CE L2 RA therapies

Question 1

Innate or adaptive immune system are involved in chronic inflammation

Answer 1

both

Question 2

Aetiology of chron inflammation hypothesis

Answer 2

Infection results in chronic activation of the immune system, inflammation and tissue damage.
Presence of APC and cytokines facilitates response to self antigen.
Abundance of self antigen leads to continued immune system activation

Question 3

What is APC?

Answer 3

antigen presenting cells

Question 4

Two over all options for dampening immune response

Answer 4

Target the cells or the mediators

more often however the symptoms are the targets

Question 5

1st line treatment for RA

Answer 5

NSAIDS

Question 6

The three As of NSAID effects?

Answer 6

Analgesic
Antipyretic
Antiinflammatory

Question 7

Problems with NSAIDs

Answer 7

All have side-effects. From CV events for COX2 slevtive to GI effects for COX1.

Question 8

Do NSAIDs work for RA?

Answer 8

Not all that well, we don’t want to keep pt on them for too long, the disease is still progressing.

Question 9

DMARDs stands for

Answer 9

disease modifying anti rheumatic drugs

Question 10

e.g. of DMARDs (6)

Answer 10

Methotrexate
sulfasalazine
gold
penicillamine
hydroxychloroquine
leflunomide

Question 11

2nd line treatment for RA

Answer 11

DMARDs

Question 12

Do DMARDs work?

Answer 12

Improved symptoms
Remission
but long term effect on progression is controvertial

Question 13

Risks of DMARDs

Answer 13

Severe toxicity - skin, kidney, bone

Question 14

Problem with DMARD concordance

Answer 14

Several weeks until effect

Question 15

Recommendations for DMARD treatment

Answer 15

Use early.

Question 16

Combination of DMARD therapy?

Answer 16

Results are disappointing (1+1<2) - odd because pharmacologies are totally different

Question 17

How do DMARDs work?

Answer 17

They have different pharmacologies, specific action is modifying the disease process.

Question 18

For most DMARDs how many people get an effect?

Answer 18

10% remission
30% some response
30% no response
30% toxicity
at 1 year. At 2 years 50% remain on the drug.

Question 19

Methotrexate works by…

Answer 19

folate antagonist
(antiproliferative effect via inhibition of dihydrofolate reductase)
mechanism in RA unknown

Question 20

Methotrexate was originally…

Answer 20

anti-tumor agent

Question 21

Does resistance to methotrexate develop?

Answer 21

Yes - initially effective at low doses

Question 22

s/e of methotrexate (2)

Answer 22

GI damage and suppression of bone marrow

Question 23

Proposed mechanism of methotrexate in RA

Answer 23

Block proliferation of endothelial cells required for angiogenesis.
Supress IL1 induced IL6 - decreases synovial cell proliferation and reduces ROS.

Question 24

Gold administration options

Answer 24

IM (aurothiomalate)

Oral (auranofin)

Question 25

Does gold work?

Answer 25

Effective in halting the progress of bone and joint damage.

Question 26

Maximum effect of gold is when?

Answer 26

After 2-3 months

Question 27

What factors decrease with gold?

Answer 27

IgM against self IgG

Question 28

s/e of gold

Answer 28

toxic in 10%, rashes, ulcers, encephalopathy, peripheral neuropathy, hepatitis

Question 29

How does gold work?

Answer 29

Unknown - may bind to plasma protein and accumulate in joint macrophages

Question 30

In trials gold has been shown to (6)

Answer 30

inhibit lymphocyte proliferation
inhibit neutrophil chemotaxis

decrease mast cell degranulation
decrease TNF and IL1
decrease lysosomal enzymes
decrease toxic 02 production from phagocytes

Question 31

Mechanism of action of sulphasalazine?

Answer 31

Unknown - alter macrophages to favor anti-inflammatory cytokine produciton

Question 32

Penicillamine works by…

Answer 32

preventing maturation of newly synthesised collagen

Question 33

s/e of penicillamine

Answer 33

thrombocytopenia

autoimmune disease

Question 34

problems with penicillamine therapy?

Answer 34

long delay in effect

works in 75% of pt though

Question 35

chloroquine is originally for the treatment of…

Answer 35

malaria

Question 36

does chloroquine work?

Answer 36

reduces swelling but doesn’t slow progression

Question 37

how does chloroquine work?

Answer 37

similar to gold, also inhibits PLA2 and cytokine transcription

Question 38

How does Leflunamide work?

Answer 38

Inhibits orotate dehydrogenase - this may suppress B cell activity

Question 39

Over all DMARDs seem to have 3 effects

Answer 39

Inhibit cell proliferation
inhibit macrophage activation
decreased release of proinflam cytokines and ROS

Question 40

After NSAIDs what is a pt moved on to?

Answer 40

Methotrexate and if no effect a second DMARD is tried.

Question 41

3rd line treatment for RA

Answer 41

Steroids

Question 42

3/4th line treatment for RA

Answer 42

Biologicals

Question 43

Infliximab developed for

Answer 43

crohn’s disease

Question 44

Infliximab is given with ……………… to ………….

Answer 44

methotrexate

minimise immunogenic reactions

Question 45

Monitoring requirements for infliximab?

Answer 45

infections

Question 46

Humiria is also called ………..

Answer 46

adalimumab

Question 47

Humiria is suitable for….

Answer 47

pt who fail to respond to DMARD and other anti-TNF

Question 48

Humiria has a risk of ….

Answer 48

recurrence of tuberculosis