Immunosuppression

Question 1

List the 4 categories of immunosuppression

Answer 1

Steroids
Biological Agents
Antimetabolites
Cytokine Inhibitors

Question 2

Give 2 examples for each of the 4 categories of immunosuppression

Answer 2

Steroids- prednisolone, hydrocortisone, methylpred
Biologics- Adalimumab, Infliximab, Etanercept
Antimetabolites- MTX, Azathioprine
Cytokine Inhibitors- Cyclosporine, Tacrolimus

Question 3

What are steroids used for? (3)

Answer 3

Immune suprression in RA and autoimmune conditions.
Anti-inflammatory in asthma, giant cell arteritis.
Replacement therapy in Addisons, hypoadrenalism

Question 4

What is the mechanism of action of steroids?

Answer 4

Binds to cytoplasmic receptor, is transported to the nucleus to increase/promote or decrease/inhibit gene transcription.

Question 5

What is a secondary, slower MoA of steroids?

Answer 5

Prevents production of of Interleukin 1 and 6 by macrophages.
This therefore inhibits T cell activation.

Question 6

What advice to you need to give to somebody taking steroids long term?

Answer 6

Never stop suddenly, need to be weaned off. (as it leads to supression of the adrenal axis)
Should carry steroid card
May need to double dose during infection/trauma

Question 7

List some side effects of steroids (8)

Answer 7

Hair loss, Cataracts, Glaucoma, Insomnia, Psychosis, mood changes, weakened immune system, increased infection risk, weight gain, central obesity, bruising, striae, pancreatitis, gastritis, increased insulin resistance, mucsle wastage in limbs, fluid retention, hypertension, adrenal crisis if stopped suddenly

Question 8

List 2 conditions that may need long term steroid use

Answer 8

Addisons

Step 5 asthma

Question 9

What is the gold standard treatment for Rheumatoid Arthritis?

Answer 9

Methotrexate

Question 10

Give 4 indications for MTX?

Answer 10

Rheumatoid A
Crohns
Psoriasis
Malignancy

Question 11

What is the MoA of MTX?

Answer 11

Competitively inhibits DHFR. Therefore inhibits the synthesis of DNA and RNA and proteins.

Question 12

What is the most important thing to remember with Methotrexate

Answer 12

NEVER GIVE DAILY!!

It is given once weekly due to long half life

Question 13

What commonly used drug can displace MTX, which is 50% protein bound?

Answer 13

NSAID’s

Question 14

List 6 adverse reactions of MTX

Answer 14

Mucositis
Marrow suppresion (this and mucositis are improved with folate supplements)
Hepatitis/Cirrhosis
Pneumonitis (uncommon)
Teratogenic
Abortifacient

Question 15

What drug should be given alongside MTX?

Answer 15

Folic acid supplements

Question 16

What is the advantage of giving MTX IM or SC over oral?

Answer 16

Better bioavailability (76% from 33%)

Question 17

List 2 antimetabolite drugs

Answer 17

Methotrexate

Azathioprine

Question 18

Name a steroid sparing drug

Answer 18

Azathioprine

Question 19

List 6 indications for azathioprine

Answer 19

SLE
IBD
Post renal transplant
Polymyaliga Rheumatica
ILD
Atopic Dermatitis

Question 20

List 5 side effects of Azathioprine

Answer 20

Increased risk of infection
Neutropenia (monitor FBC)
Liver toxicity (monitor LFT)
Myelosuppression
Increased risk of malignancy

Question 21

What is the mechanism of action of Azathioprine?

Answer 21

Inhibits purine synthesis

converted to 6-MP

Question 22

What metabolises Azathioprine?

Answer 22

TPMT

Question 23

What deficiency would lead to increased side effects and toxicity of azathioprine?

Answer 23

deficiency of TPMT (everyone has different base levels and so need to measure before begin treatment)

Question 24

Which drug interacts with Azathioprine? What effect does this have?

Answer 24

Allopurinol

inhibits metabolism of azathioprine, therefore if taking you need to decrease dose.

Question 25

What needs to be measured before beginning Azathioprine?

Answer 25

TPMT