HPA axis (Exam 3) Flashcards
1
Q
CRH pathway
A
CRH (hypothalamus) –> ACTH (anterior pituitary) –> adrenal cortex –> cortisol
2
Q
anterior pituitary hormones traits
A
all peptides
can be water soluble or lipid solube
3
Q
anterior pituitary hormones
A
Growth hormone
ACTH
Follicular stimulating hormone
Lactating hormone
Thyroid stimulating hormone
Prolactin
4
Q
long feedback loop of CRH pathway
A
cortisol inhibits release of CRH
5
Q
short feedback loop of CRH pathway
A
cortisol inhibits release of ACTH
6
Q
mineralocorticoids
A
aldosterone
maintains sodium and fluid balance
7
Q
glucocorticoids
A
cortisol
provides the body with materials for energy
8
Q
androgens
A
testosterone
9
Q
hyper secretion of testosterone can cause
A
masculinizing changes
10
Q
how are adrenal hormones regulated?
A
adrenocorticotropic hormone
11
Q
how is aldosterone secretion primarily accomplished?
A
through RAAS
12
Q
11 beta hydroxylate defect
A
aldosterone and cortisol production greatly reduced
excessive production of 11-deoxycorticosterone
13
Q
what can 11-deoxycorticosterone do in high concentrations?
A
act as an effective mineralcorticoid
14
Q
defective 21-hydroxylase leads to
A
pregnenolone being diverted to androgens, no feedback activity on ACTH secretion
15
Q
congenital adrenal hyperplasia
A
genital abnormalities due to deficiencies of adrenal gland
caused by decreased 21 hydroxylase
16
Q
females with congenital adrenal hyperplasia are exposed to ___________ and are born with _______________
A
excess androgens prenatally
virilized external genitalia
17
Q
complications of chronic exogenous corticosteroid use
A
decreased ACTH and CRH
zona fasciculata atropy
suppressed/quiescent HPA axis
18
Q
glucocorticoid effects (strongest–> least)
A
dexamethasone > prednisone > cortisol
19
Q
most potent glucocorticoid?
least?
A
dexamethasone (25x)
cortisol (1x)
20
Q
full recovery of endogenous cortisol secretion may require up to ___________ following steroid withdrawal
A
18 months
21
Q
classic CAH symptoms
A
ambiguous genetalia in female infants
enlarged penis in male infants
premature signs of puberty
development of male characteristics in females
abnormal menstrual periods
benign testicular tumors
infertility
22
Q
salt wasting CAH symptoms
A
dehydration
hyponatremia
hypotension
arrhythmia
blood sugar
metabolic acidosis
23
Q
classic CAH is treated with
A
steroids
24
Q
infants and children with CAH treatment
A
hydrocortisone
25
adults with CAH treatment
hydrocortisone
prednisone
dexamethasone
26
adults with classic CAH can also take ______________ to replace aldosterone
fludrocortisone
27
what can help salt-wasting CAH patients?
eating salty foods
taking salt pills
28
classic CAH patients may need more medication when
stress
having an illness with a high fever
undergo surgery
sustain a major surgery
29
over treatment with steroids leads to
hypercortisolism
30
underetreatment with steroids can lead to
hyperandrogenism
31
secondary hyper secretion due to hypothalamic problem leads to
high CRH levels
high ACTH levels
high cortisol levels
32
secondary hyper secretion due to pituitary problem
low CRH levels
high ACTH levels
high cortisol levels
33
primary hyper secretion due to problem with adrenal cortex
low CRH levels
low ACTH levels
high cortisol levels
34
primary adrenocorticol insufficiency is also called
Addisons disease
35
addisons disease
autoimmune destruction of the adrenal cortex --> acute adrenal crisis
36
characteristics of Addison's disease
dec glucocorticoids
dec androgen
dec mineralcorticoids
inc ACTH
dec cortisol --> hypoglycemia
dec aldosterone leads to hypotension, hyperkalemia
37
secondary adrenocorticol insufficiency
caused by deficiency of ACTH
38
adrenocortical excess can be
cushings syndrome/disease or
aldosterone secreting tumor
39
characteristics of cushings syndrome/disease
inc cortisol and androgen levels
hyperglycemia, poor wound healing, and central obesity (cortisol)
hypertension (cortisol)
virilization of women (androgen)
40
aldosterone secreting tumor (Conn's syndrome)
inc Na reabsorption
inc ECF volume and blood volume --> HTN
inc K secretion --> hypokalemia
41
clinical manifestations of Addisons disease
hyperpigmentation of skin
muscle weakness and fatigue
hypotension
hypoglycemia
loss of hair
N/V, weight loss, diarrhea
42
adrenal crisis (acute adrenal insufficiency)
sudden decrease or absence of adrenocorticol hormones
43
adrenal crisis occurs when a person is exposed to
major stresses such as trauma, surgery, infection or major illness
44
cushings disease is when there is hyper secretion of
ACTH
45
cushings syndrome is when there is hyper secretion of
cortisol
46
corticosteroid agonist examples
prednisone (glucocorticoids)
fludrocortisone (mineralocorticoids)
47
corticosteroid antagonist examples
receptor antagonists
synthesis inhibitors (ketoconazole)
48
receptor antagonists (of corticosteroid antagonists) examples
glucocorticoid antagonists (mifepristone)
mineralocorticoid antagonists (spironolactone)
49
prednisone is a
prodrug
50
active form of prednisone
prednisolone
51
what occurs during pregnancy to protect the fetus from high levels of glucocorticoids?
placenta expresses 11 beta hydroxydehydrogenase (11B-HSD2) which inactivates cortisol/prednisolone by converting them into inactive forms
52
what converts prednisone to prednisolone?
11 beta hydroxydehydrogenase
53
fludrocortisone is frequently used in the treatment of
addison's disease
54
plasma half life of fludrocortisone?
biological half life?
duration of action?
3.5 hours
18-36 hours
12-24 hours
55
mifepristone exhibits
anti-glucocorticoid and weak anti-androgenic activity
56
MOA of mifepristone
prevents binding to glucocorticoid receptors which prevents downstream signaling pathways
57
mifepristone indication
control hyperglycemia secondary to hypercortisolism
in patients with endogenous cushings syndrome and T2DM or glucose intolerance
58
limitation of mifepristone
do not use for the treatment of T2DM unrelated to endogenous cushings syndrome
59
two marketed forms of mifepristone
Mifeprex (200mg)
Korlym (300mg)
60
peak plasma concentration of mifepristone?
half life?
90 minutes
18 hours
61
counseling points for mifepristone
CYP3A4 metabolism -- avoid grapefruit products
take with food
62
spironolactone is used to treat
primary and secondary aldosteronism
63
spironolactone competitively binds at the
aldosterone dependent sodium potassium exchange site in the distal convoluted renal tubule
64
ketoconazole
anti fungal agent
non-selective inhibitor of steroid hormone biosynthesis
65
ketoconazole inhibits various
enzymes in biosynthetic pathway of cortisol
66
elimination of ketoconazole
hepatic/billary
67
ketoconazole undergoes
extensive liver metabolism via CYP3A4
68
what drugs can interfere with ketoconazoles oral bioavailability?
antacids
H2 antihistamines
69
ketoconazole has a greater propensity to inhibit
mammalian CYP450
70
mitotane MOA
adrenal cortex inhibitor
induces tumor cell death and reduces steroid production
71
mitotane is used to treat
adrenocortical tumors
72
mitotane is a
adrenolytic isomer of the insecticide DDT
73
bioavailability of mitotane
40%
74
mitotane has nonselective
cytotoxic action on the adrenal cortex
75
how many patients on mitotane show a reduction in tumor mass?
1/3
76
how to treat Waterhouse-friderichsen syndrome
antibiotics
fluid resuscitation
corticosteroids
77
waterhouse-friederichsen syndrome
one or both adrenal glands stop working
bleeding into glands due to infection
78
antiestrogens examples
full antagonists (fulvestrant)
SERMs (tamoxifen)
aromatase inhibitors (anastrozole)
GnRH agonists
79
suppression of LH leads to what?
reduction of testosterone production
80
Leuprolide
GnRH receptor super-agonist
treats prostate cancer
81
Abarelix
GnRH receptor antagonist
potent inhibitor of gonadotropin secretion (LH and FSH)
treats advanced prostate cancer
82
Degarelix
GnRH receptor antagonist
treats advanced prostate cancer
83
anastrozole inhibits ___________ which blocks the conversion of _______________
aromatase
androstenedione to estrone and
testosterone to estradiol
84
anastrozole is used to treat
hormone receptor positive breast cancer in postmenopausal women
85
letrozole
non steroidal competitive inhibitor of aromatase
third generation type II
86
letrozole is used to treat
breast cancer in post menopausal women
87
exemestane
irreversible aromatase inhibitor
used to treat after tamoxifen is used
88
danazol
inhibit several CYP450 enzymes
weak partial agonist of progestin, androgen and glucocorticoid receptors
89
danazol is used to treat
endometriosis and fibrocystic disease of the breast
90
tamoxifen is used to treat
hormone responsive breast cancer
91
what does it mean that tamoxifen is a SERM?
it acts as an antagonist to prevent receptor activation in the breast
it acts as an agonist promoting endometrial hyperplasia which increases the risk of endometrial cancer
92
toremifene
estrogen receptor antagonist
down regulates and degrades estrogen receptor
93
raloxifene
antagonist effects on breast tissue
no estrogenic effects on endometrial tissue
94
raloxifene is used to
prevent and treat osteoporosis in postmenopausal women
95
fulvestrant
pure estrogen receptor antagonist
96
fulvestrant is used to treat
women with breast cancer resistant to tamoxifen
97
examples of 5 alpha reductase inhibtiors
finasteride
dutasteride
98
MOA of 5 alpha reductase inhibitors
inhibits 5 alpha reductase (converts testosterone to DHT in prostate tissue)
99
finasteride is ___________ and dutasteride is ______________
selective
nonselective
100
_________________ is the primary form of the enzyme present in prostate tissue
5 alpha reductase II
101
main ADR of 5 alpha reductase inhibitors
sexual dysfunction
102
hypo secretion of growth hormone leads to
dwarfism
103
reduced GH secretion can be linked to
reduced GHRH production/release
diminished responsiveness of somatotrophs to GHRH
104
hyper secretion of growth hormone leads to
gigantism
acromegaly
105
difference between gigantism and acromegaly
gigantism is over secretion of GH before puberty
acromegaly is after
106
metabolic effects of GH
increases lipolysis
increases blood sugar and anti insulin effects
increased cartilage formation and skeletal growth
increased protein synthesis and cell growth and proliferation
107
somatropin
agonist action
recombinant human GH
108
somatropin is used to treat
GH deficiency in adults and children
treatment of children with genetic diseases associated with short stature
109
mecasermin (Increlex)
agonist action
rhIGF-1
given to children with IGF-1 deficiency
110
ocreotide
antagonist action
111
somatostatin inhibits the release of
GH
glucagon
insulin
gastrin
112
ocreotide, lanreotide, and pasireotide is ___________ in inhibiting GH secretion than _______________
more potent
endogenous somatostatin
113
pegvisomant (Somavert)
antagonist action
genetically engineered GH derivative that binds to GH receptors and inhibits IGF-1 production
114
Menotropins
contain both FSH and LH
human menopausal gonadotropins (hMG)
115
where do menotropins come from?
why?
the urine of postmenopausal women
they produce high levels of FSH and LH due to cessation of ovarian steroidogenesis
116
FSH analogs
urofollitropin
follitropin alpha
follitropin beta
117
which FSH analogs are recombinant?
follitropin alpha
follitropin beta
118
LH analogs
human chorionic gonadotropin (hCG)
Lutropin
119
which LH analogs are recombinant?
human chorionic gonadotropin (hCG)
Lutropin
120
GnRH antagonist
Ganirelix
121
GnRH agonist
Gonadorelin
122
GnRH agonist with antagonist action
leuprolide
123
oxytocin agonist
oxytocin
124
oxytocin antagonist
atosiban
125
oxytocin effects
stimulates uterine contraction
induces labor
used in immediate postpartum period to stop vaginal bleeding
126
vasopressin agonist
desmopressin
127
vasopressin antagonist
conivaptan/tolvaptan
128
what is the treatment of choice for pituitary diabetes insipidus?
vasopressin and desmopressin
129
conivaptan has high affinity for
both V1a and V2 receptors
130
tolvaptan has a 30x higher affinity for
V2 than for V1 receptors
131
how is conivaptan administered?
tolvaptan?
IV
oral
