Immunosuppressive Drugs Flashcards
Which are more effectively suppressed: primary or secondary immune responses?
primary
Is imune suppression more likely to occur if you start therapy before exposure or after exposure?
before exposure
Immunosupression increases the risk of what?
infection, lymphomas
What are the four major calsses of immunosuppressive drugs?
glucocorticoids
calcineurin inhibitors
antiproliferative/antimetabolic drugs
antibodies
What are the three primary uses of immunosuppression?
Autoimmune disease, transplanation, hemolytic anemia of the newborn
What are the two classes of steroids synthesized by the adrenal cortex?
glucocorticoids and mineralocorticoids
What’s the main endogenous glucocorticoid? mineralocorticoid?
gluco = hydroxortisone (cortixol) mineral = aldosterone
Which one is anti-inflammatory?
glucocorticoids
What are the four synthetic steroids we need to know that are used as anti-inflammatory drugs?
betamethasone
dexamethasone
methylprednisolone
prednisone
Where are the receptors for steroids?
NOT on the plasma membrane - in the cytosol and then they dimerize and go to the nucleus
Why are the effects of steroid usually delayed?
because they alter gene transcription, which taikes a while
What are steroid effects on neutrophils/
release from marrow is accelerated and half time in circulation is increased, so you get more circulatin, HOWEVER< there’s a blockage of the neutrophil migration into inflammatory sites, so there are more but they can’t do their job
What are steroid effects on lymphocyts?
profound transient lymphopenia
the cells aren’t lysed, but move to extracellular compartments like the spleen, LNs, htoracic duct and bone marrow
What are the steroid effects on monocytes and eosinophils?
decreased in peripheral blood
Which COX is more inhibited by steroids?
COX 2 (reduced expression)
How do steroids inhibit prostaglandin and leuketriene formation (beyond just inhibiting COX)?
They inhibit the release of AA form phospholipids
What effect do steroids hae on mast cells and basophils?
inhibit degranulation
True of false: the negative side effects of steroids start to occur with the first dose?
false - one dose is totally harmeless
a few days is likely not harmful except at high doses
Abrust cessation of prolonged high dose steroids will increase risk of organ failure?
renal insufficiency
What are the adverse effects of continued use?
immunosuppression peptic ulceration behavioral disturbances cataracts osteoporosis and compression factors inhibition of growth
The withdrawal is associated with adrenal insufficiency - what adverse effects relfect this?
fever, myalgia, arthralgia, malaise, death with hypotension and shock!
What does cyclosporine bind to? To inhibit what?
binds to cyclophilin to inhibit calcineurin activity and blocks the dephosphorylation event critical for cytokine gene expression and T cell activation
What’s the most common use for cycloposinr?
long term therapy after transplantation
WHat’s the major adverse effect of cyclosporine?
renal toxicity - in as many as 75% of patients!
