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 Gastritis peptic ulcers bleeding

1.3.5. Fluid retention d/t electrolyte imbalances 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 weakness in extremities d/t catabolism of skeletal muscle

1.3.10. Euphoria

1.3.11. Psychiatric depression panic attacks Phobias

1.3.12. Dysplipidemia

1.3.13. Hyperglycemia leads to Diabetes

1.3.14. Increases susceptibility to infxn

2. Calcineurin Inhibitors

2.1. Cyclosporine

2.1.1. Uses Prevention only!!!

2.1.2. MOA Binds cyclophilin Drug-cyclophilin complex bind calcineurin Inhibits IL-2 & IL-2 dependent T-cell proliferation

2.1.3. PK Narrow TI Eliminated by CYP3A4 D-D interaxn: azoles and erythromycin inhib CYP3A4

2.1.4. Side Effects Nephrotoxicity Must distinguish btwn tox and kidney transplant rejection! Biopsy only definitive Dx test. Neuro and hepatic tox Gingival hyperplasia Hirsutism Hyperkalemia! DON'T give with ACEi!!! They decrease aldosterone release

2.2. Tacrolimus

2.2.1. MOA Similar to cyclo except Tacro-FKBP complex binds calcineurin

2.2.2. Side Effects Similar to cyclo NO hirsutism or gingival hyperplasia!!!

3. Antiproliferative Agents (Anti-cancer drugs)

3.1. Sirolimus

3.1.1. Use Prophylaxis (in combo) only!! + Calc inh + steroid

3.1.2. MOA Binds FKBP (like Tacro), but... Siro-FKBP complex binds mTOR down stream of calcineurin (i.e. DOESN'T block IL-2 production Inhibits cell proliferation

3.1.3. Side effects Hyperlipidemia Profound BMD NO RENAL TOX!!!

3.1.4. PK Metabolized in liver by CYP3A4

3.2. Azathioprine

3.2.1. MOA Prodrug, purine antimetabolite Interferes w/ purine necleotide de novo synthesis -> inhib DNA synthesis Cytotoxic to proliferating cells, esp. T-cells

3.2.2. PK Inactivated by xanthine oxidase reduce dose when allopurinol is being used

3.2.3. Side effects BMD

3.3. Mycophenolate mofetil

3.3.1. MOA Selective non-competative inhibitor of IMPDH (needed for de novo G synthesis Used in combo: MM + Calc inh + steroid

3.3.2. SE BMD; but less than with azathioprine

3.4. Methotrexate

3.4.1. Use GVHD RA Psoriasis

4. Antibodies

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

4.2. ALG

4.2.1. Use Kidney transplants

4.2.2. MOA polyclonal anti-lymphocyte globulin

4.2.3. Use and SE: same as ATF

4.3. ATF

4.3.1. Use Used to Tx donor BM prior to transplant to destroy T-cells and avoid GVHD SE: alleric rxns; eventually body with reject Ab as foreign Acute rejection episodes

4.3.2. MOA polyclonal anti-thymocyte globulin

4.4. Muromonab (OKT3)

4.4.1. MOA T-cell specific murine monoclonal Ab Directed against CD3 thymocytes and T-cells Shuts down activation of T-cell prolif and impairs CD8 function

4.4.2. Use Acute rejection episodes Tx donor BM to prevent GVHD

4.4.3. SE Cytokine storm! Usually w/ 1st doses Body will make Ab against OKT3. Only get one shot w/ this one!

4.5. Daclizumab

4.5.1. MOA Ab to CD25 receptor on IL-2; acts as IL-2 antagonist No t-cell depletion

4.5.2. Use Prophylaxis and Tx of AREs

4.5.3. SE Allergic Sx and infxn