effects

Question 5

Describe mechanism of action of GC

Answer 5

Act intracellularly to modify transcription either by
1. induction
2. Repression
(therefore induce anti-inflammatory molecules or inhibit production of pro-inflam molecules)
Increasing interest in non-genomic effects mediated by membrane-bound receptors (e.g. immunosuppression of T-cells)

Question 6

What does annexin-1 do to PG pathway?

Answer 6

nnexin inhibits PG pathway - direct PLE2 directly turns off prostaglandin and leukotriene production downstream

Inhibits neutrophil accumulation
- involved acute inflammation
Inhibits monocyte-macrophage accumulation
Inhibits macrophage phagocytosis
Inhibits production of cytokines by macrophages
[All beneficial results]

Question 7

Glucocorticoids inhibit synthesis of what inflammatory mediators

Answer 7

GENE REPRESSION - due to GC binding 
arachidonic acid metabolites
NO (via iNOS)
inflammatory cytokines (e.g. TNFα, IL-1, IL-8,   IL-12)
Chemokines (CXCL)
adhesion molecules

Question 8

Adverse effects of glucocorticoids

Answer 8

Glucocorticoids have severe significant side effects which prohibit long-term use
- Used short term at low dose
Multi-systemic metabolic effects, such as –
GI tract bleeding
Osteoporosis
Ulcer formation