Adrenal Steroids Flashcards
1
Q
Steroidal Biochemical Pathways:
A
- Zona glomerulosa: cholesterol → pregnenolone → desoxycorticosterone → aldosterone
- Zona fasciculata and reticularis: cholesterol → pregnenolone → desoxycortisol → cortisol
- Zona fasciculata and reticularis: cholesterol → pregnenolone → androstenedione
2
Q
- What regulates synthesis of cortisol?
- What regulates synthesis of aldosterone?
A
- Corisol: ACTH
- Alodsterone: angiotensin II and plasma potassium
3
Q
Steroids are not stored:
A
- synthesized when needed
- rate of secretion = rate of synthesis
- 90% bound in plasma by CBG and albumin
4
Q
How are steroids inactivated?
A
- Inactivated in liver:
- Reduction of A ring
- Sulfate conjugation
- Glucuronide conjugation
- make substances more polar
5
Q
Describes the basics of this loop:
A
-
Negative feedback loop:
- ACTH provides a stimulatory effect on the adrenal gland
- Adrenal gland produces cortisol
- Cortisol has inhibitory effects on the production of ACTH
6
Q
What is the Basic Pharmacological Mechanism of Action for Adrenocortical Steroids?
A
- Binds to cytosolic steroid receptor
- Translocated to nucleus
- Stimulates transcription of mRNA
- Stimulates mRNA directed protein synthesis
- Proteins mediate glucocorticoid effect
7
Q
How do glucocorticoids effect peripheral carbohydrate and amino acid metabolism?
A
Mediated by Glucocorticoid receptor:
- Enhances liver gluconeogenesis from protein
-
Stimulates amino acid mobilization (skeletal muscle, skin, etc.)
- cause muscle wasting
-
Increases plasma glucose
- cause glycosuria
- Increases liver glycogen
- Increases urinary nitrogen excretion
- Reduces peripheral glucose utilization
8
Q
How are lipids affected?
A
Lipid metabolism:
-
Redistribution of body fat
- moon face, buffalo hump
- Stimulates release of fatty acids from adipose tissue
9
Q
What is the primary effect of mineralcorticoids (MCs)?
A
- Increases sodium reabsorption
- Increases potassium and hydrogen ion excretion
- Responsible for cardiovascular effects - hypertension
10
Q
When would this situation occur?
Cortisol = Aldosterone >> Cortisone
A
- When 11-ß hydroxysteroid dehydorgenase is inhibited
- activates cortisol ⇒ cortisone
-
Inhibitors:
- certain drugs, foods or pathological states
-
glycyrrhizic acid found in licorice
- mimics symptoms of excess mineralcorticoids
- edema, hypokalemia, hypertension
11
Q
CNS effects:
A
- sleepiness
- lability of mood
- i.e. mood swings
12
Q
Immune System effects:
Cell traffic/accumulation
A
GC effects:
- Lymphocytopenia and monocytopenia: redistribution of cells out of vascular space
- Prevent neutrophil adherence to endothelium
- via NF-κB
- Inhibit action of chemotactic factors
13
Q
Immune System effects:
Cell function
A
- 1) Macrophage
- Inhibits antigen processing
- Inhibit binding to Fc receptors
- Inhibit synthesis and release of IL-1
- 2) B-Lymphocytes
- 3) T-lymphocytes
- Interfere with macrophage antigen processing
- Interfere with actions of lymphokines:
- IL-2
- macrophage MIF
- macrophage aggregating factor
- monocyte chemotactic factor
- lymphotoxin
- Absence of IL-1 prevents activation
- Reduces IL-2 synthesis
14
Q
How do corticosteroids act as anti-inflammatory drugs?
A
- Inhibits signs and symptoms of inflammation by inhibiting immune system
- Inhibits arachidonic acid release so synthesis of prostaglandins and leukotrienes is reduced
- Inhibits induction of COX-2 by cytokines
- Decrease capillary permeability
15
Q
What are the therapeutic principles of corticosteroid use?
A
-
Therapeutic dose is variable and may change with therapy.
- Reevaluate frequently
- Single dose is usually without harmful effects
- Prolonged therapy has lethal potential
-
Palliative or symptomatic therapy
- Use is not etiological or curative in most cases
-
Abrupt discontinuation may be life-threatening
- adrenal insufficiency
17
Q
Cortisol:
- Anti-inflammtory potency:
- Action:
A
- Anti-inflammtory potency: low
-
Action: binds to the mineralcoticoid receptor, which leads to transcriptional activation
- also can act as a glucocorticoid
18
Q
Dexamethasone (Decadron®):
- Anti-inflammatory potency:
- MC potency:
A
- Anti-inflammatory potency: high
- MC potency: none
19
Q
Prednisolone:
- Anti-inflammatory potency:
- MC potency:
A
- Anti-inflammatory potency: intermediate
- MC potency: low
23
Q
What are the consequences of prolonged corticosteroid therapy?
A
-
Suppression of pituitary: adrenal function
- Related to dose and duration of therapy (Large doses for period longer than 2 weeks)
- May last for periods longer than 12 mo
- Reduce dosage slowly
-
Cushings syndrome:
- Moon face and Buffalo hump
- Poor wound healing
- Thin skin
- Hypertension
- Thin extremities
- Striae
