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
How to reduce the risks of corticosteroid side effects
use the lowest effective dose, for the shortest amount of time
give at the time the physiological corticosteroids are most active to reduce the risk of atrophy to the adrenal cortex
Long-term treatment of corticosteroid
STEROID TREATMENT CARD: lists the drug and the dosage so that if you go to the doctor they know to give you your drugs
if you withdraw suddenly, your atrophied adrenal cortex will not suddenly kick back in and you will suffer acute adrenal insufficiency, hypotension, and possibly death
have to be careful around infections (due to increased severity and susceptibility and atypical presentation) and live injections
CHICKEN POX AND MEASLES ARE THE BAD GUYS if a non-immune patient is exposed they should be given a passive immunization within 3 days of exposure and no later than 10 days
withdrawal of corticosteroids
gradual withdrawal required for patients who are unlikely to relapse and have:
- received repeated course
- treated for longer than 3 weeks
- taking a short course within a year of taking a long course
- received more than 40 mg prednisolone daily (or equivalent)
- repeated dose in the evening
OR
- other causes of adrenal suppression
if none of the above apply, can stop abruptly
can be rapidly reduced to equivalent to 7.5mg of prednisolone, then reduced more slowly
hydrocortisone
indicated: addison’s disease, inflammatory bowel disease, skin conditions
has the most mineralcorticoid effects
doses: replacement therapy: 20-30 mg/day
IBD: 125 mg of foam rectally 1/2 daily
skin conditions: 1% cream 1/2 daily
Prednisolone
indicated: asthma, inflammatory bowel disease, rheumatic disease, as an immunosuppressant for those who are at risk of rejection
CONTRAINDICATIONS: systemic infections, live vaccines in those who are immunosuppressed
Dose: orally: initially 10-20mg/day (up to 60mg in severe disease), with a maintainence dose of 2.5-15mg daily
intramuscular injection: 25-100mg 1-2 weekly
drops
foam: 20mg application 1-2 daily
Betamethasone
indicated: inflammatory and allergic disorders, eg:
eye: anterior segment inflammation
ear: eczematous inflammation
skin: psoriasis, atopic dermatitis
available as an ointment, cream, solutions
Dexamethasone
indicated: inflammatory and allergic disorders, congenital adrenal hyperplasia, cerebral oedema associated with malignancy
dose: orally: 0.5-10mg daily
im or slow iv injection: cerebral oedema 10mg initially, then 4mg every 6 hours
topical: eye drops
