Corticosteroids Flashcards
Where are corticosteroids synthesized and stored and what are they made with?
adrenal cortex, cholesterol
What are the two types of corticosteroids?
glucocorticoids, mineralocorticoids
Which is the primary example of glucocorticoid?
Cortisol
Which is the primary example of mineralocorticoid?
Aldosterone
What does Aldosterone do?
Na retention
What effects does Cortisol have (3)?
metabolism, anti-inflammatory, immunosuppression
Do Mineralocorticoids have any effect on glucocorticoid receptors?
No!
Do glucocorticoids have affinity for mineralocorticoid receptor?
Yes! cross-reactivity (side effects)
Hypothalamic-Pituitary-Adrenal (HPA) Axis: what hormone is released from hypothalamus?
Corticotropin releasing hormone (CRH)
HPA axis: Which hormone is released from anterior pituitary?
Adrenocorticotropic hormone (ACTH)
HPA axis: Which hormone is released from adrenal cortex?
Cortisol
What is the regulatory mechanism of cortisol release?
negative feedback by cortisol at hypothalamus AND anterior pituitary (increases of cortisol is due to decreased negative feedback!)
What is an example of a hypo-secretion pathology (cortisol)?
Addisons Disease
What is an example of a hyper-secretion (cortisol) pathology?
Cushings Syndrome
What are the corticosteroids to know (7)?
hydrocortisone, Prednisone, Triamcinolone, Dexamethasone, Betamethasone, Fluticasone, Fluocinonide
Which corticosteroid is a prodrug?
prednisone
Which corticosteroid is inhaled?
Fluticasone
Which corticosteroid is topical?
fluocinonide
Which corticosteroid is actually cortisol?
hydrocortisone
What are the physiological actions of cortisol (5)?
1) activated gluconeogenesis and hyperglycemia (increase liver production of glucose)
2) activates catabolism of protein and lipids (permissive) (increase amino acids for gluconeogenesis)
3) maintains blood volume (activated mineralocorticoid receptors, just like aldosterone)
4) maintains vascular function (blood pressure) (enhance effect of catecholamines)
5) anti-inflammatory/immunosuppression (higher doses)
What are the “activation” effects of glucocorticoids?
increase: gluconeogenesis genes, protein catabolism genes, and lipid catabolism genes…metabolism genes
What are the “repression” effects of glucocorticoid?
decrease: prostaglandins, leukotrienes, cytokines…inflammatory-response genes
What are 2 effects of corticosteroids on immune cells?
1) inhibition of migration from vascular space to site of injury (decrease endothelial intracellular adhesion molecules for leukocyte localization)
2) inhibition of phospholipase A2 and cycooxygenase-2 (decrease prostaglandins and leukotrienes)
What is effect of corticosteroids on mast cells and basophils?
decrease histamine release
What is effect of corticosteroids on monocytes and macrophages (3)?
decrease production of proinflammatory cytikines, decrease chemotaxis response, decrease differentiation into macrophages
What is effect of corticosteroids on lymphocytes (3)?
decrease T cell response to antigens, mitogens, decrease proliferation, decrease proinflammatory cytokine gene expression
What is the net effect of corticosteroids?
immunosuppression, anti-inflammatory, decreased pain and tissue destruction
Are the anti-inflammatory effects of corticosteroids curative or palliative?
Palliative!
What is the short-acting corticosteroid?
hydrocortisone
What are the intermediate acting corticosteroids?
prednisone, triamcinolone
What are the long acting corticosteroids?
dexamethasone, betamethasone
Which ones don’t cause any Na retention?
Triamcinolone, Dexamethasone, Betametasone
What are the two other corticosteroids and what’s unique about them?
Fluticasone (inhaled, reduced systemic effects), Fluocinonide (topical)
What is the toxicity of corticosteroids with continued use?
Iatrogenic Cushing’s Disease
What are the toxicities of chronic use of corticosteroids (Iatrogenic Cushing’s Disease) (8)?
hypertension (mineralocorticoid receptors and vasoconstriction), hyperglycemia (diabetes), susceptibility to infection/poor wound healing, osteoporosis (calcium loss), muscle myopathy/weakness, GI ulcers (NSAIDs), cataracts, psychosis
What does withdrawal of corticosteroids cause?
iatrogenic adrenal insufficiency
What are the characteristics of iatrogenic adrenal insufficiency?
adrenal-pituitary suppression due to feedback inhibition and adrenal atrophy…therefore suppresses normal response to stress. (ACTH and Cortisol release inhibited by prednisone)
What are the symptoms of iatrogenic adrenal insufficiency? how long to restore hormone levels?
decreased response to stress: nausea, fatigue, weight loss, hypotension, shock. may require 2-6 months to restore normal ACTH/cortisol production
What are the two dosage schedules for systemic oral corticosteroids?
Tapering dose, alternate day therapy
What are the characteristics of tapering dose schedule (3)?
gradual reduction in dose over 2-3 months. prevents flare of inflammatory process. may allow recovery of adrenal-pituitary suppression
What are characteristics of alternate day therapy (2)?
reduces side effects with chronic therapy metabolism/infection/growth. may prevent adrenal-pituitary suppression
What are the therapeutic indications of corticosteroids (10)?
adrenal insufficiency, rheumatic disorders, renal disease, allergic disease, asthma, ocular, skin disease, GI diseases, organ transplantation, spinal injury
Should you go look at the lecture practice problems?
probably.
