25.7 Biochem: Iatrogenic complications of steroid therapy Flashcards
When do cortisol levels peak in normal diurnal variation?
8.30am or so
Why do we see pigmentation/bronze glow in Addison’s disease?
Melanocortin secreted
What are the signs/symptoms of Addison’s disease?
Fatigue, anorexia, nausea, vomiting, low blood pressure, hypoglycaemia
What do we use to treat Addison’s patients?
Cortisol (20mg) or cortisone (25mg)
What do we need to give Addison’s patients if there are signs of Aldosterone deficiency?
Fludrocortisone
What are some side effects of glucocorticoid treatment? (2x supressions)
Immunosupression, adrenal supression
What can occur if we overtreat aka have too much cortisol?
Weight gain, muscle/bone loss, salt retention
How does too much cortisol get dealt with by the kidney and the liver?
Cortisol gets converted in kidney to cortisone (with 11-B HSD 1) which is inactive
The liver then converts cortisone back to cortisol
Which has a longer half life, cortisone or cortisol?
Cortisol because it gets converted and reconverted
Why can we use fludrocortisone to supplement lack of aldosterone?
Because its mineralocorticoid activity is 300x that of cortisione
What does a ‘dissociated steroid’ refer to?
Better at either trans activation or trans repression
What is a long term complication of steroid therapy? What can we do to minimise this?
Atrophy of adrenals
Allow for ACTH secretion (use short half life drugs, alternate day dosing and minimise systemic absorption)
What is Ciclesonide?
Why is it better than previous drugs?
What is its bio availability like?
A 3rd generation pro-drug
Enzymes for degradation found in lungs (not mouth or larynx so no fungal infections)
Also has low oral bioavailability because is lipophilic and protein bound
What is the role of glucocorticoids in development of peptic ulcers?
Debatable (chronic inflammatory disease may cause someone to prescribe an NASAID and a glucocorticoid resulting in a synergistic effect)
What is some evidence that contradicts the connection between cortisol and peptic ulcers?
In rats cortisol is protective against stress ulcers
What is the relationship between glucocorticoids and osteoporosis?
Yes glucocorticoids cause osteoporosis in high doses
How can dexamethisone cause osteoporosis?
Increase RANKL, decrease OPG (enhances reabsorption, decreases bone mass)
What can inhaled corticosteroids do in premenopausal women?
12 puffs a day for 20 years, doubles the risk of hip fracture
What can happen in children given asthma medication?
Budesonide can cause a loss of 1.1cm in stature
but shoudn’t be a contraindication
RANKL and OPG, how do they alter osteoclast signalling?
RANKL: promotes bone reabsorption
OPG: inhibits bone reabsorption
(bone reabsorption is bad)
