Corticosteroids Flashcards
When should corticosteroids be given
ATCH levels are highest at 6am, and lowest at 10 pm, with the most glucocorticoids released at 8am and the least at midnight
if corticosteroids are given at night they inhibit ATCH levels, which stops the body from producing any glucocorticoids naturally
to prevent this single morning doses are given or alternate day therapy is used
Adrenal steroid synthesis
CRH (corticotrophin-releasing hormone) from the hypothalamus stimulates ACTH (adrenocorticotrophic hormone) in the anterior pituitary which stimulates the adrenal cortex to turn cholesterol into corticosteroids
the main type of glucocorticoid is cortisol, and the main type of mineralcorticoid is aldosterone. some sexual hormones are also formed here
glucocorticoids and mineralcorticoids have interacting effects, and some glucocorticoids have mineralcorticoid effects
they are regulated by homeostasis, and there is a negative feedback loop as corticosteroids reduce crh and acth production. this also works with exogenous corticosteroids, so they prevent production of endogenous cortisol
disorders from the mismanagement of adrenal steroids
DECREASED PRODUCTION: Adison’s disease. autoimmune caused by the destruction of the adrenal cortex by chronic inflammation. or acute adrenocortical insufficiency, when you do the dose timing poorly so they body stops making endogenous hormones
EXESSIVE PRODUCTION OF GLUCOCORTICOIDS: cushing’s syndrome. caused by too much secretion by the body or prolonged administration of corticoids (the symptoms are the same)
EXCESSIVE PRODUCTION OF MINERALCORTICOIDS: hyperaldosteronism. can be primary with Conn’s syndrome or secondary to other diseases such as cirrhosis
types of adrenal steroid effects
mineralcorticoids (aldosterone) affects water and electrolyte balance
glucocorticoids (cortisol) affect carbohydrate and protein metabolism, and has anti-inflammatory and immunosuppressive activity
mechanism of action of corticosteroids
travels around the body bound to corticosteroid-binding globulin.
the receptor is inside the cell, not on the membrane.
when the steroid bind into the receptor it dimerises and passes into the nucleus and affects gene transcription, and therefore protein production (inducing some and inhibiting others)
metabolic actions of glucocorticoids
most mediator proteins are enzymes
decreases the uptake and utilisation of glucose and increase in gluconeogenesis. hyperglycaemia
reduces protein synthesis, and increases protein breakdown (why Cushing’s syndrome looks like that)
lipids are broken down, but also created, and insulin is stimulated. this causes fat redistribution
mineralcorticoid actions. Na+ retention and K+ loss, retaining liquids, and reduce Ca2+ absorption and increase excretion in the kidneys (causes osteoporosis)
anti-inflammatory and immunosuppressive effects of glucocorticoids
some non-genomic effects have been observed, and there are cellular, inflammatory, and immune mediator actions
in acute inflammation: modifies the influx and activities of cells that mediate inflammation (eg leukocytes)
in chronic inflammation: decreases the activity of mononuclear cells, the proliferation of blood vessels and fibroblast function (reducing the ability to heal)
in lymphoid areas: decreases the clonal expansion of B and T cells, and the action of cytokine-secreting Tcells
decreases inflammatory mediators: prostanoids, platelet activating factor, cytokines such as IL and TNF, compliment components, NO, histamine
inhibits: the early manifestations of inflammation such as pain heat and swelling, and also in chronic inflammation it reduces wound repair and healing, and proliferative reactions
Uses of local corticosteroids
skin inflammation (creams, ointments), joint and soft tissue inflammation (intra-articular injections), allergic rhinitis (nasal drops, nasal sprays), allergic conjunctivitis or local inflammation (eye drops and eye ointments), oral ulceration or aphthous ulcers (sprays, tablets), ulcerative colitis and crohn’s disease (foam preparations and enemas), asthma (inhaled), hemorhoids (creams, ointments, suppositories)
different corticosteroids are used in different preparations
systemic treatment with corticosteroids
replacement treatment: for addison’s disease, acute adrenocortical insufficiency, hypopituitarism (hypofunction of pituitary) (given hydrocortisone)
Non-replacement treatment: diseases with autoimmune components, diseases with inflammatory components (eg, Crohns, asthma, graft-vs-host, rheumatoid arthritis), and some neoplastic diseases (cancer)
Equivalent anti-inflammatory doses
Prednisolone: 5mg
betamethasone: 750 ug
deflazacort: 6mg
dexamethasone: 750 ug
hydrocortisone: 20mg
methylprednisolone: 4mg
triamcinolone: 4mg
Systemic glucocorticoid side effects
hyperglycaemia (because it affects carb metabolism)
proximal myopathy (affects on protein metabolism)
osteoporosis (low calcium absorption) and associated injures
avascular necrosis of the femoral head (low blood vessel proliferation)
suppression of response to infection and injury (immunosuppressant)
peptic ulceration (affects arachidonic acid pathway)
Cushing syndrome (moon face, stretch marks, diabetes, buffalo hump and belly bump)
mental disturbances (euphoria, paranoia, insomnia, depression)
local glucocorticoid side effects
SYSTEMIC SIDE EFFECTS AT HIGH DOSES OR AFTER LONG PERIODS
thinning of the skin
stretch marks
steroid glaucoma
thinning of the cornea and sclera
local sensitivity reactions
dry, itchy or ulcerated nose
nasal septal perforations
Mineralcorticoid side-effects
hypertension, sodium and water retention, potassium deficiency
corticosteroids ranked by mineralcorticoid effects
Hydrocortisone > prednisolone»_space;»> dexamethasone > methylprednisolone
patient groups in which taking corticosteroids is complicated
Children: supresses growth in treatment over 6 months. (in asthmatic children they reach their full height, just slower and also asthma reduces height in and of itself)
pregnancy: prednisolone and hydrocortisone can cross the placenta and harm the foetus, ergo the risks of the disease must way out weigh the risks of treatment
the elderly: or multimorbid people who are already at risk of high blood pressure, osteoporosis, or diabetes
