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lect 12 corticosteroids Flashcards

1
Q

what is inflammation

A

body’s immune response to an irritant or foreign object

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2
Q

changes leading to inflammation at site of injury

A

blood flow, increase in blood flow permeability, recruitment of proteins, white blood cells, microphages, neutrophils from circulation to site of injury

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3
Q

what diseases involve unwanted inflammation and why

A

almost all because diseases change your inflammatory response to grow and thrive

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4
Q

class of drugs that lower inflammation in body and reduce immune system

A

corticosteroids

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5
Q

doctors often prescribe corticosteroids for which two disease

A

asthma and arthritis

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6
Q

Biologically active compound with four rings arranged in a specific molecular configuration

A

steroids

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7
Q

2 principal functions of steroids

A
  1. are signalling molecules

2. important component in cell membrane that can alter membrane fluidity

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8
Q

corticosteroids = ? + ?

A

glucocorticoids + mineralocorticoids

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9
Q

class of corticosteroids produced in adrenal cortex that influence salt water balance

A

mineralocorticoids

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10
Q

primary mineralocorticoid

A

aldosterone

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11
Q

immune response of cortico.

A

pain induces hypothalamus to release hormones that stimulate adrenal gland to release cortico to reduce pain and inflammation

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12
Q

system that is the circuit board of the body through which cell communicate. Complex network of glands and organs

A

endocrine system

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13
Q

how does endocrine system use hormones (7)

A

to control and coordinate body metabolism, energy level, reproduction, growth, response to injury, stress, resolution of inflammation

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14
Q

cell produces ligand which interacts with receptor on same cell

A

autocrine

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15
Q

cell’s ligand interacts with receptor in nearby cell

A

paracrine

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16
Q

cell’s chemical messenger circulates in body and affects speecific receptors on distant cells

A

endocrine

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17
Q

Major components of endocrine system

A

brain
hypothalamus
target organs: thyroid, pancreas, adrenal glands, ovaries, testes

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18
Q

forward path in response to stress, illness ect

A

Hypothalamus –> CRH release –> Pituitary –> ACTH release–> adrenals –> Cortisol

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19
Q

how does cortisol work

A

comes back and interacts with glucorticoid receptors in pituitary and hypothalamus and dowregulate the drive to increase itself (negative feedback)

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20
Q

41 aa peptide prohormone produced in hypothalamus. amino acids are cleaved for activation

A

Corticotrophin-releasing hormone (CRH)

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21
Q

how does CRH act in the pituitary

A

acts on g-protein coupled receptors in the anterior pituitary to stimulate POMC synthesis which is processed to release ACTH and beta LPH

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22
Q

roles of ACTH

A
  1. increases delivery of cholesterol to inner mitochondrial membrane
  2. increase transcription of steroidogenic enzymes
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23
Q

what happens to adrenal glands in forward pathway

A

ACTH regulates glucocorticoid synthesis in adrenal cortex

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24
Q

places in adrenal cortex that make corticosteroids and which type

A

both zona fasciculata/reticularis make glucocorticoids but only zona glomerusola makes mineralocorticoids

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25
process where cholesterol becomes steroids
steroidogenesis
26
first critical step of steroidogenesis
CYP11A that cleaves side chain then make different steroids
27
enzyme involved in aldosterone formation | which regulates salt secretion
CYP11beta2
28
enzyme involved in cortisol formation | which affect metabolism and regulates glucose levels
CYP11beta1
29
turning cholesterol to glucocorticoids needs what to make cortisol from prior metabolites
CYP17 and CYP11beta1
30
issues with feedback mechanism of cortisol can cause what
diseases
31
true or false? external corticosteroids can affect loop mechanism of cortisol
true
32
explain mechanism of action of glucocorticoids to receptor
they bind to ligand-binding domain of steroid hormone receptors. the ligand-bound receptor moves from cytoplasm to nucleus and initiate signal transduction for steroid hormones which lead to changes in gene expression for hours to days
33
dna-binding domain of steroid hormone receptors binds to what
specific areas of the genome like glucocorticoid response element
34
transcription-activating domain of steroid hormone receptor does what
turns on transcription of very specific genes that are related to the effects of the hormone
35
up to 20% of immune cell genes are regluated by what
glucocorticoids
36
Glucocorticoids can transactivate or transrepress genes by binding to what receptor
GRalpha
37
what can block the action of GRalpha by blocking transactivation and transrepression
GRbeta
38
mechanism of tolerance with glucocorticoid relating to GRalpha
when one becomes tolerant to glucocorticoids, more GRbeta is produced and inhibits more GRalpha which causes decrease effect of glucocorticoid
39
summary of glucocorticoid mechanism and gene
glucocorticoid bind steroid hormone receptor like GRalpha or GRbeta. This interacts then areas of genome like GRE (gluco. resp. element) to transactivate or transrepress
40
anti-inflammatory effects of glucocorticoids in body
1. change in cell proliferation, migration, survival 2. decreases proinflammatory cytokines, interleukins, prostaglandins 3. Block things at transcriptional level of proinflammatory molecules
41
metabolic effects of glucocorticoids in body
1. increase glucose to protect brain, heart by transcriptional activation. 2. Increase blood glucose by increasing glycogen breakdown (glycogenolysis), increasing glucose synthesis (gluconeogenesis), decrease fat deposit (increase lipolysis), increase protein catabolism
42
pharmacokinetics of glucocorticoids
administered to most routes because small and lipid soluble but local administration preferred to minimize adverse effects
43
glucocorticoids bind to what for circulation
steroid hormone binding globulins
44
Cortisol is 80-90% bound by what and why | what about the 5-10%
bound to corticosteroid-binding globulin (CBG, transcortin) for better circulation. 5-10% loosely bound to albumin
45
problem with bioavailabilty of CBG bound glucocorticoids
hormone is transported but CBG modulates availability of hormone so another reaction is needed to make it available
46
which synthetic glucocorticoids can CBG bind or not bind
1. Can bind to prednisone and prednisolone | 2. cant bind to dexamethasone so 100% plasma dexamethasone bioactive
47
absorption of glucocorticoids
absorbed rapidly from GI tract, synovial (joints) and conjunctival (eyes) due to lipophilic but slowlly absorbed from skin
48
what hormone increases CBG biosynthesis in liver and requires increased plasma cortisol to maintain correct bioavailability
elevate estrogen concentrations
49
can circadian rythm affect endogenous corticosteroids levels
yes
50
glucocorticoids as grugs structure
backbone: 4 rings | structurally modified side chain to increase bioavailabilty, half life
51
what changes were made to synthetic glucocorticoids betamethasone and dexamethasone and why
adding methyl group at C16 to increase activation of glucocorticoid receptor and virtually eliminate mineralocorticoid receptor activity. Increases duration of action of these compounds
52
introduction of other side chain than methyl c16 and on who enhances gluco and mineralo activities
Fluorine at C9 prednisone, prednisolone, methylprednisolone, dexamethasone, betamethasone
53
which gluco. has longer-acting and higher half-life over which gluco.
beta/dexamethasone over pednisone, prednisolone
54
asthma treatment
inhalers targeting the inflammation in lungs
55
eczema treatment
cream form to prevent inflammation on skin or pill to be systemic
56
EVALI (vaping) treatment
vitamin E acetate is not the cause of high inflammation. glucocor. can help breath and better prognosis on ventilator
57
immunosupressive action use of glucocor. example
for organ transplants
58
Rare adrenal insufficiency disease where glands do not make enough aldosterone and cortisol
Addison's Disease
59
treatment of addisons disease
systemic glucocorticoid therapy over period of time. Replacement drugs (gluco. and mineralo.) given on schedule time to mimic 24hr fluctuation of cortisol
60
types of blood cancer that cant be cured that begin with abnormal mutation in stem cell and causes overproduction of white b cells and reduction of RBC's
myeloproliferative diseases
61
treatment of myeloproliferative diseases
glucocorticoids to keep RBC count up and increase lifespan
62
low treatment of cortisol effects (7)
hariness, acne, greasy skin, irregular periods, fatigue, tiredness reduced fertility
63
high treatment of cortisol effects (8)
increased appetite, weight gain, muscle weakness, thin skin, easy bruising high BP, diabetes, osteoperosis
64
Adverse effects of prolonged gluco. therapy (7)
osteoporosis decreased bone density, glucose intolerance diabetes, central obesity, muscle weakening, increase risk of infections, depression, cataracts
65
oral candidiatis is what and how can it be avoided
adverse effect when using inhaler. avoided by rinsing mouth after using inhaler
66
what is HPA axis supression and how avoided
long term steroid use shutting down hypothalamus, pituitary, adrenal axis and adrenal atrophy. no more ACTH to keep adrenal functioning. avoid by slowly decreasing amount taken
67
growth inhibition of steroid use how to avoid
important in having right dose in inhaler for prepubertal patients to keep glucocort. in lungs and prevent systemic effects
68
oral corticosteroid used for extreme cases and short duration
prednisone
69
genetic disease caused by excess cortisol
cushing's syndrome
70
causes of cushing syndrom (2)
1. overuse of steroids 2. cancer, ectopic production of ACTH 3. inhibition of HPA axis, exogenous cortisol act like endogenous overproduction so excess intake of cortisol that cannot be controlled
71
people using corticosteroids are more susceptible to develop what famous disease and why
COVID 19 and dut to imunnosupressant nature of glucortocoids
72
people with obesity need more or less glucocorticoid?
more to have right blood concentration as the fat absorbs
73
common features in cushing syndrome (6)
obesity, hump shoulder blades, mood face, muscle wasting, weakness, psychiatric issues

Phar300 (18 decks)

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