Adrenal Pharm - Burkin Flashcards
(132 cards)
1
Q
what are the hormones released from the hypothal?
A
GHRH somatostatin TRH GnRH LHRH Dopamine
2
Q
what is the function of dopamine released from the hypothal?
A
prolactin inhibiting
3
Q
Hormones released from the ant. pit. are released in what kind of timing?
A
pulsatile
4
Q
What regulates the timing of the release of hormones from the ant. pit?
A
neuronal fluctuations; GH releases diurnally
5
Q
what type of hormones are released from the ant. pit?
A
smal peptide
6
Q
Is GH used to Dx or Tx?
A
Dx
7
Q
What drug is a synthetic somatostatin analog?
A
Octreotide or Ianoreotide
8
Q
what is used to treat acromegaly, carcinoid, gastrinoma, glucagonoma?
A
octreotide
9
Q
Protirelin is what hormone analog?
A
TRH
10
Q
t/f: TRH increases prolactin production
A
true
11
Q
t/F: TRH has no effect on the release of GH or ACTH
A
true
12
Q
TRH is used diagnostically to test for…
A
thyroid dysfunction
13
Q
ACTH can be expressed by tumors outside the pit. such as the….
A
lung
14
Q
Do extra-pituitary tumors that secrete ACTH respond to CRH?
A
NO
15
Q
In Cushings, ACTH is almost always (inc/dec) in response to CRH
A
increased
16
Q
What is leuprolide?
A
synthetic GnRH
17
Q
what happens if you give leuprolide in pulsatile doses?
A
stimulate gonadotrophin release
18
Q
what happens if you give leuprolide in a steady dose?
A
inhibits gonadotrophin release
19
Q
what is leuprolide used for?
A
both the Dx and Tx of hypogonadal states in men and women
20
Q
GnRH (agonist/antagonists) are used in the Tx of prostatic carcinoma, gonadal steroid sensitive tumors, endometriosis, and precocious puberty
A
GnRH agonists
21
Q
GnRH (agonist/antagonists) are used to prevent surges in LH during controlled ovarian hyperstimulation, used to Tx endometriosis, uterine fibroids, and prostatic cancer
A
GnRH antagonists
22
Q
what do we give to treat GH def?
A
somatotrophin
23
Q
What do we give to treat Turner’s syndrome?
A
somatotrophin
24
Q
Giving somatotrophin to pts with Turner’s syndrome has what affect?
A
increase in final adult height
25
Besides Turner's, what other dzs do we Tx with somatotrophin?
failure to thrive d/t chronic renal failure or HIV
| AIDS assc'd wasting
26
What are the three major effects of LH?
1. gonadal steroid production
2. follicular development
3. ovulation
27
LH regulates the production of what hormone in men?
testosterone
28
What is used in place of LH to treat hypogonadism ans as part of the Tx in assisted reproduction?
b-HCG
29
up to 25% of infertile women have hyper....
prolactinemia
30
What are the three classic symptoms of hyperprolactinemia?
galactorrhea
| oligomenorrhea or amenorrhea
31
t/f: dopamine can be used to treat hyperprolactinemia as it inhibits prolactin release
false; not an effective Tx!
32
What is the Tx to reduce prolactin secretion from both the mammary gland and from prolactinomas?
bromocriptine
33
What are the two functions of oxytocin?
1. stimulates release of milk
| 2. initiates uterine contraction during labor
34
Oxytocin alters (blank) in myometrial smooth muscle to produce sustained uterine contractions
transmembrane ion currents
35
How is oxytocin used therapeutically?
IV to start or enhance labor or nasal spray to induce postpartum lactation
36
Vasopressin is released from the post. pit in response to what two things?
1. rising plasma tonicity
| 2. drop in BP
37
Vasopressin acts on V2 receptors in what cells?
renal tubule cells; increases expression of aquaporins
38
the increase in aquaporins form ADH has what two effects on the nephron/
1. increased water permeability
| 2. increased water reabsorptoin int he COLLECTING DUCT
39
What is the effect of vasopressin on blood vessels?
vasocosntriction
40
Def of ADH leads to...
diabetes insipidus
41
What is used to treat nocturnal enuresis (bedwetting)
desmopressin at bedtime
42
ACTH stimulates the adrenal cortex to produce what three steroids?
cortisol
corticosterone
aldosterone
43
t/f: ACTH can also stimulate aldosterone release from teh zona glomerulosa
true; but it is less senstive to ACTH so that's why it doesn't atrophy post puituitary-ectomy
44
Prolonged admin of ACTH will result in hypertrophy of the adrenals with continuous high ouput of what two things?
corticosteroids and aldosterone
45
Where is DHEA released from?
adrenal cortex
46
what is the function of DHEA?
main source of androgens in women
47
What are the systemic effects of cortisol?
1. stimulates protein catabolism to amino acids from skeletal muscle
2. lipid breakdown in adipose tissue to FA and glycerol
3. gluconeogeneis from amino acids, FA, and glycerol
48
changes in cortisol and corticosterone release are the result of fluctiations in the secretion of (blank) which is in turn controlled by (blank)
cortisol controlled by ACTH controlled by nervous system
49
CRF is released from what specific cells?
nuclei of the median eminence
50
CRF is transported by what vein to the ant. pit?
hypophyseal portal vein
51
ACTH is made by what type of cell in the ant. pit?
basophils
52
t/f: ACTH exists as a prohormone
true
53
what are the four end products of POMC?
MSHg
ACTH
LPHg
b-endorphin
54
which residues in POMC are necessary for steroidogenic activity?
6-10
55
which residues in POMC are necessary for ACTh receptor binding?
15-18
56
what is the major regulator of the zona glomerulosa?
angiotensin
57
what is the major regulator for the zonae fasciculata and reticularis?
ACTH
58
ACTH stimulate steroid synth via what pahtway?
cAMP-PK
59
What is the rate limiting step in steroid synthesis?
delivery of cholesterol to the mitochondrial 450scc (side chain cleavage enzyme)
60
What protein transfers the cholesterol to the mitochondria?
steroidogenic acute regulatory protein (StAR)
61
ACTH can be given parenterally as what?
Achtar or Cosyntropin
62
what is the half life of Achtar or Cosyntropin?
15 minutes
63
Explain how Achtar or Cosyntropin are used as a diagnostic in adrenal insufficiency?
normal rise in cortisol rules out adrenal failure
64
t/f: synthesis of all adrenal hormones begins with cholesterol
true
65
what is the first product formed from cholesterol in all steroid synth?
pregnenolone
66
What stimulates the conversion of cholesterol to pregnenolone in the zona glomerulosa?
ANG II
67
What stimulates the conversion of cholesterol to pregnenolone in the zona fasciculata/reticularis?
ACTH
68
when is cortisol production the highest?
in the morning
69
diurnal cortisol synth is controlled in response to....
light-dark cycles
70
How much cortisol is released daily?
10mg
71
cortisol circulates bound to what?
transcortin and albumin
72
Can you survive without your adrenals?
only if food, water, and salt are always available and there is no large fluctuations in temperature
73
explain what is meant by cortisol being a permissive hormone?
low levels of catecholamines have little effect on lipolysis, but in the presence of cortisol you see lots of lipolysis
74
how many times stronger is prednisone to cortisol?
4 x
75
how many time stronger is dexamethasone to cortisol?
25x
76
why does it take several hours for steroids to take an effect?
they upregulate gene expression
77
t/f: glucocorticoids may decrease the transcription of target genes
true
78
t/f: corticosteroids may have immediate actions via membrane bound receptors
true! the exception to the rule!
79
What types of things bind in the nucleus instead of the membrane?
```
hydrophobic ligands:
steroids
thyroid hormones
Vit. D
retinoids
```
80
What part of the steroid receptor allows it to interact with the DNA?
two zinc fingers
81
what part of the steroid receptor allows it to bind to steroids?
sequence at the carboxy terminus
82
What are the three things bound to the GR prior to steroid binding?
HSP90
HSP70
IP
83
S-GR binding to DNA inhibits the transcription of what large glycoprotein?
POMC
84
t/f: the mineralcorticoid receptor also associates with HSP90
true
85
the mineralcorticoid receptor has expression restricted to whhich organs?
```
kidney
colon
salivary glands
sweat glands
hippocampus
```
86
what parts of the nephron express the mineralcorticoid receptor?
distal tubule and collecting duct
87
What is the effect of aldosterone on the principle cells of the distal tubule and collecting duct?
Na reuptake and K excretion
88
What is the effect of aldosterone on the intercalated cells of the distal tubule and collecting duct?
H+ excretion
89
Aldosterone induces serum and glucocorticoid regulated kinases which phosphorylate what?
Na/K ATPase on the apical membrane
90
Na influx from aldosterone stimulates the Na/K ATPase on which membrane?
basolateral
91
What enzyme converts cortisol to cortisone?
11b-OHase
92
(Cortisol/cortisone) binds to the mineralcorticoid receptor
cortisol
93
Why is cortisol converted to cortisone?
Protects the mineralcorticoid receptor from being overly active during high levels of cortisol to maintain specific action to aldosterone
94
t/f: brief periods of starvation will lead to depletion of glycogen stores post adrenalectomy
true
95
What is the relationship between insulin and fasting post adrenalectomy?
development of hyperSENSITIVITY to insulin
96
Prolonged exposure to glucocorticoids prodcues a (blank) like change
```
diabetic
inc. fasting glucose
inc. insulin resistance
dec. glucose tolerance
glucosuria
```
97
prolonged glucocorticoid exposure leads to what syndrome?
iatrogenic cushings
98
What are some of the most common effects of cushings?
```
osteoporosis
susceptibility to infection
buffalo hump
moon facies
loss of fat from extremities
AVN of femoral head
HTN
cataracts
benign intracranial HTN
```
99
What is a negative dex suppression test?
Pt is given 1mg dexamethasone at bedtime. levels should be less than 5ug/dL in the morning.
100
What are the two effects of corticosteroids on lipid metabolism?
1. redistribution of body fat
| 2. permissive effect that allows other agents to trigger lipolysis
101
t/f: cortisol induces lipolysis by directly acting on cAMP
false; changes how the body responds to elevated cAMP via NorEpi and Epi
102
t/f: steroids effect mood
true
103
describe the psychological state of someone with Addison's
apathetic, depressed, and irritable, may have frank psychosis
104
What are the effects of glucocorticoids on RBC production?
inc. RBC Hgb
ic. Hct.
secondary polycythemia
105
what are the effects of glucocorticoids on WBC production?
inc. PMN leukocyte
70% dec. in circulatings lymphs
90% dec. in circulating monocytes
106
t/f: glucocorticoids can suppress inflammatioin regardles if the stimulating event was heat, mechanical, chemical, infectious, or immunological
true
107
What are the early inflammatory events that cortisol adn its derivatives can suppress?
```
Edema
fibrin deposition
capillary dilation
leukocyte chemotaxis
phagocytosis
```
108
what are the late inflammatory events that cortisol can suppress?
angiogenesis
fibroblast proliferation
deposition of collagen
109
what factors do glucocorticoids inhibit in macrophages and monocytes?
arachidonic acid
prostaglandins
leukotrienes
acute phase reactants
110
what cytokines do glucocorticoids inhibit in macrophages and monocytes?
IL1
IL6
TNFa
111
what factors do glucocorticoids inhibit in endothelial cells?
ELAM-1
ICAM-1
acute phase reactants
arachinodic acid/prostaglandins/leukotrienes
112
what cytokines do glucocorticoids inhibit in endothelial cells?
IL1
113
what factors do glucocorticoids inhibit in fibroblasts?
arachidonic acid
prostaglandins
leukotrienes
114
what factors do glucocorticoids inhibit in basophils?
histamine
| Leukotriene C4
115
what cytokines do glucocorticoids inhibit in lymphocytes?
```
IL1
IL2
IL3
IL6
TNFa
GM-CSF
IFNg
```
116
Positive sodium balanc, increased ECF, mild hypernatremia, hypokalemia, and alkalosis are seen in (hyper/hypo)corticism
hypercorticism
117
The major issue associated with cortical insufficiency is the loss of..
Na from the kidneys
118
what are the treamtents for cortical insuff/
NaCl solution and mineralcorticoid replacement
119
Contracted blood volume, increased viscosity, and hypotension leading to CV collapse, along with inc. capillary permeability, poor vasomotor response in small vessels, and dec. cardiac muscle mass is seen in....
ABSENCE of corticosteroids
120
The primary findings in primary aldosteronism are..
HTN and hypokalemia d/t chronic Na retention
121
how long can it take for normal cortisol production to return following the cessation of steroid therapy?
several months
122
Abrupt withrdawl from steroids can lead to...
adrenal failure!
123
Metyrapone inhibits what enzyme that converts desoxycorticosterone to corticosterone?
11-bOHase
124
t/f: desoxycorticosterone and corticosterone have sig. effects on the the release of CRH and ACTH
false; no effect!
125
the continued block of 11B-OHase leads to a (dec/inc) in adrenal production of aldosterone precursors
inc. from feedback regulation
126
where do you find tetrhydro-11-desoxycortisol and 17-hydroxy steroids during metyrapone Tx?
in the urine; they are metabolites of 11-desoxycorticosterone and corticosterone
127
Metyrapone is indicated for..
adrenal insuff.
128
t/f: because metyrapone inhibits aldosterone production it causes sodium wasting
false! desoxycorticosterone that is produced has mineralcorticoid activity!
129
what step in steroid genesis does aminoglutethimide inhibit?
the first step from cholesterol to pregnenolone
130
What are the three enzymes that aminoglutethimide inhibits?
P450scc
| P45011b and aromatase (converts androgens to estrogen)
131
when do you use aminoglutethimide ?
1. to decrease hypersecretion of cortisol in autonomously functioning adrenal tumors or from ACTH overproduction
2. cushings
3. steroid dependent tumors (breast and prostate)
132
If aminoglutethimide is given for cushings, what other thing must you give with it?
cortisol; you'll knock out ALL production
