Immunosuppressants

Question 1

What are the major clinical conditions for which immunosuppressants are most commonly used?

Answer 1

Transplantation
Autoimmune disease
Inflammatory disease

Question 2

Glucocorticoids
Characteristics:
MOA:
USes:
AE

Answer 2

Characteristics: decrease blood lymphocytes, downreg key cytokines, inhibit IL-2 prod by T cells, Reduce neutrophil chemotaxis. little effect on humoral immunity
MOA: binds to receptor in cytosol, or intercalates into the membrane and messes up cell signaling
USes: transplant, AI dz, Inflamm
AE: Growth retard, infection, wound heal, HTN, avascular necrosis of bone, cataracts, hyperglycemia, adrenal crisis

Question 3

Define the nomenclature used to describe Prednisone equivalent dosages
*****

Answer 3

Low dose: equiv of less than 7.5 mg prednisone
Med Dose: Between 7.5 and 30 mg prednisone
High dose: greater than 30 mg per day
Very high dose: greater than 100 mg/day
Pulse therapy: greater than 250 mg/day

Question 4

Cyclosporins
Characteristics:
MOA:
USes:
AE
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Answer 4

Characteristics: from fungus, iv and oral
MOA: suppresses T cell mediated immunity. Binds to cyclophilin then activates calcineurin, which prevents the dephosphorylation of NFAT - no translocation to nucleus and no cytokines from T cells.
USes: RA, Transplant, Psoriasis, usually combined
AE: Nephrotoxicity, HTN, Hyperlipidemia, Tremors, swollen gums, Hirsutism, skin ca,

Question 5

Tacrolimus
Characteristics:
MOA:
USes:
AE

Answer 5

Characteristics: from fungus strep tsukubaensis
MOA: Calcineurin inhibitor, no dephosphorylation of NFAT - no translocation to nucleus, no cytokines from T cells
USes: prophylaxis for allograft rejection
AE: Nephrotoxicity, HTN, DM, Neurotoxicity, Concen can be inc by grapefruit juice

Question 6

Azathioprine
Characteristics:
MOA:
USes:
AE

Answer 6

Characteristics: oral or iv, purine antimetabolite
MOA: conv to 6 MP decreases purines, lymphocytes dont have a good purine salvage pathway and die
USes: Prevent rejection, RA, Crohn’s, MS, etc
AE: Hepatotoxicity, Bone marrow suppress, Chicken pox, Ca risk elev

Question 7

Mycophenolate Mofetil
Characteristics:
MOA:
USes:
AE

Answer 7

Characteristics: oral iv
MOA: inhibitor of Inosiune monophosphate dehydrogenase - no guanine nt. B and T cells need this.
USes: prevent transplant rejection. combo w/glucocorticoids/calcineurin inhib
AE: Hematologic, GI, CMV, Preg congenital

Question 8

Sirolimus
Characteristics:
MOA:
USes:
AE

Answer 8

Characteristics: from fungus strep hygroscopius Oral only
MOA: inhib T cell prolif by binding to FKBP, similar to tacrolimus, but instead of inhibiting calcineurin, this inhibits MTOR
USes: transplant rejection, alternative to calcineurin inhibitors
AE: infections, neoplasms risk

Question 9

Antithymocyte Globulin
Characteristics:
MOA:
USes:
AE

Answer 9

Characteristics: Rabbit, resuspend in water
MOA: Contains AB that bind to CDlots of #s, on surface of T cells. antibodies deplete them by both Complement mediated cytotoxicity and Inhibition of lymphocyte functions - both kill it and inhibit the rest
USes: Intense immunosuppression in time right after transplant, tx of acute rejection
AE: serum sickness, cytokine storm

Question 10

Muromonab-CD3
Characteristics:
MOA:
USes:
AE

Answer 10

Characteristics: Mouse ab directed against CD 3
MOA: ab directed here kill t cell. also kills and inactivates
USes: Glucocorticoid resistant rejection episodes. T cells are gone withing a few minutes of administering. Can only use 1x bc body makes ab against it
AE: Cytokine storm! Prior glucocorticoid administration redues this rxn

Question 11

Anti-TNF alpha reagents
Characteristics:
MOA:
USes:
AE
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Answer 11

Characteristics:
Infliximab - mouse human
Adalimumab - Human igG
Etanercept - Human TNF alpha/IgG mix
MOA: bind directly to TNF alpha to keep frmo binding to its receptor
USes: RA if MTX has failed, Crohn’s who failed, B27 diseases
AE: Serious infections, lymphomas/malignancies