Regal- Anti-inflammatory Steroids and Immunosuppressives Flashcards
What drugs are anti-inflammatory steroids (glucocorticoids)?
Cortisol Hydrocortisone prednisone methylprednisone betamethasone desamethasone
What is the MOA of glucocorticoids?
Block steroid receptors that normally stimulate pathways that increase transcription of pro-inflammatory cytokines
- decrease COX2 expression (preferentially over COX 1)
- Inhibit AA release from phospholipids, affecting PG & LT formation
- Inhibit mast cell & basophil degranulation
- Inhibit synthesis & release of TNF (cachectin), IL-1, IL-2 & IFN → less immune cells circulating/functioning
How are glucocorticoids eliminated?
M: liver
E: renal
What toxicities are associated w/ glucocorticoids?
systemic therapy–> increased susceptibility to infections and OSTEOPOROSIS
What glucocorticoid has a short t 1/2?
Hydrocortisone
What glucocorticoids have intermediate t 1/2?
Prednisone
methylprednisone
What glucocorticoids have long t 1/2?
Betamethasone
Dexamethasone
What SE are associated w/ glucocorticoids?
- Peptic ulceration
- Behavioral disturbances
- Cataracts
- Inhibition of growth
Discontinuation of long term use → adrenal insufficiency (fever, myalgia, arthralgia, malaise, death d/t hypotension & shock)
What glucocorticoid is good for tx ITP, AHA, acute glomulonephritis, autoimmune disease ?
Prednisone
What glucocorticoids have the best anti-inflammatory properties?
Betamethasone
dexamethasone
What drugs are the three categories of immunosuppressive drugs?
calcineurin inhibtors
anti-proliferative
Abs
What drugs are calcineurin inhibitors?
cyclosporine
tacrolimus
What is the MOA of cyclosporine?
Binds cyclphillin to inhibit calcineuran phosphatase activity>
blocks cytokine gene expression and T cell activation
How is cyclosporine eliminated?
Extensive liver metabolism
What are the SE associated w/ cyclosporine?
drug interactions
nephrotoxicity (75% of pts)
What is the MOA of tacrolimus?
Binds FKBP to inhibit mTOR >
blocks cell cycle progression
(G1/S)
What SE are assoicated w/ tacrolimus?
nephrotoxicity
What drugs are anti-proliferative?
sirolimus (rapamycin)
mycophenolate mofetil
What is the MOA of siroliums?
Binds to FKBP to inhibit mTOR → blocks cell-cycle progression
(G1/S)
What are the SE of sirolimus?
Dose dependent increase in cholesterol and triglycerides
Nephrotoxicity w/ cyclosporine
CYP34A drug intrxns
What drug is used in combination therapy for organ transplant rejection?
sirolimus
What is the MOA of mycophenolate?
Inhibits IMPDH in de novo guanine nucleotide synth pathway → blocks B & T cell proliferation preferentially
What are the SE of mycophenolate?
Hematological : leukopenia
GI: diarrhea, vomiting
When is mycophenolate used?
organ transplant
What drugs are Abs?
anti-thymocyte globulin
muromonab-CD3
Daclizumab
Basiliximab
What is the MOA of ANti-thymocyte globulin?
Binds thymocytes in the circulation → lymphopenia & impaired T cell immune responses
What are the SE of anti-thymocyte globulin?
Serum sickness
Nephritis
Anaphylaxis rare
What is the MOA of muromonab CD-3?
Binds ε chain of CD3 of T-cells → TCR is internalized → prevents Ag recognition
What are the SE of muromonab CD-3?
Cytokine release syndrome: mild flu like illness to life-threatening shock
*Reduced w/ glucocorticoid admin 1st
How is muromonab CD-3 used?
to prevent Acute rejection of kidney, liver, heart transplants
What is the MOA of daclizumab and basiliximab?
Anti- IL-2 receptor (CD25) → block IL-2 mediated T-cell activation events
What are the SE of Daclizumab and basiliximab?
NO cytokine release syndrome
Anaphylaxis
What drugs are commonly used in organ transplantation?
Daclizumab
Basiliximab
Which drugs have a lower incidence of lymphoproliderative disorders & opportunistic infections than most other immunosuppressant drugs?
Daclizumab
Basiliximab
