Immunosuppressive therapy Flashcards
what is an immunosuppressive drug?
a drug used to prevent the production of antibodies
When do you use immunosuppressive therapy?
organ transplant rejection prevention, treatment of autoimmune disorders.
What are the calcineurin inhibitors and what are they derived from?
cyclosporine, tracrolimus. From fungus
What is the MOA of calcineurin inhibitors?
bind with cytoplasmic proteins, inhibits calcineurin (calcium & calmodulin dependent phosphatase). Reduces the number of T lymphocytes. T-cell dependant B cell responses are inhibited. Immune response is decreased.
What are the routes of cyclosporine?
IV, oral and opthalmic (for keratoconjunctivitis sicca-dry eyes)
What is cyclosporine used for?
solid organ transplantation, graft vs host disease and several autoimmune diseases like RA
Why is cyclosporine not used as a first line agent as frequently any more?
its highly toxic
What are adverse effects of cyclosporine
Nephrotoxicity (primary complication), HTN (treat with calcium channel blockers), Neurotoxicity (tremor, HA, Seizures, blindness), infection (viral and fungal), increaed risk of developing cancers (squamous cell skin cancer, lymphoproliferative disease), hyperkalemia, hypomagnesemia, glucose intolerance, hyperuricemia
What should you monitor when a patient is taking cyclosporine?
Renal function( creatinine, BUN), bp, serum electrolytes and magnesium, LFT (bilirubin can be elevated)
What routes are there for tacrolimus
IV, oral and topical
What are tacrolimus uses?
preventing organ rejection(newer and less toxic treatments are becoming available), used with methotrexate for the prevention of acute GVHD, topical for severe plaque psoriasis and sever atopic dermatitis.
What are adverse effects of tacrolimus?
Nephrotoxicty, Neurotoxicity(HA, tremors, paresthesias, coma), htn, dyspnea, GI(n/v, diarrhea, abn disc.), fatigue, hyperkalemia, hypomagnesemia, hyperglycemia.
What should you monitor with tacrolimus treatment?
renal function, electrolytes and magnesium, bp, fasting glucose, tacrolimus lvls.
What is the MOA of Sirolimus?
bind to intracellular proteins and inhibits the growth of hematopoietic and lymphoid cells.
When is sirolimus used?
it is a second line agent for use in combination with other immunosuppressive agents for prophylactic organ rejection.
What are adverse effects of sirolimus?
GI (n/v/diarrhea), elevated LFT’s, hypertriglyceridemia, thrombocytopenia, leucopenia, bp changes, HA, mucous membrane irritation, infections, epistaxis, rarely nephrotoxicity.
What are the dose limiting factors of Sirolimus?
thrombocytopenia( decreased platelet count), neutropenia (decreased neutrophil count)
What do you monitor for when treating with sirulimus?
cbc, bp, lipid panel
Prednisolone MOA?
glucocorticoids diffuse across the cell membrane and bind with specific receptor then enter the nucleus and interact specifically with DNA
How does prednisolone decrease inflammation?
inhibits production of almost all cytokines and proinflammatory mediators.
How does prednisolone inhibit innate immunity?
suppresses phagocytic function of neutrophils and macrophages by- causing neutrophilic leukocytosis, decreases circulating T cells, chronic administration decreases IgG and IgA.
What is prednisolone used to treat?
prophylaxis for prevention of organ transplant rejection, autoimmune disease, inflammatory disorders, alleregic conditions, malignancies.
What are adverse effects of prednisolone?
These are related to dosage and if on long term therapy. Skin thinning, cushing type sxs (moon face, buffalo hump), cataracts, glaucoma, HTN, hyperlipidemia (can lead to atherosclerosis, GI (gastritis, ulcers, initial appetite increase), osteoporosis, neuropsyciatric (euphoria/insomnia, depression, mania, psychosis), hyperglycemia (can lead to DM), hypothalamic-pituitary-adrenal insufficiency, heightened risk of infections
How should you treat someone who is on Prednisolone who has trauma?
give extra cortisol since there adrenal system is suppressed
What should you monitor for prednisolone treatment?
bp, cmp(glucose), lipids, long term (exam for glaucoma and cataracts, DEXA (osteoporosis check)
When should a pt on prednisolone call or go to the ER?
severe abn pain, vomiting blood, ulcer, depression, psychosis, sever HA, sever eye pain
What is the MOA of azathioprine?
purine antagonist and inhibits the syntghesis of proteins, RNA, DNA.
What are the clinical uses of azathioprine (Imuran)?
immunosupression in renal homografts, autoimmune diseases(lupis, RA, ect)
What are adverse effects of azathioprine?
fever, nausea, bone marrow suppression (decreased leukoctyes-infectionns, decreased platelets-bleeding, decreased RBC count), hepatotoxicity, skin cancer
What should you monitor with azathioprine treatment?
CBC with platelet counts weekly at first (discontinue or hold temporarily if neutropenia occurs), LFT (bilirubin and alkaline phosphatase)
What is the MOA of cyclophosphamide?
one of the most potent immunosuppressive therapies, inhibits DNA synthesis by binding and damaging DNA, prefers highly dividing cells……
What is cyclophosphamide used to treat?
leukemias and lymphomas, sever glomerulonephritis, rheumatoid vasculitis and systemic vasculitis. given intermittently or daily
What are adverse effects of cyclophosphamide?
bladder toxicity (CA, hemorrhagic cystitis), severe NV, myelosuppression, hemorrhagic cystitis, hepatitis, cardiac damage, pulmonary fibrosis, opportunistic infections, later malignancies
What should you monitor in cyclophosphamide treatment?
CBC with differential(lymphopenia and neutropenia), renal function and UA for blood, LFT, after ward yearly bladder cystoscopy(bladder CA check)
How can you help negate the bladder toxicity of CYC?
adequate hydration, give MESNA
