9. Steroid Drugs Flashcards
Describe the layers of the adrenal glands
Mnemonic : GFR
The adrenal glands consist of an outer cortex and an inner medulla. The outer cortex produces steroid hormones and can be divided into 3 layers:
1) zona glomerulosa
2) zona fasiculata
3) zona reticularis
What types of hormones do each of the layers of the adrenal cortex produce?
Glomerulosa: mineralocorticoids e.g. aldosterone
Fasiculata: glucocorticoids e.g. cortisol
Reticularis: androgens
What are corticosteroids synthesised from?
From cholesterol
Hence are lipid soluble
Cholesterol is normally converted to cortisol
The drug hydrocortisone is another for what?
Cortisol
Explain the HPA axis for steroid drugs
- the hypothalamus produces CRH
- acts on pituitary to produce ACTH
- Acts on the adrenals to produce cortisol
Negative feedback system. Increasing levels of cortisol reduces CRH and v versa
Describe the metabolic actions of glucocorticoids
- stimulate glycogenolysis (breakdown of glycogen)
- stimulate gluconeogenesis (formation of glucose)
- hyperglycaemia (as a result of the above)
- lipolysis - release fatty acids
- proteinolysis - increases amino acids
So cortisol as a stress hormones is mobilising potential energy sources. And this can lead to deposition of fat in the body and redistribution of fat which is what we see in Cushing’s syndrome.
Describe the side effects of excess cortisol.
Patients would adopt a cushingoid appearance:
- weight gain
- increased appetite
- hyperglycaemia
- hypertension
Describe what we would see if someone had a deficiency of cortisol:
Looks like Addison’s disease:
- hypoglycaemia
- hypotension
- weight loss/underweight
- nausea
What is the action of the mineralocorticoid aldosterone?
Aldosterone acts primarily in renal collecting ducts to stimulate reabsorption of Na+ as well as secretion of K+ and H+.
What would we see in patients with excess mineralocorticoid (aldosterone)?
- hypernatraemia
- hypertension
- hypokalaemia
What would see in patients with a deficiency of mineralocorticoid (aldosterone)?
- hyponatraemia
- hypotension
- dehydration
- hyperkalaemia
Do steroid hormones work at 1 receptor or multiple?
There is a lot of crossover so many steroid hormones can act at both receptors i.e. glucocorticoid and mineralocorticoid receptor.
if for example you wanted to replace aldosterone, you would give a drug which is more selective for the MC receptor e.g. fludrocortisone.
Describe the pharmacokinetics
- oral steroids have similar bioavailability
- hepatic and renal clearance
- hepatic: all steroids metabolised in liver and undergo phase 1 and phase 2 metabolism. In phase 2 undergo glucoronidation to make it more water soluble for the kidneys
- kidneys convert the active cortisol into the inactive cortisone
Name 5 ways you can administer steroids
- Oral e.g. prednisolone
- IV e.g. methylprednisolone
- Topical e.g. hydrocortisone
- Inhaled e.g beclomethasone
- Intra articular e.g. triamcinolone
Explain the effects of corticosteroids on the immune system
- help to reduce inflammation
- a certain degree of immunosuppression
- inhibition of T and B cells
- inhibitor of NK-KB (key signalling molecule in inflammation)
- reduce phagocyte function
- reduce transcription of cytokines and expression of cell adhesion molecules
