Immunosuppressants

Question 1

cortisone
hydrocortisone
prednisone
prednisolone
methylprednisolone
triamcinolone
dexamethasone
betamethasone

Answer 1

• glucocorticoids
• MOA: bind DNA–> activate or inhibit gene expression–> inhibit transcription factors–> decreased immunoregulatory and inflammatory cytokines; influence cell signaling pathways; intercalate into cell membrane–> alter ion transport–> rapid immunosuppression
• effects: decrease lymphocytes, decrease pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha, interferon gamma), inhibit IL-2 (T cell proliferation), reduce neutrophil chemotaxis
• use: prevent/treat transplant rejection, treat graft-vs-host disease, block cytokine storm w/ muromonab-CD3 tx, treat autoimmune diseases
• adverse effects: growth retardation, risk of infection, poor wound healing, hypertension, avascular necrosis of bone, cataracts, hyperglycemia, adrenal crisis

Question 2

glucocorticoid dosages

Answer 2

• *prednisone equivalent**
• low dose: less than 75 mg/day
• medium dose: greater than 7.5 mg but less than 30 mg/day
• high dose: greater than 30 mg but less than 100 mg/day
• very high dose: greater than 100 mg/day
• pulse therapy: greater than 250 mg/ day for 1 day or few days

Question 3

cyclosporine

Answer 3

• calcineurin inhibitor
• MOA: complex w/ cyclophilin–> binds calcineurin–> prevent dephosphorylation of transcription factor NFAT–> no T cell cytokine production (IL-2–> NO proliferation)
• IV or oral admin
• use: prophylaxis for kidney, liver, heart, and other organ transplants, tx of graft-vs-host disease, RA, psoriasis
• combo with other agents
• adverse effects: nephrotoxicity, hypertension, hyperlipidemia, tremors of hands and feet, swollen gums, hirsutism, increased risk of skin cancer, increased blood conc. by grapefruit juice

Question 4

tacrolimus

Answer 4

• calcineurin inhibitor
• MOA: complex w/ cyclophilin–> binds calcineurin–> prevent dephosphorylation of transcription factor NFAT–> no T cell cytokine production (IL-2–> NO proliferation)
• injectable or oral
• uses: prophylaxis of allograft rejection in organ transplant
• adverse effects: nephrotoxicity, hypertension, diabetes, neurotoxicity, increased conc. in blood with grapefruit juice

Question 5

azathioprine

Answer 5

• antiproliferative/ antimetabolic agent
• MOA: metabolized–> incorporated into DNA–> inhibit lymphocyte proliferation; inhibit de novo pathway of purine synthesis (lymphocytes lack salvage pathway)
• use: prevent organ transplant rejection, severe RA, Crohn’s, MS, prednisone resistant thrombocytopenic purpura, hemolytic anemia
• adverse effects: bone marrow suppresion, hepatotoxicity, risk of infection (varicella-zoster, HSV), increased risk of cancer (lymphoma)

Question 6

mycopenolate mofetil

Answer 6

• antiproliferative/ antimetabolite agent
• MOA: activated–> inhibitor of inosine monophosphage dehydrogenase–> inhibit de novo synthesis of guanine nucleotides–> inhibit lymphocyte proliferation
• use: prophylaxis of transplant rejection, admin in combo w/ glucocorticoids and calcineurin inhibitor, SLE
• adverse effects: leukopenia, RBC aplasia, diarrhea, vomiting, infection w/ CMV
• contraindicated: pregnancy (congenital abnormalities, pregnancy loss)

Question 7

sirolimus

Answer 7

• antiproliferative/ antimetabolic agents
• MOA: bind FKBP–> bind ad inhibit protein kinase mTOR–> block G1-S phase transition of cell cycle–> inhibit T-lymphocyte proliferation
• use: prophylaxis of organ transplant rejection in combo w/ glucocorticoids and calcineurin inhibitor, renal transplant pts who can’t tolerate calcineurin inhibitor
• adverse effects: anemia, leukopenia, thrombocytopenia, hypokalemia, GI effects, delayed wound healing, risk of infection, risk of neoplasm (lymphomas)

Question 8

antithymocyte globulin

Answer 8

• biological agent
• rabbit IgG
• MOA: Ab bind CD2, CD3, CD4, CD8, CD11a, CD18, CD25, CD44, CD45, and HLA class I and II on T lymphocytes–> complement-mediated cytotoxicity or inhibition of lymphocyte functions
• use: induction and prophylactic immunosuppression, acute rejection of solid organ transplant
• adverse effects: cytokine storm (give prophylactic glucocorticoids), serum sickness, anaphylaxis, leukopenia, thrombocytopenia, malignancy, infection

Question 9

muromonab-CD3

Answer 9

• biological agent
• MOA: bind CD3 on T lymphocytes–> complement-mediated destruction or functional inactivation or inhibition of T cell activation
• uses: organ transplant rejection
• repeated use not efficacious–> pt Abs formed against Ab treatment
• adverse effects: cytokine storm (gluococoticoids prior to reduce), tremor, nausea, vomiting, diarrhea, myalgia, arthralgia, generalized weakness, anaphylaxis, pulmonary edema, ARDS

Question 10

infliximab

Answer 10

• biological agent
• anti-TNF-alpha reagent
• MOA: bind to cytokine–> prevent TNF-alpha from binding receptors
• chimeric recombinant monoclonal antibody containing human constant and murine variable region
• uses: pts w/ RA who don’t respond to methotrexate alone, Crohn’s, ulcerative colitis, ankylosing spondylitis, plaque psoriasis, psoriatic arthritis
• adverse effects: risk of infection, risk of lymphoma and other malignancies

Question 11

adalimumab

Answer 11

• biological agent
• anti-TNF-alpha reagent
• MOA: bind to cytokine–> prevent TNF-alpha from binding receptors
• recombinant human IgG1 monoclonal
• uses: pts w/ RA who don’t respond to methotrexate alone, Crohn’s, ulcerative colitis, ankylosing spondylitis, plaque psoriasis, psoriatic arthritis
• adverse effects: risk of infection, risk of lymphoma and other malignancies

Question 12

etanercept

Answer 12

• biological agent
• anti-TNF-alpha reagent
• MOA: bind to cytokine–> prevent TNF-alpha from binding receptors
• ligand-binding portion of human TNF-alpha receptor fused to Fc portion of human IgG1
• uses: pts w/ RA who don’t respond to methotrexate alone, Crohn’s, ulcerative colitis, ankylosing spondylitis, plaque psoriasis, psoriatic arthritis
• adverse effects: risk of infection, risk of lymphoma and other malignancies