Corticosteroids Flashcards
local cortical hormones in the blood leads to what two things?
stimulates the hypothalamus to secrete more CRH and stimulates the anterior pituitary to produce more ACTH
what does a stimulated anterior pituitary producing more ACTH lead to?
leads to more ACTH secretion which stimulates the adrenal cortex to release cortical hormones
what does releasing cortical hormones lead to? two downstream effects of this?
increase of cortical hormones in the blood which inhibits the hypothalamus (little CRH released) and the anterior pituitary is inhibited
with less ACTH being secreted what is inhibited and ultimately leads to what?
leads to inhibition of adrenal cortex and ultimately leads to low cortical hormones in the blood
3 layers of the adrenal cortex from outermost to innermost?
zona glomerulosa
zona fasiculata
zona reticularis
3 layers of the adrenal cortex (outer to inner) and their products?
glomerulosa: mineralcorticoids (aldosterone)
fasiculata: glucocorticoids (cortisol)
reticularis: sex steroids (DHEA, T, E, Pg)
glucocorticoids helps regulate what?
metabolism of proteins, CHO and lipids
promote gluconeogenesis in the liver which leads to increased blood sugar levels
precursor of all steroid hormones?
progesterone
where is cortisol synthesized from?
progesterone
what is the main hormone secreted by the adrenals?
cortisol
in what two circumstances is cortisol released?
in response to stress & when serum glucose levels drop
two ways cortisol increases blood sugar levels?
gluconeogenesis and glycogenolysis
name for cortisol when it is prescribed?
hydrocortisone
how does cortisol affect insulin?
counteracts insulin and leads to hyperglycemia and ultimately leads to insulin resistance
how do glucocorticoids affect the immune system and its cells specifically?
causes increase in # of circulating PMNs
decrease circulating lymphocytes, eosinophils, basophils, monocytes and MOs
how do glucocorticoids affect prostaglandins and leukotrienes?
decrease both and lead to lower levels of inflammation
b/c of glucocorticoids effects on WBCs what condition can they be useful in treating?
leukemia b/c help decrease the overall count
also increase Hgb and RBC counts
7 indications for glucocorticoid use?
inflammatory or allergic conditions reactive airway dz allergies arthritis AI conditions replacement tx for Addison's dz
glucocorticoid effects on immature bone cells? effects with high doses on mature bone cells?
immature: essential for differentiation
mature: increased apoptosis, decreased proliferation
glucocorticoid effects on immature cartilage cells? effects with high doses on mature cartilage cells?
immature: essential for differentiation
mature: reduced collage and proteoglycan synth, reduced proliferation
glucocorticoid effects on immature muscle cells? effects with high doses on mature muscle cells?
immature: early differentiation
mature: increased proteolysis, atrophy, decrease in GF expression
glucocorticoid effects on immature synovium/skin cells? effects with high doses on mature synovium/skin cells?
immature: not essential for differentiation
mature: decreased inflam signaling, reduced collagen synth, reduced proliferation
glucocorticoid effects on immature adipose cells? effects with high doses on mature adipose cells?
immature: differentiation
mature: increased lipoprotein lipase activity, hypertrophy
what can inhaled steroids be used to tx?
asthma but also for pts w/emphysema and chronic bronchitis
why are inhaled steroids preferred over oral for airway conditions?
b/c lowered SEs and enhanced effectiveness
when using topical steroids, with pts w/dry skin what is a better vehicle to use? with oily skin or seborreha?
dry skin: do better w/ointments or pastes
oily/seborrhea: creams, lotions or shake lotions
when are weaker topical steroids used?
whenever possible for use in thin-skinned and sensitive areas such as armpit, groin, perianal area and breast folds
when are moderate strength topical steroids used?
atopic dermatitis, nummular eczema, lichen sclerosis of the vulva, scabies and severe dermatitis
when are stronger strength topical steroids used?
psoriasis, lichen planus, discoid lupus, severely chapped feet, lichen simplex chronicus, severe poison ivy, alopecia areata, nummular eczema and severe atopic derm in adults
what is tachyphylaxis and how can you prevent it? how quickly can tachyphylaxis develop?
tachy: rapid decrease in response to a drug over a relatively short time period
can prevent by prescribing its use to one week on and one week off routine
can develop after a single initial dose! mech not understood…
with drugs affecting the NS, what is the mech behind tachyphylaxis?
felt to be depletion of neurotransmitter that is involved in the action of the drug
mech behind glucocorticoid tachyphylaxis?
not well understood but postulated that it is dt drug tolerance whereby the reduced responsiveness is dt cellular mechanisms
6 mechanisms of tolerance?
- change in receptors
- loss of receptors
- exhaustion of mediators
- increased metabolic degradation
- physiological adaptation
- active extrusion of drug from cells
rectal preparations of glucocorticoids can be used to tx what?
hemorrhoids, anal pruritis, proctitis, UC
active ingredient in preparation H?
phenylephrine! vasoconstrictor
concerns with prolonged use of higher concentration glucocorticoids?
allergic rxn
not proven to be safe in PG or breast feeding
may increase blood sugar in diabetics
may exacerbate glaucoma, myasthenia gravis, osteoporosis
may increase hypothyroidism or cirrhosis
may lead to increased gastric acid levels
may cause slower wound healing and increased infxns
may worsen acute psychosis
may cause wt gain, swelling, acne, sweating, increased hair
ocular glucocorticoids can be used how?
tx allergic conjunctivitis, corneal ulcers, corneal injuries, iritis, keratitis, optic neuritis, after ophthalmologic procedures such as keratoplasty
when are IV steroids used?
severe acute allergic response, moderate to severe cases of reactive airway dz, spinal cord trauma, shock, Addisonian crisis, bacterial meningitis, cerebral edema, septic shock, blood transfusion rxns, idiopathic or immune thrombocytopenia purpura
mechanism of anti-inflammation of glucocorticoid drugs?
inhibit phospholipase A2 which blocks the release of arachadonic acid which is the precursor of prostaglandins and blocks release of leukotrienes from membrane bound phospholipids
also suppress histamine and kinin activity
adverse effects of glucocorticoids?
reduced resistance to infxns hyperglycemia possibly DM severe bone loss avascular necrosis cataracts myopathy thinning of skin diminished wound healing easy bruising insomnia mental status changes increased appetite leading to wt gain from excess calories as well as salt and water retention
causes of avascular necrosis?
poor bone healing post-fracture, corticosteroid use, long term EtOH use and abuse, radiation therapy, sickle cell anemia
where are glucocorticoids absorbed? metabolized?
absorbed from the GI
metabolized by the liver’s microsomal oxidizing enzymes
short acting 8-12 hrs glucocorticoid? intermediate acting 18-36 hrs?
long acting 24-72 hrs?
short acting: hydrocortisone, cortisone
intermediate: prednisone, pednisolone, methylprednisoone, triamcinolone
long: paramethasone, dexamethasone, betamethasone
order of 4 most used glucocorticoid medications ranked from least potent to most?
hydrocortisone (1)
prednisone (4)
dexamethasone (30)
betamethasone (35)
what is an important rule to remember in regards to glucocorticoids and mineralcorticoids?
the stronger the glucocorticoid (corticosteroid) the weaker the mineralcorticoid effect
the reverse is also true
ex: prednisone, a lower potency corticosteroid, has a greater mineralcorticoid effect than beclomethasone which is a more potent corticosteroid and therefore has a lower mineralcorticoid effect
what can abrupt discontinuation of glucocorticoids cause?
acute adrenal insufficiency syndrome aka Addisonian crisis which can be lethal
how to manage an Addisonian crisis?
immediate IV of 100 mg hydrocortisone followed by 100-200 g hydrocortisone
fluid admin 1000 mL 0.9% NaCl during 1st 60 mins
further fluid admin guided by central venous P
monitor
ssxs of adrenal insufficiency aka Addison’s dz?
chronic, worsening fatigue muscle weakness loss of appetite wt loss hyperpigmentation N/V diarrhea low BP irritability and depression craving for salty foods dt salt loss hypoglycemia H/A sweating irregular or absent menstrual periods
Addisonian crisis sxs?
severe lethargy severe V/D often resulting in dehydration low BP confusion hyponatremia and hypoglycemia LOC convulsions if untreated it is fatal
class of hydrocortisone/cortef? preferred for treating what? MOA?
class: glucocorticoid/corticosteroid
preferred for: cortisol replacement therapy
MOA: affects gene transcription to either stimulate or repress protein production
how to administer hydrocortisone/cortef? chemically identical to what? DOA?
administer PO, IV, IM
chemically identical to naturally occurring cortisol
short DOA
class of prednisone/deltasone? preferred for treating what? MOA?
class: glucocorticoid/corticosteroid
preferred for treating moderate to severe allergic rxns, important drug for leukemia rxns
MOA: affects gene transcription to either stimulate or suppress protein production
how to rx prednisone/deltasone? DOA?
take PO
intermediate DOA
class of dexamethasone/decadron? useful to tx what? MOA?
class: fluroinated corticosteroid
extremely potent anti-inflammatory, also useful in IV form for reducing ICP
MOA: affects gene transcription to either stimulate or repress protein production
how to rx dexamethasone/decadron? DOA?
PO/IV/topical/inhaled
long DOA
minimal mineralcorticoid effects
class of triamcinolone inhaler/azmacort? indications? MOA? how to rx?
class: corticosteroid
indications: asthma, COPD, not indicated for tx acute asthma attack once it has already begun
MOA: diminishes inflammation of bronchial wall, affects gene transcription and alters protein production
take orally via inhaler
SEs of triamcinolone inhaler/azmacort?
thrust, sore throat, nosebleeds, increased coughing, H/A, runny nose
what is beclomethasone/qvar or vancenase? what can it be used for?
pro-drug of the corticosteroid beclometasone
can be used for prophylaxis asthma attack as an inhaler or to tx rhinitis, hay fever and sinusitis if used as a nasal spray
what is the outer most section of the adrenal cortex? what does it produce? what are it’s hormones responsible for?
glomerulosa –> produces mineralcorticoids such as aldosterone which are responsible for regulating intravascular volume and BP (cause retention of Na, bicarb and H2O and decrease reabsorption of K)
in what dz will you see decreased levels of aldosterone? in what dz will you see increased levels?
decreased in Addison’s dz
increased in Conn’s syndrome
class of fludrocoritone/florinef? indications? MOA?
class: halogenated glucocorticoid/mineralcorticoid agonist
indications: mineralcorticoid replacement for pts w/Addison’s dz and other cases of hyponatremia
MOA: Na retention, reduction of Na loss to urine at renal tubular cells
how to rx fludrocortisone/florinef? DOA? what is not an indication of it? SEs?
take PO, potent mineralcorticoid DOA: long minimal glucocorticoid effects no indicated as an anti-inflammatory SEs: Na retention, edema, HTN, rash, N/V
innermost layer of the adrenal cortex? what does it produce? examples?
zona reticularis
produces sex hormones such as DHEA, T, E, Pg
when can it be useful to supplement with DHEA?
osteoporosis, depression, SLE, pts undergoing skin grafting
when should DHEA use be decreased or discontinued?
when pts experience acne or hirsutism
when is DHEA supplementation c/i?
in pts w/PMHx of sex hormone responsive CAs such as breast, uterine, ovarian or prostate CA
risk vs benefits of supplementation w/DHEA should also be considered in women with (+) FHx of estrogen sensitive CAs and in men w/benign prostatic hypertrophy or a FHx of CaP
