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Flashcards in Iatrogenic complications of steroid treatments Deck (24)
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1

Describe the diurnal pattern of cortisol release?

Three spikes correspond to meals (involved in glucose regulation)

Very low during early morning 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

2

Describe how cortisol is converted to cortisol, and vice versa?

In liver, 11b-HSD1 converts cortisone to cortisol 

In kidney, 11b-HSD2 converts cortisol to cortisone

 

3

Cortisol has high affinity for mineralocorticoid receptors in the kidney. Describe why it does not activate these receptors?

11b-HSD2 colocalised with mineralocorticoid receptor in kidney > cortisol converted to inactive metabolite cortisone > cortisone does not activate receptors 

4

Describe the difference in half-life between cortisol, cortisone, and cortisol regenerated from cortisone?

Cortisol: short (~30 mins)

Cortisone: longer (~60 mins)

Regenerated cortisol: longer (~60 mins) (similar to the cortisone that it was regenrated from)

PICTURE SLIDE 10

5

Describe the clinical presentation of cortisol deficiency?

Weakness

Fatigue

Anorexia

Nausea

Vomiting

Hypotension

Hypoglycaemia

6

In cortisol deficiency due to primary adrenal hypofunction, which other deficiency also occurs?

Mineralocorticoid deficiency

7

Describe the clinical signs of mineralocorticoid deficiency?

Hyperkalaemia

Hyponatremia

Acidosis

Dehydration 

8

Why is adrenocortical insufficiency difficult to diagnose?

Presneting signs and symptoms are very nonspecific

Disorder rarely occurs without concomitant injury

9

Describe the consequences of untreated adrenocortical insufficiency?

Dismal prognosis

Death

10

Describe how treatment for adrenocortical insufficiency is administered?

Cortisol or cortisone

Short half-life > multiple doses a day

Divide doses to mimic physiological time course 

Extra doses for infections and periods of stress (cortisol usually rises during these periods)

Add fludrocortisone if required (to replace aldosterone in primary adrenal insufficiency)

11

Describe the side effects of treatment with cortisol/cortisone?

No side effects from well managed treatment

But: Cushingoid syndrome, adrneal suppression, immunosuppression, peptic ulcers, osteoporosis, inhibition of linear growth in children

12

List the iatrogenic complications of glucocrticoid therapy?

Cushingoid syndrome

Adrenal suppression

Immunosuppression

Peptic ulcers

Osteoporosis

Inhibition of linear growth in children 

13

Why do iatrogenic complications of glucocorticoid therapy often occur?

Often given in supra-physiological doses

14

Describe why adrenal suppression may occur as an iatrogenic complication of glucocorticoid therapy?

Increased cortisool > negative feedback to ACTH

15

Why may immunosuppression be a problem as an iatrogenic complication of glucocorticoid therapy?

Reactivation of latent infection (eg. TB)

16

Describe why immunosuppression occurs with glucocorticoid therapy?

Glucocrticoids inhibit inflammatory cytokines released from macrophages amd other inflammatory mediators 

 

17

Describe the effects of hypercortisolism?

Weight gain

Wasting of muscle, skin and bone

Hyperglycaemia

Hypertension

Inhibition of linear growth

18

Describe the difference between transactivation and transrepression?

Transactivation: activation of gene transcription via GREs

Transrepression: reduction of gene transcription via inhibition of AP-1 and NF-kB

19

What determines the level of adrenal suppression that occurs as an iatrogenic complication of glucocorticoid therapy?

Dose and duration of therapy

Varies between drugs

Varies between patients 

20

How can adrenal suppression due to glucocorticoid administration be minimised? 

Allow for ACTH secretion: avoid long lasting drugs, alternate day dosing, morning dosing

Minimise systemic absorption: inhaled or topical

Use third generation glucocorticoid drugs 

21

Describe the third generation glucocorticoid drugs?

Have reduced systemic effects because they are pro-drugs, lipohilic, have low oral bioavailability and are highly protein bound in plasma 

 

22

Describe the role that glucocorticoids play in the development of petic ulcers?

Causal role is debatable

Mostly occurs in patients also taking NSAIDs (possible synergistic action)

Cortisol seems to be protective in rats 

23

Describe why glucocorticoid administration promotes osteoporosis?

Glucocorticoid administration leads to maturation of osteoclasts, via decreasing OPG and increasing RANKL

Osteoclast activation leads to bone resorption 

(RANKL stimulates RANK receptor on osteoclast precursors, whereas OPG binds RANLK and prevents binding to RANK)

24

Describe the effect of glucocrticoid treatment on growth in childhood?

Children taking glucocorticoids lag a little in growth, but can recover later in treatment

Modest effect size with moderate dosing

However, growth suppression may be worse if disease is not treated