Stimulation and Inhibition of Mineralocorticoid and Glucocorticoid Receptors Flashcards
What analog of ACTH is administered to patients?
• MOA?
ACTH
ACTH receptor is a Gs couple protein
Cosyntropin
Indication: testing the HPA axis to identify patients needing steroids
A woman with lupus is about to undergo a masectomy. How might you adjust her medications?
Glucocorticoids
• Therapy Maintenance: you need to anticipate times that a patient may increase their cortisol levels to dangerous concentrations so that you can decrease dose used to treat condition. (e.g. high stress conditions like surgery – mastectomy, etc you may want to pull back on steroid dose)
What are some stressors to watch out for when giving someone chronic glucocorticoids so that you don’t give them too much?
Stresses that may produce these: Emotional, Physical, Hypoglycemia, Pain, Cold, Surgery
What is the relationship between anti-inflammatory effects of glucocorticoids and their potency in altering glucose metabolism?
Glucocorticoids have anti-inflammatory potencies that parallel their potency in glucose metabolism
Why might physicians tend to over prescribe glucocorticoids?
Initial treatments with glucocorticoids can result in euphoria, feelings or well-being, high motor activity, insomnia – which may cause over prescription of these by physicians
Do steriods have any immediate effects?
Generally these act in the nucleus on protein transcription so they take a while to have a major effect. BUT the effect persists even after the drug is eliminated. Some immediate effects may be mediated by membrane receptors.
What effects of long term glucocorticoid use is specific to:
• Men
• Women
• Children
- MEN – Hypogondaism
- WOMEN – Amenorrhea, Dysmenorrhea
- CHILDREN – Impaired Linear Growth (decreased FH and Inhibition of IGF-1)
What is the effect of Glucocorticoids on bone and blood sugar?
• Osteoporosis
• Diabetogenic effect
What stomach problems might someone taking glucocorticoids chronically have?
Stomach problems: increased incidence of ulcers and Lack of detection of perforated ulcers
What should be your mentality towards dosing when giving glucocorticoids?
Administration: Use smallest dose that achieves therapeutic effect
What are the short acting glucocorticoids from least to most potent?
Listed from Most Potent to Least Potent:
SHORT-MEDIUM ACTING GLUCOCORTICOIDS
Cortisol
Prednisone
Prednisolone
Methylprednisolone
Dexamethasone
What are the long acting glucocorticoids from least to most potent?
Listed from Most Potent to Least Potent:
LONG ACTING GLUCOCORTICOIDS
Betamethasone
Triamcinolone
What are the short AND long acting glucocorticoids?
• what are their relative effects on salt retention?
Listed from Most Potent to Least Potent:
SHORT-MEDIUM ACTING GLUCOCORTICOIDS
Cortisol
Prednisone
Prednisolone
Methylprednisolone
Dexamethasone
LONG ACTING GLUCOCORTICOIDS
Betamethasone
Triamcinolone
***note that as you progress from cortisol down to triamcinolone these drugs have a progressively SMALLER salt retaining effect***
Why do glucocorticoids have an effect on salt retention in the 1st place?
If they are present in too great of concentrations they will overwhelm 11ß-HSD and act on the aldosterone receptor.
What are two aerosolized forms of glucocorticoid used in the treatment of asthma and rhinitis?
Budesonide inhalation
Fluticasone – indicated for allergic rhinitis
When would you use a mineralocorticoid/aldosterone analog?
• Indication?
Mineralcorticoids
Fludrocortisone
MOA: mineralocorticoid receptor agonist
Toxicity: Predictable – salt retention, CHF
Indication: Adrenal Insufficiency
What drug acts as a mineralocorticoid antagonist?
Glucocorticoid Receptor Antagonist
Mifepristone
Mifepristone
• MOA
• Indication
• Administration
MOA: antagonist of glucocorticoid and progesterone receptors
Indication: Medical Abortion (very rarely cushings)
Administration: Oral
Aminoglutethimide
MOA/Use?
Aminoglutethimide
MOA/Use:
Used in Cushing’s and acts by blocking P450ssc (Cholesterol Desmolase)
What is the effect of ketoconazole on the adrenal cortex?
• Administration
• Toxicity
Ketoconazole
MOA: inhibition of cholesterol desmolase and 17alpha
Administration: Oral or Topical
Toxicity: Hepatic dysfunction, Adrenal insufficiency
