SAIDs

Question 1

How is ACTH secretion regulated?

Answer 1

Positively regulated by CRF released from hypothalamus

Negative regulated by blood glucocorticoids

Question 2

How are glucocorticoids naturally released/how does the HPA axis regulate cortisone release?

Answer 2

Stress –> Hypothalamus release CRF –> Pituitary gland secrete ACTH –> Adrenal cortex release hydrocortisone –> hydrocortisone inhibits CRF release from hypothalamus

Question 3

What physiological effects do mineralocorticoids have?

Answer 3

Electrolyte and fluid balance*
Sodium and water retention*

Question 4

What physiological effect do glucocorticoids have?

Answer 4

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*

Question 5

What physiological effect do sex hormones have?

Answer 5

Regulation of reproduction
Development of sex organs

Question 6

What genes do glucocorticoids inhibit to exhibit anti-inflam/immunosupp effect?

Answer 6

Glucocorticoids inhibit transcription of genes for:
- COX-2 –> dec prostanoid production
- Cytokine and interleukins
- iNOS

Question 7

What genes do glucocorticoids inc transcription of to exhibit anti-inflam/immunosupp effect?

Answer 7

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

Question 8

How does lipocortin influence COX cascade?

Answer 8

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

Question 9

Why is the number of glucocorticoid alpha receptors in a person important?

Answer 9

High concentrations of the inactive/unresponsive glucocorticoid beta receptor means SAIDs will be less responsive in these individuals

Question 10

Which SAIDs have the greatest mineralocorticoid (Na-retaining) activity?

Answer 10

Short-acting drugs = fludrocortisone > hydrocortisone (cortisol) > cortisone

Question 11

Which SAIDs have the least mineralocorticoid (Na-retaining) activity?

Answer 11

betamethasone (long acting) = dexamethasone (long acting) = triamcinolone (intermediate)

Question 12

Which SAIDs have the most glucocorticoid activity?

Answer 12

1) Betamethasone = Dexamethasone
2) Methylprednisolone = triamcinolone
3) prednisone
4) hydrocortisone
5) cortisone

Question 13

What are some clinical uses for glucocorticoids?

Answer 13

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

Question 14

How are glucocorticoids used in cancer?

Answer 14

E.g. treatment in lymphoma + leukaemia –> supress white cells & induce lymphopenia

Question 15

Describe the physical dependence associated with glucocorticoid use

Answer 15

Simple = body thinks we no longer need to make cortisol

HPA suppression –> may be long lasting following chronic use (hazardous if therapy stopped abruptly)

Question 16

Describe the psychological dependence associated with glucocorticoid use

Answer 16

CNS effects –> euphoria, can become depression when dose is lowered or withdrawal of drug

Question 17

What metabolic effects on glucose that are observed with glucocorticoids?

Answer 17

Hyperglycaemia –> inc gluconeogenesis, dec reuptake/utilisation of glucose, dec insulin sensitivity

Question 18

Describe the mechanism behind steroid induced muscle atrophy

Answer 18

Inc proteolysis and decreased protein synthesis

Question 19

Generally, sum up the toxicities associated with glucocorticoids

Answer 19

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

Question 20

What effect do glucocorticoids have on osteoblasts?

Answer 20

dec func
inc apoptosis
dec differentiation

Question 21

What effect do glucocorticoids have on osteoclasts?

Answer 21

dec genesis
dec apoptosis

Question 22

What effect do glucocorticoids have on osteocytes?

Answer 22

dec function
inc apoptosis