SAIDs Flashcards
How is ACTH secretion regulated?
Positively regulated by CRF released from hypothalamus
Negative regulated by blood glucocorticoids
How are glucocorticoids naturally released/how does the HPA axis regulate cortisone release?
Stress –> Hypothalamus release CRF –> Pituitary gland secrete ACTH –> Adrenal cortex release hydrocortisone –> hydrocortisone inhibits CRF release from hypothalamus
What physiological effects do mineralocorticoids have?
Electrolyte and fluid balance*
Sodium and water retention*
What physiological effect do glucocorticoids have?
Resistance to stress
Metabolic effects* –> dec uptake and utilisation of glucose and inc gluconeogenesis –> inc glycogen storage –>
- dec protein synth and inc protein breakdown (muscle wasting)
- redistribution of body fat (central obesity)
Anti-inflammatory
immunosuppressant*
What physiological effect do sex hormones have?
Regulation of reproduction
Development of sex organs
What genes do glucocorticoids inhibit to exhibit anti-inflam/immunosupp effect?
Glucocorticoids inhibit transcription of genes for:
- COX-2 –> dec prostanoid production
- Cytokine and interleukins
- iNOS
What genes do glucocorticoids inc transcription of to exhibit anti-inflam/immunosupp effect?
Annexin-1/lipcortin (PLA2 inhibitors) –> potent anti-inflam effect on cells and mediator release
Inc release of lipocortin, also mediate negative feedback at hypothalamus and anterior pituitary gland
How does lipocortin influence COX cascade?
glucocorticoids inhibit release/action of Phospholipase A2 > inhibit conversion of mem phospholipids to AA –> Prevent PGG2 –> prevent PGH2 –> dec TXA2, PGE2, PGD2, PGI2, PGF2a
Giving SAIDs their anti-inflammatory action
Why is the number of glucocorticoid alpha receptors in a person important?
High concentrations of the inactive/unresponsive glucocorticoid beta receptor means SAIDs will be less responsive in these individuals
Which SAIDs have the greatest mineralocorticoid (Na-retaining) activity?
Short-acting drugs = fludrocortisone > hydrocortisone (cortisol) > cortisone
Which SAIDs have the least mineralocorticoid (Na-retaining) activity?
betamethasone (long acting) = dexamethasone (long acting) = triamcinolone (intermediate)
Which SAIDs have the most glucocorticoid activity?
1) Betamethasone = Dexamethasone
2) Methylprednisolone = triamcinolone
3) prednisone
4) hydrocortisone
5) cortisone
What are some clinical uses for glucocorticoids?
Replacement therapy for adrenal failure
Anti-inflammatory/immunosuppressive therapy
- Musculoskeletal conditions, asthma
- topically/inhaled in inflammatory conditions (e.g. allergic rhinitis)
- hypersensitivity state (allergic reactions)
- Autoimmune/inflam disease
- graft-host disease
- treat cancer
How are glucocorticoids used in cancer?
E.g. treatment in lymphoma + leukaemia –> supress white cells & induce lymphopenia
Describe the physical dependence associated with glucocorticoid use
Simple = body thinks we no longer need to make cortisol
HPA suppression –> may be long lasting following chronic use (hazardous if therapy stopped abruptly)
Describe the psychological dependence associated with glucocorticoid use
CNS effects –> euphoria, can become depression when dose is lowered or withdrawal of drug
What metabolic effects on glucose that are observed with glucocorticoids?
Hyperglycaemia –> inc gluconeogenesis, dec reuptake/utilisation of glucose, dec insulin sensitivity
Describe the mechanism behind steroid induced muscle atrophy
Inc proteolysis and decreased protein synthesis
Generally, sum up the toxicities associated with glucocorticoids
Metabolic effects:
- hyperglycaemia
- loss of muscle bulk
- Redistribution of body fat
growth retardation in children (inhibit GF or insulin-like growth factor)
Immunosuppression –> sus to opportunistic infection, impaired wound healing
Effects on reproduction –> hypogonadism
Cardiovascular effects - HTN, dyslipidaemia
Osteoporosis
What effect do glucocorticoids have on osteoblasts?
dec func
inc apoptosis
dec differentiation
What effect do glucocorticoids have on osteoclasts?
dec genesis
dec apoptosis
What effect do glucocorticoids have on osteocytes?
dec function
inc apoptosis
