corticosteroids

cortisol and corticosterone

• 1)androgens (mainly DHEA) which are also produced in response to ACTH and
• 2)MC (aldosterone and deoxycorticosterone) which are regulated mainly by Ang II and K+

• 1)suppress immune function and inflammation
• 2)treat adrenal insufficiency

cholesterol

GC

• 1)intermediary metabolism
• 2)decrease capillary permeability, decrease WBC migration, decrease WBC activation
• 3)decrease absorption of ca++ in GI tract, increase absorption of Ca++ from bone
• 4)increase (via increase adrenergic recept.?)

• 1)a.a's get broken down into pyruvate and then glc
• 2)protein gets broken down into a.a's
• 3)triglycerides get broken down into fatty acid's (enhanced catecholamine induced lipolysis)

• 1)aldosterone's release is stimulated by Ang II and III and K+
• 2)aldosterone secreted by adrenal gland causes increased Na+ reabsorption, increased water reabsorption and decreased K+ and H+ reabsorption (in kidney)
• 3) #2 leads to low BP, bld volume and bld Na+
• 4) #3 stimulates secretion of renin from the kidney to convert angiotensinogen to Ang I (Ang I to Ang II conversion done by ACE)

• 1)suppression of inflammation and allergic responses
• 2)chronic hypoglycemia
• 3)replacement therapy for adrenal insufficiency

• 1)acute: adrenal damage, GC withdrawal; chronic: disease (Addison's)
• 2)hypoglycemia (upon fasting) and hypotension
• 3)decrease BP and bld flow leads to decrease CV/renal function
• 4)GC and/or MC

• 1)GC=1, MC=1; Short
• 2)GC=.8, MC=.8; short
• 3)GC=4, MC=.8; intermediate
• 4)GC=4, MC=.8; intermediate
• 5)GC=5, MC=.3; intermediate
• 6)GC=5, MC=0; intermediate
• 7)GC=30, MC=0; long
• 8)GC=30, MC=0; long

• *1-2=topical use, used for hypoglycemia and produces minimal side effects
• *3-8=systemic anti inflammatory activity
• *3-6=first choice drug; has more side effects than 1-2 and 7-8=second choice drug; has a lot more adverse effects than drugs 3-6

• 1)GC=.2, MC=3000; very short (1-2 hours)
• 2)GC=0, MC=20; short (6-12 hours)
• 3)GC=10, MC=250; intermediate (12-24 hours)

• 1)oral
• 2)parenteral (im, iv, sc)
• 3)topical(prodrugs not effective as topical)

• 1)plasma glc leads to diabetes; a.a's lead to decrease muscle mass; ca++ leads to osteoporosis; increase AR?, Na+, H2O lead to hypertension (HTN)
• 2)decrease inflammation, immunosuppression, increased infections
• 3)glaucoma, cataracts, peptic ulcers, psychosis, growth suppresion in children

• potential for adrenal insufficiency
• duration vs dose
• route of administration
• length of suppression variable (1wk-1yr)
• measures to minimize suppression=taper drug after therapy and alternate day of dosing

symptomatic tx usually doesn't correct underlying problem

diet: high protein, high K+, low Na+, antacids

prolonged administration leads to HPA suppression which requires GC supplements

exacerbate pre existing conditions

• 1)defect in corticoid synthesis: decrease corticoids (no negative feedback), increase ACTH, increase androgen
• 2)adrenal insufficiency, hyperandrogenism (virilization/precocious puberty)
• 3)GC/MC, anti androgen ?, aminoglutethimide ?

• 1)21 beta OHase-deficiency of both MC and GC
• 2)11 beta OHase-deficiency of this enzyme can't make GC or aldosterone but CAN MAKE deoxycorticosterone

• 1)pituitary tumor (cushing disease)-75%; adrenal tumor-20%; other tumor-5%
• 2)increase GC; metabolic, immune or other
• 3)surgery and antagonists ?

• 1)decrease SCC enzyme activity
• 2)decrease 11 beta OHase activity
• 3)decrease several OHase enzymes
• 4)MC receptor antagonists
• 5)GC receptor antagonists