Corticoid therapy Flashcards
What is a hormone?
A chemical substance produced in the body that controls and regulates the activity of certain cells or organs
What is a steroid?
Any of a large group of fat-soluble organic compounds, as the sterols, bile acids, and sex hormones, most of which have specific physiological action
What is a mineralocorticoid?
A corticosteroid which is involved with maintaining the salt balance in the body, such as aldosterone
What is a glucocorticoid?
Any of a group of corticosteroids (e.g. hydrocortisone) which are involved in the metabolism of carbohydrates, proteins, and fats, and have anti-inflammatory activity
What are catecholamines?
Any of a class of aromatic amines which includes a number of neurotransmitters such as adrenaline and dopamine
Why does the zona reticularis have a brown-ish colour?
Due to the presence of lipofuscin in this region
Function of mineralocorticoids
Help maintain Na+, K+ and Cl- ion concentrations in the body
- They do this by affecting the fluid volume in the extracellular and intravascular compartments, so they play a key role in blood pressure and normal cardiac output
What can happen without sufficient supply of the mineralocorticoids?
Induction of shock due to diminished cardiac output
Which organ do mineralocorticoids target?
The kidney
How are mineralocorticoids produced?
These are the steps of transformation (1 is transformed into 2 and then 3 etc)
- Start point is cholesterol (lipid based molecule)
- Pregnenolone
- Progesterone
- 11-deoxycorticosterone
- Corticosterone
- Aldosterone
What are glucocorticoids?
- They increase gluconeogenesis
- They induce glycogen synthase activity & blood glucose levels
- Act as anti-inflammatory and immunosuppressant agents in times of stress
What is the principal glucocorticoid?
Cortisol
What are the effects of cortisol?
- Increases the catabolism of protein in bone, skin, muscle and connective tissue
- Decreases cellular utilisation of glucose
- Increases output of glucose from the liver
Which organ do glucocorticoids specifically target?
None
- They target the whole body! Unlike mineralocorticoids which target the kidney
How are glucocorticoids produced?
These are the steps of transformation (1 is transformed into 2 and then 3 etc)
- Cholesterol
- Pregnenolone
- 17-a-hydroxypregnenolone
- 17-a-hydroxyprogesterone
- 11-deoxycortisol
- Hydrocortisone
- Each change is associated with the side chains not the carbon backbone
What are androgens?
Hormones which influence the growth and development of the male
What is the predominant male androgen?
Testosterone
How are androgens produced?
These are the steps of transformation (1 is transformed into 2 and then 3 etc)
- Cholesterol
- Pregnenolone
- 17-a-hydroxypregnenolone
- Dehydroepandrosterone
- Androstenedione
- Testosterone
- Oestradiol
- Changes to the side chains rather than the backbone, this is mediated by enzymes
What is the name of the enzyme which converts cholesterol to pregnenolone? (Key step to each pathway we have discussed)
Cholesterol desmolase
Why is the enzyme 21-hydroxylase important?
- Its role is to convert progesterone into deoxycorticosterone (mineralocorticoid pathway) and progesterone into 11-deoxycortisol (glucocorticoid pathway)
- It is important because it is linked to congenital adrenal hyperplasia, which is a condition present at birth, effect of this is reduction in mineralocorticoids and glucocorticoids which have multiple effects. At the same time, due to the availability of metabolites to enter the androgen pathway, there is an increase in androgen levels which leads to physical changes and early puberty etc…
What are the two types of congenital adrenal hyperplasia?
- MOST COMMON = Salt wasting. This is due to decrease in aldosterone levels
- Simple virilisation = where aldosterone levels are normal but decrease in glucocorticoid and increases in androgen levels
How is glucocorticoid production controlled?
- Hypothalamus detects low glucocorticoid level
- Causes synthesis and release of CRH to act on the anterior pituitary where it causes release of ACTH
- ACTH acts on the adrenal cortex to cause release of glucocorticoids/cortisol
- Increased glucocorticoid level will be recognised by the hypothalamus and causes a negative feedback loop, whereby release of CRH is now reduced
- The cortisol will have metabolic/anti-inflammatory/immunosuppressive effects
Mechanism of glucocorticoids
- They are able to pass through the lipid bilayer
- So they bind to their receptor in the cytoplasm
- Now bound, this complex translocates to the nucleus and binds to GRE on DNA and alter gene expression
- They will transactivate anti-inflammatory genes and transrepress pro-inflammatory genes
Clinical use of glucocorticoids - physiological doses vs pharmacological doses (what do we use them for in each setting)
Physiological doses: SMALL REPLACEMENT DOSE
- Replacement therapy in adrenal failure: Addison’s disease
- Anti-inflammatory: asthma, arthritis, skin, shock
Pharmacological doses: SUPER PHYSIOLOGICAL DOSE
- Rheumatoid arthritis (dexamethasone)
- Organ transplantation (prednisolone)
- Cancer treatment
- End of life care
