Pharmacology Steroids Flashcards
what are all corticosteroids derived from?
cholesterol
if cortisol is used as a drug, what is it called?
hydrocortisone (given IV in patients)
why can giving a lower dose of dexamethasone achieve the same effect as giving a higher dose of cortisol?
dexamethasone= more potent
effects of cortisol in body?
glycogenolysis, gluconeogenesis in liver, causing hyperglycameia
proteolysis- free up aa
lipolysis at low concs, lipogenesis at high concs e.g. in cushings disease, and with very potent steroid drugs
redistribution of fat- cushing’s syndrome, high dose of steroid drug
effects of glucocorticoid deficiency in body?
hypoglycameia weight loss hypotension nausea underweight
effects of excess glucocorticoids in body?
hyperglycaemia
weight gain-water retention, increased appetite
hypertension
cushinoid
effects of mineralocorticoid deficiency?
hyponatraemia
dehydration
hypotension
hyperkalaemia
effects of high mineralocorticoids in body?
hypernatraemia
hypertension
hypokalaemia
examples of steroid drugs selective for glucocorticoid receptors in body, with minimal effect at mineralocorticoid receptors?
dexamethasone
betamethasone
example of a steroid drug that is much more selective for mineralocorticoid receptors in body, rather than glucocorticoid receptors?
fludrocortiosone
would use if wanted to mimic aldosterone in body
why do steroid drugs have good oral bioavailability?
very good lipid-solubility, so easily absorbed in gut
passive factor
how are steroids metabolised in the body?
by the liver, via both phase I and II metabolism, II= glucuronidation
small amount of metabolism capable in kidney- can convert cortisol in body to cortisone=inactive.
steroids given IV?
methylprednisolone
hydrocortisone
what route could you give a steroid to treat eczema, and give an example of a steroid given this way?
topical
betamethasone
very well absorbed across skin due to being highly lipid soluble
passive factors affecting oral bioavailability of a drug?
size
charge
lipid solubility
example of a steroid drug that can be given as an intra-articular for inflammatory joint conditions?
triamcinolone
how do corticosteroids suppress inflammation?**
transrepression and transactivation= switch on protein synthesis, of genes
inhibit B and T cell responses
inhibit nuclear factor kappa B
reduced transcription of cytokines
reduced expression of cell adhesion molecules
reduced phagocytic function
immunosuppression
mechanism of action of steroids?
lipophilic- cross cell membrane to enter cytoplasm, where bind to cytoplasmic receptor, often associated with heat shock proteins, heat shock protein dissociates and activated receptor passes across nuclear membrane into nucleus, DNA binding domain has been unmasked on receptor following steroid binding. Bind onto hormone response element of DNA= glucocorticoid response element for steroid drugs.
some can access nucleus directly, binding to receptor in nucleus and then to hormone response element in DNA.
transcription switched on and off for particular proteins
takes time to happen
examples of proteins transactivated by steroid drugs?
annexin 1- inhibits phospholipase A2 which normally forms arachidonic acid, so inhibit PG production by producing annexin-1
ADRs of steroid drugs can occur with cis-repression of particular proteins. what examples are there of these proteins?
POMC- contains sequence for ACTH
osteocalcin- secreted by osteoblasts and promotes bone formation, so reduction causes increased risk of osteoporosis.
keratin- reduced so skin thinned, alongisde effect of increased proteolysis in steroid tment
trans-repression reduces inflammatory mediators
how can NF kappa B be inhibited by glucocorticoids, inhibiting inflammatory pathway?
receptor with steroid bound can bind to CBP (cAMP response element binding protein) which inhibits NF kappa B.
steroids used in replacement therapy?
hydrocortisone
fludrocortisone
e.g. addison’s disease, or adrenolectomy
what have steroids been co-administered with in malignancy which have shown improved outcomes?
chemotherapy
use of steroid drugs clinically?
asthma GI inflamm diseases e.g. Crohn's and UC inflammatory skin conditions: eczema, psoriasis nephrotic syndrome haematological conditions vasculitis sarcoidosis cerebral oedema RA
women in premature labour- induce surfactant production in fetus to mature lungs by stimulating type 2 pneumocytes= simple cuboidal cells. steroids lipid soluble so can cross placenta. big problem with premature birth in past= resp distress syndrome= restrictive lung defect e.g. dexamethasone.
mineralocorticoid SEs of given steroid drugs?
fluid retention- ptn may complain of putting on weight, feeling bloated, moon shaped face
hypertension
hypokalaemia
glucocorticoid ADRs?
immunosuppression, increased infection risk e.g. oral candidiasis
hypertension
osteoporosis
cushinoid appearance- central obesity, moon shaped face, easy bruising, purple striae, buffalo hump= dorso-cervical fat pad- redistribution of fat in body.
hyperglycameia, diabetes
avascular necrosis
peptic ulcers- *trasnrepression of COX-1 in stomach responsible for PGE2 production necessary for protective mucus and HCO3- prod in stomach against gastric acid.
impaired growth in children
skin thinning
cataracts
corneal damage
what factors mean that steroid drugs increase risk of osteoporosis?
inhibit osteoblast formation
increased osteoclast proliferation
reduced Ca2+ absorption in gut
reduced sex steroid production- oestrogen necessary to maintain balance between osteoblast and clast activity.
why must a patient not be suddenly taken off steroids?
will have HPA suppression, so adenals not stimulated.
suppression occurs after 3 wks
abrupt withdrawl can cause adrenal insufficency crisis
surgery is a big stress to body? what must be done if patient on steroidds is going to have surgery?
must increase dose of steroid
ptnt must carry steroid card with them to tell drs
bicohemical disturbances in hypoadrenal crisis?
hypotension hypoglycaemia hyponatraemia hyperkalaemia severe dehydration death if untreated
