Corticosteroids Flashcards
What is the role of corticosteroids?
- Glucocorticoids - immunosuppressant effects
- Mineralocorticoids - role is to deal with water balance
What is the general effect of exogenous corticosteroids?
Disrupt normal phys, treat symptoms but not will treat the underlying problem
How are glucocorticoids released?
Circadian rhythm. Nocturnal animals will have a peak during the night and diurnal animals will have a peak during the day.
What is the mechanism of action of corticosteroids?
- Highly protein bound
1. Binds to cell and moves into nucleus
2. Alters the mRNA strand therefore interrupting protein synthesis by inhibiting or stimulating certain protein production
Give examples of proteins induced by corticosteroids
Angiotensin converting enyme
B2 - adrenoceptor
Lipocortin 1
Give examples of proteins inhibited by corticosteroids
Ctokines
Cyclo-oxygenase (COX)
Collagenase
Inducible NOS
What is the mechanism of action of glucocorticoids?
Metabolic, systemic, anti-inflammatory, immune suppressive
Give examples of short acting glucocortcoids
Prednisolone, prednisone, methyprednisolone (<24hrs)
GIve examples of long acting glucocorticoids
Dexamethasone, betamethasone, triamcinolone (>24hrs)
How do combination with water soluble salts aid the formulation of corticosteroids?
- ideal for IV administration
- readily absorbed and eliminated within 8-24hrs
- high conc reached rapidly
- sodium phosphate sals and soluble esters e.g. succinate
- useful for shock and allergy
How do combination with insoluble esters aid formulation of corticosteroids?
- useful for more sustained therapy
- longer acting e.g. joints
- SC or IM
- slow release from injection site
What are the different routes of adminstering corticosteroids?
- topically - skin problems; allergy, inflammation. Pro-drug, metabolised to active compound
- inhalation - specifically target the lungs
- intra-articular injection - joints
What are the general principles of corticosteroid therapy?
- minimal activity is preferred
- use as low a dose as possible, start with low dose then increase if required
- withdraw treatment gradually, esp if given systemically
- greater risk of toxicity with longer acting compounds
- need to treat the underlying cause of the problem
Why do corticosteroids need to be withdrawn gradually?
Exogenous corticosteroids have a negative feedback effect causing suppression of ACTH followed by atrophy o the adrenal gland. Adrenal gland can no longer produce endogenous corticosteroid. So sudden termination of exogenous corticosteroid can result in a life threatening situation.
What are the side effects of corticosteroids?
- Gastric and corneal ulceration (inhibition of epithelium renewal)
- Suppression of immune system
- Muscle and cutaneous atrophy
- Hyperglycaemia
- Osteoporotic effect (increase Ca excretion)
- Na and water retention (blood pressure), loss of K
- Polyuria and polydypsia
- Iatrogenic Cushing’s
- Suppression of HPA leading to Addison’s disease on drug withdrawal
- Laminitis
Name 2 disease casued by abnormal functioning of the adrenal gland and HPA axis
Addison’s disease and Cushing’s disease
What is Addison’s disease?
- Deficiency of adrenocortical steroid production
- Mineralocorticoid and glucocorticoid deficiency
- Underlying pathology usually immune mediated destruction of adrenal cortices
- Central hyoadrenocorticism is most commonly iatrogenic
What are the clinical signs of Addison’s disease?
Anorexia, vomiting, diarrhoea, weakness, exercise intolerance, polydypsia, polyurea. May be precipated by a stressful event.
How is addison’s diagnosed?
Circulating ACTH conc elevated in primary addison’s
How is Addison’s treated?
Permanent mineralocorticoid therapy
What is Cushing’s disease?
Overproduction of glucocorticoids due to a pituitary adenoma (ACTH increase) or to an adrenal tumour (ACTH v low).
Iatrogenic Cushing’s can result from prolonged treatment with glucocorticoids
What are the clinical signs of Cushing’s?
Polydypsia, polyurea, polyphagia, elevated liver enzymes, pot belly (redistibution of fat), thin skin, coat chnages, muscle wastage
How is Cushing’s diagnosed?
- ACTH test - elevated corticosteroid before ACTH and rise after administration
- Low dose dexamethasone suppression test - won’t suppress cortisol
- High dose dexamethasone suppression test - sometimes used to differentiate between pituitary and adrenal probelm. If pituitary, high dose will not suppress cortisol production
- X-ray or ultrasound
How can Cushing’s be treated?
- Trilostane
- Ketoconazone - interferes with synthesis of adrenal steroids
- Mitotane - cytotoxic - removes layers of adrenal cortex to reduce corticosteroid production, adrenal tumours
