Corticosteroid & Respiratory Systems Flashcards
what are the arachidonic acid pathway
how are corticosteroids produced
synthesized and released as required –> no storage needed
what is endogenous control of corticosteroids
hippocampus <——> amygdala
hypothalamus –> corticotropin releasing hormone –> pituitary –> adrenocorticotropic hormone –> adrenals –> cortisol
what are exogenous corticosteroids useful for
treating symptoms of conditions
but do not treat underlying cause
what is the mechanism of action of corticosteroids (5)
- binding of steroid hormone to receptor
- translocation of steroid-receptor complex to nucleus
- binding of complex to DNA regulatory site
- transcription
- translocation
what is the structure of corticosteroids
basic structure is: 3 hexane rings and a pentone ring
what are examples of proteins whose synthesis is induced by glucocorticoids
- angiotensin converting enzyme
- B2-adrenoceptro
- lipocortin 1 (inhibits phospholipase)
what are examples of protein synthesis is inhibited by glucocorticoids
- cytokines
- cyclo-oxygenase
- collagenase
- inducible NOS
what are mechanism of action of glucocorticoids
- metabolic effects and systemic effects –> normal physiological actions
- anti-inflammatory effects and immune suppressive effects –> pharmacological actions
physiological function –> anti-inflammatory activity –> immunosuppression –> cytotoxicty
what are the duration of action of corticosteroids
different glucocorticoids have different inherent durations of action
prenisolone, prednisone, methylprednisolone are short acting (<24 hours)
dexamethasone, betamethasone, triamcinolone are all long acting (>24 hours)
what are water soluble salts ideal for and why
ideal for IV
readily absorbed and eliminated within 8-24hrs
high concentrations, rapidly
what are examples of water soluble salts
sodium phosphate salts and soluble esters (succinate)
ex. betamethasone sodium phosphate (betsolan soluble), dexamethasone (axium, colvasone, dexadreson)
what are insoluble esters useful for
more sustained therapy
what are examples of insoluble esters
acetate, adamantoate, diproprionate, pivalate, phenylproprionate, isonicotinate, adamantoate
dexamethasone isonicotinate (voren 14)
methylprednisolone acetate (depo-medrone V)
what are the general principles of corticosteroid therapy (5)
- minimal mineralocorticoid activity preferred
- use a low dose
- withdraw treatment gradually
- long acting compounds greater risk of toxicity
- treat underlying cause of problem
how is the HPA axis suppressed
- negative feedback of exogenous corticosteroids
- suppression of ACTH followed by atrophy of adrenal gland
- sudden termination of exogenous corticosteroid –> life-threatening crisis
essential for gradual reduction in corticosteroid dose
what are some side effects of corticosteroids (11)
- gastric and corneal ulceration
- suppression of responses (injury or infection)
- muscle and cutaneous atrophy
- hyperglycemia
- osteoporotic effect
- sodium and water retention (blood pressure) and loss of potassium
- polyuria and polydipsia
- increased susceptibility to infection
- iatrogenic cushing’s disease
- suppression of HPA leading to Addison’s disease on drug withdrawal
- laminitis
what is addison’s disease
deficiency of adrenocortical steroid production
mineralocorticoid and glucocorticoid deficiency
usually immune mediated destruction of adrenal cortices
most commonly iatrogenic
what are the symptoms of addison’s disease
anorexia, vomiting, diarrhea, weakness, exercise intolerance, polydipsia and polyuria
what breeds are predisposed to addisons
standard poodles
west highland terriers
great danes
some collies
how is addison’s diagnosed
circulating ACTH concentrations increased in primary (adrenal) addison’s but not so in central hypoadrenocorticism
how is addison’s disease treated
acute hypoadrenal crisis is a medical emergency
hydrocortisone sodium succinate IV
chronic therapy requires permanent mineralcorticoid therapy (fludrocortisone acetate orally)
what is cushing’s disease
hyperadrenocorticism
overproduction of glucocorticoids due to a pituitary adenoma (ACTH increased) or due to an adrenal tumour (ACTH very low)
Iatrogenic cushing’s can result from prolonged treatment with glucocorticoids
what are common symptoms of cushing’s diease in dogs
polydipsia, polyuria, polyphagia
elevated liver enzymes
pot belly
thin skin
coat changes
muscle wastage
what are breeds most commonly affected by cushing’s
poodles
dachshunds
terriers
german shepherds
golden retrievers
what are the two types of cushing’s in dogs
- pituitary: 80% –> increase in ACTH, increase in cortisol
- adrenal: 20% –> decrease in ACTH, increase in cortisol
what are the 3 tests for cushing’s (3)
- ACTH test: elevated corticosteroids before ACTH and a rise after admin
- low dose dexamethasone suppression test: in cushing’s it won’t suppress cortisol
- high dose dexamethasone suppression test: sometimes used to differentiate between pituitary and adrenal problem (if pituitary high dose will suppress cortisol production, if adrenal –> will not)
what are pharmacological interventions in cushing’s disease (3)
enzyme blockers
- trilostane (vetoryl): oral, well tolerated, careful monitoring required
- ketoconazole (antifungal): interferes with synthesis of adrenal steroids (expensive)
- mitotane: cytotoxic –> easy to use, inexpensive but potentially very serious side effects, requires regular monitoring
