Corticosteroids Flashcards
What is the HPA axis
Stands for hypothalamic, pituitary, adrenal feedback mechanism
What does the cortex of the adrenal gland secrete
- Adrenocorticosteroids
2. Adrenal androgens
What are the 2 adrenocorticosteroids
- Glucocorticoids
2. Mineralcorticoids
What does the outer zone of the cortex secrete (zone glomerulosa)
Aldosterone (mineral corticoid)
Zona fasciculata secretes
Glucocorticoids (Cortisol)
Mineralocorticoids are responsible for what
Regulating salt and water metabolism
Glucocorticoids are responsible for what
- Dramatically reduces the inflammatory response (inhibition of phospholipase A)
- Suppress immunity
- Help resist stress
- Maintain normal metabolism
How does the HPA work
Hypothalamus releases corticotropin releasing hormone (CRH), which stimulates pituitary to release and ACTH, which stimulates the adrenals, causing the release of cortisol or aldosterone
Why do you give a morning dose of corticosteroids
Because normal body cortisol starts to peak at 6-8am and ACTH peaks at midnight to 2AM. Which allows the drug to work synergistically with the body’s natural corticosteroid release
What are the two inner zones controlled by
The pituitary adrenocorticotropic hormone (ACTH)
What stimulates the release of ACTH
The hypothalamus releases hypothalamic corticotropin releasing hormone (CRH)
What are feedback INHIBITORS of corticotropin(ACTH) and CRH
Glucocorticoids (cortisol)
What happens if you have low glucocorticoid
You can get hypoglycemia (may occur during stress or fasting)
Glucocorticoids promote the making of what
glucose (glucogenesis). So if you have low glucocorticoids you may have low levels of glucose
Glucocorticoid actions
- Decrease inflammatory response
- Promote glucogenesis
- Increases neutrophils
- Decreases lymphocytes, eosinophils
How does glucocorticoid decrease the inflammatory response
By inhibiting phospholipase A, which decreases the production of arachidonic acid (prostoglandins/leukotrienes)
What are the 2 arachidonic acids
Lipooxygenase (leukotrienes) and Cyclooxygenase (prostaglandins)
What are marginated neutrophils
Neutrophils that are going to be activated during an infection and will travel out to interstitium (neutrophil count goes up)
What are demarginated neutrophils
Neutrophils that do not get activated during an infection (still in bloodstream)
What happens to the neutrophil concentration in the bloodstream during demargination
The neutrophil count in the blood will be significantly higher because the neutrophils did not get activated and sent out into the interstitial tissues
What causes demargination
Glucocorticoids (corticosteroids) - —this is one of the ways that steroids help keep inflammation down
What part of the nephron does aldosterone work at
The Collecting ducts
What does aldosterone do at the collecting ducts
Causes reabsorption of Na+ and water (HCO3 too)
What affect does aldosterone have on K+
It decreases the reabsorption of K+, so it is therefore lost in the urine
What is cushing syndrome caused by
Hypersecretion of glucocorticoids due to excessive release of corticotropin (pituitary) or an adrenal tumor
Clinical uses of corticosteroids
- Allergic rhinitis and asthma
- Arthritis
- Autoimmune disorders
- Brain and spinal cord tumors
- Replacement therapy for adrenocortical insufficiency (addison)
What are leukotrienes involved in
Inflammation and bronchospasm
What are prostaglandins involved in
- Vasodilation
- Bronchodilation
- Platelet aggregation
- Some vasoconstriction (decreases edema, fever)
- Pathogenesis of pain
What is the difference among commonly prescribed steroids
The potency and the amount in mg of the drug
Which drug is the least potent
Cortisol
Which drug is the most potent
Dexamethasone
Common corticosteroids
- Cortisol
- Prenisone
- Methlyprednisolone
- Dexamethasone
- Hydrocortisone (identical to natural cortisol)
What is the difference in mg and potency between prednisone and methylprednisolone
P = 5mg MP = 4mg P= 3.5 potency (x more potent than cortisol) MP = 5 potency
What is prednisolone
The activated form of prednisone (occurs via metabolism in the body)
What type of patient is prednisone preferred in
Pregnant women (because the prednisolone derivative does not go to the fetus)
Where are corticosteroids metabolized
Liver, then excreted by the kidneys
How much of the glucocorticoids are bound by plasma protein during absorption
90%
What can happen if a patient is on steroids for too long
Suppression of the HPA axis, so alternate day dosing may be needed
Which drug would you give to an Addison patient
Hydrocortisone of prednisone in order to mimic the natural cortisol that is missing in these patients
Short term adverse effects
- Dose dependent
- Hyperglycemia (diabetic)
- GI bleeding
- Na+ retention
- Hypokalemia
- Emotional disturbances
Long term adverse effects
- Continuation of short term effects
- HPA axis suppression after 2 weeks
- Muscle weakness
- Thinning of skin, bruising
- Osteoporosis
- Cataracts/glaucoma
- Increased risk of infection
- Body fat distributed around waist (cushingnoid)
What is the most common long term effect
Osteoporosis
physiological dose
Doses of steroid that are made by the adrenal gland under normal conditions
Why do you have to taper long term steroids
It can cause acute adrenal insufficiency (especially in pts who have already had HPA suppression)
How many months does it take to fully restore HPA in a patient taking steroids for more than 30 days
9-12 months after slow withdrawal and complete removal
When can you taper rapidly
In patients who received steroids for less than 14 days
What drug blocks the effects of prostaglandins
NSAIDS and the indirect actions of glucocorticoids
How do you taper with short-term high dose
Rapid taper from high dose is ok, but don’t go below the chronic dose
