Corticosteroids Flashcards
the secretion of adrenocortical steroids is controlled by the
pituitary release of corticotropin (ACTH)
in the pituitary, ACTH is synthesized as part of
pro-opiomelanocortin (POMC)
ACTH production is stimulated by
corticotropin-releasing hormone (CRH), synthesized in the hypothalamus
ACTH’s actions are mediated by
the melanocortin receptor 2 found in adrenal cortex
most endogenous cortisol is metabolized in the
liver
following metabolic conversion due to cortisol in the liver, steroids are excreted by the
kidneys
where 90% excreted in urine and can be measured as 17-OH
more than 90% of cortisol circulates bound to
corticosteroid-binding globulin
Molecular MOA of adrenocortical hormones
MOA is mediated by?
ligand-bound receptor complex is transported into nucleus, where it interacts with?
besides GREs, the complex influences function of other transcription factors which regulate?
- glucocorticoid receptors or mineralocorticoid receptors
side note: two genes for the corticoid receptor - glucocorticoid receptor elements in promoters of responsive genes
- growth factors, cytokines, mediate anti-growth, anti-inflammatory, immunosuppressive
Physiologic effects - intermediate metabolism
glucocorticoids affect
carb, protein and fat metabolism
net result of glucocorticoid effects is to maintain an adequate glucose supply to the brain
Water and electrolyte balance
mineralocorticoids promotes the reabsorption of?
sodium in renal distal tubules
renal excretion of K+ and H+ is enhanced
Cardiovascular and blood cells
glucocorticoids potentiate vasocontrictor action of?
glucocorticoids casuse vasocontriction by?
- adrenergic stimuli
- suppressing mast cell degranulation
Cardiovascular and blood cells
glucocorticoids ___ plasma hemoglobin conc (erythrocytes and neutrophils) and ___ the total WBC count
increase; elevate
Cardiovascular and blood cells
glucocorticoids ___ the number of circulating eosinophils, basophils, monocytes, and lymphocytes
decrease
Immune system
glucocorticoids inhibit?
glucocorticoids suppress the release of?
- prostaglandin and leukotriene production by inhibiting phospholipase A2
- inflammatory cytokines and chemokines
CNS
corticosteroids ___ the blood brain barrier and can influence mood, sleep patterns
can cross
skeletal muscle
large amounts of glucocorticoids simulate
proteolysis, pain, and muscle weakness
Stress
glucocorticoid secretion in response to stressful stimuli is protective and
cortisol secretion increases with stress
Nonendocrine Use: inflammatory, allergic, and immunological disorders
chronic disease may require the
prolonged use of suppressive doses
but be careful bc of side effects
Allergic Disorders
inhaled steroids are first-line therapy for?
anaphylactic rxns, steroids are used as adjuncts
treatment?
- asthma
- prednisone, methylprednisone, triamcinolone, dexamethasone
Cerebal Edema
glucocorticoids most effective in?
treatment?
vasogenic type edema -> brain tumors
treatment may include prednisone
Bacterial meningitis
TNF-alpha and interleukin 1-beta play a role in?
Lipopolysaccharide (LPS) may trigger?
treatment?
- meningeal inflammation
-cytokine release - dexamethasone
Collagen disorders
high doses of glucocorticoids beneficial?
azathioprine or cyclophosphamide may slow progression of renal failure in?
agents of choice for?
treatment?
- acute exacerbations
- lupus nephritis
- polymyositis and dermatomyositis
- prednisone, methylprenisolone, triamcinolone, dexamethasone
Hematological disorders
glucocorticoids treat?
recommend as initial therapy for?
inhibit?
treatment?
-autoimmune hemolytic anemia (type II drug allergy)
- idiopathic thrombocytopenic purpura
-phagocytosis, increasing life span of platelet
- prednisone, dexamethasone
Hepatic disease
glucocorticoids are initial therapy for?
- subacute hepatic necrosis and autoimmune chronic hepatitis
azathioprine allows for reduction of glucocorticoid dose
Renal disease
methylprednisolone treats?
- idiopathic nephrotic syndrome
Respiratory disorders
glucocorticoids like prednisone are used to treat?
treatment for respiratory distress syndrome is neonates?
- pulmonary sarcoidosis
- betamethasone or dexamethasone
enhances maturation of lungs
Gastrointestinal rxns
decrease the protection provided by the?
gastric ulcers may be formed in patients with?
synergism with NSAIDs may lead to increase in?
-gastric mucus barrier
- rheumatoid arthritis
- GI events
may mask symptoms of peptic ulcers so hemorrhage may occur without pain
Edema
cause fluid retention in patients with
-heart or kidney disease
restrict dietary Na
Carb and lipid metabolism
treatment may result in?
can aggravate?
serum triglyceride are ___
- hyperglycemia
- diabetes
- elevated
Hypokalemia
- admin of high doses may cause hypokalemia and metabolic alkalosis
severe hypokalemia may cause?
- asthenia, paralysis or arrhythmias
restrict Na and eat more K
Osteonecrosis
most commonly affects the?
osteonecrosis associated with?
- femoral head
- prolonged corticosteroid treatment and high doses of glucocorticoids
growth suppression
long term glucocorticoid therapy
suppresses child growth
Myopathy
glucocorticoid doses cause?
myopathy associated with?
protein catabolism, myopathy and loss of muscle mass
- triamcinolone
Skin and soft tissues
common skin cancers when taking oral glucocorticoids?
other adverse effects of the skin?
- non-melanoma skin cancers
- acne, alopecia, striae
Cushingoid features
truncal obesity, buffalo hump, moon face, weight gain
Ocular effects
- may elevate intraocular pressure causing?
- may enhance development of
- dont use in patients with ocular herpes bc of?
- prolonged use may lead to?
- open-angle glaucoma
- 2nd ocular infections by fungi or viruses
- risk of corneal perforation
- posterior subcapsular cataracts
HPA suppression
exogenous admin will result in suppression of?
- HPA axis thru negative feedback
doses admin just before or at bedtime are more suppressive than those given earlier in day
Pregnancy and lactation
large doses used during pregnancy may result in?
- fetal adrenal hypoplasia and increase risk of cleft palate
glucocorticoids are classified as FDA pregnancy category C
Pregnancy and lactation
large doses used during pregnancy may result in?
- fetal adrenal hypoplasia and increase risk of cleft palate
glucocorticoids are classified as FDA pregnancy category C
Physiologic and pharmacologic effects
aldosterone promotes reabsorption of Na from
distal part of distal convoluted tubule, from the cortical collecting renal tubules
Drug selection
fludrocortisone and what it is used to treat?
potent steroid with both glucocorticoid and mineralcorticoid activity
- adrenocortical insufficiency
Endocrine Disorders
Cushing’s Syndrome
cortisol excess due to?
- tumor in pituitary gland releasing ACTH
- ectopic tumor
- benign adrenal adenomas
Treatment of excessive cortisol
- metyrapone
- ketoconozale (antifungal)
- ketoconazole
Conn’s syndrome (hyperaldosteronism)
results from increased?
most cases caused by?
treatment?
- plasma aldosterone which results in hypokalemia, metabolic alkalosis and hypertension
- adrenal adenomas or bilateral zona glomerulosa hyperplasia
- surgery, spironolactone
Hypoadrenalism
results from?
- inadequate secretion of ACTH or CRH
- congential defects in steroidogenesis
Primary adrenocotical insufficiency or ADDISONS disease
autoimmune disease characterized by antibodies against adrenal antigens
Secondary adrenocortical insufficiency
caused by surgical ablation of pituitary, pituitary disease or pituitary suppression after longterm glucocorticoids
Diagnosis for Hyposecretion of adrenocortical hormones
synthetic ACTH used to test adrenal function
in normal individuals, after single iv injection, there is a peak of plasma cortisol and aldosterone 30-60 min later
subnormal response confirms diagnosis of adrenal insufficiency
Cosyntropin test
no rise in cortisol or 17OHCS result in
slow rise in cortisol and 17OHCS result in
- addison’s due to adrenal failure
- pituitary failure
treatment for adrenocortical insufficiency
- hydrocortisone and cortisone for initial treatment
- fludrocortisone added when hydrocortisone reduced
- prednisone and prednisolone potentially
Hydrocortisone (activity, half life, uses)
- potent mineralcorticoid activity
- half life 80-118 min
- adrenocortical insufficiency, anti-inflammatory, ulcerative colitis
Prednisone (activity, half life, uses)
- mineralocorticoid activity
- half life 60 min
- allergic states, autoimmune disorders, dermatologic conditions, edematous states, endocrine disorders, gastrointestinal diseases, hematologic disorders, multiple sclerosis, neoplastic diseases, ophthalmic diseases, respiratory diseases, rheumatic disorders, TB meningitis
Triamcinolone (activity, half life, uses)
- no mineralocorticoid activity
- half life greater than 200 min
- intralesional, nasal inhalation, ocular inflammatory, bronchial asthma, oral lesions and ulcerative lesions, adrenocortical insufficiency, derm issues, endocrine disorders, gastro issues, hemtolotic, neoplastic, nephrotic, allergic, respiratory, lupus erythematosus
Dexamethasone (activity, half life, uses)
- no mineralocorticoid activity
- half life greater than 300 min
- anti-inflammatory or immunosuppressant, conjuctivitis, ear issues
Fludrocortisone acetate (activity, half life, adverse effects, uses)
- mineralocorticoid activity
- half life greater than 35 min
- cardiovascular, CNS, derm, endocrine, GI, neuromuscular, ocular
- treat addisons disease, adrenogential syndrome
Spironolactone (activity, activity, pharmacodynamics, half life)
- renal competitive aldosterone antagonist
- increasing sodium chloride and water excretion while conserving potassium
- mineralocorticoid activity
- half life greater than 10 min
BLACK BOX WARNING: show tumors in chronic toxicity studies in rats
Cosyntropin
- synthetic derivative of ACTH
- stimualtes adrenal cortex to secrete glucocorticoids, androgenic substances, and aldosterone
- used in diagnostic test to differentiate primary adrenal from secondary adrenocortical insufficiency
