0625 - Immunosuppressive Medications

Question 1

Identify the role of immunosuppressive medications in rheumatology

Answer 1

Second-line therapy, or used when major organs are threatened. Can be valuable in RA, vasculitis or SLE.

Question 2

What 4 classes of immunsuppressive drugs are used in rheumatology? Examples?

Answer 2

Alkylating agents - Cyclophosphamide
Antimetabolites - Purine antagonists - Azathioprine
Calcineurine Inhibitors (CNI) - Cyclosporin and Tarcrolimus
Purine synthesis inhibitors - Mycophenalate Mofetil

Question 3

Describe the general mechanism of action of the immunosuppressive medications used in rheumatology

Answer 3

Can interfere with cell life cycle and replication, or signalling pathways, or ability of (immune system) to respond to specific stimuli.
In turn, this reduces intensity of inflammation in the target organ.

Question 4

What is the MoA of Azathioprine?

Answer 4

Antimetabolite (Purine analogue) Prodrug, metabolised to 6-mercaptopurine (6 MP).
6 MP prevents DNA (purine) synthesis. Cytotoxic effect in cell division.
Reduces circulating T and B cells, reduced Ig synthesis, and IL-2 secretion.

Question 5

What is the MoA of cyclophosphamide?

Answer 5

Alkylating agent - Prodrug.

Cross-links DNA, impairing replication and transcription, leading to cell death or altered function.

Question 6

What is the MoA of Cyclosporin and Tacrolimus?

Answer 6

Calcineurine inhibitors.
Inhibit transcription of IL-2 and other cytokines by binding to a receptor, and the complex blocking action of calcineurin (phosphatase). Predominantly affect T-cell immunity.

Question 7

What is the MoA of mycophenolate Mofetil?

Answer 7

Purine synthesis inhibitor - prevents lymphocyte proliferation. Prodrug.
Mycophenolic acid (MPA - active form) prevents purine synthesis, thus preventing cell proliferation.

Question 8

What are the side effects of Azathioprine?

Answer 8

GI side effects, Bone marrow suppression, infection, skin malignancy, infertility.

Question 9

What are the side effects of cyclopsphamide

Answer 9

Haematological toxicity (leukopenia), infections, bladder toxicity, malignancy, teratogenic, gonadal toxicity.

Question 10

What are the side effects of cyclosporin/tacrolimus?

Answer 10

Renal dysfunction, hypertension, tremor, gum hyperplasia, hirsutism, diabetes (tacrolimus)

Question 11

What are the side effects of mycophenolate mofetil?

Answer 11

Safer than many. GI side effects, cytopenia (perform a regular blood count), infections, and potentially teratogenic.