Immunosuppressants Flashcards
Immunosuppressants
Clinical uses
1) organ transplant- prevent immune mediated rejection
2) autoimmune disorders
Lupus
RA
Psoriasis
MS
Chrons disease
Myasthenia gravis
Immunosuppressants
Adverse effects/ considerations
⬆️ risk of infection: persist and become severe
Bacterial infections- risk is very high during 1st month
Viral infections
Pneumocystis carinni- high risk no matter what
* vaccines- avoid live attenuated- will get disease
-dead can be given but may not work
- malignancy
Risk of causing cancer
- skin cancer- use SPF
Immune system is used to find/terminate abnormally behaving cells- this is lowered when taking immunosuppressants
Immunosuppressants
MOA
Used to turn down/off the immune system
-classes differ by the degree of which they effect the immune system
Glucocorticoids Anti IL-2 agents -calcineurin inhibitors -mTOR inhibitors Cytotoxic agents Biologic agents -polyclonal antibodies -monoclonal antibodies -fusion proteins -kinase inhibitors
Immunosuppressants
Glucocorticoids
MOA
Lysis and redistribution of lymphocytes -altered gene transcription -apoptosis of activated cells -down regulation of pro inflammatory cytokines Decrease T cell regulation Inhibition of a rift cytotoxic T cells Decrease chemotaxis * regulate immune system in many ways
Glucocorticoids
Adverse effects
- HPA axis suppression: stopping can be life threatening
- close monitoring
- body regulates production of steroids
- high risk of GI bleeding: block cox 1&2, act like NSAID
- mood changes- acute psychosis
- infection risk- leukocytosis, non infectious high WBC, type of WBC matters
Dyslipidemia
HTN
Weight gain
Hyperglycemia
Cataracts
Osteopenia
Steroid related “immunosupression”
Dose of steroid that is considered immunosuppressant: >2mg or 20 mg of prednisone admin for 2+ weeks
- wait t least one month after stopping systemic corticosteroids before administering a live vaccine
- for other immunosuppressants wait af least 3 months before giving a live vaccine
Cortisone Hydrocortisone Prednisone Methylprednisone Triamniclone Betamethasone Dexamethasone
Steroids/glucocorticoids/corticosteroids
Systemic
Calcineurin inhibitors
MTOR inhibitors
Anti L2 agents
Calcineurin inhibitors-3
MOA
Prevent IL-2 production
- used in transplant setting
- really effective in preventing rejection of a transplant
Calcineurin inhibitors
AE
* nephrotoxicity (cyclosporine, tacrolimus), monitoring of renal fxn is needed Dyslipidemia HTN Neurotoxicity Hirsituism Gingival hyperplasia * high drug inx risk
Cyclosporine (gengraf, neoral, sandimmune, *restasis)
Tacrolimus (prograf, astagraf XL, *protopic)
Pimerolimus (* elidel)
Calcineurin inhibitors
Anti IL 2 agents
* restasis: not systemic, eye drops for chronic dry eye
*protopic: topical, not systemic, can have systemic AE, *liver damage
*elidel: topical, can have systemic AE
-dermatological, psoriasis
mTOR Inhibitors-2
Anti IL-2 agents
MOA
Inhibit response to IL-2
Used in transplant setting really effective at preventing rejection after transplant
Sirolimus (rapamine)
Everolimus (zortress, afinitor)
mTOR inhibitors
Anti IL-2 agents
mTOR inhibitors
AE
Dyslipidemia HTN Myelosupression -nephrotoxicity is less vs calcineurin inhibitors -high drug inx risk
Risk with all Anti IL-2 agents
Atherosclerosis is high in transplanted organ blood vessels , plaque is high, lipids are off
*main cause of transplant failure
Cytotoxic agents
2 types
Specific
Non specific
Specific cytotoxic agents
Kills only immune cells: inhibits the enzymes needed for lymphocyte production of purines and pyrimidines
- built to look like purines and pyrimidines
- deprives cell of p & p which are needed to make DNA and protiens
Mycophenolate (cellcept, myfortic): enterohepatic recycling, antibiotic inx risk
Leflunomide (arava): long half life
Specific cytotoxic agents
Non specific cytotoxic agents
Kills only rapidly dividing cels (t cells etc)
Problem with cells that are always dividing: repro, blood etc
Azathiopurine/6-mercaptopurine
- methotrexate: dose dependent toxicity, anti cancer dose (>100-500) RA dose (5-30/wk)
- first choice for TX of RA
Cyclophosphamide
Non specific cytotoxic agents
Cytotoxic agents
AE
Myelosuppression N/V Diarrhea Alopecia (hair loss) Hepatotoxicty GI ulcers Anemia Thrombocytopenia Reproductive cells
Polyclonal antibodies
Monoclonal antibodies
Fusion protiens
Kinase inhibitors
Biologic agents
Biologic agents
MOA
Target one or more mediators of the immune system response
Polyclonal antibodies
Biologic agent
Used to treat a variety of antigens in a patient
Anti human
Short term not a chronic approach
Used right before and right after a transplant
ATG (atgam)- horse
RATG (thymoglobulin)- rabbit
Bind to a variety of lymphocyte receptors: CD 2,34,8,25,45
Polyclonal antibodies
Biologic agent
Anaphylaxis ⬆️⬇️ BP ⬆️HR Dyspnea Urticaria Rash Infusion relayed reactions -need some premedication: anti histamine, NSAID, etc Used right before or right after a transplant
Monoclonal antibodies -“mab”
Specific to one antigen
Much more human vs polyclonal
* the more human- less risk of infusion related teachings
-differ by how human they are
*IV or SQ products: monthly, 1x or weekly, not daily products
Monoclonal antibodies
Biologic agent
AE
Low risk of infusion related rxn
Premeditate: NSAID, steroid, antihistamine
High risk of infection
Myelosupression
Fusion protiens
Biologic agents
Etanercept (enbrel)- anti-TNF Belatacept (nulcjix): anti CTLA4 Abatacept (orencia):anti CTLA4 * high risk of infection -postransplant lymphoprolifetative disorder
Etanercept (enbrel)
Belatacept (nulcjix)
Abatacept (orencia)
Fusion proteins
Biologic agents
Kinase inhibitors
Biologic agents
Tofacitinib (Xeljanz)
Ruxolitinib (jakafi)
Tofacitinib (Xeljanz)
Kinase inhibitor
High risk of infection- not to be used with biologics or strong immunosupressants
PO
Many drug inx
Ruxolitinib (Jakafi)
Kinase inhibitor
Similiar product used to treat myelofibosis
-dosing individualized: platelet count, renal fxn etc
