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Additional Pharm Lecture > Corticosteroids > Flashcards

Corticosteroids Flashcards

1
Q

the secretion of adrenocortical steroids is controlled by the

A

pituitary release of corticotropin (ACTH)

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2
Q

in the pituitary, ACTH is synthesized as part of

A

pro-opiomelanocortin (POMC)

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3
Q

ACTH production is stimulated by

A

corticotropin-releasing hormone (CRH), synthesized in the hypothalamus

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4
Q

ACTH’s actions are mediated by

A

the melanocortin receptor 2 found in adrenal cortex

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5
Q

most endogenous cortisol is metabolized in the

A

liver

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6
Q

following metabolic conversion due to cortisol in the liver, steroids are excreted by the

A

kidneys
where 90% excreted in urine and can be measured as 17-OH

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7
Q

more than 90% of cortisol circulates bound to

A

corticosteroid-binding globulin

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8
Q

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?

A
  • 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
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9
Q

Physiologic effects - intermediate metabolism
glucocorticoids affect

A

carb, protein and fat metabolism
net result of glucocorticoid effects is to maintain an adequate glucose supply to the brain

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10
Q

Water and electrolyte balance
mineralocorticoids promotes the reabsorption of?

A

sodium in renal distal tubules
renal excretion of K+ and H+ is enhanced

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11
Q

Cardiovascular and blood cells
glucocorticoids potentiate vasocontrictor action of?
glucocorticoids casuse vasocontriction by?

A
  • adrenergic stimuli
  • suppressing mast cell degranulation
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12
Q

Cardiovascular and blood cells
glucocorticoids ___ plasma hemoglobin conc (erythrocytes and neutrophils) and ___ the total WBC count

A

increase; elevate

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13
Q

Cardiovascular and blood cells
glucocorticoids ___ the number of circulating eosinophils, basophils, monocytes, and lymphocytes

A

decrease

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14
Q

Immune system
glucocorticoids inhibit?
glucocorticoids suppress the release of?

A
  • prostaglandin and leukotriene production by inhibiting phospholipase A2
  • inflammatory cytokines and chemokines
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15
Q

CNS
corticosteroids ___ the blood brain barrier and can influence mood, sleep patterns

A

can cross

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16
Q

skeletal muscle
large amounts of glucocorticoids simulate

A

proteolysis, pain, and muscle weakness

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17
Q

Stress
glucocorticoid secretion in response to stressful stimuli is protective and

A

cortisol secretion increases with stress

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18
Q

Nonendocrine Use: inflammatory, allergic, and immunological disorders
chronic disease may require the

A

prolonged use of suppressive doses
but be careful bc of side effects

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19
Q

Allergic Disorders
inhaled steroids are first-line therapy for?
anaphylactic rxns, steroids are used as adjuncts
treatment?

A
  • asthma
  • prednisone, methylprednisone, triamcinolone, dexamethasone
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20
Q

Cerebal Edema
glucocorticoids most effective in?
treatment?

A

vasogenic type edema -> brain tumors
treatment may include prednisone

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21
Q

Bacterial meningitis
TNF-alpha and interleukin 1-beta play a role in?
Lipopolysaccharide (LPS) may trigger?
treatment?

A
  • meningeal inflammation
    -cytokine release
  • dexamethasone
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22
Q

Collagen disorders
high doses of glucocorticoids beneficial?
azathioprine or cyclophosphamide may slow progression of renal failure in?
agents of choice for?
treatment?

A
  • acute exacerbations
  • lupus nephritis
  • polymyositis and dermatomyositis
  • prednisone, methylprenisolone, triamcinolone, dexamethasone
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23
Q

Hematological disorders
glucocorticoids treat?
recommend as initial therapy for?
inhibit?
treatment?

A

-autoimmune hemolytic anemia (type II drug allergy)
- idiopathic thrombocytopenic purpura
-phagocytosis, increasing life span of platelet
- prednisone, dexamethasone

24
Q

Hepatic disease
glucocorticoids are initial therapy for?

A
  • subacute hepatic necrosis and autoimmune chronic hepatitis
    azathioprine allows for reduction of glucocorticoid dose
25
Q

Renal disease
methylprednisolone treats?

A
  • idiopathic nephrotic syndrome
26
Q

Respiratory disorders
glucocorticoids like prednisone are used to treat?
treatment for respiratory distress syndrome is neonates?

A
  • pulmonary sarcoidosis
  • betamethasone or dexamethasone
    enhances maturation of lungs
27
Q

Gastrointestinal rxns
decrease the protection provided by the?
gastric ulcers may be formed in patients with?
synergism with NSAIDs may lead to increase in?

A

-gastric mucus barrier
- rheumatoid arthritis
- GI events
may mask symptoms of peptic ulcers so hemorrhage may occur without pain

28
Q

Edema
cause fluid retention in patients with

A

-heart or kidney disease
restrict dietary Na

29
Q

Carb and lipid metabolism
treatment may result in?
can aggravate?
serum triglyceride are ___

A
  • hyperglycemia
  • diabetes
  • elevated
30
Q

Hypokalemia
- admin of high doses may cause hypokalemia and metabolic alkalosis
severe hypokalemia may cause?

A
  • asthenia, paralysis or arrhythmias
    restrict Na and eat more K
31
Q

Osteonecrosis
most commonly affects the?
osteonecrosis associated with?

A
  • femoral head
  • prolonged corticosteroid treatment and high doses of glucocorticoids
32
Q

growth suppression
long term glucocorticoid therapy

A

suppresses child growth

33
Q

Myopathy
glucocorticoid doses cause?
myopathy associated with?

A

protein catabolism, myopathy and loss of muscle mass
- triamcinolone

34
Q

Skin and soft tissues
common skin cancers when taking oral glucocorticoids?
other adverse effects of the skin?

A
  • non-melanoma skin cancers
  • acne, alopecia, striae
35
Q

Cushingoid features

A

truncal obesity, buffalo hump, moon face, weight gain

36
Q

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?

A
  • open-angle glaucoma
  • 2nd ocular infections by fungi or viruses
  • risk of corneal perforation
  • posterior subcapsular cataracts
37
Q

HPA suppression
exogenous admin will result in suppression of?

A
  • HPA axis thru negative feedback
    doses admin just before or at bedtime are more suppressive than those given earlier in day
38
Q

Pregnancy and lactation
large doses used during pregnancy may result in?

A
  • fetal adrenal hypoplasia and increase risk of cleft palate
    glucocorticoids are classified as FDA pregnancy category C
38
Q

Pregnancy and lactation
large doses used during pregnancy may result in?

A
  • fetal adrenal hypoplasia and increase risk of cleft palate
    glucocorticoids are classified as FDA pregnancy category C
39
Q

Physiologic and pharmacologic effects
aldosterone promotes reabsorption of Na from

A

distal part of distal convoluted tubule, from the cortical collecting renal tubules

40
Q

Drug selection
fludrocortisone and what it is used to treat?

A

potent steroid with both glucocorticoid and mineralcorticoid activity
- adrenocortical insufficiency

41
Q

Endocrine Disorders
Cushing’s Syndrome
cortisol excess due to?

A
  • tumor in pituitary gland releasing ACTH
  • ectopic tumor
  • benign adrenal adenomas
42
Q

Treatment of excessive cortisol

A
  • metyrapone
  • ketoconozale (antifungal)
  • ketoconazole
43
Q

Conn’s syndrome (hyperaldosteronism)
results from increased?
most cases caused by?
treatment?

A
  • plasma aldosterone which results in hypokalemia, metabolic alkalosis and hypertension
  • adrenal adenomas or bilateral zona glomerulosa hyperplasia
  • surgery, spironolactone
44
Q

Hypoadrenalism
results from?

A
  • inadequate secretion of ACTH or CRH
  • congential defects in steroidogenesis
45
Q

Primary adrenocotical insufficiency or ADDISONS disease

A

autoimmune disease characterized by antibodies against adrenal antigens

46
Q

Secondary adrenocortical insufficiency

A

caused by surgical ablation of pituitary, pituitary disease or pituitary suppression after longterm glucocorticoids

47
Q

Diagnosis for Hyposecretion of adrenocortical hormones

A

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

48
Q

Cosyntropin test
no rise in cortisol or 17OHCS result in
slow rise in cortisol and 17OHCS result in

A
  • addison’s due to adrenal failure
  • pituitary failure
49
Q

treatment for adrenocortical insufficiency

A
  • hydrocortisone and cortisone for initial treatment
  • fludrocortisone added when hydrocortisone reduced
  • prednisone and prednisolone potentially
50
Q

Hydrocortisone (activity, half life, uses)

A
  • potent mineralcorticoid activity
  • half life 80-118 min
  • adrenocortical insufficiency, anti-inflammatory, ulcerative colitis
51
Q

Prednisone (activity, half life, uses)

A
  • 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
52
Q

Triamcinolone (activity, half life, uses)

A
  • 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
53
Q

Dexamethasone (activity, half life, uses)

A
  • no mineralocorticoid activity
  • half life greater than 300 min
  • anti-inflammatory or immunosuppressant, conjuctivitis, ear issues
54
Q

Fludrocortisone acetate (activity, half life, adverse effects, uses)

A
  • mineralocorticoid activity
  • half life greater than 35 min
  • cardiovascular, CNS, derm, endocrine, GI, neuromuscular, ocular
  • treat addisons disease, adrenogential syndrome
55
Q

Spironolactone (activity, activity, pharmacodynamics, half life)

A
  • 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
56
Q

Cosyntropin

A
  • 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

Additional Pharm Lecture (2 decks)

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