B&L: Immunosuppressants

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B&L: Immunosuppressants by Mind Map: B&L: Immunosuppressants

1. Glucocorticoids: Prednisone

1.1. Uses

1.1.1. Prevention and treat of rejection and GVHD

1.1.2. DOC: autoimmune Dz

1.2. MOA

1.2.1. wipes out entire immune system; decreases all lymphocyte & cytokine levels

1.2.2. inhib IL-2 production -> inhib T-cell proliferation

1.3. Side effects

1.3.1. Thinning of skin/purpura

1.3.2. Cushing-like syndrome

1.3.3. cataracts

1.3.4. GI

1.3.4.1. Gastritis

1.3.4.2. peptic ulcers

1.3.4.3. bleeding

1.3.5. Fluid retention

1.3.5.1. d/t electrolyte imbalances

1.3.5.2. Usually only a problem for pts w/ previous heart and kidney Dz

1.3.6. HTN

1.3.7. Amenorrheoa; infertility

1.3.8. osteoporosis

1.3.9. Muscle weakness

1.3.9.1. weakness in extremities d/t catabolism of skeletal muscle

1.3.10. Euphoria

1.3.11. Psychiatric

1.3.11.1. depression

1.3.11.2. panic attacks

1.3.11.3. Phobias

1.3.12. Dysplipidemia

1.3.13. Hyperglycemia

1.3.13.1. leads to Diabetes

1.3.14. Increases susceptibility to infxn

2. Calcineurin Inhibitors

2.1. Cyclosporine

2.1.1. Uses

2.1.1.1. Prevention only!!!

2.1.2. MOA

2.1.2.1. Binds cyclophilin

2.1.2.2. Drug-cyclophilin complex bind calcineurin

2.1.2.3. Inhibits IL-2 & IL-2 dependent T-cell proliferation

2.1.3. PK

2.1.3.1. Narrow TI

2.1.3.2. Eliminated by CYP3A4

2.1.3.2.1. D-D interaxn: azoles and erythromycin inhib CYP3A4

2.1.4. Side Effects

2.1.4.1. Nephrotoxicity

2.1.4.1.1. Must distinguish btwn tox and kidney transplant rejection! Biopsy only definitive Dx test.

2.1.4.2. Neuro and hepatic tox

2.1.4.3. Gingival hyperplasia

2.1.4.4. Hirsutism

2.1.4.5. Hyperkalemia!

2.1.4.5.1. DON'T give with ACEi!!! They decrease aldosterone release

2.2. Tacrolimus

2.2.1. MOA

2.2.1.1. Similar to cyclo except Tacro-FKBP complex binds calcineurin

2.2.2. Side Effects

2.2.2.1. Similar to cyclo

2.2.2.1.1. NO hirsutism or gingival hyperplasia!!!

3. Antiproliferative Agents (Anti-cancer drugs)

3.1. Sirolimus

3.1.1. Use

3.1.1.1. Prophylaxis (in combo) only!!

3.1.1.1.1. + Calc inh + steroid

3.1.2. MOA

3.1.2.1. Binds FKBP (like Tacro), but...

3.1.2.1.1. Siro-FKBP complex binds mTOR down stream of calcineurin (i.e. DOESN'T block IL-2 production

3.1.2.1.2. Inhibits cell proliferation

3.1.3. Side effects

3.1.3.1. Hyperlipidemia

3.1.3.2. Profound BMD

3.1.3.3. NO RENAL TOX!!!

3.1.4. PK

3.1.4.1. Metabolized in liver by CYP3A4

3.2. Azathioprine

3.2.1. MOA

3.2.1.1. Prodrug, purine antimetabolite

3.2.1.1.1. Interferes w/ purine necleotide de novo synthesis -> inhib DNA synthesis

3.2.1.2. Cytotoxic to proliferating cells, esp. T-cells

3.2.2. PK

3.2.2.1. Inactivated by xanthine oxidase

3.2.2.1.1. reduce dose when allopurinol is being used

3.2.3. Side effects

3.2.3.1. BMD

3.3. Mycophenolate mofetil

3.3.1. MOA

3.3.1.1. Selective non-competative inhibitor of IMPDH (needed for de novo G synthesis

3.3.1.2. Used in combo: MM + Calc inh + steroid

3.3.2. SE

3.3.2.1. BMD; but less than with azathioprine

3.4. Methotrexate

3.4.1. Use

3.4.1.1. GVHD

3.4.1.2. RA

3.4.1.3. Psoriasis

4. Antibodies

4.1. Always used in combo, usually in acute transplant rejection episodes

4.2. ALG

4.2.1. Use

4.2.1.1. Kidney transplants

4.2.2. MOA

4.2.2.1. polyclonal anti-lymphocyte globulin

4.2.3. Use and SE: same as ATF

4.3. ATF

4.3.1. Use

4.3.1.1. Used to Tx donor BM prior to transplant to destroy T-cells and avoid GVHD

4.3.1.1.1. SE: alleric rxns; eventually body with reject Ab as foreign

4.3.1.2. Acute rejection episodes

4.3.2. MOA

4.3.2.1. polyclonal anti-thymocyte globulin

4.4. Muromonab (OKT3)

4.4.1. MOA

4.4.1.1. T-cell specific murine monoclonal Ab

4.4.1.1.1. Directed against CD3 thymocytes and T-cells

4.4.1.1.2. Shuts down activation of T-cell prolif and impairs CD8 function

4.4.2. Use

4.4.2.1. Acute rejection episodes

4.4.2.2. Tx donor BM to prevent GVHD

4.4.3. SE

4.4.3.1. Cytokine storm! Usually w/ 1st doses

4.4.3.2. Body will make Ab against OKT3. Only get one shot w/ this one!

4.5. Daclizumab

4.5.1. MOA

4.5.1.1. Ab to CD25 receptor on IL-2; acts as IL-2 antagonist

4.5.1.1.1. No t-cell depletion

4.5.2. Use

4.5.2.1. Prophylaxis and Tx of AREs

4.5.3. SE

4.5.3.1. Allergic Sx and infxn