Adrenal Corticosteroid Drugs Iszard Flashcards
What enzyme converts inert steroids into active steroids?
- 11 Beta-HSD1 11 ketoreductase
- cortisol, corticosterone, prednisilone are active
What enzyme converts active steroids to inert steroids?
- 11B- HSD2 11B-dehydrogenase
- cortisone, 11-dehydrocorticosterone, prednisone are inert
Primary therapeutic effects of glucocorticoids?
- Immunosuppression and Anti-inflammatory
- anti-allergy
- pain relief
- decrease blood vessel permeabilty
Glucocorticoid AE’s?
- htn
- cataracts and glaucoma
- HPA insufficiency
- hyperglycemia/weight gain/fluid retention/ cushingoid appearance
- skin thinning
- osteoporosis
- infection
What makes the difference betwen therapeutic and AE of steroids?
- potency
- pharmacokinetics
- daily dose and timing of the dose
- duration of treatement
Application of adrenal corticosteroids?
- endocrine conditions → replacement therapy
- primary adrenal insufficiency (addisons) use comno of glucocorticoid like hydrocortisone and mineralocorticoid like fludrocortisone
- CAH use hydrocortisone and fludrocortisone
- Non endocrine conditions:
- immunosuppression
- inflammatory & alleric conditions
How should steroids be used in a medical emergency?
- high doses can be given for few days with little risk
- should NOT be given for more than a few days
- use cant replace or delay specific primary therapies
How should steroids be used for chronic therapy?
- cannot be given chronically without the risk of AE’s
- need to consider dose frequency administration route
Guidelines for corticosteroid therapy?
- only start if there is published evidence of objective theapeutic benefit
- only after other therapies have failed
- don’t use longer than necessary
- stop use if therapeutic benefit is not observed, complications occur, or max benefit has been reached
How do glucocorticoids impact carb metabolism?
- inc. gluconeogenesis
- inc. glucose output
- inc. glycogen synthesis
- dec. glucose uptake → hyperglycemia
Effects of glucocorticoids on lipid metabolism?
- inc. lipolysis
- inc. FFA and glycerol into gluconeogenic path
- inc. lipogenesis
- inc. fat deposition
- change in fat distribution
How do glucocorticoids impact protein metabolism?
- decreased AA uptake
- dec protein synthesis
- dev of myopathy and muscle wasting
In what patient populations would systemic glucocorticoid administration be an issue?
- HIV
- diabetic
- patients with infection
- peptic ulcers
- CV conditions
- psychiatric conditions
- osteoporosis → postmenopausal women
- kids
What results if there is decreased activity of 11B HSD2? What are known inhibitors of this enzyme? (WILL BE ON EXAM)
- excessive activation of mineralocorticoid mediated by cortisol, results in an inc. in sodium and water retention and incr in K loss leading to increased BP
- glycyrrhizin (found in licorice root extract)
- carbenoxolone (used for tx of esophageal ulcers in UK)
What is the anti-insulin activity of glucocorticoids?
- inc. gluconeogenesis in the liver
- dec. of glucose intake and glycogen synthetase activity and increase in proteolysis in muslce
- dec glucose uptake and incr lypolysis in adipose tissue
- all leads to hyperglycemia
What are the short-med acting (<12 hrs)
- hydrocortisone (cortisol)
- cortisone
Intermediate acting (12-36 hr)
- prednisone
- prednisolone
- Methylprednisolone
- Triamcinolone
Long acting (>36hrs)
- betamethasone
- dexamethasone
What can treat cancer of the adrenal glands?
Mitotane
Desscribe the glucocorticoid, Prednisolone’s MOA, application, & pharmacokinetics?
- activation of GR alters gene transcription
- inflammatory conditions, organ transplants, hematologic cancer
- intermediate length acting
Glucocorticoid Receptor Antagonist Mifepristone use MOA pharmacokinetics AE’s?
- antagonist of glucocorticoid and progesterone receptor
- used for medical abortions and rarely cushing syndrome
- PO
- vaginal bleeding, abd pain, diarrhea, HA
Mineralocorticoid influences?
influences salt and water balance, can cause sodium and water retention and active excretion of potassium and protons
Describe the mineralocorticoid agonist Fludrocortisone’s MOA, use, pharmacokinetics, and AE’s.
- agonist at MR receptors and activation of glucocorticoid receptors
- used in adrenal insufficiency (Addison’s Disease)
- long duration of action
- salt and fluid retention, CHF, glucocorticoid excess symptoms
What is Metyrapone used for?
used in diagnosis of adrenal insufficiency and occasionally in tx of cushings
