Glucocorticoids & Immunosuppressants Flashcards
Glucocorticoids…what do they do?
Promote gluconeogenesis, protein catabolism, and lipolysis. (huh?)
– This allows for critters to respond to overwhelmingly stressful situations
• THE “Stress Hormone”
cortisol – Vasoconstriction and glucose release
• Therefore a strong insulin antagonist! (<You gotta understand why this is so…) both too much cortisol and insulin cause insulin resisitance
Glucocorticoids…what do they Decrease
WBC’s #’s and functionality (what’s this do?)
*All glucocorticoids are
immunosuppressive even as a single dose!
Glucocorticoids are POTENT
anti-inflammatory (NOT an analgesic!)
Glucocorticoids Break down
muscle and fat (lipolysis)to produce more glucose and the need for more glycogenolysis
• So these are catabolic steroids as opposed to anabolic steroids (except for the liver which is busy making glycogen, right?)
GLUGlucocorticoids…what do tHEY Cause “feedback inhibition” OF
further glucocorticoid and thyroid-stimulating hormone production.
– What’s this mean for discontinuing glucocorticoid therapy?
Glucocorticoids…what do they do? (cont.)
• Myriad other things at high doses (hey, after all, they’re hormones!)
*Bone density loss *Myopathy *”Steroid rage” and personality changes *Gastric ulcers *Diabetogenic *”Moon Face & Humpback”
What diseases are hyper- and hypoglucocorticism called?
addisons and cushings
Cortisol is the “archetypical
glucocorticoid and given a value of “1” when comparing anti-inflammatory and salt-retaining properties
Cortisol half-life is
1-2 hours.
hydrocortisone =
Cortisol
-Hydrocortisone
(Solu-Cortef)
-Prednisolone
nothing
-Prednisone
nothing
-Methylprednisolone
(medrol)
Dexamethasone
Decadron)
• Two General Immunosuppressant Categories:
1) Induction Drugs: Used at the time of
transplantation
2) Maintenance Drugs: Required for long- term immunosuppression.
Five Major Pharmacological Classes of Immunosuppressives #1) Glucocorticoids
- A standard component of Induction & Maintenance (high doses initially tapering over time.)
- D.O.C.s for moderate rejection episodes
- Complex mechanism, but profoundly suppress T-lymphocytes (What are these? What do they do? What other kinds of lymphocytes are there?)
1) Glucocorticoids
* Most side-effects of
any immunosuppressive
category when given at high doses over the long term!
2) Calcineurin Inhibitors
-Calcineurin is the major T-cell activator (what’s this? humoral or cell-mediated?)
cyclosporin
Calcineurin Inhibitors (Sandimmune)
-Tacrolimus
Calcineurin Inhibitors (Prograf)
Cyclosporin
• The“break-through”drug that
allowed transplants to successfully occur
Cyclosporin dose dependent
nephrotoxicity,immune suppression (duh!), hepatotoxicity, cardiotoxicity, and many others (what’s that mean for us?) • Cyclosporin levels must be monitored closely.
• Used in combination therapy to reduce dosage and side-effects.
Tacrolimus
• Orders of magnitude more potent than
Cycylosporins. also more efficacious
Tacrolimus nephrotoxicicity and cardiotoxicity compared to cyclosporins
More nephrotoxic/less cardiotoxic than Cyclosporins.
• More efficacious than Cyclosporin
3) mTOR Inhibitors
- Blocking mTOR prevents maturation and proliferation of T-cells.
- Side effects: nephrotoxicity, delayed wound healing.
-Sirolimus
m tor inhibitor (Rapamune) *Only available orally.
4) Antiproliferative Agents
-By preventing proliferation of cells, rapidly dividing cells (like B- and T- lymphocytes) don’t multiply.
Azathioprine
Antiproliferative Agent. (Imuran)
Mycophenolate mofetil
Antiproliferative Agent (Cellcept)
-Mycophenolate sodium
Antiproliferative Agent (Myfortic)
Azathioprine
Prototypical “early” immunosuppressant • Works best on acute rather than chronic
immunogenic response (why?)
• Numerous & severe side-effects (especially bone marrow suppression…what’s that mean to us?) have dramatically decreased its use.
Mycophenolate mofetil
• Much less severe side-effects than azathioprine.
-Mainly GI and bone- marrow suppression.
Mycophenolate mofetil
• Much less severe side-effects than azathioprine.
-Mainly GI and bone- marrow suppression.
Mycophenolate Sodium
- Designed to be a “slower-releasing” and “enterically-pleasing” form of Mycophenolate Mofetil.
- No real evidence that it is more effective or safer.
#5) Monoclonal Antibodies -What the heck are these?
*Monoclonal antibodies contain ONLY one type of antibody that is derived from a single cloned B-lymphocyte
Monoclonal Antibodies
• Directed against a
single cell-surface protein of target cells
types of monoclonal antibodies
A) Antithymocyte Antibodies
B) Antilymphocyte antibodies
-Muromonam-CD3A
(Othoclone OKT3) Antilymphocyte antibodies
