Adrenal Corticosteroid drugs Flashcards
what are the effects of glucocorticoids?
antiinflammatory
immunosuppressive
glucocorticoids can be produced naturally _
glucocorticoids can be produced synthetically _
cortisol
hydrocortisone/prednisone
pharmalogical doses of corticosteroids are used to treat patients with
inflammation, allergic disorders, immunologic disorders
in endocrine patients corticosteroids are give to? (3)
establish a diagnosis of cushings syndrome
treat adrenal insuficciency
treat congential adrenal hyperplasia
what are the corticosteroid agonists
glucocorticoids and mineralcoticoids
what is a glucocorticoid synthetic
prednisone
what is a mineralocorticocoid synthetic
fludrocortisone
what are the corticosteroid antagonists
receptor antagonsits and synthesis inhibitors
what are the corticosteroid sythensis inhibitors
ketoconazole
what are the corticosteroid receptor antagonists
glucocorticoid antagonists: mifepristone
mineralcorticoid antagonsits: spironolactone
adrenal corticosteroids belong to the receptor _
superfamily
steroid nuclear receptor
ligand binds displacing HSP90 and the glucocorticoid receptors and mineralocorticoreceptors are activated
once the mineralocorticoid receptor is stimulated what is released
what about the glucocorticoid receptor
aldosterone
cortisol
they have equal affinities
what is the parent compound of steroids
cholesterol
what enzyme takes active steroids to their inactive form
11B dehydrogenase 2
side effects of corticosteroids
infections, myopathies, osteoporosis, skin thinning, HPA insufficiency , hypertension, hyperglycemia !
what are some factors that influence theraputic and adverse effects of corticosteroids
potency (inherent strength of steroid)
pharmokinetics (short vs long term)
daily dose (how frequently)
timing og dose (given in AM)
metabolism differences
duration of treatment
how do you treat primary adrenal insufficiency (addisons)
give a glucorticoid (hydrocotisone) and a mineralocorticoid (fludrocortisone)
this is the same way you would treat congential adrenal hyperplasia
give common examples of non-endocrine conditions we treat with steroids
following bone marrow transplant, autoimmune diseases (MS/psoriasis), hematological cancers, IBD, asthma, RA, hypersensitivity rxns, skin diseases
can corticosteroids be given in medical emergencies?
yes, high doses for a few days with little risk
DO NOT GIVE MORE THAN A FEW DAYS AND DO NOT REPLACE OR DELAY PRIMARY THERAPIES
can steroids be given for chronic conditions?
yes but you really must monitor your patients: you need to see if there is evidence for therapy in a particular preparation: dosem frequency, route of administration, and assessement of theraputic efficacy
closely monitor patients
steroids cannot be given chronically without the risk of
adverse events
only initiate steroids id there is published evidence of objective theraputic _
benefit
use steroids after other therapies have _
failed
you must identify the specific _ objective and have criteria to gage the response of the steroid
theraputic
administer as much to get theraputic effect, taper off when no longer necessary, terminate if expected result has not be achieved, complications arise or maximum benefit has occurred.
steroids decrease production of _ and _
prostaglandins and leukotrienes
steroids _ production of proteolytic enzymes and _ apoptosis of immune cells
decrease
increase
steroids _ transmigration of neutrophils and macrophages from the blood into tissues
decrease
steroids _ expression of cell adhesion molecules
decrease
consequences of steroids
decreased inflammation, immune suppresion, decreased allergies/hypersentitivity reactions
metabolic effects of steroids
carbohydrate metabolism - hyperglycemia
lipid metabolism - lipolysis, fat redistribution (hump back)
protein metabolism- myopathy and muscle wasting, dreased AA uptake, decreased protein synthesis
in what patient populations are systemic glucocorticoids problematic
immunocompromised, diabetics, people with infections, peptic ulcers, cardiovascular conditions, physciatric conditions, osteoporosis, children
decreased activity/inhibition of the enzyme 11BHSD2 results in excessive activation of _ mediated by _
MR mediated by cortisol
this increases Na+ and water retention leading to K+ loss and increased BP
what are known inhibitors of 11B-HSD2
glycyrrhizin (licorice root extract)
carbenoxolone
glucocorticoids have an anti _ action
insulin
they increase gluconeogenesis, decrease glucose uptake, and increase lipolysis all leading to hyperglycemia
what are the short to medium acting glucocorticoids (12 hrs)
hydrocortisone (cortisol) and cortisone
what are the intermediate acting glucocorticoids (12-36 hrs)
prednisone
predinisolone
methylprenisolone
triamicnolone
what is a long acting steroid (>36 hrs)
betamethasone, dexamethasone
corticosteroid drug dosing
use the lowest doe for the shortest duration possible
use short/intermediate vs long acting
use topical/inhalation over systemic
give single doses in the AM
can do alternate day with short course pulse therapy
taper off- for HPA recovery
how can you test the integrity of the HPA axis
morning cortisol
ACTH test
CRH test
prednisolone MOA
applications
pharmaokinetics
toxicities
activates the GR receptors and alters gene transcription
inflammatory conditions, cancers, transplantation etc.
intermediate acting 12-36 hrs
adrenal suppresion, hyperglycemia, osteoporosis, salt retention (high blood pressure)
mifepristone MOA
applications
pharmokinetics
effects (adverse)
anatagonist at glucocorticoid and progesterone receptors
medical abortion and CUSHINGS disease
oral administration
vaginal bleeeding, gi upset, diarrhea
mineralocorticoids are a class of steroid hormones that influence _ and _ balance
salt and water
mineralocorticoids primarily act on the _ where they cause sodium and water retnetion and excretion of _ and _
kidney
postassium and protons
the primary mineralocortcoid is _
aldosterone (also progesterone and deoxycorticosterone )
fludrocortisone MOA
applications
pharmokinetics
toxicities
agonsit at mineralocortioid receptors and glucocorticoid receptors
primary adrenal insuffuciency (addisons)
long duration of action
salt and fluid retention, hyperglycemia, CHF
what are the mineralocorticoid receptor antagonisrs?
spironolactone and eplernone
spironolactone MOA
applications
pharmokinetics
toxicities
antagonists at mineralocorticoid receptor and weak antagonist at androgen receptors
aldosteronism and hypokalemia (applications)
slow onsent and offset
toxicities: hyperkalemia, gynecomastia
eplernone MOA
clinical applications
pharmacokinetics
toxicities
mineralocorticoid receptor anatgonist (specific)
HTN
cleared ny cypP450 metabolism
hyperkalamia and increased creatine
ketaconazole MOA
application
pharmacokinetics
toxcicities
blocks fungal and mammalian CYP450 enzymes
inhbitis steroid hormone synthesis and fungal ergosterol synthesis
oral/topical administration
hepatic dysfunction, CYP450 interactions
what is metyrapone
a medication used in the diagonsis of adrenal insufficiency and occasionally in the treatment of cushing disease
