What is the physiological role of cortisol?
Regulates metabolism, immune response, and stress response
Cortisol is a glucocorticoid that plays a crucial role in various bodily functions.
What are the main hormones regulated by the hypothalamic-pituitary-adrenal (HPA) axis?
Corticotropin Releasing Hormone (CRH) from hypothalamus, Adrenocorticotropic Hormone (ACTH) from anterior pituitary, Cortisol from adrenal cortex
These hormones are involved in the stress response and regulation of cortisol production.
What is the mechanism of action of corticosteroids?
Nuclear receptor mechanism involving binding of homodimer to HRE (hormone response element) resulting in transactivation and transrepression of a target gene and thus, protein (effect)
Corticosteroids act by binding to glucocorticoid receptors in the cytoplasm, affecting gene expression.
What are the anti-inflammatory effects of corticosteroids?
Decreased cytokine production, inhibition of inflammatory enzymes, and reduced adhesion molecule expression
Corticosteroids target various pathways to reduce inflammation.
List some gene targets decreased by corticosteroids.
Decrease cytokine production
* TNF-α
* IL-1β
* IL-6
Decrease inflammatory enzymes
* COX-2
Decrease adhesion molecules
* ICAM-1
* VCAM-1
Decrease receptors
* T-Cell Receptor
These targets are crucial in the inflammatory response.
What are the metabolic effects of cortisol?
- Increased gluconeogenesis
- Decreased peripheral glucose uptake
- Increased glycogen deposition
- Increased lipolysis and lipogenesis
These effects contribute to the regulation of energy metabolism.
What is the role of aldosterone?
Regulates salt (Na+) and water metabolism
Aldosterone is a mineralocorticoid that affects blood pressure and fluid balance.
Fill in the blank: Excess aldosterone can lead to _______.
Hypernatremia
Hypernatremia is an elevated sodium level in the blood, often due to excess aldosterone.
What are the side effects of corticosteroids related to the endocrine system?
- Hyperglycemia
- Moon face
- Truncal obesity
- Growth retardation
- Skin thinning
These side effects are due to the metabolic changes induced by corticosteroids.
True or False: Corticosteroids have more effects on cellular immunity than humoral immunity.
True
Corticosteroids primarily affect T cells and macrophages, impacting cellular immune responses.
What are some common dosage forms of corticosteroids?
- Oral
- IV
- IM
- Topical
- Inhalation
- Nasal sprays
Different forms are used to minimize systemic side effects and target specific conditions.
Identify a synthetic mineralocorticoid analog.
Fludrocortisone
Fludrocortisone is used to replace aldosterone in conditions like Addison’s disease.
What is iatrogenic Cushing’s syndrome?
A condition caused by prolonged corticosteroid use
It results in symptoms similar to Cushing’s syndrome due to excess glucocorticoids.
What are the adverse effects of corticosteroids on the musculoskeletal system?
- Osteoporosis
- Aseptic necrosis of femoral head
- Myopathy
These effects are due to the catabolic action of corticosteroids on bone and muscle.
What is the feedback inhibition effect of cortisol?
Decreases ACTH secretion
Cortisol exerts negative feedback on the HPA axis to regulate its own levels.
List some common side effects of steroids based on duration of therapy.
- Weight gain
- Mood changes
- Glucose intolerance
- Osteoporosis
- Central obesity
These side effects can vary depending on how long corticosteroids are administered.
What is the difference between glucocorticoids and mineralocorticoids?
- Glucocorticoids: Primarily anti-inflammatory effects
- Mineralocorticoids: Regulate salt and water balance
Both types of corticosteroids have distinct roles in the body.
What are the catabolic effects of glucocorticoids?
*breakdown of proteins in lymphoid, muscle, skin, bone, connective tissue
* negative nitrogen and calcium balance
Protein breakdown —> less nitrogen
Slow wound healing is a result of less calcium
What results in feedback inhibition of cortisol?
*decreased ACTH secretion
Adrenocorticotropic hormone —> stimulates adrenal cortex —> produce glucocorticoid & mineralcorticoid
What is the difference between cortisone and hydrocortisone (cortisol)
*Cortisone is no longer in use unlike hydrocortisone.
*Cortisone is a prodrug while hydrocortisone is an active drug.
*Cortisone has a ketone group (=O) at C11 while hydrocortisone has a hydroxy group (-OH) at C11.
Compare the structures of prednisone and prednisolone.
*Prednisone is from cortisone while prednisolone is from hydrocortisone.
*They both contain an additional C=C between C1 and C2.
Compare the structures of methylprednisolone and triamcinolone.
*Both originate from prednisolone
*methylprednisolone has an additional -CH3 on C6 while triamcinolone has an additional -F on C9
Compare the structures of Dexamethasone and betamethasone.
*They both originate from triamcinolone.
*Dexamethasone has an additional -CH3 at C16 in the alpha configuration while betamethasone has the same addition but in beta configuration.
How does the duration of action compare to the corticosteroids that we learnt?
Cortisol & cortisone: 8-12 hr
Prednisone, prednisolone, methylprednisolone, triamcinolone: 12-36 hr
Betamethasone, dexamethasone: 24-72 hr
