Corticosteroids Flashcards
(41 cards)
Describe the structure of corticosteroids
Describe the mechanism of action of glucocorticoids (summary)
Layman’s explanation of exogenous adrenal insuffiency
Tabulate pharmacology key aspects of systemic corticosteroids
Describe dosing of corticosteroids
Write short notes on intra-muscular corticosteroids
Write short notes on
-pulse intravenous corticosteroids
-intralesional corticosteroids
Write short notes on
-topical steroids
-monitoring of corticosteroids
Write short notes on glucocorticoid effects on different organ systems
Name contra-indications of c/s use
Write short notes on c/s use in pregnancy
Write short notes on the structure and metabolism of glucocorticoids
Write short notes on the absorption and distribution of glucocorticoids
- Oral glucocorticoids- absorbed in jejenum (peak in plasma 30-90min intake)
- If taken with food - delay absorption but doesnt decrease the amount absorbed
- Once in plasma - primary carrier = corticosteroid binding globulin (CBG) transcortin + lower affinity for albumin
The Hypothalamic - Pituitary- Adrenal axis (HPA) axis
- Hypothalamus -> release corticotropin release hormone -> anterior pituitary gland produce ACTH -> ACTH act on middle layer of adrenal cortex -> release cortisol (greatest early morning hours). ACTH also involved in control mechanisms of renin-angiotensin and serum potassium levels (mineralocorticoid)
3 Main control mechanisms for endogenous cortisol secretion
1. Negative feedback by plasma cortisol -> inhibit corticotropin - release hormone and ACTH
2. Pulsatile secretion of ACTH (based on circadian cycle) peak release of cortisol 6-8 am (if abnormal sleep cycle will adjust peak just prior to waking)
3. Neural effect on HPA axis in response to emotional/physical stress eg release catecholamines from brainstem, cRH from other sites other than hypothalamus, vasopressin release
Molecular mechanisms
- unbound fraction of glucocorticoid enter cell -> bind to cytoplasmic glucocorticoid receptor (which is within protein complex that include HSP -> translocate to nucleus -> affect transcription + induces/repress mRNA and protein synthesis
Glucocorticoid receptor also interact with other transcription factors eg CREB-binding protein, Nf-KB (control inflammation, cytokine, adhesion, enzymes, growth factors. Glucocorticoid inhibit NfKB and reduce inflammatory process
Glucocorticoid receptor inhibit AP-1 transcription factor, control expression of growth factors + cytokines
How to taper oral glucocorticoids
Mechanisms of glucorticoid induced bone loss
- DIRECT EFFECT
- INDIRECT EFFECT
Directly
- directly decrease proliferation and function of osteoblastz
- increase apoptosis of osteoblast
- increase prolif of osteoclasts
Indirectly
- increase urinary calcium excretion
-decrease intestinal absorption of calcium
- this decrease in s-calcium stimulate PTH which drive osteoclast to resorb bone
Plain XR can detect compression fracture, but not osteoporosis until 20-60% of bone mass lost. Dexa preferred d/t its sensitivity + low radiation exposure. If longterm c/s -> baseline DEXA of hip + low radiation exposure. If longterm c/s ~> baseline DEXA of hip + low radiation exposure. If longterm c/s -> baseline DEXA of hip and lumbar spine
Rpt study every 1-3y @same sites
Osteopenia = T-score between -1 and -2.5 below mean
Mangement of bone loss in glucocorticoids
Write short notes on osteonecrosis in glucocorticoids
Write short notes on growth retardation in c/s
Write short notes on myopathy in corticosteroids
Write short notes on cataracts in c/s
Write short notes on the metabolic side-effects of glucocorticoids
Write short notes on the cardiovascular effects of glucocorticoids
Gastro-intestinal effects of glucocorticoids
