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.Pharmacology > Part 10: Corticosteroids and immunosuppressants > Flashcards

Part 10: Corticosteroids and immunosuppressants Flashcards

1
Q

t/f very extensive (near complete) suppression of the immune system is needed for some systemic autoimmune diseases and organ transplants

A

t

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2
Q

what are corticosteroids?

A

endogenous hormones

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3
Q

what bodily signals cause corticosteroids to be made?

A

stress, inflammation

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4
Q

stressful stimuli are received by the ____ (brain region), triggering the release of ___ from the adrenal gland

A

hypothalsmus; cortisol

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5
Q

one of the important functions of cortisol is to regulate ___ cells and reduce their activity

A

immune cells

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6
Q

t/f the normal levels of cortisol in the blood fluctuate throughout the day to help in th eregulation of physiologic processes

A

t

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7
Q

Normal cortisol secretion patterns can be affected by ___, _____, ____ and ____

A

sleep deprivation, stress, light, and disease

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8
Q

cortisol is produced in the ____ cells of the adrenal cortex

A

zona fascicilata

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9
Q

cortisol is made from ___

A

cholesterol

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10
Q

cortisol is very _____ (hydrophillic/lipophillic) in nature

A

lipophillic

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11
Q

due to its lipophilic nature, cortisol must travel in the blood bound to ____

A

plasma proteins

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12
Q

which plasma protein is cortisol bound to once it levels the adrenal gland?

A

corticosteroid binding globulin (CBG)

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13
Q

once cortisol reaches a target cell, it can diffuse through ____ to get to intracellular receptors. Is this passive or active?

A

cell membrane; passive

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14
Q

ligands for intracellular receptors are typically ___ (hydrophillic or lipophilic)

A

lipophilic

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15
Q

the cortisol–intracellular receptor complex dimerizes and is translocated to the nucleus, where changes in ___ are initiated

A

gene transcription

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16
Q

binding of cortisol to a glucocorticoid receptor results in binding of _____ to regulatory regions of DNA, causing changes in transcription

A

glucocorticoid response elements

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17
Q

at a systems level, cortisol signalling conributes to the balance of ____ metabolism

A

energy

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18
Q

what are the glucocorticoid effects of corticol involved in?

A

energy metabolsim

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19
Q

mineralocorticoid activity is important to __

A

elctrolytes and water balance in the kidneys

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20
Q

what is the most common use of corticosteroids?

A

modulate the immune system

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21
Q

corticosteroids reduce the production of _____

A

prostaglandins, lekotrienes and other proinflammatory mediators

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22
Q

the anti-inflammatory effects of corticosteroids reduce ___, ___ and ____ at the site of injury

A

pain, heat, swelling

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23
Q

the difference between anti-inflammatory and immunosuppressive actions of corticosteroids is dependent on ___

A

potency and dose

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24
Q

t/f corticosteroids reduce the activation of mast cells, T cells etc and reduce the production of cytokines

A

t

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25
COX 1 is expressed in a variety of tissues and helps maintain cellular functions such as ____, ____ and ____
mucous secretion to protect endothelial cells of the stomach lining, regulating platelet aggregation, and smooth muscle contraction
26
COX2 is usually expressed in several tissues, including the ___ and ____ cells
kidney and endothelial
27
which is the inducible form of COX?
COX 2
28
expression of COX2 is increased in tissues during inflammation to promote the production of proinflammatory prostaglandins, especially ___
PGE2
29
the increased production of prostaglandins caused by COX2 causes ____
pain, swelling (peripheral inflammation) and fever
30
what is the function of thromboxane and prostacyclin?
regulate platelet aggregation
31
in the arachidonic acid pathway, lipoxygenase makes ___ and ___
lipoxins and leukotrienes
32
what are leukotrienes?
pro-inflammatory mediators that increase vascular permeability and recruit immune cells to injury site
33
t/f corticosteroids inhibit the whole arachidonic acid cascade
t
34
____ is the synthetic analogue of natural cortisol
hydrocortisone
35
the activity of all corticosteroids is measured against ___
hydrocortisone
36
which corticosteroids have both glucocorticod and mineralocorticoid activity?
hydrocrotisone (1:1), flucortisone (10:200) and predisone (3.5:0.5)
37
which corticosteroid receptor are we usually trying to target?
glucocorticoid (mineralocorticoid may cause side effects)
38
what is prednisone?
oral corticosteroid commonly used to mimic the effects of cortisol
39
which has a higher glucocorticoid potency, prednisone or hydrocortisone?
prednisone
40
dexamethasone is a ____ potency corticosteroid
high
41
high potency corticosteroids like dexamethasone are used systemically in what situations
if a less potent corticosteroid didnt work, or if you need something like immunosuppression for organ transplant
42
what is fluticasone?
high potency glucocorticoid receptor agonist with good anti-inflammatory effecst
43
the inhaled dosage form of fluticasone is used for ___
asthma
44
the intranasal formulation of fluticasone is used for ___
allergic rhinitis
45
what is tramcinoclone? what doasge forms is it available as?
moderate potency corticosteroid, comes as cream or ointment
46
what is tramcinoclone usually used for?
dermatitis and psoriasis
47
corticosteroids can have significant cellular effects due to modification of gene transcription and altered protein synthesis of many pathways involved in ___, ____ and ___ metabolism
carbohydrate, fat, and protein
48
presence of synthetic corticosteroids can influence the ____ pathway that will influence the natural secretion of cortisol
adrenal endocrine pathway
49
what is a consequence of overuse of topical steroids causing thinning of the skin?
thinner skin lets more drug in, leading to more ADRs
50
when systemic levels of corticosteroids rise, symptoms of ____ syndrome present
Cushing's
51
what are some ADRs of topical corticosteroids?
impaired wound healing and thinning and easy bruising of the skin
52
what are some systemic ADRs of corticosteroid overuse?
cushings, osteoporosis, growth retardation, HPA axis suppression, immunosuppression & impaired wound healing, altered glucose homeostasis and energy use
53
cushings syndrome is a generalized state of elevated circulating ____ levels
cortisol
54
what distinguishes cushing's disease from cushing's syndrome?
the cause of source of the excess cortisol
55
what causes cushing's disease?
an ATCH producing pituitary tumour that stimulates adrenal glands to over produce cortisol
56
what are some possible causes of excessive cortisol levels?
pituitary tumour (cushing's disease), adrenal tumour, chronic disease, pharmacologic cause
57
what are some Cushing's like symptoms?
alterations in mood, emotional distrubances, fat deposits around the face, shoulders and abdomen, thinning and ulceration of the skin, rupturing of small blood vessels near the surface of the skin
58
Cushing's symptoms can also involve the development of conditions with long-term cosequences like :
cardiac hypertrophy, osteoporosis
59
if the cause of Cushing's symptoms is an adrenal tumour and the adrenal glands need to be removed, the patient then present as if they have ____ disease due to lack of these glands
Addison's disease
60
the use of corticosteroids in chidren can result in slowed grwoth due to negative impacts on ___ and ____
growth hormone and bone development
61
corticosteroids ____ (increase/decrease) blood glucose levels in some patients
increase
62
t/f corticosteroid use can increase blood glucose to the point of needing insulin therapy
t
63
if you wanted to see the extent of a patient's drug induced cushings effects, which tests would you order?
WBC to determine immunosuppression ; adrenal function to determine if endogenous cortisol producing capabilities are impaired
64
adrenal impairment is known as ___
HPA axis suppression
65
the normal production of cortisol has a ____ feedback loop on the pituitary and hypothalmus to prevent over-production of cortisol
negative
66
what happens to the adrenal, pitutary, hypothalamus negative feedback loop when exogenous corticosteroids are given?
cause the negative feedback loop to shut down the production of endogenous cortisol
67
what is a consequence of synthetic corticosteroids causing HPA axis suppression?
if the body encounters stress (such as surgery), the HPA isnt able to produce cortisol to respond
68
t/f acute adrenal crisis is extremely rare
t
69
how does acute adrenal axis suppression present?
rapid onset of wide range of systemic effects such as naausea, vomiting, confusion, hypoglycemia, hypotension, tachycardia, muscle weakness, loss of consciousness, respiratory and cardio disress
70
acute adrenal supression may cause death if not promptly managed with ____ and ___
supportive therapies and added glucocorticoids
71
how can acute adrenal suppression be avoided?
patients on corticosteroids are given an extra dose b4 surgery, long-term pateints are slowly tappered off
72
give 2 examples of calcineurin inhibitors
cyclosporin and tacrolimus
73
sirolimus is an example of a ___
mTOR inhibitor
74
basiliximab is an example of a ___
immunosuppressive antibody
75
calcineurin inhibitors, mTOR inhibitors, and immunisuppressive antibodies are all examples of ____
immunomodulators
76
calcineurin activation is a key component in the ability of T cells to produce ____, an important cytokine for the amplification of cell-mediated immune responses
IL-2
77
T cell stimulation from APC causes an influx of ____ which activates the pathway to make cytokines
Ca ions
78
calcineurin is a Ca dependent phosphatase needed for the activation of _____
NF-ATc (nuclear factor, which is a transcription factr)
79
calcineurin activating NF-ATc causes transcription of ___ to activate immune cells
IL-2
80
how does cyclosporine inhibit calcineurin?
binds to cyclophylin and the complex inhibits calcineurin
81
how does tacrolimus inhibit calcineurin?
binds to FK binding protein (FKBP) and the complex inhibits calcineurin
82
reduced transcription of IL-2 caused by calcineurin inhibitor will reduce the activation of ___ cells
T
83
reducing IL-2 production has a lesser effect on ___ cells and innate immune responses will remain intact
B
84
t/f calcineurin inhibitors are "less complete" but still effective in reducing autoimmune responses and organ rejections when used in combinations
t
85
what is one of the common ADRs of calcineurin inhibitors?
increased risk of infection
86
what is a dose-dependent ADR of calcineurin inhibitors that needs to be monitored?
nephrotoxicity
87
cyclosporine and tacrolimus are metabolized by
CYP
88
activation of mTOR carries signals to ____
proliferate
89
activation of the mTOR pathway upon the stimulation of "resting" T cells by proinflammatory cytokines like IL-2 results in signals for the cell to become ____
active
90
the proliferative signals caused by mTOR activation are required for the activation of ___ and ___ cells and ____ immune responses
T and B, innate
91
how does sirolimus work?
mTOR inhibitor; complexes with FK binding protein in inactive immune cells, then the complex binds to and inhibitis the actiavtion of mTOR
92
basiliximab acts as a ____ antagonist
IL-2
93
basiliximab targets ____ expressed on T cells
IL-2 receptor extracellular alpha-chain
94
how does basiliximab work?
binding to the IL-2 receptor obstructs the active site of the receptor, preventing IL-2 binding and activation of the receptor , so the downstream effects of T cell activation cant happen
95
t/f antibody therapeutics are very specific in their binding targets
t

.Pharmacology (55 decks)

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