Glucocorticosteroids

Question 1

Normal amount of endogenous glucocorticosteroid production:

Answer 1

10-20mg/day

Question 2

Endogenous glucocorticosteroid production under stressed conditions:

Answer 2

20-300mg/day

Question 3

General use of exogenous corticosteroids:

Answer 3

Used in disease management only - not curative!

Question 4

Physiological effect

Answer 4

Production of glucose - stress response

Question 5

Mechanism of action of glucocorticosteroids

Answer 5

Bind to cytoplasmic glucocorticoid receptor (via glucocorticoid response elements) and alter gene expression (either induce or inhibit)

Question 6

Therapeutic uses of glucocorticosteroids: anti-inflammatory effects

Answer 6

1. Chronic GIT (IBD)
2. Inflammation
3. Asthma / COPD

Question 7

Therapeutic uses of glucocorticosteroids: Immunosuppressive effects

Answer 7

1. Allergic reactions
2. Organ transplantation
3. Cancer (haem)
4. Autoimmune disease
5. Rheumatic disease
6. Skin disorders
7. Hypersensitivity states

Question 8

Therapeutic uses of glucocorticosteroids: Other uses

Answer 8

1. Adrenal insufficiency
2. Premature neonates
3. Multiple sclerosis
4. Renal disease

Question 9

Therapeutic uses of glucocorticosteroids: Uses in premature neonates

Answer 9

Stimulates surfactant synthesis in the lungs = reduces respiratory distress

Question 10

Examples of affected genes: Transcription Stimulation

Answer 10

1. Lipocortin (annexin-1): inhibits phospholipase A2 activity and decreases inflammation
2. Gluconeogenic pathway enzymes

Question 11

Effect of up-regulation of the gluconeogenic pathway enzymes

Answer 11

Gluconeogenetic drive = catabolic effect on metabolism and increased appetite (especially craving carbs and sweets)

Question 12

2 main adverse effects to consider when giving glucocorticosteroids

Answer 12

1. Effects on HPA axis - adrenal crisis

2. Adverse effects related to physiological responses

Question 13

Therapeutic considerations for adverse effects (2 things to consider)

Answer 13

1. Preparations available

2. Potency

Question 14

CS induced acute adrenal crisis: what is the cause?

Answer 14

Adrenal insufficiency (CS use > 14 days) 
= suppression of HPA axis by exogenous glucocorticosteroids

Question 15

CS induced acute adrenal crisis: what can be done to preserve the HPA axis?

Answer 15

Alternate day dosing or morning dose (not effective in high potency / long acting CS)

Question 16

CS induced acute adrenal crisis: triggers

Answer 16

stress, surgery, trauma, infection

Question 17

Symptoms of mild acute adrenal crisis

Answer 17

myalgias, malaise, anorexia, weakness

Question 18

Symptoms of severe acute adrenal crisis

Answer 18

vomiting, fever, hypotension, shock

Question 19

Management of acute adrenal crisis

Answer 19

Parenteral hydrocortisone

Question 20

NB: what should be done when giving CS for longer than 14 days

Answer 20

Dose tapering

Question 21

Route of delivery of glucocorticosteroids

Answer 21

1. Parenteral
2. Oral
3. Site specific delivery (lungs, skin, intra-articular injections)

Question 22

What should the duration and dose of therapy be?

Answer 22

The shortest and lowest

Question 23

What can be done regarding dosing to preserve the HPA axis?

Answer 23

Alternate day dosing - oral therapy

(not effective in long acting CS

Question 24

What is important about the metabolism of glucocorticosteroids?

Answer 24

First pass effect

E.g. Budesonide, Fluticasone (95-99% metabolized)

Question 25

What is osteonecrosis?

Answer 25

Aseptic necrosis of joints

Question 26

What causes osteonecrosis?

Answer 26

High dose, short term use and long term use of corticosteroids

Question 27

What is the mechanism of osteoporosis in corticosteroid therapy?

Answer 27

``` Inhibition of gonadal steroid synthesis - decreased absorption of Ca from the GIT - increased PTH - suppresses osteoblast activity AND: catabolic effect on bone matrix ```

Question 28

Management of osteoporosis due to corticosteroid therapy:

Answer 28

(therapy >3 months) - monitor bone density, give calcium and Vitamin D supplementation - replacement of gonadal steroids

Question 29

How does osteonecrosis present?

Answer 29

As shoulder, knee, hip pain

Question 30

What behavioral changes are seen due to corticosteroid use?

Answer 30

- commonly aggression / psychosis - steroid rage * Not C/I in psychiatric illness despite this

Question 31

What negative effects of topical corticosteroids are seen on the skin?

Answer 31

- catabolic effect, damages collagen (thins skin) - atrophy, striae, acneform eruptions, perioral dermatitis, fungal and bacterial infections, rosacea - penetrates skin and causes systemic ADRs especially in children

Question 32

Topical Glucocorticosteroids: Which agent is the most potent?

Answer 32

Clobetasol | Group IV

Question 33

Topical Glucocorticosteroids: Which agents are very potent?

Answer 33

Beclomethasone, betamethasone, mometasone, fluticasone, triamcinolone (Group III)

Question 34

Topical Glucocorticosteroids: Which agent is moderately potent?

Answer 34

Betamethasone (½ strength) | Group II

Question 35

Topical Glucocorticosteroids: Which agent is weakly potent?

Answer 35

Hydrocortisone | Group I

Question 36

For a serious infection, what topical corticosteroid should be chosen?

Answer 36

It is better to use Clobetasol (most potent) only for a few days than to use a weaker agent for longer. - must be used carefully however, need to use small amount

Question 37

What are the inhaled glucocorticoids used in asthma?

Answer 37

- Beclomethasone - Budesonide - Fluticasone - Ciclesonide (newest)

Question 38

What are the systemic glucocorticoids used in asthma?

Answer 38

- Prednisone - Prednisolone - Methylprednisone - Hydrocortisone

Question 39

What method of administration of glucocorticoids is preferable in asthma?

Answer 39

Inhaled is preferred over systemic. | - 95% first pass metabolism, therefore very little adverse effects are seen vs. systemic

Question 40

What is the difference between prednisone and prednisolone?

Answer 40

Prednisone is a pro-drug activated to prednisolone in the liver. It a patient has liver failure however it is better to give prednisolone.

Question 41

What are common adverse effects of inhaled glucocorticoids?

Answer 41

1. Oropharyngeal candidiasis | 2. Vocal cord effects: hoarseness, dysphonia, cough

Question 42

What are less common adverse effects of inhaled glucocorticoids and which drugs are these effects seen with?

Answer 42

Low incidence with budesonide and fluticasone - cataracts - growth retardation in children - osetoporosis - easy bruising - thinning of skin - HPA and adrenal suppression

Question 43

Therapeutic considerations in long term use:

Answer 43

- Repeated evaluation of dose and route of administration is important. - Adverse effect vs. therapeutic effects

Question 44

Therapeutic considerations: dose tapering

Answer 44

No dose tapering for short courses (1-2 weeks) | - for longer courses dose tapering should be done

Question 45

What should be monitored if oral / IV glucocorticoids are given?

Answer 45

- blood glucose - blood pressure - fluid status