Glucocorticosteroids Flashcards
Normal amount of endogenous glucocorticosteroid production:
10-20mg/day
Endogenous glucocorticosteroid production under stressed conditions:
20-300mg/day
General use of exogenous corticosteroids:
Used in disease management only - not curative!
Physiological effect
Production of glucose - stress response
Mechanism of action of glucocorticosteroids
Bind to cytoplasmic glucocorticoid receptor (via glucocorticoid response elements) and alter gene expression (either induce or inhibit)
Therapeutic uses of glucocorticosteroids: anti-inflammatory effects
- Chronic GIT (IBD)
- Inflammation
- Asthma / COPD
Therapeutic uses of glucocorticosteroids: Immunosuppressive effects
- Allergic reactions
- Organ transplantation
- Cancer (haem)
- Autoimmune disease
- Rheumatic disease
- Skin disorders
- Hypersensitivity states
Therapeutic uses of glucocorticosteroids: Other uses
- Adrenal insufficiency
- Premature neonates
- Multiple sclerosis
- Renal disease
Therapeutic uses of glucocorticosteroids: Uses in premature neonates
Stimulates surfactant synthesis in the lungs = reduces respiratory distress
Examples of affected genes: Transcription Stimulation
- Lipocortin (annexin-1): inhibits phospholipase A2 activity and decreases inflammation
- Gluconeogenic pathway enzymes
Effect of up-regulation of the gluconeogenic pathway enzymes
Gluconeogenetic drive = catabolic effect on metabolism and increased appetite (especially craving carbs and sweets)
2 main adverse effects to consider when giving glucocorticosteroids
- Effects on HPA axis - adrenal crisis
2. Adverse effects related to physiological responses
Therapeutic considerations for adverse effects (2 things to consider)
- Preparations available
2. Potency
CS induced acute adrenal crisis: what is the cause?
Adrenal insufficiency (CS use > 14 days) = suppression of HPA axis by exogenous glucocorticosteroids
CS induced acute adrenal crisis: what can be done to preserve the HPA axis?
Alternate day dosing or morning dose (not effective in high potency / long acting CS)
CS induced acute adrenal crisis: triggers
stress, surgery, trauma, infection
Symptoms of mild acute adrenal crisis
myalgias, malaise, anorexia, weakness
Symptoms of severe acute adrenal crisis
vomiting, fever, hypotension, shock
Management of acute adrenal crisis
Parenteral hydrocortisone
NB: what should be done when giving CS for longer than 14 days
Dose tapering
Route of delivery of glucocorticosteroids
- Parenteral
- Oral
- Site specific delivery (lungs, skin, intra-articular injections)
What should the duration and dose of therapy be?
The shortest and lowest
What can be done regarding dosing to preserve the HPA axis?
Alternate day dosing - oral therapy
(not effective in long acting CS
What is important about the metabolism of glucocorticosteroids?
First pass effect
E.g. Budesonide, Fluticasone (95-99% metabolized)
What is osteonecrosis?
Aseptic necrosis of joints
What causes osteonecrosis?
High dose, short term use and long term use of corticosteroids
What is the mechanism of osteoporosis in corticosteroid therapy?
Inhibition of gonadal steroid synthesis - decreased absorption of Ca from the GIT - increased PTH - suppresses osteoblast activity AND: catabolic effect on bone matrix
Management of osteoporosis due to corticosteroid therapy:
(therapy >3 months)
- monitor bone density, give calcium and Vitamin D supplementation
- replacement of gonadal steroids
How does osteonecrosis present?
As shoulder, knee, hip pain
What behavioral changes are seen due to corticosteroid use?
- commonly aggression / psychosis
- steroid rage
- Not C/I in psychiatric illness despite this
What negative effects of topical corticosteroids are seen on the skin?
- 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
Topical Glucocorticosteroids: Which agent is the most potent?
Clobetasol
Group IV
Topical Glucocorticosteroids: Which agents are very potent?
Beclomethasone, betamethasone, mometasone, fluticasone, triamcinolone
(Group III)
Topical Glucocorticosteroids: Which agent is moderately potent?
Betamethasone (½ strength)
Group II
Topical Glucocorticosteroids: Which agent is weakly potent?
Hydrocortisone
Group I
For a serious infection, what topical corticosteroid should be chosen?
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
What are the inhaled glucocorticoids used in asthma?
- Beclomethasone
- Budesonide
- Fluticasone
- Ciclesonide (newest)
What are the systemic glucocorticoids used in asthma?
- Prednisone
- Prednisolone
- Methylprednisone
- Hydrocortisone
What method of administration of glucocorticoids is preferable in asthma?
Inhaled is preferred over systemic.
- 95% first pass metabolism, therefore very little adverse effects are seen vs. systemic
What is the difference between prednisone and prednisolone?
Prednisone is a pro-drug activated to prednisolone in the liver. It a patient has liver failure however it is better to give prednisolone.
What are common adverse effects of inhaled glucocorticoids?
- Oropharyngeal candidiasis
2. Vocal cord effects: hoarseness, dysphonia, cough
What are less common adverse effects of inhaled glucocorticoids and which drugs are these effects seen with?
Low incidence with budesonide and fluticasone
- cataracts
- growth retardation in children
- osetoporosis
- easy bruising
- thinning of skin
- HPA and adrenal suppression
Therapeutic considerations in long term use:
- Repeated evaluation of dose and route of administration is important.
- Adverse effect vs. therapeutic effects
Therapeutic considerations: dose tapering
No dose tapering for short courses (1-2 weeks)
- for longer courses dose tapering should be done
What should be monitored if oral / IV glucocorticoids are given?
- blood glucose
- blood pressure
- fluid status
