Immunosuppressive Therapy

Question 1

What is an immunosuppressive drug?

Answer 1

a drug used to prevent the production of antibodies, as well as suppression of T and B lymphocytes

Question 2

3 uses of immunosuppressive drugs

Answer 2

1. prevent organ transplant rejection
2. treat graft-versus-host-disease
3. treat autoimmune disorders

Question 3

What is cyclosporine?

Answer 3

a lipophilic cyclic peptide of 11 amino acids, isolated from a fungus

Question 4

What is tacrolimus?

Answer 4

a macrolide antibiotic, isolated from a fungus

Question 5

What is the MOA for cyclosporine and tacrolimus?

Answer 5

bind to cytoplasmic proteins
drug-protein complex inhibits calcineurin (calcium and calmodulin dependent phosphatase)
leads to reduced transcriptional activation for IL-2, TNF-alpha, GM-CSF
reduction of number of T lymphocytes
T cell-dependent B cell responses are inhibited
immune response is decreased

Question 6

Cyclosporine: ROA

Answer 6

IV, oral, ophthalmic

Question 7

Cyclosporine: uses

Answer 7

IV mainly
Oral variably, incompletely absorbed
Ophthalmic: treats dry eyes
solid organ transplantation, GVHD, autoimmune diseases

Question 8

Cyclosporine: adverse effects

Answer 8

nephrotoxicity, HTN, neurotoxicity, infection (viral, fungal), hyperkalemia, hypomagnesemia, glucose intolerance, hyperuricemia
increased risk of development of cancers (squamous cell skin cancer, benign and malignant lymphoproliferative disease)

Question 9

Cyclosporine: monitoring

Answer 9

renal function (BUN, creatinine)
BP
serum electrolytes (magnesium, potassium, glucose)
LFTs (bilirubin can elevate)

Question 10

Tacrolimus: ROA

Answer 10

IV, oral, topical

Question 11

Tacrolimus: uses

Answer 11

topical: severe plaque psoriasis, severe atopic dermatitis
prevention of organ rejection
used with methotrexate for prevention of acute GVHD

Question 12

Tacrolimus: adverse effects

Answer 12

nephrotoxicity, neurotoxicity (HA, tremors, paresthesias, coma), HTN, pulmonary (dyspnea), GI (N/V/D, abdominal discomfort), fatigue, hyperkalemia, hypomagnesemia, hyperglycemia

Question 13

Tacrolimus: monitoring

Answer 13

renal function
electrolytes and magnesium
BP
fasting blood glucose
tacrolimus levels

Question 14

What is sirolimus?

Answer 14

macrolide antibiotic structurally similar to tacrolimus but doesn’t inhibit calcineurin

Question 15

Sirolimus: MOA

Answer 15

binds to intracellular proteins and inhibits the growth of hematopoietic and lymphoid cells

Question 16

Sirolimus: uses

Answer 16

used in combination with other immunosuppressive agents for prophylactic organ rejection

Question 17

Sirolimus: adverse effects

Answer 17

GI (N/V/D, elevation of LFTs)
hypertriglyceridemia
thrombocytopenia, leukopenia (dose-limiting toxicity)
BP changes
HA, mucous membrane irritation, infections, epistaxis

Question 18

Sirolimus: monitoring

Answer 18

CBC and differential (including platelets)
Lipid panel
BP
Hydration

Question 19

Prednisolone: MOA

Answer 19

glucocorticoid that diffuses across cell membrane, binds with specific receptor, enters nucleus, interacts specifically with DNA
inhibits production of cytokines and pro-inflammatory mediators
inhibits innate immunity by suppressing phagocytic function of neutrophils and macrophages
decreases the number of circulating T cells
decreases IgG and IgA
causes neutrophilic leukocytosis

Question 20

Prednisolone: uses

Answer 20

used in combination for:
organ transplant rejection prophylaxis
autoimmune diseases
inflammatory disorders (COPD, severe asthma)
allergic conditions
malignancies

Question 21

Prednisolone: adverse effects

Answer 21

skin thinning and purpura
cushingoid appearance (moon-facies, buffalo humps) and weight gain
cataracts and glaucoma
HTN, hyperlipidemia
GI: gastritis, ulcers, increased appetite
osteoporosis
neuropsychiatric (euphoria, insomnia; depression and mania, psychosis)
hyperglycemia (DM)
hypothalamic-pituitary-adrenal insufficiency
increased risk of typical/opportunistic infections

Question 22

Prednisolone: monitoring

Answer 22

BP
CMP (blood glucose)
lipids
ophthalmic exam (cataracts, glaucoma)
DEXA scan (osteoporosis)

Question 23

Azathioprine (Imuran)

Answer 23

antimetabolite that acts as a purine antagonist and inhibits the synthesis of proteins, DNA, RNA

Question 24

Azathioprine (Imuran): uses

Answer 24

immunosuppression in renal homografts

autoimmune diseases

Question 25

Azathioprine (Imuran): adverse effects

Answer 25

fever, nausea, hepatotoxicity, skin cancer

bone marrow suppression (anemia, leukopenia and infections, thrombocytopenia and bleeding)

Question 26

Azathioprine (Imuran): monitoring

Answer 26

CBC with platelet counts, LFTs with total bilirubin and ALP

Question 27

Cyclophosphamide: MOA

Answer 27

alkylating agent that inhibits DNA synthesis by binding and damaging DNA itself

Question 28

Cyclophosphamide: uses

Answer 28

cancer treatment (leukemias, lymphomas)
severe glomerulonephritis
rheumatoid vasculitis and other types of systemic vasculitis

Question 29

Cyclophosphamide: adverse effects

Answer 29

severe N/V, myelosuppression, hemorrhagic cystitis, hepatitis, cardiac damage, pulmonary fibrosis, opportunistic infections, development of later malignancies

Question 30

Cyclophosphamide: monitoring

Answer 30

frequent CBCs with differential
renal function (including a UA)
LFTs

Question 31

Cyclophosphamide: affects on bladder

Answer 31

metabolite is acrolein, which is toxic to the bladder (causes hemorrhagic cystitis and bladder cancer)