Adrenal Corticosteroid Drugs Flashcards
Corticosteroids are only given in endocrine practice for what? (2)
Establish the diagnosis and cause of Cushing’s syndrome
Treatment of congenital adrenal hyperplasia (CAH)
Which 2 corticosteroids bind to the MR with equal affinity? What are their daily production rates?
Aldosterone (mineralcorticoid) - 10 mg/day
Cortisol (glucocorticoid) - 0.125 mg/day
…both bind the mineralcorticoid receptor with equal affinity
Which 2 corticosteroids are considered agonists?
Glucocorticoids (prednisone)
Mineralcorticoids (fludrocortisone)
What are the 2 subclasses of corticosteroid antagonists?
Receptor antagonists: glucocorticoid antagonists (mifepristone) and mineralcorticoid antagonists (spironolactone)
Synthesis inhibitors (ketoconazole)
What 2 enzymes are responsible for the conversion of active steroids (cortisol, corticosterone, prednisolone) to inert steroids (cortisone, 11-dehydrocorticosterone, prednisone)?
Active to inert = 11b-HSD2, 11b-dehydrogenase
What 2 enzymes are responsible for the conversion of inert steroids (cortisone, 11-dehydrocorticosterone, prednisone) of active steroids (cortisol, corticosterone, prednisolone)?
Inert to active = 11b-HSD1, 11-ketoreductase
What is the criteria for initiating cortisol therapy in medical emergencies? (3)
High doses can be given for a few days with little risk
Should not be given for more than a few days
Use must never replace or delay more specific therapies (Abx for shock, EPI for anti-histamines in anaphylaxis, etc.)
What must be considered before initiating chronic cortisol therapy?
Dose, frequency, route of administration
Chronic use presents significant risk
Common clinical applications of adrenal corticosteroids in endocrine conditions include: (2)
What are the drug combos are given for both?
Replacement therapy
- Primary adrenal insufficiency (Addison’s dz): glucocorticoid (hydrocortisone) and mineralcorticoid (fludrocortisone)
- Congenital adrenal hyperplasia (CAH): hydrocortisone + fludrocortisone
What are 4 common clinical applications for the use of adrenal corticosteroids in non-endocrine conditions?
Immunosuppression
Inflammatory/Allergic conditions
Skin diseases
Hypersensitivity reactions
What are 3 consequences of glucocorticoid use on the immune system and inflammation?
Decreased inflammation and its manifestations
Immune suppression
Decreased allergic/hypersensitivity reactions
How does administration of glucocorticoids affect the following:
Carbohydrate metabolism
Lipid metabolism
Protein metabolism
Carbohydrate metabolism - increased glucose levels
Lipid metabolism - increased lipid production and fat deposition
Protein metabolism - decreased AA uptake and decreased AA synthesis
Impaired activity/inhibition of which enzyme results in excessive activation of MR mediated by cortisol?
What are 2 known inhibitors of this enzyme?
11b-HSD2
Glycyrrhizin (licorice root extract)
Carbenoxolone
How can excess black licorice cause an increase in BP?
Licorice leads to an increase in cortisol 2 MR.
This causes Na+/water retention, and K+ loss which leads to hypertension.
Patient populations in which systemic glucocorticoid administration is problematic include…
Immunocompromised patients Diabetics Infections Peptic ulcers Cardiovascular dz Psychiatric conditions Osteoporosis Children
Why is injection and topical routes preferred for adrenalcorticoid administration?
It reduces the distribution of the drug in systemic circulation
When should adrenalcorticoids be taken?
Morning
What is the function of Ciclesonide?
It is a prodrug that is activated by esterases present in bronchial epithelial cells. The active drug is systemically absorbed and tightly bound to serum proteins.
Prendisone (Cortisone)
MOA
Clinical applications
PKs
Toxicities/interactions
MOA: activates GR and alters gene transcription.
Clinical applications: countless - inflammatory conditions, transplantation, hematologic dz, cancers, etc.
PKs: duration of action is longer than half-life of drug, due to effects on gene transcription.
Toxicities/interactions: adrenal suppression, growth suppression, muscle wasting, osteoporosis, glucose intolerance, behavioral changes.
Mifepristone (GC receptor antagonist)
MOA
Clinical applications
PKs
Toxicities/interactions
MOA: antagonizes GC and progesterone receptors.
Clinical applications: medical abortion and very rarely for Cushing’s syndrome.
PKs: oral administration
Toxicities/interactions: vaginal bleeding in women, abdominal pain, GI discomfort, diarrhea, HA
Fludrocortisone (Mineralcorticoid agonist)
MOA
Clinical applications
PKs
Toxicities/interactions
MOA: agonizes MC receptors
Clinical applications: adrenal insufficiency (Addison’s dz)
PKs: long duration of action
Toxicities/interactions: salt and water retention, CHF, GC excess signs
Spironolactone (MR antagonist)
MOA
Clinical applications
PKs
Toxicities/interactions
MOA: antagonizes MR receptor
Clinical applications: aldosteronism, hypokalemia due to diuretic use, post-MI
PKs: slow onset and offset (24-48 hrs)
Toxicities/interactions: hyperkalemia, gynecomastia, additive interaction w/ other K+-retaining drugs
Eplerenone (MR antagonist)
MOA
Clinical applications
PKs
Toxicities/interactions
MOA: antagonizes MR receptor»_space; blocks binding of aldosterone
Clinical applications: treats HTN
PKs: cleared by CYP-3A4. Reaches steady-state in 2 days.
Toxicities/interactions: hyperkalemia and elevated creatinine.
Ketoconazole
MOA
Clinical applications
PKs
Toxicities/interactions
MOA: blocks fungal and mammalian CYP450 enzymes
Clinical applications: inhibits steroid synthesis in fungi and certain mammals
PKs: oral and topical administration
Toxicities/interactions: hepatic dysfunction, *many CYP450 interactions
