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Pharmacology > Adrenocorticosteroids > Flashcards

Adrenocorticosteroids Flashcards

1
Q

Hydrocortisone

A

naturally occuring glucocorticoids

tightly regulated by CNS

inhibited by exogenous cortosil

MOA: gene transcription

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2
Q

effects of hydrocortisone

A

95% of hormonal activity is d/t cortisol

Gluconeogenesis

increase serum glucose levels leading to stimulation of insulin release and inhibiting uptake by muscle cells

lipolysis

protein catabolism

Net: maintains adequate glucose supply to brain

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3
Q

what is cortisols catabolic effect on bone?

A

osteoporosis

major limitation for long term use

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4
Q

what is cortisols catabolic effect in children?

A

growth retardation

major limitation for long term use

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5
Q

cortisol immunosuppressive effects

A

increased neutrophils

decreased lymphocytes, monocytes, eosinophils, basophils

vasoconstriction d/t suppresion of mast cell degranulation - decreased histamine release and cap permeability

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6
Q

cortisol immunosuppressive effects

A

vasoconstriction d/t suppresion of mast cell degranulation

decreased histamine release and cap permeability

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7
Q

cortisol anti-inflammatory effects

A
  • inhibition Phospholipase A2 blocking arachidonic acid release
  • decreased prostaglandins, prostacyclin, thromboxane
  • inhibits NF-KB → inhibits COX-2
  • induction of MAPK phosphatase I (inhibits activated proinflammatory signaling pathways)
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8
Q

other effects of cortisol

A
  • behavioural changes: insomnia, euphoria leading to depression
  • large doses: increased intracranial pressure
  • suppression of ACTH, GH, TSH, LH
  • Peptic ulcers: stimulation of H. Pylori, suppression of immune response to H. Pylori
  • increase platelets and RBCs
  • Impaired renal function
  • Development of fetal lungs
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9
Q

cortisol (hydrocortisone) PK

A
  • Relatively short duration of action
  • Diffuses poorly across skin (unless inflamed)
  • Diffuses well across mucous membranes
  • Some salt-retaining effects
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10
Q

Glucocorticoids

A
  • Prednisone
  • Hydrocortisone
  • Dexamethasone
  • Beclomethasone
  • Triamcinolone
  • Methylprednisolone
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11
Q

Mineralocorticoids

A
  • Aldosterone
  • Fludrocortisone
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12
Q

synthetic glucocorticoids

A
  • Rapidly and completely absorbed orally
  • Long t1/2’s
  • Reduced salt-retaining effects
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13
Q

glucocorticoid administration

A

all can be taken orally

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14
Q

IM glucocorticoid

A

triamcinolone

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15
Q

IM, IV glucocorticoid

A
  • Dexamethasone
  • Hydrocortisone
  • Methylprednisolone
  • Prednisolone
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16
Q

Aerosol glucocorticoid

A
  • Beclomethasone
  • Triamcinolone
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17
Q

topical glucocorticoid

A
  • Beclomethasone
  • Dexamethasone
  • Hydrocortisone
  • Triamcinolone
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18
Q

Mineralocorticoid MOA

A

Major effect of activation of the aldosterone receptor:

increased expression of Na+/K+ ATPase
increased expression of ENaC

19
Q

aldosterone

A

natural mineralocorticoid

major role: salt-retaining hormones

Na+ reabsorption from renal tubule

K+ H+ excretion

20
Q

Fludrocortisone

A

synthetic mineralocorticoid, MCly prescribed

21
Q

mineralocorticoid AEs

A
  • hypokalemia
  • metabolic alkalosis
  • increased plasma volume
  • HTN
22
Q

anti-inflammatory vs. salt-retaining effects

A
23
Q

treating Chronic adrenocorticol insufficiency

(Addison’s disease)

A
  • weakness, fatigue, weight loss, hypotension, hyperpigmentation, inability to maintain blood glucose levels during fasting
  • daily oral Hydrocortisone + Fludrocortisone
  • NO dexamethasone (lacks salt-retaining effects)
24
Q

treating acute adrenocorticol insufficiency

A
  • associated with life-threatening shock, infection or trauma
  • start corticosteroids immediately
  • for patients with previous dx:
    • Large amounts of parenteral corticosteroids + correction of fluid & electrolyte abnormalities
    • give salt-retaining hormone once hydrocortisone levels are reduced (~ 5 days)
25
Q

treating undiagnosed acute attack adrenocorticol insufficiency

A

dexamethasone to avoid interference with testing of cortisol levels

fluid and electrolyte replacement

26
Q

treating congenital adrenal hyperplasia

A
  • Glucocorticoid to suppress ACTH
  • Treat initially as an acute adrenal crisis
  • Once stabilized: oral hydrocortisone or prednisone + fludrocortisone
  • fetus protected in high risk pregnancy w/ dexamethasone admin. to mother
27
Q

Cushing’s Syndrome

A
  • resection of 1 or both adrenals
  • must receive high doses of cortisol before and after surgery
  • Dose has to be slowly decreased to prevent withdrawal
  • cushing disease: irradiation of pituitary tumor
28
Q

aldosteronism

A
  • Primary aldosteronism: renal loss of K+ (hypokalemia, alkalosis & elevation of serum Na+)
  • Treat w/ spironolactone
29
Q

stimulation of lung maturation of fetus

A
  • Fetal lung maturation regulated by cortisol secretion
  • premature delivery is expected?
    • give mom large doses of glucocorticoids reduces incidence of respiratory distress syndrome
  • IM steroids - dexamethasone
30
Q

other clinical uses for synthetic corticosteroids

A
  • Numerous immunological inflammatory conditions: asthma, collagen vascular disorders (Rheumatoid arthritis), ocular diseases (uveitis, optic neuritis, exopthalmos),
  • Allergic reactions (contact dermatitis, urticaria etc)
  • Hodgkin’s lymphoma - prednisone
  • Cerebal Edema - dexamethasone
  • Chemotherapy-induced vomiting
  • Hematologic disorders (anemia, leukemia etc)
  • Organ transplants (prevention of rejection)
  • Renal disorders (nephrotic syndrome)
  • Hypercalcemia
  • Mountain Sickness
  • Inflammatory bowel disease etc.
  • Idiopathic orthostatic hypotension (fludrocortisone)
31
Q

AE of synthetic corticosteroids

A
  • Metabolic effects - Cushing’s syndrome manifestationseg, diabetes, muscle-wasting, osteoporosis
  • Peptic ulcers
  • Clinical findings of certain disorders (particularly bacterial & mycotic infections) may be masked by steroid use
  • Myopathy (part. with long-acting steroids)
  • Nausea, dizziness, weight loss
  • CNS (euphoria, psychosis, depression)
  • Increased intraocular pressure (glaucoma)
  • Posterior subcapsular cataracts
  • Sodium & fluid retention, loss of potassium
  • Growth retardation (children)
  • Adrenal suppression
32
Q

how to minimize toxicities

A
  • Local application (eg, as an aerosol in asthma)
  • low a dose as possible
  • Taper dose soon after achieving goal
  • Alternate-day therapy
  • Administer patients with adrenal insufficiency additional ‘stress dose’ during serious illness or priorto surgery
  • Prevent K+ loss with supplementation
  • Prevent effects on bone by Ca2+ & vitamin D supplements
33
Q

corticosteroids should be used in caution in patients with

A
  • Peptic ulcers
  • Heart disease or HTN with heart failure
  • TB, varicella zoster infections
  • Psychoses
  • Diabetes
  • Osteoporosis
  • Glaucoma
34
Q

___ of glucocortiocoids can be a serious problem (acute adrenal insufficiency syndrome can result)

Dose must be tapered according to individual, Monitor closely

A

Abrupt withdrawal of glucocortiocoids can be a serious problem (acute adrenal insufficiency syndrome can result)

Dose must be tapered according to individual, Monitor closely

35
Q

mifepristone

A

glucocortisol antagonist

36
Q

Spironolactone /use

A
  • mineralocorticoid antagonist
  • competes with aldosterone for its receptor (decreasing its effect peripherally)
  • USE:
    • Aldosteronism (diagnosis & treatment)
    • Hirsutism in women (acts as androgen antagonist)
    • Diuretic
37
Q

Spironolactone AE

A
  • Hyperkalemia
  • cardiac arrhythmia
  • menstrual abnormalities
  • gynecomastia
  • sedation
  • headache
  • GI disturbances
  • skin rashes
38
Q

Mifepristone

A

Antagonist at glucocorticoid & progesterone receptors

Clinical Application: Inoperable patients with ectopic ACTH syndrome or adrenal carcinoma

39
Q

synthesis inhibitors

A

Ketoconazole

Aminoglutethimide

Metyrapone

40
Q

Aminoglutethimide

A
  • corticosteroid synthesis inhibitor
  • Blocks conversion of cholesterol to prenenolone→reduces synthesis of all hormonally active steroids
  • use: adrenal cancer (+ hydrocortisone or dexamethasone)
41
Q

Ketoconazole

A

Potent & non-selective inhibitor of adrenal & gonadal steroid synthesis

Clinical Applications:
Cushings syndrome, Prostate cancer

42
Q

Metyrapone

A

Relatively selective inhibitor of steroid 11- hydroxylation (blocks cortisol synthesis)

Clinical Applications:
Tests of adrenal function
Treatment of pregnant women with Cushing’s

43
Q

Metyrapone AE

A
  • Salt & water retention
  • Hirsutism
  • Transient dizziness
  • GI disturbances

Pharmacology (19 decks)

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