Immunosuppressants

Question 1

What conditions are immunosuppressants used. to treat?

Answer 1

Inflammatory arthropathies
Ulcerative collitis
Psoriasis
Unwanted normal inflammation in solid organ transplants and bone marrow grafts

Question 2

What are the advantages to the use of steroids as immunosuppressants?

Answer 2

Rapid onset
Easy to administer
Able to treat wide variety of inflammatory conditions

Question 3

What are the disadvantages to the use of steroids as immunosuppressants?

Answer 3

Intolerable adverse effects, especially at high dose

Question 4

What are the side effects of steroid sparing agents?

Answer 4

Weight gain
Fluid retention
Glaucoma
Osteoporosis
Infection
Hypertension
Hypokalaemia
Peptic ulceration
GI bleeding
Psychological/psychiatric symptoms

Question 5

Give examples of non-steroid immunosuppressant drugs which inhibit DNA synthesis?

Answer 5

Azathioprine
Methotrexate
Mycophenolate

Question 6

Give examples of non-steroid immunosuppressant drugs which inhibit lymphocyte signalling inhibitors?

Answer 6

Cyclosporin
Tacrolimus
Sirolimus
Leflunomide

Question 7

What are the disadvantages to the use of immunosuppressants?

Answer 7

Insufficient to control inflammatory disease
Slow rate of onset so limited usefulness in acute severe disease
Significant toxicity even at. low doses
Frequent infections and bone marrow suppression

Question 8

In high doses, what is methotrexate used to treat?

Answer 8

Used as cytotoxic chemotherapeutic agent against cancers

Question 9

Describe the mechanism of action of methotrexate?

Answer 9

Inhibits dihydrofolate reductase and thymidylate synthesise to disrupt DNA synthesis and cause s-phase arrest
Folate antagonism

Question 10

What are the adverse effects of methotrexate?

Answer 10

Nausea, vomtiing, diarrohea
Hepatitis
Stomatitis
Leukopaenia
Frequent infections
Pulmonary fibrosis

Question 11

Folic acid is usually given at what dose in order to reduce methotrexate toxicity?

Answer 11

5mg

Question 12

What conditions is methotrexate most commonly used to treat?

Answer 12

Rheumatological disease (RA, psoriasis and psoriatic arthropathy)
Used as a steroid sparing agent in giant cell arteritis

Question 13

Normally, methotrexate is given orally but it can be administered via which route if there is significant GI toxicity?

Answer 13

Sub cut injection

Question 14

What is the mechanism of action of azathioprine?

Answer 14

Converted within cells into a nucleoside and incorporated in DNA and RNA chains leading to the termination of nucleic acid strands. Cell growth and metabolism halts

Question 15

Why does azathioprine have preferential action on lymphocytes?

Answer 15

Other cells have purine salvage pathways, lymphocytes do not

Question 16

How does azathioprine inhibit T cell co-stimulation?

Answer 16

Interference with CD28

Question 17

What are the possible adverse effects of azathioprine?

Answer 17

Nausea, vomiting, diarrhoea
Hepatitis and cholestasis
Leukopaenia
Thrombocytopaenia
Frewutn infection

Question 18

Why is it important to check for TPMT activity prior to treatment with azathioprine.?

Answer 18

TPMT is vital in reducing active drugs in cells. Without TPMT (0.2-0.6% of individuals lack TPMT) there is accumulation of the most active metabolites of azathioprine within cells and the development of severe toxicity

Question 19

What conditions is azathioprine most commonly used to treat?

Answer 19

Inflammatory bowel disease

Other severe autoimmune diseases such as myasthenia gravis and eczema

Question 20

How is azathioprine administered?

Answer 20

Orally

Question 21

How often should patients on azathioprine have their bloods monitored?

Answer 21

Monthly basis

Question 22

What is the mechanism of action of cyclosporin?

Answer 22

Small molecule inhibitor of calcineurin which inhibits signal transduction from activated TCR complex to inhibit T cell activation

Question 23

What are the possible adverse effects of cyclosporin?

Answer 23

Nephrotoxicity
Hypertension
Hepatotoxicity
Anorexia and lethargy
Hirsutism
Paraesthesia

Question 24

Which immunosuppressant agent does not cause bone marrow suppression?

Answer 24

Cyclosporin

Question 25

Which immunosuppressant has a similar mechanism of action to cyclosporin but with more potent activity?

Answer 25

Tacrolimus

Question 26

What conditions is tacrolimus used to treat?

Answer 26

Kidney, liver, heart or lung transplantation

Sometimes used in the treatment of inflammatory conditions

Question 27

What is the mode of administration of tacrolimus

Answer 27

Topical or Oral

Question 28

How is the appropriate dose of tacrolimus established?

Answer 28

Using therapeutic drug monitoring

Question 29

How are biologics usually administered?

Answer 29

Parenterally

Question 30

What are the possible adverse effects of biologics?

Answer 30

Hypersensitivity reactions
Infusion reactions
Mild GI toxicity

Question 31

Which infections are patients on anti-TNF therapy at increased risk of?

Answer 31

TB particularly disseminated TB
Salmonella
Listeria

Question 32

Which infections are patients on abatacept at increased risk of?

Answer 32

TB
Pneumonia
Respiratory tract infection

Question 33

Which infections are patients on rituximab at increased risk of?

Answer 33

Generalised increased risk of serious infection

Hep B reactivation

Question 34

Which infections are patients on anti-IL1therapy at increased risk of?

Answer 34

Respiratory tract infection

Pneumonia