Burkin: Adrenal Pharmacology Flashcards Preview

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Flashcards in Burkin: Adrenal Pharmacology Deck (84):
1

Describe the feedback regulation of the anterior pituitary hormones

Hormone regulation can be ultra-short-loop, short-loop, or long-loop.
Ultra-short loop regulation occurs when hypothalamic hormones regulate the release of hormones from the hypothalamus itself.
Short-loop regulation occurs when pituitary hormones regulate the release of hormones from the hypothalamus. Long-term regulation occurs when hormones released from the target tissue feed back on the hypothalamus.

2

6 hormones released from the hypothalamus, and their effects on the pituitary

corticotropin-releasing hormone --> increases ACTH
thyroptropin-releasing hormone --> increases TSH & prolactin
gonadotropin-releasing hormone --> increases LH/FSH
growth hormone-releasing hormone --> increases GH
somatostatin --> decreases GH
dopamine --> decreases prolactin

3

Describe the pattern of release of growth hormone from the anterior pituitary

low pulsatile pattern throughout the day, large increase in GH at night

4

What does growth hormone do to the following?

insulin sensitivity
lipolysis
IGF-1
protein synthesis
epiphyseal (bone) growth

decreases insulin sensitivity
increases lipolysis
increased IGF-1
increased protein synthesis
increased epiphyseal bone growth

5

What things stimulate growth hormone synthesis?

GHRH
hypoglycemia
exercise
certain amino acids
sleep

6

What things inhibit growth hormone synthesis?

somatostatin
IGF-1 via negative feedback
hyperglycemia

7

What happens when you have excess growth hormone?

gigantism (if early in life)
acromegaly (excess soft tissue hyperplasia after body growth has stopped)

8

How do you treat excess growth hormone?

remove tumor
give somatostain analog like octreotide

9

Things that can lead to primary GH deficiency?

hypothalamic (GHRH) or pituitary lesions

**can cause dwarfism (if occurs early in life) or adult hypopituitarism (weakness, pale skin, no sex drive, genital atrophy, menstrual cycle cessation)

10

What are some reasons for retarded growth when GH levels are normal?

GH receptor defect
IGF-1 deficiency (African pygmies)

11

(blank) is a recombinant form of human GH and is used to treat patients with GH deficiency.

somatrophin

12

What conditions is growth hormone used to treat?

Turners syndrome --> increases final adult height
Children with FTT due to chronic renal failure or HIV infection
Adults with AIDS-associated wasting

**recombinant bovine GH can be used to increase milk production in dairy cows

13

Discuss the feedback of growth hormone secretion

GHRH causes release of GH from the pituitary - increases body growth, lipolysis, and decreases glucose uptake, also acts on liver to produce IGF-1

Somatostatin decreases GH secretion from pituitary

14

What cells produce prolactin?

lactotropes & somatomammotropes of the anterior pituitary

15

What are the actions of prolactin?

milk production
increased maternal behavior
antagonizes gonadotropin action in the gonads --> decreased steroidogenesis

16

How are prolactin levels controlled?

inhibited by hypothalamic dopamine
stimulated by oxytocin, TRH, VIP & estrogen

17

What are some causes of excess prolactin? How can you treat this?

microadenoma of lactotropes
dopamine receptor blockers (antipsychotics)
stress
vigorous exercise

treat with dopamine agonist (Bromocryptine)

18

What does increased prolactin cause in males? In females?

in males: inferility
in women: amenorrhea, galactorrhea, infertility

19

Stimulates release of milk during lactation and contributes to the initiation of uterine contraction during labor; used intravenously to induce or reinforce labor and as a nasal spray to induce postpartum lactation

oxytocin

20

Secreted in response to rising plasma tonicity or falling blood pressure. Deficiency causes diabetes insipidus.

vasopressin (ADH)

21

(blank) is used to treat diabetes insipidus. Bedtime administration is also used to treat nocturnal enuresis.

desmopressin acetate (ADH analog)

22

Partial or complete loss of adrenocortical function

Addison's disease

23

Suppression in the ability of the adrenal cortex to produce corticosteroids

Adrenal suppression

24

A metabolic disorder caused by excess secretion of adrenocorticoid steroids

Cushing's disease

25

POMC is cleaved to form which endocrine peptides?

ACTH
melanocyte stimulating hormone (MSH)
beta-endorphin

26

Three layers of the adrenal cortex & what do they produce?

Zona glomerulosa --> aldosterone
Zona fasciculata --> cortisol
Zona reticularis --> androgens

27

The adrenal medulla is made up of chromaffin cells & produces (blank)

catecholamines

28

Which zone of the adrenal cortex is ACTH independent and is sensitive to Ang II? Which zones are ACTH dependent?

glomerulosa is ACTH independent
reticularis/fasciculata are ACTH dependent

29

How does ACTH increase the production of steroid hormones in the zona fasciculata? What is the rate limiting step in this process?

ACTH binds to Gs --> increases cAMP --> activates a protein kinase --> cholesterol is then delivered to the mitochrondrial matrix via the StAR protein --> increased synthesis of steroid hormones (takes hours)

**rate limiting step is the delivery of cholesterol to the mito via StAR

30

Describe the mineralocorticoid pathway from cholesterol to aldosterone

cholesterol --> pregnenolone (via ACTH)--> progesterone --> 11-deoxycorticosterone --> corticosterone --> 18-hydroxycorticosterone (via AngII) --> aldosterone

31

(blank) has a large affect on the production of aldosterone

Ang II

32

What enzyme catalyzes the transformation of cortciosterone to 18-hydroxycorticosterone (which is converted to aldosterone)?

Ang II

33

How much cortisol is released daily?

10mg

34

When is cortisol secreted?

first thing in the morning (high levels)

**corresponds to light-dark cycles

35

Cortisol circulates bound to (blank) and (blank)

transcortin (cortisol binding globulin); albumin

36

Parenterally administered form of ACTH, with a T1/2 of 15 minutes

Cosyntropin
Acthar

37

Used as a diagnostic agent in adrenal insufficiency
normal rise in cortisol rules out adrenal failure

Cosyntropin (ACTH synthetic peptide)

38

Cortisol is a permissive hormone. What does this mean?

low levels of catecholamine have little effect on lipolysis, but in the presence of cortisol, there is marked activation of lipolysis

39

(blank) is the major form of glucocorticoid; it is bound to (blank) in the circulation

cortisol; transcortin

40

Cortisol is essential to life. What does cortisol do in regards to metabolism of carbohydrates, proteins & lipids?

stimulates protein breakdown to amino acids (especially muscles)
facilitates lipid breakdown in adipose tissue to fatty acids & glycerol
promotes hepatic gluconeogenesis from amino acids, glycerol, & fatty acids
makes glucose available to the brain by inhibition utilization by other tissues

41

This is a major form of adrenal androgens
A weak androgen that is not important in males, but is an important source of androgen in females

DHEA

42

What does DHEA do in females?

enhances pubertal growth spurt
maintains secondary sex characteristics - pubic & axillary hair
libido

**there is some conversion of DHEA to estrogen in peripheral tissues

43

A glucocorticoid with a low degree of protein binding, is given to pregnant women in premature labor to hasten fetal lung maturation (increase surfactant)

Betamethasone

44

Has significant glucocorticoid activity, but because of its long duration of action compared to aldosterone it is favored in conditions requiring mineralocorticoid therapy (e.g. adrenalectomy)

Fludrocortisone

45

Mineralocorticoids and glucocorticoids work in essentially the same manner. Specificity relies on the (blank) and the association of response elements in specific genes.

target cell

mineralocorticoids act on renal tubule vs glucocorticoids in the tissues

46

What is it called when you have aldosterone excess?

Conn's syndrome (primary)

or

secondary hyperaldosteronism

47

What causes aldosterone excess?

hypersecreting tumor of Z. glomerulosa (primary)

high renin-angiotensin (secondary)

48

Symptoms of excess aldosterone?

hypernatremia --> HTN
hypokalemia

49

What is it called when you have excess cortisol?

Cushing's syndrome

50

What can cause excess cortisol?

excess CRH/ACTH (hypothal disorder vs pituitary tumor)
adrenal tumor
ectopic ACTH (lung cancer)

51

What are the symptoms of excess cortisol?

hyperglycemia
excess protein breakdown --> muscle weakness
abnormal fat distribution
insulin resistance
decreased immune response & inflammatory response

52

What is it called when you have androgen excess?

congenital adrenal hyperplasia

53

What can cause androgen excess?

genetic deficiencies in cortisol synthesizing enzymes
(21- and 11-OH)

54

What are the symptoms of excess androgens?

inappropriate masculinization -->
pseudohermaphroditism in females
precocious puberty in males

55

What is it called when you have cortisol & aldosterone deficiency?

primary adrenal insufficiency (Addison's disease)

56

What can cause primary adrenal insufficiency?

destruction or atrophy of the adrenal cortex

57

What are the symptoms of primary adrenal insufficiency (Addison's disease)?

related to cortisol deficiency -->
poor response to stress
hypoglycemia
low metabolic activities

58

What is it called when you just have a cortisol deficiency? What causes this?

secondary adrenal insufficiency;
insufficient ACTH due to hypothalamus/pituitary failure

59

What are these signs & symptoms of?

myopathy, central obesity, Moon face, Acne, hirsutism, bruising and capillary fragility, hypertension, glucose intolerance, hypokalemia, arteriosclerosis, infections, oestoporosis, hypogonadism

Cushings syndrome

60

Most cases of Cushings syndrome are (blank) dependent

ACTH

**~80% are ACTH dependent (either pituitary tumors or lung cancers), while 20% are ACTH independent (benign adrenal adenomas or malignant adrenal carcinomas)

61

To confirm Cushings disease (blank) can be ordered. Treatment with (blank) causes a reduction in cortisol in normal patients. In Cushings patients cortisol will remain the same or even elevated.

dexamethasone suppression test; dexamethasone

62

How do corticosteroids affect carbohydrate & protein metabolism?

stimulate formation of glucose
diminish peripheral utilization of glucose & promote the storage of glucose as glycogen

63

How do corticosteroids affects lipid metabolism?

redistribute body fat in the hypercorticoid state

**buffalo hump, moon face, thin extremities

64

What affects do corticosteroids have on the CNS?

Addison’s patients are apathetic, depressed and irritable some displaying frank psychosis
Administration of corticosteroids to normal patients induces a feeling of well being

65

What affects do corticosteroids have on the blood?

increase red cell hemoglobin & red cell content of blood --> people with Cushings get polycythemia & people with Addison's get normochromic normocytic anemia

increase neutrophils
decrease lymphocytes, eosinophils, basophils, & monocytes

66

What are the anti-inflammatory effects of glucocorticoids?

decrease circulating lymphocytes & suppress cytokines
suppress inflammation to all stimuli
block early & late events in the inflammatory process

67

Glucocorticoids are extremely useful as (blank) agents in numerous clinical settings, such as transplantation

anti-inflammatory

68

Glucocorticoids cause decreased synthesis of pro-inflammatory (blank) by decreasing the effectiveness of transcription factors like AP-1. In this way, they reduce (blank).

cytokines; inflammation

69

Corticosteroid can be administered in the following ways

inhaled
oral
topical
injectible
enema

70

What happens when you withdraw from corticosteroids after being on a high dose?

adrenal insufficiency
fever, myalgia (muscle pain), joint pain & malaise

71

How should you withdraw from a high dose steroid treatment after weeks to months?

delayed return of adrenal function

**must slowly reduce the dose over 1-2 weeks

72

What are the side effects of high dose corticosteroid use?

hypokalemia alkalosis & edema
increased susceptibility to infection
peptic ulceration (with H pylori infection)
myopathy
behavioral disturbance
cataracts
osteoporosis
growth arrest in children

73

(blank) act on the distal tubules of the kidney to enhance reabsorption of Na+

mineralocorticoids

74

In hypercorticoid state, what happens to Na+, water, and K+?

too much Na+, higher extracellular fluid volume, hypokalemia

75

What are the four inhibitors of adrenal steroid biosynthesis?

aminoglutethamide
ketoconazole
trilostane
metyrapone

76

Inhibits the first step in steroid biosynthesis (P450scc) from cholesterol interrupting production of both cortisol and aldosterone
Useful in decreasing hypersecretion of cortisol from autonomously functioning adrenal tumors and hyper-secretion due to overproduction of ACTH
Is employed in the treatment of Cushing’s disease, cortisol and mineralocorticoid supplements can be added to manage the induced insufficiency

Aminoglutethimide

77

How does aminoglutethimide work? When is it used?

inhibits the first step in steroid biosynthesis from cholesterol --> interrupts the production of both cortisol & aldosterone

used in Cushing's disease

78

Anti-fungal drug

Inhibits P450 17a enzymes required for cortisol synthesis

Inhibits P450scc enzyme at high concentrations

Is used to in a number of conditions to inhibit steroid synthesis: adrenal carcinoma, hirsutism, breast and prostate cancer

Ketoconazole

79

Inhibits 3-beta-hydroxy steroid dehydrogenase
blocks formation of cortisol and aldosterone and causes increased excretion of 17-keto steroids
Can be used in the treatment of Cushing’s disease
Benefit over aminoglutethamide is not clear and drug has not received extensive use

Trilostane

80

Blocks 11-beta-hydroxylation terminating synthesis at 11-desoxycortisol and resulting in renal excretion of 17-OH-steroids
11-desoxycortisol is a weak inhibitor of ACTH production
Result is an increase in ACTH production permitting assessment of the pituitary release of ACTH and adrenal response in the form of 17-OH-steroid in the urine

Metyrapone

81

Which enzymes does ketoconazole block?

P450 17 alpha (for cortisol synthesis) & P450 at high concentration

82

What enzyme does trilostane inhibit? What does it block?

3-beta-hydroxy steroid dehydrogenase;
blocks formation of cortisol & aldosterone --> increases 17-keto steroids

83

What enzyme does metyrapone block?

11-beta-hydroxylase

84

What can metyrapone be used for?

for the assessment of Cushing's disease --> when administered, it results in an increase in ACTH production & increased steroid precursors. If no increase in 11-deoxycortisol --> indicates adrenal insufficiency