Pharm 20- Glucocorticoids & Immunosuppressants Flashcards
In stress, hypothalamus releases what?
Corticotropin-releasing factor
Corticotropin-releasing factor acts on what part of the body?
Anterior pituitary
Anterior pituitary releases what?
Cortiocotropin (ACTH)
Corticotropin (ACTH) acts on what? Which then releases what?
Adrenal Medulla; aldosterone/cortisol/androgens
Whats the classic stress hormone?
Glucocorticoids
What do glucocorticoids do?
Promote gluconeogenesis, protein catabolism, and lipolysis; which allows critters to respond to overwhelmingly stressful situations
POTENT anti-inflammatory (NOT analgesic)
Glucorticoids result in what physiologically?
Vasoconstriction, glucose release
Break down fat and muscle (lipolysis) to produce more glucose and the need for more glyconeogenesis
Why are glucocorticoids insulin antagonists?
They inhibit the uptake of glucose by fat and muscle and increase hepatic glucose output
What is an adverse affect of glucocorticoids?
Decrease WBC #’s
All are immunosuppressive even as a single dose
Are glucocorticoids catabolic steroids or anabolic steroids? Why?
Catabolic steroids; because they involve the breakdown of complex molecules in living organisms to form simpler ones
Anabolic
construct molecules from smaller units
Describe the “feedback inhibition” of glucocorticoids.
Causes feedback inhibition of further glucocorticoid and thyroid-stimulating hormone production
What’s important to note about discontinuing glucocorticoids, based on the feedback inhibition?
Wean off little by little bc instead of having too much you’ll have none
Effects of Glucocorticoids at high doses
Bone density loss Myopathy Steroid rage and personality changes Gastric Ulcers Diabetogenic Moon Face & Humpback
What is hyperglucocorticism?
Cushing Syndrome
What is hypoglucocorticism?
Addison’s Disease
What is the archetypical glucocorticoid?
Cortisol, given a value of “1” when comparing anti-inflammatory and salt-retaining properties
What is the half-life of cortisol?
1-2 hours
Another name for cortisol?
Hydrocortisone
List the Glucocorticoids.
Hydrocortisone (Solu-Cortef) Dexamethasone (Decadron) Prednisone Prednisolone Methylprednisolone (Medrol)
Which (Short-acting) glucocorticoids do we care about for bypass?
Hydrocortisone
Cortisone
(1-12 hours)
When would we use long acting glucocorticoids? Name them.
Transplant patient; immunosuppressed for a long time. Bethamethasone, Dexamethasone
(36-55 hours)
What are the two general immunosuppressant categories?
- Induction Drugs: Used at the time of transplanation
2. Maintenance Drugs: Required for long term immunosuppresion
What are the 5 Major pharmacological classes of Immunosuppressives
- Glucocorticoids
- Calcineurin Inhibitors
- mTOR Inhibitors
- Antiproliferative Agents
- Monoclonal Antibodies
What is a standard component of induction and maintenance? (high doses initially tapering over time)
Glucocorticoids
What is the drug of choice for moderate rejection episodes?
Glucocorticoids
What do glucocorticoids suppress?
T-lymphocytes
Calcineurin Inhibitors
Cyclosporin (Sandimmune)
Tacrolimus (Prograf)
Calcineurin
Major T-cell activator
What is the break through drug that allowed transplants to successfully occur?
Cyclosporin
Describe the side effects of cyclosporin.
Dose-dependent Nephrotoxicity Immune suppression Hepatotoxicity Cardiotoxicity (patients on these if not balanced well will be coming back for second or third kidney transplants)
What’s important to note about monitoring patients on cyclosporin?
Cyclosporin levels must be monitored closely
How to reduce dosage and side-effects of cyclosporins?
Use in combination therapy
Tacrolimus
Better, safer form of cyclosporin; orders of magnitude more potent than cyclosporins
More efficacious than cyclosporin
Describe the toxicity of Tacrolimus.
More nephrotoxic/less cardiotoxic than cyclosporins
How do mTOR Inhibitors work?
Blocking mTOR prevents maturation and proliferation of T-cells
mTOR side effects
Nephrotoxicity
Delayed wound healing
mTOR Inhibitor example
Sirolimus (Rapamune); only available orally
How to antiproliferative agents work?
By preventing proliferation of cells, rapidly dividing cells (like B- and T- lymphocytes) don’t multiply
Antiproliferative Agent Examples
Azathioprine (Imuran) Mycophenolate mofetil (Cellcept) Mycophenolate sodium (Myfortic)
Azathioprine (Imuran)
Prototypical “early” immunosuppressant
Works best on acute rather than chronic immunogenic response (Why?)
Numerous and Severe side effects (bone marrow suppression)
Mycophenolate Mofetil (Cellcept)
Much less severe side-effects than azathioprine; mainly GI and bone-marrow suppression
Mycophenolate Sodium (Myfortic)
Designed to be a “slower-releasing” and “enterically-pleasing” form of Mycophenolate Mofetil
No real evidence that it is more effective or safer (marketed better)
Monoclonal Antibodies
Train B lymphocytes to turn into plasma cell and make one antibody against one specific clone antibody.
Contain only one type of antibody that is derived from a single cloned B-lymphocyte
Monoclonal Antibodies are directed against what?
Single cell-surface protein of target cells
Two types of Monoclonal Antibodies
Antithymocyte Antibodies- attacks thymocytes; immune cells Antilymphocyte antibodies (Othoclone OKT3)
