Iszard- Adrenal Corticosteroid Drugs Flashcards
What are non endocrine uses of corticosteroids?
A. Inflammation
B. Allergic disorders
C. Immunological disorders (immune suppression)
What are endocrine uses of corticosteroids?
A. Establish the diagnosis and cause of Cushing’s Syndrome
B. Treatment of adrenal insufficiency using physiologic replacement doses
C. Treatment of congenital adrenal hyperplasia for which the dose and
schedule may not be physiologic
What are corticosteroid agonists?(2)
- Glucocorticoids - Prednisone
2. Mineralocorticoids - fludrocortisone
What are the corticosteroid receptor antagonists? (2)
- Glucocorticoid antagonists-mifepristone
2. Mineralocorticoid antagonists (spironolactone)
What are the corticosteroid synthesis inhibitors?(1)
Ketoconazole
What is the replacement therapy for primary adrenal insufficiency (Addison’s disease)?
glucocorticoid (hydrocortisone)+mineralcorticoid (fludrocortisone)
What is the treatment for Congenital Adrenal Hyperplasia?
Hydrocortisone+fludrocortisone
How long should corticosteroids be given?
Emergency-> give high does for a few days with little risk
Chronic therapy–> more risks
What are the effects of corticosteroids steroids on the immune sx? (5)
- Decrease production of prostaglandins and leukotrienes
- Decreased production and increased apoptosis of immune cell types
- Decreased production of cytokines and their receptors
- Decreased transmigration of neutrophils and macrophages from blood into tissues
- Decreased expression of cell adhesion molecules
What are the consequences of corticosteroids on the immune sx? (3)
- Decreased inflammation and its manifestations
2, Immune suppression
- Decreased allergic/hypersensitivity reactions
What are the effects of glucocorticoids on carbohydrate metabolism?
- increased Gluconeogenesis
- increaed Glucose Output
- increased GlycogenSynthesis
- Decreased Glucose Uptake. –>Development of Hyperglycemia
What are the effects of glucocorticoids on protein metabolism?
- Decreased AA Uptake
- Decreased Protein Synthesis
- Dev. Of Myopathy and Muscle Wasting
What are the effects of glucocorticoids on lipid metabolism?
-increasedFFA & Glycerol into the gluconeogenic pathway
- increased Lipogenesis
- increased Fat Deposition
- change in Fat Distribution
Glucocorticoid administration can be problematic in what patients? (8)
- Immunocompromised patients (HIV/AIDS)
- Diabetics
- Patients with infections
- Patients with peptic ulcers
- Patients with cardiovascular conditions(HTN, CHF, Angina)
- Patients with psychiatric conditions
- Patients with osteoporosis
(postmenopausal women) - Children
Decreased activity of what enzyme results in excessive activation of MR by cortisol causing an increase in blood pressure
11β-HSD2
What inhibits 11β-HSD2? (2)
- Glycyrrhizin (Licorice root extract)
2. Carbenoxolone (UK approved for Rx-esophageal ulcers)
Glucocorticoids act as anti-insulins to cause what?
Hyperglycemia
- increase gluconeogenesis in liver
- increase proteolysis in skeletal muscle
- Increase lipolysis in adipose tissue
What are the short to medium acting glucocorticoids?
- Hydrocortisone (cortisol)
- Cortisone
<12 hours
What are the Intermediate-Acting glucocorticoids?
- Prednisone
- Prednisolone
- Methylprednisolone
- Triamcinolone
12-36 hours
What are the long acting corticosteroids?
- Betamethasone
- Dexamethasone
> 36 hours
How should corticosteroids be dosed?
- lowest dose for the shortest duration possible
- try to avoid systemic circulation –> topical/inhaled routes
- alternate days
- single does in AP
What can treat cancer of the adrenal glands (adrenal cortical carcinoma)?
Mitotane
What is Prednisolone MOA?
- Activation of GR alters gene transcription
- used in Many Inflammatory conditions, organ transplantation, hematologic cancers
What is Mifepristone MOA?
Pharmacologic antagonist of glucocorticoid and progesterone receptors
