Rose: Adrenal Pharmacology Flashcards

(42 cards)

1
Q

What is an ACTH stimulation test? What does it tell you?

A

Compares blood cortisol levels before and after 250 micrograms of tetracosactide (synthetic ACTH) (IV) is given.

If cortisol exceeds normal levels (↑ by at least 2x) by 1 hour, then primary adrenal gland fxn = normal

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2
Q

When do you do a long ACTH Stimulation test?

A

if short test reveals that cortisol is abnormal

used to differentiate between primary and secondary adrenal insufficiency

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3
Q

How do you do a long ACTH stimulation test? What does it tell you?

A

1 mg tetracosactide (IV/IM) multiple administrations → blood taken 1, 4, 5, and 24 hrs later

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4
Q

How does a LONG ACTH stimulation test allow you to differentiate between primary and secondary adrenal insufficiency?

A

o In 1- Addison’s Dz → cortisol level is ↓ at all time points

o In 2- corticoadrenal insufficiency (adrenal gland is small but still responsive) → delayed but normal response of ↑ cortisol is seen

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5
Q

What are the 5 steps to establish hypercortisolism and determine the origin of Cushing syndrome?

A
  1. 24 hr urine sample measurement of FREE cortisol
  2. Late night salivary cortisol (>2 tests)
  3. Special populations (prego and epilepsy)
  4. Once hypercorisolism is established a baseline plasma ACTH is obtained
  5. Dexamethosone challenge test
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6
Q

High levels of cortisol in a 24 hr urine sample indicate….

A

Hypercorisolism (overwhelms metabolism conversion to inactive cortisone)

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7
Q

Late night salivary cortisol tests that show a LOSS of circadian rhythm and ABSENCE of late night nadir are indicative of…

A

CUshings syndrome

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8
Q

What should you not use to test a pregnant women that you suspect may have hypercortisolism?

A

Urine sample–urine tends to be FREE of cortisol

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9
Q

What test should not be used in epileptics in that you suspect have hypercortisolism?

A

dex text (antiepileptic drugs ENHANCE dex clearance)

Use urine or salivary cortisol

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10
Q

Once hypercortisolism is established a baseline ACTH is obtained. What is hte difference between a high and low level?

A

LOW ACTH> ACTH indep disease

HIGH ACTH> ACTH dep disease

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11
Q

What is the gold standard screening test for hypercortisolism?

A

A. Low Dose Dex Test: 1 mg dexamethasone test overnight or 48 h 2 mg/d dexamethasone test

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12
Q

How do you interpret a low dose dex test?

A

o If blood levels of cortisol are lower than normal (post-test) → Cushing Syndrome can be ruled out

o If blood levels of cortisol are NOT lower than normal (post-test) → fail test

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13
Q

How does estrogen affect dex drug clearance?

A

Estrogen ↑ the cortisol-binding globulin (CBG)
→ result in false positive rates with dex test

(estrogen containing drugs like OCPs should be stopped 6 weeks before test)

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14
Q

How do antiepileptics affect dex drug clearance?

A

(phenytoin, carbamazepine, and EtOH)

→ induce hepatic enzymatic clearance of dexamethasone

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15
Q

How does liver disease affect dex drug clearance?

A

DECREASES clearance of dex

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16
Q

What test is used to distinguish Cushing pituitary ACTH secreting tumor from ectopic cells?

A

High Dose Dex Text

pituitary ACTH secreting tumor will show ↓ to dexamethasone in cortisol

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17
Q

What will Cushing syndrome caused by an adrenal tumor show on a dex test?

A
  • Low dose test: no change
  • ACTH level: low

In most cases, the high dose test is not needed

18
Q

What will Dex tests show in a pt with Cushing Syndrome related to ectopic ACTH producing tumor?

A

Low dose test: no change

ACTH level: high

High-dose test: no change

19
Q

What will dex tests show in a pt with CS cuased by a pituitary tumor (Cushing disease)?

A

Low dose test: no change

High dose test: normal suppression (if there is no suppression → another test is needed)

20
Q

How do glucocorticoids affect the CVS?

A
  • Positive inotropic effect (↑ strength of muscular contraction)
  • Na+/H2O retention → ↑ BP
  • Maintains the sensitivity of small vessels to catecholamines → retains tone and BP
21
Q

How do glucocorticoids affect the CNS?

A
  • ↓ seizure threshold

* Behavioral Δs: mood depression/elevation (common), euphoria and restlessness (some), anxiety and psychosis (possible)

22
Q

How do glucocorticoids affect the GI System?

A
  • ↑ gastric acid and pepsin
  • may suppress the local immune response against H. pylori → ulcer formation
  • ↓ Ca++ absorption from the gut
23
Q

How do glucocorticoids affect bone metabolism?

A
  • direct inhibition of osteoblasts
  • 2o stimulation of parathyroid hormone → stimulates osteoclasts
  • Net absorption of bone matrix
24
Q

How do glucocorticoids cause skeletal muscle wekaness and fatigue?

A
  • Hypokalemia
  • Muscle wasting – loss of protein
  • May result in a greater disability than the original inflammation
25
What are the hematologic effects of glucocorticoids?
* Lymphocyte levels ↓ → ↑ susceptibility to infection * Eosinophil and basophil levels ↓ * Neutrophil and erythrocyte levels ↑ * Inhibits leukocyte extravsation
26
Why are glucocorticoids often used to treat non-adrenal disorders?
o ↓ in AA metabolites o ↓ in peripheral LEUKOCYTE and tissue MPHAGE concentration → ↓ immune factor production of interleukins, TNF, and platelet activating factor o ↓ EDEMA o lysosomal membranes stabilized → proteases not released → less FIBROSIS o ↓ in release of VASOACTIVE FACTORS that promote vasodilation and shock o maximal effect is 6 hr after treatment and completely cleared by 24 h
27
What is the role of glucocorticoids in organ transplants?
inflammation occurs at boundary of donated tissue> glucocorticoids acts as an immunosuppressant> decreases action of IMMUNE FACTORS> INHIBITS Ag release from grafted donor tissue Downside is that it increases suscpetibility to infection
28
Why do glucocorticoids have anti-allergic effects?
Inhibit synthesis of histamine by mast cells → limits duration of an allergic attack There is NO effect at the histamine receptor or with the action of released histamine
29
Why are synthetic glucocorticoids better than natural?
↑ glucocorticoid POTENCY (ratio of glucocorticoid to mineralocorticoid effect) synthetics are LESS protein bound SLOWER metabolism
30
Synthetic glucocorticoids often have many biochemical substitutions. What side chains are added on to enhance potency?
* C1-C2 double bond * Methyl or fluoride at C6 or fluoride at C9 * Hydroxyl group rather than a keto group at C11 * Alpha-methyl or beta-hydroxy at C16
31
What converts inactive prednisone to prednisolone?
Liver 11b-hydroxydehydrogenases **if liver fxn is BAD avoid giving inactive form
32
What is iatrogenic cushing syndrome?
effects of long-term, high-dose glucocorticoid therapy (>2 wks)
33
What are SE of glucocorticoid treatments?
* Hyperglycemia, glucosuria (insulin) * Infection * Peptic ulcer (Tx or DC) * Myopathy (DC) * Osteoporosis * Behavioral disturbances * Cataracts (↑ risk for kids) * Mineralcorticoid effect (Na+/H2O retention and K+ loss)
34
How must ACTH analogs be given? What is their t1/2? What must they be hydrolyzed by to be active?
injected 10-15 mins blood and tissue enzymes
35
What are ACTH analgos used for?
• Distinguishes 1o and 2o adrenal insufficiency • Anticonvulsant for infantile spasms • Prevent neurotoxicity with cisplatin o Prevention of adrenal atrophy during chronic glucocorticoid therapy – not useful • Toxicity related to increase glucocorticoids
36
What are ACTH analogs NOT used for?
Not used to increase adrenocorticoid levels for therapeutic benefits o Replacement – not realistic o Prevention of adrenal atrophy during chronic glucocorticoid therapy – not useful
37
What is the treatment for Cushing Syndrome?
1) Surgery w/ support of glucocorticoids until recovery of ACTH function 2) Irradiation for those that are poor surgical candidates 3) Medical treatment for those who fail surgical treatment or are ineligible
38
What does ketoconazole do? SE?
inhibits side chain cleavage and other CYP enzymes → blocks glucocorticoid and androgen synthesis (SE: hepatotoxicity)
39
What does metyrapone do?
inhibits 11b-hydroxylase in the adrenal gland with the goal of interfering with cortisol production
40
What meds are used to suppress ACTH from pituitary adenomas?
SST analog: pasireotide D2 analog: cabergoline
41
When is Mifepristone used?
Pts w/ inoperable disease
42
What is mifepristone?
Glucocorticoid receptor antagonist synthetic steroid w/ a high affinity for progesterone receptors but at higher doses binds strongly to glucocorticoid receptors