Immunosuppressants

Question 1

Aspirin

Answer 1

NSAID

Mech:
irr. inhibitor of COX

Toxicity:
GI distress/ ulcerations/ renal dysfunction

Notes:
Very effective with platelets
Causes Reyes syndrome in children with influenza
Low dose

Question 2

Ibuprofen (Naproxen)

Answer 2

NSAID

Mech:
Non-specific Cox inhibitor

Toxicity:
GI distress/ ulcerations/ renal dysfunction

Notes:
medium doses

Question 3

Methotrexate

Answer 3

Mech:
1. inhibits enzymes that increase extracellular adenosine –> increases cAMP/PKA –> decreases inflammation

2. cancer treatment drug (inhibits DHFR)

Toxicity:
Bone marrow depression

Question 4

Prednisone

Answer 4

Glucocorticoid steroid

Mech:
1. Block Nf-kb and induce Ikb (inhibitor of nf-kb) –> decreases cytokine release -> altered leukocyte trafficking and inhibits leukocyte function

2. Induction of IkB alpha –> decreases AA release –> decreasing inflammation

Toxicity:
Chronic use : increases toxicity
- osteoporosis/ muscle wasting/ diabetes/ adrenal suppression

notes:
Must taper off slowly or will have adverse effects

Question 5

Etanercept

Answer 5

Mech:
decoy TNF alpha receptor –> prevents binding of TNF alpha –> decreasing NfKB –> decreasing inflammation

Toxicity:
Injection site reactions

Question 6

Rituximab

Answer 6

Mech:
mAB –> CD2- –> causes apoptosis of B cell (normal or maglinant)

Toxicity:
Anemia/ neutropenia

Uses:
Refractory Rh. Arthritis
B cell lymphoma/leukemia
Other auto immune diseases

Question 7

Mycophenolate Mofetil

Answer 7

Mech:
inhibits inosine monophosphate dehydrogenase –> inhibits GTP synthesis –> decreases B + T cell proliferation

Toxicity:
Bone marrow depression
GI dysfunction

Notes:
Combo with cyclosporin + glucocorticoids for transplants
Autoimmune disease like RA

Question 8

Cyclosporin

Answer 8

Immunophilin inhibitors

Mech:
binds cyclophilin and inhibits calcineurin –> decreases NFAT –> decreases cytokine

Toxicity:
Nephro/neuro toxicity
HTN

Question 9

Tacrolimus

Answer 9

Immunophilin inhibitors

Mech:
Binds FKBP-12 –> inhibits calcineurin

Question 10

Sirolimus

Answer 10

Immunophilin inhibitors

Mech:
Binds FKBP-12 –> inhibits mTOR –> decreaes T cell activation and proliferation

Toxicity:
Increased cholesterol and TG
bone marrow depression
Hepatotox

Question 11

Anakinra

Answer 11

Mech:
Recombinant version of IL-1 receptor antagonist

Toxicity:
Increased risk of infections

Uses:
RA