Iatrogenic complications of Steroid Treatments

Question 1

What does the amount of drug bound to a carrier protein depend on?

Answer 1

Affinity and the relative concentrations of drug and protein

Question 2

What is the general binding protein in the serum?

Answer 2

Albumin is a general binding protein, but specific proteins exist for several hormones (e.g. thyroxin binding globulin)

Question 3

What binds thyroxin in the plasma?

Answer 3

Thyroxin binding globulin (TBG)

Question 4

When does thyroxine (T4) mostly act?

Answer 4

After conversion to T3

Question 5

Where is 99.96% of thyroxine protein?

Answer 5

Bound in the plasma (mostly to thyroxine binding globulin)

Question 6

What is the volume of distribution of thyroxine?

Answer 6

10L

Question 7

What is the half life of Thyroxine (T4)?

Answer 7

~7 days

Question 8

Which is more active, Liothyronine (T3) or Thyroxine (T4)?

Answer 8

Liothyronine (T3)

Question 9

Which is more strongly bound to its carrier protein, T3 or T4?

Answer 9

T4 is more strongly bound

Question 10

What is the half-life of T3?

Answer 10

~1 day

Question 11

Which has more stable levels during the day, T3 or T4?

Answer 11

T4

Question 12

Are TSH levels easily interpreted in patients taking T3?

Answer 12

No

Question 13

When is Liothyronine (T3) used as a therapeutic instead of T4?

Answer 13

When treating severe hypothyroid and myxoedema coma. For most patients, use T4 rather than T3.

Question 14

What is the interplay between T3 and cortisol?

Answer 14

Cortisol inhibits conversion of T4 to T3 and T3 inhibits cortisol production.

Question 15

When do cortisol levels peak in the diurnal cycle?

Answer 15

In the morning, between 8-9am.

Question 16

When are cortisol levels at their lowest?

Answer 16

Between midnight and 1am.

Question 17

What happens to cortisone at the liver?

Answer 17

It is converted to cortisol

Question 18

What happens to cortisol at the kidney?

Answer 18

It is converted to cortisone

Question 19

What is the difference between cortisone and cortisol?

Answer 19

Cortisone is inactive at the mineralocorticoid receptor, whereas cortisol is active.

Question 20

Which enzyme is responsible for converting cortisone to cortisol in the liver?

Answer 20

11β-HSD-1

Question 21

Which enzyme is responsible for converting corisol to cortisone in the kidney?

Answer 21

11β-HSD-2

Question 22

What can be used as an in vivo assay for analysis of human 11β-HSD2 activity?

Answer 22

11α-deuterium cortisol

Question 23

What does cortisol deficiency present with?

Answer 23

Weakness, fatigue, anorexia, nausea, vomiting, hypotension and hypoglycaemia.

Question 24

Why is the hyperkalaemia, hyponatraemia, acidosis and dehydration in adrenal hypofunction?

Answer 24

Because cortisol deficiency is combined with mineralocorticoid deficiency to cause hyperkalaemia and hyponatraemia, acidosis and dehydration.

Question 25

What is used to treat cortisol deficiency?

Answer 25

Cortisol (hydrocortisone) or cortisone

Question 26

What is done to the cortisol dosage in cortisol deficiency?

Answer 26

The dose is divided to mimic the physiological timecourse.

Question 27

What is oral cortisone’s bioavailability compared to cortisol?

Answer 27

Slightly less (25mg cortisone = 20mg cortisol)

Question 28

What are some iatrogenic complications of glucocorticoid therapy?

Answer 28

• Cushingoid syndrome
• Adrenal suppression
• Immunosuppression (reactivation of latent tuberculosis)
• Peptic ulcers
• Osteoporosis
• Inhibition of linear growth in children

Question 29

What is the major complication of glucocorticoid therapy?

Answer 29

Adrenal suppression

Question 30

How can adrenal suppression in glucocorticoid therapy be minimised?

Answer 30

• Allow for ACTH secretion if possible
• Avoid long-lasting drugs
• Alternate day dosing
• Morning dosing
• Minimise systemic absorption of steroids
• Inhaled or topical (but note: still absorbed!)
• Third generation glucocorticoid drug

Question 31

How does circlesonide (3rd generation glucocorticoid) reduce systemic effects?

Answer 31

• Pro-drug, activated in lungs (not in mouth or larynx)
• Lipophilic: retained in tissue
• Low oral bioavailability (hepatic first pass)
• Highly protein bound in plasma

Question 32

Do glucocorticoids cause peptic ulcers?

Answer 32

• Debatable
• Mostly occur in patients also taking NSAIDs
• Synergistic interaction is plausible.

Question 33

What does cortisol protect rats against?

Answer 33

Stress-induced ulceration.

Question 34

What is the effect of inhaled glucocorticoids on bone density?

Answer 34

12 puffs daily (1200 μg) from age 30 to 50 would double the risk of hip fracture (Triamcinolone Acetonide)

Question 35

What effect does dexamethasone have on OPG and RANKL?

Answer 35

• Decreases OPG
• Increases RANKL

Question 36

What does effect does Budesonide have on growth?

Answer 36

Suppresses growth (1.1cm)

Question 37

What will happen to growth if childhood asthma is untreated?

Answer 37

Growth is reduced

Question 38

What effect do glucocorticoids have on immunosuppression?

Answer 38

They inhibit release of inflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α) from macrophages.