Immunosuppressive Drugs

Question 1

Outline how corticosteroids work:

Answer 1

Bind to intracellular corticosteroid receptors - detach from Heat-Shock proteins

Increases up-regulation of anti-inflammatory signals
- annexin -1 (blocks Phospholipase A2)

Reduces gene expression of NFkB

Question 2

Methotrexate at different dosages has different effects, outline these:

Answer 2

Low dose - immunosuppression

High dose - chemotherapy - cytotoxic agent

Question 3

Methotrexate has an effect on two enzymes, which are they:

Answer 3

Dihydrofolate reductase

Thymidylate synthase

Question 4

At lower doses, it is thought methotrexate carriers out more its action outwith cellular arrest, what are these?

Answer 4

Adhesion molecules

Adenosine signalling

cytokines

Eicosanoids

MMP activation

Question 5

Name some side effects of methotrexate:

Answer 5

D&V

Hepatitis

Leukopenia

Question 6

What is the dosing of methotrexate for RA, and what is it given with to reduce toxicity?

Answer 6

Once a week

folic acid

Question 7

How does azathioprine work?

Answer 7

Transformed into 6 mercaptopurine

acts as purine analogue, blocking cellular growth and metabolism

Preferential towards lymphocytes

Question 8

What are the indications of use for azathioprine?

Answer 8

Ulcerative colitis
Chrons

Myasthenia gravis
Eczema

Question 9

Azathioprine at low doses is thought to work through other mechanisms to bring about immunosuppression - what are these?

Answer 9

Interferes with co-T cell stimulation by interacting with CD28

Question 10

What enzyme degrades azathioprine, and what are some clinical consideration that need to be taken into account with this?

Answer 10

TPMT enzyme

0.2-0.6% people lack this. If they lack this, they are at significant risk of toxicity of the drug

So must be checked prior to starting treatment

Question 11

How does cyclosporine work?

Answer 11

Binds to cylophilin creating complex.

these bind to calcineurin - which prevent NFAT - which transcribes for pro-inflammatory NFkB and IL-2

in consequence - no T cell activation. primarily through lack of IL-2

Question 12

What are some side effects of cyclosporine?

Answer 12

Hypertension

Nephrotoxicity

Hepatotoxicity

Hirsutism

Question 13

Name a drug which is slightly more potent that cyclosporin, but works in the same way:

Answer 13

Tacrolimus

Question 14

Give the indication for use of cyclosporine and tacrolimus:

Answer 14

Solid organ transplants

Certain skin inflammatory conditions
- used topically

Question 15

List some TNF- alpha inhibitors, and a serious risk with their use:

Answer 15

Adamuzumab

Infliximab

Entercept

**serious risk of reactivation of TB - due to macrophages being unable to regulate the granuloma

Need to screen for TB prior

Question 16

Name a CD20 inhibitor and a risk associated with it:

Answer 16

Rituximab

Hep B infection

Question 17

Name IL-1 inhibitor and CD80/86 inhibitors and their risks:

Answer 17

Anakinra - IL-1

Abatacept - CD80/86

Pneumonia and respiratory tract

Abatacept - also TB (but not as much as TNF-alpha)