CORTICOID THERAPY Flashcards
What is a mineralocorticoid?
a corticosteroid that is involved with maintaining the salt balance in the body e.g. aldosterone
what is a glucocorticoids?
any group of corticosteroid involved in the metabolism of carbs, proteins and fats and have an anti-inflammatory activity
what are catecholamines?
any of a class of aromatic amines which includes a number of neurotransmitters adrenaline and dopamine
what are the 3 distinct regions of the adrenal gland?
capsule, adrenal cortex, adrenal medulla
what are the 3 distinct zones of the adrenal cortex?
zona glomerulosa
zona fasiculata
zona reticular is
which zone of the adrenal cortex can contain lipofuscin?
zona reticular is
what hormones does the zona glomerulosa release?
mineralocorticoids
what hormones does the zona fasiculata release?
glucocorticoids
what hormones does the zona reticularis release?
androgens
e.g. dehydroepiandrosterone
what hormone does the adrenal medulla release?
stress hormones e.g. noradrenaline and
what does dehydroepiandrosterone help produce?
testosterone and oestrogen
whats the function of mineralocorticoids?
promote sodium and potassium transport, usually followed by changes in water balance -> key role in bp and normal CO
outline the moa of mineralocorticoids?
they can bind to mineralcorticoid receptors inside the cell, it can move to the nucleus to drive gene expression. This activates the Na+ transporter which can be transported to the surface to increase Na+ uptae and therefore water will follow
whats an example of a mineralocorticoid?
aldosterone
what are examples of mineralocorticoid antagonists?
Spironolactone and eplerenone
outline the production chain of mineralocorticoids?
cholesterol -> pregnenolone -> 11-deoxycorticosterone -> corticosterone -> aldosterone
where does angiotensin 2 exert its effect?
on the enzyme that converts corticosterone to aldosterone
what is conn’s syndrome?
primar hyperaldosteronism
what is primary hyperaldosteronism?
a condition that occurs when the adrenal glands produce too much aldosterone - leading to hypertension and hypokalaemia
what is secondary hyperaldosteronism?
increased adrenal production of aldosterone in response to nonpituitary, extra-adrenal stimuli such as renal hypoperfusion.
whats the function of glucocorticoids?
prmotes overall catabolic effects in the body; in adipose tissue it triggers lipolysis, in the muscle it stimulates proteolysis. These free fatty acids and amino acids serve as a substrate for gluconeogenesis. At the same times it decreases cellular utilization of glucose. This increases the output of glucose from the liver. they can also increase insulin resistance in tissues which means that insulin becomes less effective at moving glucose into cells, leading to an increase in blood glucose levels; this in turn then stimulates the release of more insulin. The end result is a lot more glucose in the blood to use as fuel during times of stress.
They also help regulate the immune response by inhibiting prostaglandins and leukotrienes and interluekin 2 production by WBCs.
Finalyl, they play a role in maintaining bp levels since it up-regulates alpha 1 adrenergic receptors in blood vessels, causing vasoconstriction.
what are glucocorticoids moa?
cross the cell membranes and bind with the cytoplasmic receptor protein called a glucocorticoid receptor, Now this complex can enter the nucleus and bind with glucocorticoid respeone elements. Thus induces transcription of specific mRNA thats used t synthesize different proteins which in turn modifies various cell functions and metabolic effects in the body.
how are glucocorticoids produced?
cholesterol -> pregnolone -> 17-alpha-hydoxypregenolone -? 17-alpha hydroxyprogesterone -> 11-deoxycortisol -> hydrocortisone
what effects do synthetic glucocorticoids have?
the same as endogenous glucocorticoids but also increase the number of neutrophils in the blood through demmargination (and prevent their apoptosis)
they can also decrease lymphocyte, monocyte, basophil and eosinophil counts
what are examples of short acting glucocorticoids?
cortisone and hydrocortisone
whats the difference between cortisone and hydrocortisone?
cortisone is taken orally and converted to hydrocortisone in the liver whilst hydrocortisone is already active so can be taken oral, IV or IM
what are examples of intermediate acting glucocorticoids?
prednisone
prednisolone
methylprednisolone
triamcinolone
what are corticosteroids?
steroid drugs that closely relate to cortisol (glucocorticoid)
what are some examples of long acting glucocorticoids?
betamethasone and dexamethasone
what steroid is in the brown inhaler?
beclometasone
what steroid is given to pregnant women before birth to speed up foetal lung maturation?
betamethasone
whats the production chain for androgens?
cholesterol -> pregnenolone -> 17-alpga-hydroxypregenolone -> dehydroepiandrosterone -> androstenedione -> testosterone -> oestradiol
whats the cause the congenital adrenal hyperplasia?
The most common enzyme defect, 21-hydroxylase deficiency, leads to excess amounts of male hormones being produced by the adrenal glands because there is an increase in metabolites that couldn’t be used to synthesis glucocorticoids and mineralocorticoids
outline the HPA axis for glucocorticoids?
hypothalamus secretes corticotrophin releasing factor which stimulates the anterior pituitary to secrete adrenocorticotrophic hormone. This stimulates the adrenal cortex to produce glucocorticoids.
The increase in glucocorticoids suppresses the hypothalamus to stop it secreting CRF
what are examples of using physiological dosing of glucocorticoids?
this is when you are trying to replace steroid levels e.g. Addisons disease
why do you need to slowly reduce a patients dosing of steroids to wean them off it?
because when you give steroids, edogenous steroid production is suppressed which can lead to the adrenal gland shrinking overtime
so when a patient then needs to be able to make endogenous steroids, they may not be able to do so effectively
what is cushings syndrome?
too much cortisol in the body
what are some effects of cushings syndrome?
CNS irritability red round face hypertension cardiac hypertrophy purple striae skin ulcers muscle wasting osteoporosos obesity aemonorrhoea erectile dysfunction
what is secondary adrenal insufficiency?
Secondary adrenal insufficiency occurs when the pituitary gland doesn’t make enough of the hormone ACTH
whats the test to see if the body can effectively produce ACTH?
give metyrapone which blocks the production of hydrocortisone. This should drive the production of ACTH
which steroids have glucocorticoid and mineralocorticoid activity?
hydrocortisone
cortisone
fludrocortisone
which steroids have predominantly glucocorticoid activity?
prednisone
prednisolone
methylprednisolone
dexamethasone
which steroids have only glucocorticoids activity?
triamcinolone and betamethasone
