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27 Cards in this Set
- Front
- Back
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What is a Corticosteroid?
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= both glucocorticoids and mineralcorticoids
(often used as a synonym for glucocorticoids) |
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What is a Glucocorticoid?
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Class of steroid hormones that bind the glucocorticoid receptor and trigger similar effects
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What is a Mineralcorticoid?
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Class of steroid hormones characterized by their similarity to aldosterone and their influence on salt and water balance
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Glucocorticoids (cortisol)
- main functions? |
**Works in fasted state to stimulate processes that collectively increase/maintain normal concentrations of glucose in the blood
- stim of gluconeogenesis --> synth glucose - mobilization of AAS from tissues for gluconeogensis - inhibition of glu uptake in muscle and adipose tissue (insulin resistance) to conserve glu - stim fat breakdown in adipose tissue --> FAs used for energy, glycerol for gluconeogenesis |
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Glucocorticoids (cortisol)
- MOA? |
- Bind to Glucocorticoid Receptor (GR) in cytoplasm
- Receptor-ligand complex translocates itself into nucleus - Binds to Glucocorticoid Response Elements (GREs) in promoter region of target genes - Transactivation: regulates gene expression |
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What is Transactivation?
What is the opposite process? |
Transactivation = glucocorticoid-GR complex binds to GRE in nucleus and regulates gene expression
Transrepression = opposite; prevents transcription of targeted genes - e.g., proinflammatory genes, such as IL-2 |
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For what reasons are glucocorticoids used in pharmacology?
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Endocrine:
- to establish diagnosis/cause of Cushing's - to treat Adrenal Insufficiency - to treat Congenital Adrenal Hyperplasia Non-Endocrine: to treat... - Autoimmune diseases (RA, SLE) - Allergic states - Organ transplant (rejection suppression) - Cancer (leukemias, lymphomas) - Derm diseases (steven-johnson) - Respiratory diseases (asthma) - Opthalmic conditions (keratitis) - GI diseases (colitis) - Nervous system disorders (acute sx of MS) |
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What factors influence therapeutic AND adverse effects of glucocoritcoids?
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- pharmacokinetic properties of the specific one (determined by side chain)
- daily dosage - timing of doses - duration of treatment - differences in steroid metablism |
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What is the warning for topical/inhaled glucocorticoids?
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**All are absorbed to some extent -- have the potential for causing Hypothalamic/Pituitary/Adrenal axis suppression --> Cushing's Syndrome
**Topicals can cause skin atrophy, ecchymosis, purple striae, dermatoses, cataracts |
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What factors affect the absorption of topical glucocorticoids?
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- Area of body:
intratriginous > forehead > scalp > face > forearm - If it contains other agents that increase absorption or if the area is covered with an extra-absorbative dressing - Inflammation/desquamation > normal skin - Think skin of infants > skin of adults - Inhaled fluticason safe in adults; causes H-P-A axis suppression in preterm, low birth weight infants |
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What is the #1 side-effect of Glucocorticoids? Explain...
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**Hypothalamic-Pituitary-Adrenal Axis Suppression!!
- glucocorticoids exert negative feedback on H-P-A axis by suppressing CRH and ACTH secretion --> leads to adrenal atrophy and loss of cortisol secretory capability |
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What patients on glucocort tx are at risk of H-P-A Axis suppression??
What patients on glucocort tx are NOT at risk of H-P-A Axis suppression? |
At risk:
- recieving prednisone > 20 mg/day for >3 wks - taking glucocort at bed time (time for max suppression of H-P axis) - patient with clinical Cushing's Syndrome NOT at risk: - any dose of glucocort for <1 week - receiving alternat-day glucocorticoid tx (allows H-P axis to recover) |
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What is the best test for Adrenal Insufficiency?
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COSYNTROPIN TEST!
Cosyntropin = synthetic ACTH - give IV or IM dose - measure cortisol levels 30-60 min later - if < 18 - Adrenal Insufficiency - if > 18 - adrenals are ok |
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What is important to remember about STOPPING oral glucocorticoid therapy??
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Should not be abrupt!! (adrenals have atrophies -- ATCH suppression -- need to wake them back up)
***Must taper off... Sometimes can start alternative day tx when coming from chronic use (not always practical) |
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What are some side-effects of high-dose glucocorticoid therapy?
(other than H-P-A axis suppression) |
- Cushing's Syndrome - can develop within one month; depends on dosage, timing, duration, etc.
Activation of receptors in various tissues: - Adipose - moon face, buffalo hump - Carbs - hyperglycemia (diabetes!) - Proteins - muscle wasting - Bone - weakening (osteoporosis!) - Electroytes - retain Na (edema) - Immune System - opportunistic infections!!!! - Eye - cataracts - Brain - psychosis, depression - Stomach - ulcers, GI bleeding - Skin - impaired wound healing, stretch marks - Repro - oligomenorrhea, decreased libido (shuts off LH/FSH) |
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What are good ways to minimize glucocorticoid side effects?
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- minimize exposure to them
- exercise programs - helps reduce risk of myopathy and osteoporosis - calcium, vitamin D, bisphosphonates, and (in post-menopausal women) estrogen therapy - min bone loss in lumbar vertebrae (but doesnt work femur or radius) |
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What is important to remember about glucocorticoid tx during times of STRESS/ILLNESS?
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patient should double/triple dose (bc normally cortisol increases on its own, but these people cant do that... without it, could go into HYPOTENSIVE CRISIS)
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Mineralcorticoids
- What is the primary endogenous example? - What is the main synthetic example? - MOA?? - stimulated by? |
- endogenous: Aldosterone
- synthetic: Fludrocortisone MOA: act in distal tubules of kidneys --> increase # of sodium channels --> increases reabsorption of sodium (then water) into blood --> increase urinary excretion of K+ and H+ Stimulated by: - decrease in BP - hyperkalemia |
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Fludrocortisone
- what is? - indications? |
= synthetic aldosterone (mineralocorticoid)
Indications: - replacement tx for primary adrenocortical insufficiency - tx of hypoaldosteronism - tx of salt-losing adrenogenital system - tx of orthostatic hypotension |
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Fludrocortisone
- side effects? - how can you monitor response? |
Side Effects:
- edema - hypertension - hypokalemia Monitor: - clinical presentation - check supine/standing BP - measure plasma renin |
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Adrenal Androgens
- what is the main synthetic one? - synthesis?? metabolism?? - effects in males v. females? |
= DHEA-S
- DHEA converted to DHEA-S in adrenals and liver by sulfotransferase - In adrenals and peripheral tissue (hair follicles, prostate, ext genitalia, adipose), converted to more active androgens and estrogen Males: have testicles making lots of androgens... adrenal effects is minimal **Females: DHEA/DHEA-S contribute widels to overall androgen production and effects (conversion to estrogen in females is controversial! but in women with AI, benefits may outweigh risks!!!) |
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What are medical drugs used to block adrenal steroids?
- Use/Purpose?? - Which is first line treatment??? - Side effects? |
MITOTANE
= adrenocorticolytic (inhibits corticol synth) - acts as medical adrenolectomy after pituitary irradiation - spares zona glomerulosa (mineralocorticoids ok) ***Gold standard for adreno-cortisol carcinoma - also for Cushing's Syndrome KETOCONAZOLE (at therapeutic doses; at low dose, antifungal) = inhibits first step in corticol biosynthesis - inhibits ACTH ****Most common!!! First Line Tx!**** - Side Effects: increase LFTs, hepatitis |
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What protective things should a person with Adrenal Insufficiency always have with them in case of an emergency?
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1. Medic-Alert bracelet
2. Prefilled dexamethasone syringes |
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What does Sprionolactone do?
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- Blocks mineralocorticoid receptors (used in hyperaldosteronism)
- Blocks testosterone receptors |
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What does Eplerenon do?
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- Blocks mineralocorticoid receptors (used in hyperaldosteronism)
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What does Drospirenone do?
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antagonizes effects of aldosterone (used in hyperaldosteronism
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What does Triamterene do?
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Blocks Na+ conductance channels (reduces Na+ reabsorption and blood pressure)
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