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Flashcards in pharmacology 10 - corticosteroids Deck (24):

what is the main problem with corticosteroids?

they are very widely used but also widely disused!!


what are the 2 classes of corticosteroids? where are they produce and give an example of each?

they are produced in the adrenal cortex.
1. mineralocorticoids - zona glomerulosa and aldosterone!!
2. glucocorticoids - zona fasiculata and reticularis eg. cortisol and corticosterone.


what is the precursor for all corticostreoids? where is it?

cholestrol and it is produced in the plasma and stored in the adrenals.


endogenously how do the corticosteroids work? RAAS? hegative feedback?

they work via the HPA axis. the hypothalamus releases CRF. this acts on the pituitary gland (anterior) to produce ACTH. This then acts on the adrenal gland. there is negative feedback loops at all levels. RAAS also has an effect on aldosterone (mineralocorticoids.)


explain the structure of the glucocorticoids?

four ring, 21 carbon chain. double bond at c4-5 and a ketone at c3. subtiutues can increase glucocorticoid potency and decrease mineralocorticoid activity.


pharmacokinetics? ppb? (2) half life? metabolised? excreted? name to pro-drugs?

highly ppb - 90% to both albumen and to CBG. (endogenous and prednisolone only)
short half life
metabolised in liver
exreted in urine
cortisone and prednisone are pro-dugs - for hydrocortisone and prednisolone.


what is the mechanism of action of glucocorticoids?

cross cell membrane by diffusion. bind to cytoplasmic receptors.
complex then translocate to the nucleus and up-down regulates transcription of MRNAS's (gene expression)

or they bind indirectly by action of a transcription activator protein. - acts to enhance gene expression.


what are the proteins targeted by glucocorticoids? which are induced? which are inhibited?

angiotensin converting enzyme!! (RAAS)
b2 adrenoreceptors - bronchdilation = resp diseases. + ani-inflamm drugs



what are the actions of glucocorticoids? (4)

immune suppressive


what are the metabolic actions of glucocorticoids? good? bad?

increase blood glucose
increase GNG
increase glycogen storage
protein breakdown (muscle mass lost)
redistribute body fat (pot belly)
negative calcium balance (decreased absorbtion and increased excretion.)


what are the systemic affects of gluco's?

elevate liver enzymes
induce abortion/partuition
alter CNS function - behavior
have mineralocorticoid activity - RAAS - cause retention of water and lose k+ (swelling and oedema.) angiotensin converting enzyme


what are the anit-inflamm affects of gluco's?

only at pharmcological levels.
act early and late in inflamm
vessels vasoconstrict and reduce fluid exudate
decrease t helper cells
decrease leucocytes
decrease macro's
decrease fibroblasts
lower osteoblasts and increase osteoclasts. (lower bone healing)
decrease prostanoids (= lower COX)
inhibit PLA2 (above cox in chain)
reduce cytokines
reduce histamine release.


what do they do to PLA2?

they act here which is higher up then COX. this means they knock out LT'S and PAF too. this means they are potent anti-inflamm durgs and mediators.


what are their immune suppressive effects? doses?

at a low dose the celular eesponses are inhibited. eg. leukopaenia. but they cause incresed neutrophils (neutrophillia)

at a high dose - they supress the humoral responses. lowered antibodies.


what effect does glucocorticoid activity have on mineralocorticoid activity?
what is the exception?

more potent gluco = less potent mineralo. in general.
except - fludrocortisone.


2 kinds of formulations for these drugs? administration of each?

-water soluble salts = i/v injection. eg. dexamethasone.
-insoluble esters = s/c, oral or i/m. dexamethasone phenyl proprionate.


what are the different routes these drugs can be administered?

topical - eg. eye, ear,skin - (eye may still supress the hPA axis. negative feedback)


what are the clinical uses for these drugs? dosing in immune mediated?
role in shock?

-inflamm disease
-immune mediated disease - start at a high dose and decrease to lowest possible!!
-shock - support 9timing important!) high dose and short acting to stabilise vessels. and cv system.
-cerbral oedema - reduce swelling
-neoplasia - part of the regime. helps seconadary hypercalcaemia.


give two examples of intra-articular steroids?mpa? ta? plus pros and cons of each?

-methyl predmisolone acetate = rapid metabolism to MP.
-very low serum conc
levels maintained for 39 days
has adverse effects oon cartilage.

-triamcinolone acetonide:
higher and more prolonged plasma levels 9lower HPA axis)
levels in joint are gone after 2 weeks.
no alteration of bone remoddeling/fragility.


what is Addison's disease? what do we use to treat it? mainly seen in? symtoms? long term treatment with?

it is a deficiency of adrenocortical steroid production. mineralocorticoids used to treat it!!
seen in young female dogs. present collapsed, bradycardia, hyperkalaemic, hyponatraemic, dehydrated.

treat with hydrocortisone. long term with fludrocortisone!!


what are the main principals of therapy? (5)

mineral mineralo activity preferred
treat underlying cause too
use wt=ith bacterial drugs
with draw treatment gradually
long acting - high risk of toxicity.


what are the main adverse effects?

GI ulcers
muscle atrophy
cutaneous atrophy
osteoporotic effect (lowers epiphyseal cartilage in young.)


other adverse effects?

conrneal ulceration
suppress HPA
iatrogenic cushings - over production of hormones.


what is iatrogenic cushings? why reduce treatment gradually? may use alternate day treatment!!

over production of gluco's . eg. adrenal tumour, pituiatry tumour. prolonged treatment can cause this. polydipsia, polyuria, polyphagia, liver enzymnes hgher, pot belly. plus HPA axis negative feedbakck - need to reduce doses slowly as it may atrophy and could get major problem!!