Steroids Flashcards
What is the significance of the half life/ potency of prednisolone and dexamethasone over hydrocortisone?
Dexamethasone is much more potent, prednisolone has a longer half life and is slightly more potent.
Give 3 metabolic actions of glucocorticoids
- stimulated gluconeogenesis and glycogensis (leads ot hyperglycaemia)
- proteinolysis
- lipolysis (low dose- physiological)
- lipid deposition and redistribution of fat (high conc- drugs)
Give 3 features of cortisol deficiency (Addison)
- Hypoglycaemia
- Nausea
- weight loss
- hypotension due to loss of mineralcorticoid effect
How selective are hydrocortisone, dexamethasone and prednisolone for the glucocorticoid receptor over the mineralcorticoid receptor?
Hydrocortisone poorly selective, prednisolone more selective, dexamethasone very selective
Describe the pharmacokinetics of steroids
Very lipid soluble so good oral bioavailability. Hepatic metabolism and renal metabolism & clearance, which decrease with age.
What feature of steroids makes them able to be administered orally, topically, intra articular, inhaled etc
Very lipid soluble
Describe the mechanism of action of steroids at the cellular level (4)
- Inhibit Il2 and Il6 so inhibit B and T cell response
- Inhibit NF-kB which is a key signalling molecule in early inflammation
- Inhibits transcription of cytokines and cell adhesion molecules
- Reduce phagocytic function
Describe the general mode of action of steroids at the molecular level
- Cross cell membrane into cell
- Bind to steroid receptor in cytoplasm (associated with heat shock protein (HSP))
- HSP dissociates and activated receptor enters nucleus and binds to hormone response element (HRE)
- Some steroids bind directly to the HRE
- These can switch on and off transcription of proteins
- Causing transactivation, cis repression and trans repression
What is trans- activation?
Activation of anti- inflammatory agents such Annexin-1, MKP-1
What is cis repression? give 3 examples
Side effects of steroids.
- osteocalcin loss= reduced osteoblasts
- POMC loss= less ACTH and CRH
- ACTH/ CRH loss= repress HPA axis
- Keratin loss= thinner skin and hair
What is trans- repression?
Decreased production of pro inflammatory agents such as cytokines, Il2 &6, adhesion molecules etc
Give 3 uses of steroids
Asthma, IBD, skin conditions, nephrotic syndromes, immunosurpression (autoimmune conditions), addisons, cushings disease diagnosis (dexamethasone surpression test), premature births
Describe the time taken for steroids to have an effect
Hours, as need to change gene transcription. Some (eg progesterone) have some effect on cell surface receptors so work more quickly.
Give 3 side effects of steroids due to their cross activation of the mineralcorticoid receptor?
- fluid retention (weight gain, mood face, bloated)
- hypertension
- hypokalaemia
- hypernaturaemia
Give 5 side effects of steroids due to their action on the glucocorticoid receptor
- Long term use= osteoporosis due to cis repression, less oestrogen and less Ca2+ absorbtion in gut
- Avascular necrosis
- peptic ulcers
- increased infections
- hypertension
- diabetes
- impaired growth rate in children
- skin atrophy (esp if topical use)
- cateracts
- corneal damage
- cushingoid features
- psychoactive effects (ROID RAGE)
