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
Describe the mechanism of action of steroid hormones
- steroids can cross the cell membrane
- can then bind to a receptor which is often associated with HSP. HSP can then dissociate
- the activated receptor can then travel to the nucleus
- the steroid can then bind to the GRE of the nucleus
- this can then activate transcription -switch on certain proteins and switch off others
- relatively slow process - hours/days
What is meant by trans activation?
This is the positive effects we see from steroids i.e. the anti inflammatory effects when it binds to GRE.
What is meant by cis repression?
This is responsible for the negative side effects we see. Binding to the GRE leads to inhibition of osteoblasts leading to reduced bone formation, reduced keratin leading to thinning of skin and reduced ACTH and CRH.
Name some uses of steroid drugs
- inflammatory disease
- to cause immunosuppression
- malignancy
- dexamethasone suppression test
- replacement therapy e.g. in deficiency, Addison’s, adrenalectomy
How do we use steroids in preterm birth?
- single course of antenatal corticosteroids offered to women who are at risk of preterm birth between 24-34 weeks of gestation
- betamethasone or dexamethasone
- steroid of choice to enhance lung maturation and prevents respiratory distress in infants
- stimulates type 2 pneumocytes to produce surfactant
What are the main side effects from mineralocorticoids?
- fluid retention
- hypertension
- hypokalaemia
What are the main side effects of glucocorticoids?
- osteoporosis
- skin atrophy
- cushingoid features
- peptic ulcers
- increased infections
- diabetes
- hypertension
What are the effects of corticosteroids on bone?
- inhibition of osteoblasts formation
- increased osteoclast proliferation
- reduced calcium absorption in the gut
- osteoporosis is a side effect of long term steroids
Why must you not take a patient suddenly off steroids?
There is a risk of adrenal suppression: hypo-adrenal crisis.
- suppression of the HPA axis occurs after the 3 weeks
- prednisolone >20mg will suppress the HPA axis
- abrupt withdrawal may lead to hypoadrenal crisis
- must carry a steroid card if on long term steroids
- if having surgery need to boost endogenous HPA axis and increase dose
explain the signs/symptoms we might see in hypoadrenal crisis
- hypotension
- hypoglycaemia
- hyponatraemia
- hyperkalaemia
- severe dehydration
- death if untreated
Must gradually with draw oral steroids and warn the patient.
