Cook - Gluco/Mineralocorticoids Flashcards
1
Q
What is the feedback mech for ACTH release?
A
- Cortisol is the main hormone that regulates feedback from the adrenal (at the level of ACTH and CRH)
- ACTH negative feedback on CRH
- Also circardian regulation and STRESS
2
Q
Cosyntropin
A
- Synthetic ACTH to test for cortisol production
- Major use in testing the integrity of the HPA axis to identify pts needing supplemental steroids
1. Measure cortisol, inject drug IM or IV, measure cortisol again in 30-60 min - Cosyntropin preferred bc animal product may contain high levels of vasopressin
3
Q
What mediators induce/INH HPA axis release of cortisol?
A
- IL-1, 2, 6, and TNF-alpha: induce ant pit release of ACTH and hypothalamic release of CRH
- Cortisol feeds back to hypothal and pit to regulate response to inflammatory mediators -> also has direct effect on the immune system, DEC inflam and inflam cells
- Major stressors, esp. SURGERY, can overcome cortisol feedback INH, causing INC cortisol release
4
Q
What are the 2 classes of adrenocortical steroids? How are they related?
A
- Mineralocorticoids and glucocorticoids (21 carbons; androgens have 19)
- Very little difference in these structures: even for androgens and estrogens, there is some cross-binding
- All work on nuclear receptors, and production of new proteins
5
Q
How are adrenocortical steroids synthesized (basics)?
A
- ACTH stimulates synthesis of all these hormones from cholesterol
- So many CYP450 enzymes in this process, and some drugs INH all of this by INH it right at the beginning
- REMEMBER: steroid hormones work via nuclear receptors (any hormones that come from cholesterol, incl Vit D)
6
Q
What is the difference b/t physiologic and pharmacologic doses of GCS? Why is it important?
A
- Difference is the DOSE
1. Insulin example: even the insulin pump is not able to regulate levels very tightly - This has an impact on feedback regulation: much more influence, and much longer lasting
1. GCS example: may need to provide cortisol to folks who have been on GSC long-term who are going to have surgery -> DEC capacity to resist stress
7
Q
Why is the MOA of GCS relevant to their onset/duration?
A
- Most effects occur through binding to nuclear receptors, and either INC or DEC DNA transcription, leading to changes in concentration of specific proteins
- Most effects are DELAYED by several hours, and last longer
8
Q
Do adrenocortical steroids have limited or broad effect?
A
- Very BROAD effect
- Regulation of carb, protein, and lipid metabolism (cortisol)
- Maintain fluid and electrolyte balance (aldosterone)
- Capacity to resist stress
9
Q
How do GCS affect protein and carb metabolism?
A
- GCS (cortisol) protect brain during starvation (even overnight fast) by keeping glucose elevated
- MOA: INC gluconeo and glycogenolysis in liver
1. Peripheral tissues:
a. DEC glucose utilization
b. INC proteolysis (AA for gluconeo)
c. Activate lipolysis (glycerol for gluconeo and FA for energy needed for glu syn) - All of these effects OPPOSE INSULIN
1. Can create major problems in diabetic pts: any pt w/high fasting glu can be “pushed” from pre-diabetes to diabetes
10
Q
What are some of the therapeutic and AEs of GCS (image)?
A
- RA: anti-inflam, immunosuppression
- Prednisone, stronger GCS, cause euphoria
-
AEs: don’t see the effects of infections
1. Block HPA axis -> psychiatric symptoms
2. Can get perforated gastric ulcers w/NSAIDs and huge infections, but not know it because no pain (can be a very DRASTIC problem)
3. Hirsutism - Most of the time, there is an understanding of how to control the problems
11
Q
What are the symptoms of Cushing Syndrome/Disease (image)?
A
- Buffalo hump: from maintenance of brown adipose tissue
- Lots of loss of muscle, so thin arms and legs
12
Q
How do the steroids compare to e/o in terms of anti-inflam and salt-retaining effects? What is unique about Dexamethasone?
A
- See attached table
- Dexamethasone does not interfere with cortisol measurement, and is able to suppress the HPA axis
1. NO salt retaining activity, and strong (note the equivalent dose column) - REMEMBER: Hydrocortisone is exactly the same compound as cortisol
1. Stress response in cortisol is very important post-surgically (and can last several days)
2. Suppression recovery may take up to 12 months
13
Q
How do cortisol levels change after surgery?
A
- Woman after breast surgery → important stress response (still elevated, even after 4 days)
- REMEMBER: cortisol response limited in folks on long-term steroid therapy
14
Q
Why is perioperative steroid therapy concerning?
A
- Long-term steroid use can suppress the HPA axis, leading to impaired ability of the body to respond to the stress of surgery
- Can also lead to:
1. Impaired wound healing
2. INC fragility of skin, superficial blood vessels, and other tissues -> mild pressure may cause hematoma or skin ulceration, removing adhesive tape may tear skin, and sutures may tear gut wall
3. INC risk of fracture, infections, GI hemorrhage, or ulcer - Supraphysiologic admin of GCS in immediate perioperative procedures produces: 1) HTN, 2) fluid retention, 3) hyperglycemia, 4) INC risk of infection
15
Q
If pt is on low-dose, short-term GCS, how should you tx them peri-operatively?
A
- Maintain normal daily dose of GCS (HPA axis suppression NOT needed)
- Monitor for hemodynamic instability peri-operatively
- Dosing:
1. Prednisone: <=5mg/morning
2. Methylprednisone: <=4mg/morning
3. Dexamethasone: <=0.5mg/morning
4. Hydrocortisone: <=20mg/morning
20
Q
What are the symptoms of Addison’s disease? Adrenal crisis (image)?
A
31
Q
Appreciate this.
A
Good job!
