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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

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
treating undiagnosed acute attack adrenocorticol insufficiency
**dexamethasone to avoid interference with testing of cortisol levels** fluid and electrolyte replacement
26
treating congenital adrenal hyperplasia
* **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
Cushing’s Syndrome
* **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
aldosteronism
* **Primary aldosteronism**: renal loss of K+ (hypokalemia, alkalosis & elevation of serum Na+) * Treat w/ **spironolactone**
29
stimulation of lung maturation of fetus
* Fetal lung maturation regulated by cortisol secretion * premature delivery is expected? * **give mom large doses of glucocorticoids** reduces incidence of r**espiratory distress syndrome** * IM steroids - **dexamethasone**
30
other clinical uses for synthetic corticosteroids
* **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
AE of synthetic corticosteroids
* **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
how to minimize toxicities
* 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
corticosteroids should be used in caution in patients with
* **Peptic ulcers** * Heart disease or HTN with heart failure * TB, varicella zoster infections * Psychoses * **Diabetes** * **Osteoporosis** * **Glaucoma**
34
\_\_\_ of glucocortiocoids can be a serious problem (acute adrenal insufficiency syndrome can result) ## Footnote **Dose must be tapered according to individual, Monitor closely**
**Abrupt withdrawal** of glucocortiocoids can be a serious problem (acute adrenal insufficiency syndrome can result) ## Footnote **Dose must be tapered according to individual, Monitor closely**
35
mifepristone
glucocortisol antagonist
36
Spironolactone /use
* 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
Spironolactone AE
* Hyperkalemia * cardiac arrhythmia * menstrual abnormalities * gynecomastia * sedation * headache * GI disturbances * skin rashes
38
Mifepristone
Antagonist at glucocorticoid & progesterone receptors Clinical Application: **Inoperable patients with ectopic ACTH syndrome or adrenal carcinoma**
39
synthesis inhibitors
Ketoconazole Aminoglutethimide Metyrapone
40
Aminoglutethimide
* corticosteroid synthesis inhibitor * Blocks conversion of cholesterol to prenenolone→reduces synthesis of all hormonally active steroids * use: **adrenal cancer** (+ hydrocortisone or dexamethasone)
41
Ketoconazole
Potent & non-selective inhibitor of adrenal & gonadal steroid synthesis Clinical Applications: **Cushings syndrome, Prostate cancer**
42
Metyrapone
Relatively selective inhibitor of steroid 11- hydroxylation **(blocks cortisol synthesis)** Clinical Applications: **Tests of adrenal function Treatment of pregnant women with Cushing’s**
43
Metyrapone AE
* **Salt & water retention** * **Hirsutism** * **Transient dizziness** * **GI disturbances**

Pharmacology (19 decks)

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