Part 10: Corticosteroids and immunosuppressants Flashcards
t/f very extensive (near complete) suppression of the immune system is needed for some systemic autoimmune diseases and organ transplants
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what are corticosteroids?
endogenous hormones
what bodily signals cause corticosteroids to be made?
stress, inflammation
stressful stimuli are received by the ____ (brain region), triggering the release of ___ from the adrenal gland
hypothalsmus; cortisol
one of the important functions of cortisol is to regulate ___ cells and reduce their activity
immune cells
t/f the normal levels of cortisol in the blood fluctuate throughout the day to help in th eregulation of physiologic processes
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Normal cortisol secretion patterns can be affected by ___, _____, ____ and ____
sleep deprivation, stress, light, and disease
cortisol is produced in the ____ cells of the adrenal cortex
zona fascicilata
cortisol is made from ___
cholesterol
cortisol is very _____ (hydrophillic/lipophillic) in nature
lipophillic
due to its lipophilic nature, cortisol must travel in the blood bound to ____
plasma proteins
which plasma protein is cortisol bound to once it levels the adrenal gland?
corticosteroid binding globulin (CBG)
once cortisol reaches a target cell, it can diffuse through ____ to get to intracellular receptors. Is this passive or active?
cell membrane; passive
ligands for intracellular receptors are typically ___ (hydrophillic or lipophilic)
lipophilic
the cortisol–intracellular receptor complex dimerizes and is translocated to the nucleus, where changes in ___ are initiated
gene transcription
binding of cortisol to a glucocorticoid receptor results in binding of _____ to regulatory regions of DNA, causing changes in transcription
glucocorticoid response elements
at a systems level, cortisol signalling conributes to the balance of ____ metabolism
energy
what are the glucocorticoid effects of corticol involved in?
energy metabolsim
mineralocorticoid activity is important to __
elctrolytes and water balance in the kidneys
what is the most common use of corticosteroids?
modulate the immune system
corticosteroids reduce the production of _____
prostaglandins, lekotrienes and other proinflammatory mediators
the anti-inflammatory effects of corticosteroids reduce ___, ___ and ____ at the site of injury
pain, heat, swelling
the difference between anti-inflammatory and immunosuppressive actions of corticosteroids is dependent on ___
potency and dose
t/f corticosteroids reduce the activation of mast cells, T cells etc and reduce the production of cytokines
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COX 1 is expressed in a variety of tissues and helps maintain cellular functions such as ____, ____ and ____
mucous secretion to protect endothelial cells of the stomach lining, regulating platelet aggregation, and smooth muscle contraction
COX2 is usually expressed in several tissues, including the ___ and ____ cells
kidney and endothelial
which is the inducible form of COX?
COX 2
expression of COX2 is increased in tissues during inflammation to promote the production of proinflammatory prostaglandins, especially ___
PGE2
the increased production of prostaglandins caused by COX2 causes ____
pain, swelling (peripheral inflammation) and fever
what is the function of thromboxane and prostacyclin?
regulate platelet aggregation
in the arachidonic acid pathway, lipoxygenase makes ___ and ___
lipoxins and leukotrienes
what are leukotrienes?
pro-inflammatory mediators that increase vascular permeability and recruit immune cells to injury site
t/f corticosteroids inhibit the whole arachidonic acid cascade
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____ is the synthetic analogue of natural cortisol
hydrocortisone
the activity of all corticosteroids is measured against ___
hydrocortisone
which corticosteroids have both glucocorticod and mineralocorticoid activity?
hydrocrotisone (1:1), flucortisone (10:200) and predisone (3.5:0.5)
which corticosteroid receptor are we usually trying to target?
glucocorticoid (mineralocorticoid may cause side effects)
what is prednisone?
oral corticosteroid commonly used to mimic the effects of cortisol