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Respiratory Block: Pharmacology > Glucocorticosteroids > Flashcards

Glucocorticosteroids Flashcards

1
Q

Normal amount of endogenous glucocorticosteroid production:

A

10-20mg/day

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2
Q

Endogenous glucocorticosteroid production under stressed conditions:

A

20-300mg/day

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3
Q

General use of exogenous corticosteroids:

A

Used in disease management only - not curative!

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4
Q

Physiological effect

A

Production of glucose - stress response

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5
Q

Mechanism of action of glucocorticosteroids

A

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

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6
Q

Therapeutic uses of glucocorticosteroids: anti-inflammatory effects

A
  1. Chronic GIT (IBD)
  2. Inflammation
  3. Asthma / COPD
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7
Q

Therapeutic uses of glucocorticosteroids: Immunosuppressive effects

A
  1. Allergic reactions
  2. Organ transplantation
  3. Cancer (haem)
  4. Autoimmune disease
  5. Rheumatic disease
  6. Skin disorders
  7. Hypersensitivity states
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8
Q

Therapeutic uses of glucocorticosteroids: Other uses

A
  1. Adrenal insufficiency
  2. Premature neonates
  3. Multiple sclerosis
  4. Renal disease
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9
Q

Therapeutic uses of glucocorticosteroids: Uses in premature neonates

A

Stimulates surfactant synthesis in the lungs = reduces respiratory distress

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10
Q

Examples of affected genes: Transcription Stimulation

A
  1. Lipocortin (annexin-1): inhibits phospholipase A2 activity and decreases inflammation
  2. Gluconeogenic pathway enzymes
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11
Q

Effect of up-regulation of the gluconeogenic pathway enzymes

A

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

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12
Q

2 main adverse effects to consider when giving glucocorticosteroids

A
  1. Effects on HPA axis - adrenal crisis

2. Adverse effects related to physiological responses

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13
Q

Therapeutic considerations for adverse effects (2 things to consider)

A
  1. Preparations available

2. Potency

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14
Q

CS induced acute adrenal crisis: what is the cause?

A 
Adrenal insufficiency (CS use > 14 days) 
= suppression of HPA axis by exogenous glucocorticosteroids
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15
Q

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

A

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

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16
Q

CS induced acute adrenal crisis: triggers

A

stress, surgery, trauma, infection

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17
Q

Symptoms of mild acute adrenal crisis

A

myalgias, malaise, anorexia, weakness

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18
Q

Symptoms of severe acute adrenal crisis

A

vomiting, fever, hypotension, shock

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19
Q

Management of acute adrenal crisis

A

Parenteral hydrocortisone

20
Q

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

A

Dose tapering

21
Q

Route of delivery of glucocorticosteroids

A
  1. Parenteral
  2. Oral
  3. Site specific delivery (lungs, skin, intra-articular injections)
22
Q

What should the duration and dose of therapy be?

A

The shortest and lowest

23
Q

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

A

Alternate day dosing - oral therapy

(not effective in long acting CS

24
Q

What is important about the metabolism of glucocorticosteroids?

A

First pass effect

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

25
Q

What is osteonecrosis?

A

Aseptic necrosis of joints

26
Q

What causes osteonecrosis?

A

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

27
Q

What is the mechanism of osteoporosis in corticosteroid therapy?

A 
Inhibition of gonadal steroid synthesis 
- decreased absorption of Ca from the GIT 
- increased PTH 
- suppresses osteoblast activity 
AND: catabolic effect on bone matrix
28
Q

Management of osteoporosis due to corticosteroid therapy:

A

(therapy >3 months)

  • monitor bone density, give calcium and Vitamin D supplementation
  • replacement of gonadal steroids
29
Q

How does osteonecrosis present?

A

As shoulder, knee, hip pain

30
Q

What behavioral changes are seen due to corticosteroid use?

A
  • commonly aggression / psychosis
  • steroid rage
  • Not C/I in psychiatric illness despite this
31
Q

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

A
  • 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
32
Q

Topical Glucocorticosteroids: Which agent is the most potent?

A

Clobetasol

Group IV

33
Q

Topical Glucocorticosteroids: Which agents are very potent?

A

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

34
Q

Topical Glucocorticosteroids: Which agent is moderately potent?

A

Betamethasone (½ strength)

Group II

35
Q

Topical Glucocorticosteroids: Which agent is weakly potent?

A

Hydrocortisone

Group I

36
Q

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

A

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

37
Q

What are the inhaled glucocorticoids used in asthma?

A
  • Beclomethasone
  • Budesonide
  • Fluticasone
  • Ciclesonide (newest)
38
Q

What are the systemic glucocorticoids used in asthma?

A
  • Prednisone
  • Prednisolone
  • Methylprednisone
  • Hydrocortisone
39
Q

What method of administration of glucocorticoids is preferable in asthma?

A

Inhaled is preferred over systemic.

- 95% first pass metabolism, therefore very little adverse effects are seen vs. systemic

40
Q

What is the difference between prednisone and prednisolone?

A

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

41
Q

What are common adverse effects of inhaled glucocorticoids?

A
  1. Oropharyngeal candidiasis

2. Vocal cord effects: hoarseness, dysphonia, cough

42
Q

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

A

Low incidence with budesonide and fluticasone

  • cataracts
  • growth retardation in children
  • osetoporosis
  • easy bruising
  • thinning of skin
  • HPA and adrenal suppression
43
Q

Therapeutic considerations in long term use:

A
  • Repeated evaluation of dose and route of administration is important.
  • Adverse effect vs. therapeutic effects
44
Q

Therapeutic considerations: dose tapering

A

No dose tapering for short courses (1-2 weeks)

- for longer courses dose tapering should be done

45
Q

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

A
  • blood glucose
  • blood pressure
  • fluid status

Respiratory Block: Pharmacology (8 decks)

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