Antiinflammatory Steroids Flashcards
Mineralocorticoids - general function
water, electrolyte balance
Glucocorticoids general function
Carbohydrate/Protein metabolism
Inflammation
Basic corticosteroid, used for comparison of relative potency
Cortisol
Most potent corticosteroids
Betamethasone, Dexamethasone
Steroids are synthesized endogenously in response to
Stress, Trauma, Surgery, Hemorrhage, infection, cold, pain, fear.
Regulation of steroid synthesis
Corticotropin Releasing Hormone (CRH) is released from the hypothalamus, and stimulates the anterior pituitary to release Adrenocortotropic Hormone (ACTH), which stimulates the fasciculata cells of the adrenal cortex to release cortisol.
Glucocorticoid effects on carbohydrate and protein metabolism
Increase liver synthesis of glucose, glycogen deposition.
Increases protein breakdown and decreases glucose utilization by peripheral tissues.
The overall effect is to conserve glucose.
Glucocorticoid effects on lipid metabolism
Increase in free fatty acids
Glucocorticoid effects on cardiovascular, nervous, and muscle systems
Hypertension
Alterations in mood/behavior
Muscle Wasting (due to protein catabolism)
How do glucocorticoids reduce inflammation?
Alter lymphocyte activity
Alter cytokine release and synthesis by macrophages and monocytes
Decrease production of leukotrienes and prostaglandins.
Do steroids prevent or suppress the underlying disease process causing the inflammation?
No
Where do glucocorticoids act in the cell?
At receptors in the cytosol. They bind ligands and induce the expression of new proteins.
Mineralocorticoid behavior at cortisol receptor
High affinity, long duration binding.
Why doesn’t cortisol stimulate mineralocorticoid receptors in the kidney?
Mineralocorticoid tissues avoid being stimulated by cortisol by converting cortisol to cortisone using 11-betahydroxysteroid dehydrogenase 2.
What happens if you inactivate 11-betahydroxysteroid dehydrogenase 2? What can cause this?
Cortisol acts like aldosterone in the kidney, causing fluid retention and hypertension. This can be caused by eating licorice.
Why is cortisol production important during an inflammatory response?
Cortisol protects against the life threatening consequences of an uncontrolled inflammatory response (think septic shock)
Glucocorticoid receptor - 4 functions
Increased Annexin 1
Decreased prostaglandin/leukotrienes
Decreased COX-2
Decreased TNF-alpha
Annexin 1 function
Inhibits phospholipase A2, a necessary enzyme for production of Arachidonic Acid, necessary for prostaglandins/leukotrienes
COX 2 function
Conversion of Arachidonic acid to prostaglandins
TNF alpha function
Increases epithelial permeability, releases proteinases, chemokines, interferon, and something called NFkB - All of these help macrophages, lymphocytes and NK cells kill infected cells as part of the inflammatory process.
Steroids ADME
PO, IV, IM, Topical
Good systemic distribution (lipid soluble)
Hepatic Metabolism
Renal Excretion
Steroid toxicity
Cessation - adrenal involution due to prolonged high dose, can no longer produce enough.
High doses - mimics Cushing’s Syndrome
How do you withdraw steroid therapy without causing toxicity?
By slowly tapering the dose
Therapeutic Principles
Short course is unlikely to be harmful
The longer the therapy, the higher the risk of adverse effects
Use the lowest dose possible!
