Immunosupressants/DMARDS

Question 1

Where is RA initially localised to?

Answer 1

The synovium of joints

Question 2

What are the aims of RA treatment?

Answer 2

Symptom relief, prevent joint destruction and avoid long term steroids

Question 3

Name 3 side effects with long term corticosteroids

Answer 3

Weight gain/fat redistribution
Hair thinning, skin bruises easily
Growth retardation (in kids),   Osteoporosis
Glucose intolerance, hyperglycaemia
Cataract formation

Question 4

What is RA?

Answer 4

Autoimmune multi system disease (inflammatory)
Fairly common (UK prevalence about 1%)

Question 5

What type of drug is azathioprine?

Answer 5

Cytotoxic anti metabolite

Question 6

Name 3 diseases azathioprine might be indicated in

Answer 6

Vasculitis
SLE
IBD

Question 7

Azathioprine MoA

Answer 7

Active drug cleaved to 6-MP
6-MP is an anti metabolite targeting purine synthesis
(so reduces DNA/RNA synthesis)
Less clonal proliferation during the immune response

Question 8

What genetic polymorphism affects azathioprine?

Answer 8

TPMT metabolises 6-MP
Highly polymorphic, test before prescribing
If low TPMT, increased risk of myelosuppression

Question 9

ADRs azathioprine

Answer 9

Bone marrow suppression
Risk of malignancy if used long term
Hepatitis
As w all immunosuppressants- increased risk of infn

Question 10

What enzyme does methotrexate target?

Answer 10

Dihydrofolate reductase (competitive and reversible inhibition)

Question 11

Methotrexate is what type of drug? Does it act this way in RA?

Answer 11

Anti folate

But not in RA (lower dose, dif mechanism)

Question 12

What kind of drug is mycophenolate mofetil?

Answer 12

A highly selective cytotoxic anti metabolite

Question 13

Name the calcineurin inhibitors

Answer 13

Tacrolimus and ciclosporin

Question 14

Calcineurin inhibitors form complexes which block NFAT dephosphorylation. What does each drug bind to?

Answer 14

Tacrolimus binds FK (binding protein) 12

Ciclosporin binds cyclophilin A

Question 15

Why is Mycophenolate Mofetil considered highly selective?

Answer 15

Affects G (nucleotide base) synthesis
Deprives rapidly dividing B and T cells of a key nucleotide
However, other non lymphocyte cells have guanosine salvage pathways so aren’t affected

Question 16

Keeping in mind mycophenolate mofetil is highly selective

What ADRs does it have?

Answer 16

GI (most common)
Myelosuppression
Increased risk CMV

Question 17

Cyclophosphamide is what type of drug?

Answer 17

Alkylating agent

Question 18

Name some indications for using Cyclophosphamide

Answer 18

Lymphoma
Leukaemia
WG/PAN vasculitis

Question 19

Name some conditions where Methotrexate can be used

Answer 19

RA (gold standard treatment)
Psoriasis
Crohn’s

At high doses- malignancy eg ALL

Question 20

Compare MTX affinity for DHFR to dihydrofolate

Answer 20

MTX has an affinity for DHFR 1000x that of dihydrofolate

Question 21

Describe dosing for methotrexate in RA

Answer 21

Weekly not daily

Question 22

Name some ADRs of methotrexate

Answer 22

Myelosuppression
Mucositis
Hepatitis

Question 23

Why is MTX not given if you’re pregnant?

Answer 23

Teratogenic and abortaficient

Question 24

Name some drugs that would interact w methotrexate

Answer 24

Warfarin
NSAIDS
Omeprazole
Folic Acid
Penicillins, cephalosporins

Question 25

Name 3 DMARDS

Answer 25

Methotrexate
Sulphasalazine
Anti-TNF agents

Question 26

When might you use sulfasalazine?

Answer 26

Early mild RA in combination w methotrexate

Also, is safe in pregnancy

Question 27

Anti TNF agents reduce angiogenesis, inflammation and joint destruction. What is the problem?

Answer 27

They’re very expensive