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PHAR 300 > Corticosteroids and Inflammation > Flashcards

Corticosteroids and Inflammation Flashcards

1
Q

what is inflammation

A

Immune response to an irritant
Irritant might be a germ, could also be a foreign object (splinter in finger)

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2
Q

describe types of irritants

A

Mostly focus on non infectious irritants
Most autoimmune or inflammatory diseases that we treat with glucocorticoids are not infections

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3
Q

describe immune response to cut

A

Have robust immune response to cut
Swells, pain, red
Due to immune cells infiltrating area and causing of nerves in that area to react = pain
Cytokines and chemokines = cause accumulation of liquids and immune cells = swelling
Natural response
Once healed = inflammation goes away

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4
Q

what is purpose of inflammation

A

Defense mechanism that evolved in higher organisms to protect them from infection and injury
Purpose is to localize and eliminated injurious agent and to remove damaged tissue components so body can begin to heal
So will not spread
Also in infection context = isolate so will not go systemic
Many inflammatory cells seal area

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5
Q

name 5 cardinal signs inflammation

A

Pain
Heat
Redness
Swelling
Loss of function (severe, ex - bone break)

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6
Q

What happens during steps of inflammation

A

Isolation
Results in increase in blood flow
Recruitment of immune cells - innate cells or polynucleated cells = neutrophils and macrophages , Sometimes die = apoptosis, Other cells recruited to help clear dying cells
Immune cells migrated out or go from inflammatory, Fighting injury or infection to a more resolving phenotype
Lipid mediators and proteins that are soluble = Released by immune cells called cytokines and leukotrienes, Important in recruiting immune cells
Changes blood flow and amount of liquid
Usually this is an acute response
Resolved within time
Body’s natural ability to produce glucocorticoids

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7
Q

name and describe types of inflammatory responses

A

An inflammatory response that lasts only a few days is called acute inflammation
while a response of longer duration is referred to as chronic inflammation

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8
Q

describe unwanted inflammation

A

When inflammatory response not resolved
Constant recruitment of immune cells to your body - in absence of injury or infection
Could cause injury - recruits even more immune cells = slippery slope
Results in auto inflammatory (Auto = constant cycle of inflammation that is not resolved)

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9
Q

name types of diseases that involve unwanted inflammation

A

A Lot of diseases we think are not inflammatory based are = Inflammation = basis of lots of types of diseases
Arthritis
Inflammatory bowel diseases
Irregular inflammation results in gut inflammation and destruction of gut tissue
Cardiovascular diseases
Pulmonary diseases - immune system goes awry- Injury to lung and reduced lung function
Allergies
Cirrhosis - skin specifically
Inflammatory diseases can be tissue specific or systemic - Do not know what causes this
When can inflammation be bad = Asthma, Arthritis
These diseases can be debilitating if not treated and maintained

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10
Q

name common autoimmune diseases

A

Crohns, dermatomyositis, diabetes type 1, glomerulonephritis, graves disease, myasthenia gravis, multiple sclerosis, polymyositis, psoriatic arthritis, rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, vasculitis

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11
Q

Classification of immunosuppressive drugs

A

antiproliferative/antimetabolic agents
Glucocorticoids
Immunophilin-binding agents (calcineurin and mtor inhibitors)
Biopharmaceuticals (antibodies and fusion proteins)

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12
Q

describe glucocorticoids

A

Glucocorticoids are the most potent, really easy, inexpensive and can shut down inflammatory processes
HAVE some negative impacts tho

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13
Q

describe types of immunity

A

Innate
Adaptive

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14
Q

describe innate immunity

A

Macrophage, neutrophil, dendritic cell, eosinophil, basophil
Always circulating in body and replenish all the time
Not really specific

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15
Q

describe adaptive immunity

A

B cell - antibodies, t cell
Less abundant in some organs
Much more specific
Need to recognize antigen - or have experienced that before to be able to react
In autoimmune diseases = specificity goes awry

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16
Q

describe Natural killer t cell

A

Natural killer t cell = between innate and adaptive immunity

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17
Q

describe Ex = have foreign antigen

A

Even if its a dying - apoptotic cell- INNATE immune cells usually react first
If not able to clear that then take some of the proteins or antigens and present = antigen presentation to t cells = Activates t cells and causes them to proliferate and replicated into t helper cells or cytotoxic t cells = adaptive immunity now
KEY = once t cells activated by antigen presentation step = THEY PROLIFERATE , One of major steps to activate adaptive immune system, Can be target of anti inflammatory drugs to stop proliferation

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18
Q

where does immune response happen

A

Can happen in tissues

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19
Q

describe cytokines

A

Released by immune cells and can signal all throughout body
cause recruitment of immune cells
Activation of immune cells
Increase proliferation of t cells

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20
Q

describe cytokines and autoimmune diseases

A

Great but also very bad for autoimmune diseases = can perpetuate cycle of activation of immune cells
Cytokines are signalling proteins that help initiate inflammation
They can activate immune cells
They can recruit immune cells (chemokines)
Too many cytokines can lead to excess inflammation and conditions like autoimmune diseases

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21
Q

describe cytokines Ex = IL 12, TNF-ALPHA = tumour necrosis factor alpha

A

Blocking these cytokines specifically = great clinical potential
IL 12 = Main source = dendritic cells, macrophages, neutrophils, Pro inflammation, cell differentiation, activates NK cell
TNF-a = Main source = macrophages, nk cells, cd4+ lymphocytes, adipocyte

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22
Q

Innate vs adaptive (acquired)= ONSET

A

Innate = immediate
Adaptive = days to weeks to turn on, Quite potent and can activate innate immune cells

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23
Q

Innate vs adaptive (acquired)= Mechanism of antigen recognition

A

Innate = pattern recognition receptors recognize common molecules on microbes and viruses
Adaptive = antigen specific receptors (t cell receptor, b cell receptor)

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24
Q

Innate vs adaptive (acquired)=Cell types involves

A

Innate = macrophages, neutrophils, mast cells, natural killer cells, nk t cells, innate lymphoid cells
Adaptive = dendritic cells, t cells, b cells

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25
Q

Innate vs adaptive (acquired)=Soluble factors

A

Innate = complement, type 1 interferon, select cytokines and chemokines
Adaptive = select cytokine and chemokines

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26
Q

describe nsaids

A

non steroidal anti inflammatory drugs
Medicines widely used to relieve pain, reduce inflammation and bring down high temp
But these are used for short period time - only potent for 4-6 hours, not a realistic medication for chronic diseases
Cannot take them chronically

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27
Q

describe Pharmacological approaches to immunosuppressive therapy

A

involve selective eradication of immunocompetent cells (cytokines or immune cells) or down regulation of the immune response without deleting the target cell (cannot just get rid of all immune cells, need immune system at some balance- drugs are to bring balance to your life)
in either case, the goal is to balance the activity and selectivity of the drug to optimize clinical efficacy while preventing adverse effects.

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28
Q

what drugs can be used to treat inflammation - principal approaches used currently are highly effective in inhibiting the immune response

A

antiproliferative/antimetabolite agents, glucocorticoids, immunophilin-binding agents (block cytokines and chemokines), and biopharmaceuticals (antibody based drugs).
The usefulness of these compounds is limited by their severe toxicities.

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29
Q

describe Antiproliferative drugs

A

Cyclophosphamide or nitrogen mustards
Inhibit proliferation of t cells and b cells = stop from turning on adaptive arm of immune system
Global drugs that bind dna complex and inhibit replication= Have pleiotropic effects
Have to hit this drug right before inflammation gets bad = Has to be someone who has inflammatory disease - chronic and confirmed disease
The antiproliferative/ antimetabolic drugs are cytotoxic and inhibit cell division and the proliferation of both T and B cells.
The alkylating agents include cyclophosphamide,nitrogen mustards, and nitrosoureas that covalently complex to DNA

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30
Q

describe Antimetabolite agents

A

Stopping ability of immune cells to take in all they need for functional metabolism = essentially inhibit replication
Attack metabolic function = cannot eat folic acid or pyrimidine that they require to proliferate= stops and b and t cells from proliferation
The antimetabolites are compounds that resemble normal metabolic compounds, including folic acid, pyrimidines, or purines, and block the proliferation of B and T cells by inhibiting the synthesis of building blocks necessary for cell replication.

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31
Q

describe Antimetabolite agents

A

Inhibitor of dihydrofolate and stops immune cells from proliferating through inhibiting metabolism
For someone diagnosed with chronic illness and confirmed = So timing very important, Can have effects in body as well

Methotrexate Is a competitive inhibitor of dihydrofolate reductase, which converts dihydrofolic acid to tetrahydrofolic acid, thereby preventing the regeneration of folic acid required for purine and pyrimidine synthesis

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32
Q

describe immunophilin-binding agents - gen

A

calcineurin and mtor inhibitors
For someone who has been diagnosed and is suffering for a long time - from inflammatory disease
Drugs block production of - ex = IL 12= Ex = cyclophilin and FKBP-12 = drugs, Blocks production of cytokines IL 12 and TNF-a

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33
Q

describe immunophilin-binding agents - specifics

A

the immunophilins are proteins with both chaperone and enzymatic activity and have diverse functions ranging from neurotrophic actions to the regulation of cell proliferation.
Of importance for immunosuppression are the immunophilins cyclophilin and FKBP-12, both of which are targets for drug action.
In lymphocytes,cyclosporine binds to cyclophilin A
the complex formed binds to calcineurin and inhibits the phosphatase activity necessary for the expression of inflammatory cytokines such as IL-2 and TNF-α.

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34
Q

describe Glucocorticoids

A

Most widely used immunosuppressive agent
High effective for autoimmune inflammatory diseases
And for preventing graft rejection - during transplant = Usually need to be on anti inflammatory so body will not have inflammatory response

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35
Q

ex= prednisone

A

Prednisone is the prototypical glucocorticoid and exerts its effects both directly and indirectly by binding to glucocorticoid receptors

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36
Q

what do glucocorticoids do - acutely

A

the glucocorticoids inhibit the vasodilation and increased vascular permeability that ensue upon inflammatory insult, as well as prevent leukocyte migration.
Turn everything off

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37
Q

what do glucocorticoids do - decrease what

A

They also decrease T-cell activation and the expression of IL-2, IL-1, IL-6, and nuclear factor κ–light-chain-enhancer of activated B cells (NF-κB).

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38
Q

what do glucocorticoids do - bind to what

A

The glucocorticoids also bind to glucocorticoid-responsive elements on DNA to decrease the expression of proinflammatory and activate the expression of anti-inflammatory genes
Downregluate pre existing inflammation

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39
Q

do glucocorticoids need to recognize disease

A

Pleiotropic
Do not need to know what disease is

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40
Q

what is a steroid

A

Glucocorticoids = steroids
Steroids = biologically active organic compound with 4 rings arranged in a specific molecular configuration

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41
Q

Describe functions of steroids

A

2 principal functions =
Important components of cell membranes which can alter membrane fluidity
Are signalling molecules= Travel throughout body and become systemic quickly, Effective at spreading throughout body

42
Q

describe term = corticosteroids

A

In technical terms, “corticosteroid” refers to both glucocorticoids and mineralocorticoids(as both are mimics of hormones produced by the adrenal cortex), but is often used as a synonym for “glucocorticoid”

43
Q

what is mineralocorticoid

A

Mineralocorticoids Are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance).

44
Q

what is primary mineralocorticoid

A

The primary mineralocorticoid is aldosterone

45
Q

what are gluco vs mineralo corticoids useful for

A

Glucocorticoids = can turn off immune system and are important for inflammation
Mineralocorticoids= more important for calcium and sodium intake
developed drugs that specifically target glucocorticoids and not mineralocorticoids.

46
Q

describe hormone s

A

Hormones are chemically and structurally diverse compounds.
chemical messenger that circulates in body and effects on distant cells
Quickly transported
Body produces glucocorticoids to resolve inflammation
glucocorticoids play a role in your body’s natural anti-inflammatory resolution of inflammation - signalled through your hypothalamus

47
Q

describe hormone classes

A

Divided into three main classes based on chemical composition:
1. the amino acid analogues,
2. the peptides,
and 3. the steroids.

48
Q

describe hormones - amino acid analogues

A

Amino acid hormones: are all derived from tyrosine and include epinephrine (Epi)and the iodothyronines or thyroid hormones.

49
Q

describe hormones - peptide

A

peptide hormones: are subclassified on the basis of size and glycosylation state and may be single-or double-chain peptides.

50
Q

describe steroid hormones

A

steroid hormones:are all derived from cholesterol and may be subclassified as adrenal steroids or sex steroids, the former synthesized primarily in the adrenal cortex and the latter synthesized in the ovaries or testes

51
Q

describe endocrine system

A

The endocrine system is a messenger system comprising feedback loops of hormones that are released by internal glands directly into the circulatory system
hormones to control and coordinate your body’s metabolism, energy level, reproduction, growth and development, and response to injury, stress, resolution of inflammation and mood.

52
Q

describe endocrine system - glucocorticoids

A

Glucocorticoids can have many effects in body
Pharmacovigeinelnece comes in
Overuse = many systemic effects

53
Q

describe steroid synthesis

A

All secreted steroids are synthesized from cholesterol, which itself can be synthesized de novo or derived from circulating lipoproteins. - also take in cholesterol from food so amount of cholesterol we take in will also affect ability to produce drugs, or glucocorticoids - can lead to overproduction
Similar metabolic pathways mediate steroid synthesis in all organs.
The organ-specific formation of secreted steroids depends on the presence of specific catalytic enzymes.
The action of steroids is mediated largely by altering gene transcription through interaction with the deoxyribonucleic acid (DNA) of the promoter region of genes

54
Q

describe steroid synthesis - enzymes

A

CYP17
Cholesterol → aldosterone (mineralocorticoids) or cortisol (glucocorticoids)= cortisol → sex hormones
Pregnenolone and progesterone into cortisol = by enzyme CYP17 (17 alpha-hydroxylase)

55
Q

describe signalling

A

How does body signal cholesterol to turn into cortical steroids
Need adrenal, pituitary and hypothalamus glands to signal this
In vertebrates, the hypothalamus is the neural control center for all endocrine systems

56
Q

describe signalling - stress

A

During time of stress = stress, illness, hypoglycemia, hemmorage, injury, whatever
Something signals into hypothalamus to produce CRH (corticotropin releasing hormone), Also produces AVP = arginine vasopressin
CRH acts on pituitary gland = produces ACTH (adrenocorticotropic hormone)
ACTH acts on adrenal gland = where cholesterol transformed and produces cortisol or glucocorticoids

57
Q

describe action of crh

A

CRH acts as peptide, 41 aa, prohormone produced in hypothalamus
Pituitary gland promotes production of POMC
Pomc = proopiomelanocortin processed to release acth
CRH acts on g protein coupled receptors - CRHR1 and 2 in anterior pituitary to stimulate POMC synthesis

58
Q

describe pro hormone convertase

A

Pro homormone convertase ⅓ (PC1/3) sequentially cleaves POMC to pro ACTH → ACTH
a

59
Q

what does body do with acth

A

Body takes ACTH from pituitary to adrenal gland - on top of kidneys
ACTH regulates glucocorticoid synthesis in adrenal cortex
Specifically acts on one cortex
ACTH regulations glucocorticoids synthesis in zonae fasciculata/reticularis

60
Q

how does acth regulate glucocorticoids synthesis

A

Encourages CYP11B1 and CYP17 to take cholesterol and produce it into cortisol
CYP17 acts first = pregnenolone to 17 alpha-hydroxypregneneolone and then downstream = CYP11B1 acts at last step = 11-deoxycortisol to cortisol

61
Q

what does acth do

A

ACTH = increases delivery of cholesterol to inner mitochondrial membrane
Increases transcription of steroidogenic enzymes
Important for production of pregnenolone - gets cleaved into cortisol

62
Q

describe the general action of crh and hormones and stuff

A

Functions like a feedback loop
Stress= hypothalamus produces CRH → cortisol from adrenals
Cortisol signals back to hypothalamus to stop producing CRH
Feedback loop
When reach threshold of cortisol = stops producing more
Pathway affected when exogenous glucocorticoids

63
Q

describe how hormones act

A

Hormones exert their effects by binding to and activating receptors on target cells.

64
Q

describe receptors for hormones

A

These receptors can be located on the cell surface, as for peptide hormones, or within the cell, as in the case of steroids and thyroid hormones.
Glucocorticoids block transcription - bind directly to dna

65
Q

what happens after receptor activation

A

After receptor activation, intracellular signalling pathways (e.g., second messenger systems or ligand-activated transcription factors) are modulated, which acutely or chronically alter cellular physiology and potentially whole organism physiology

66
Q

describe steroid hormone receptor

A

Are generally intracellular receptors (typically cytoplasmic or nuclear) and initiate signal transduction for steroid hormones which lead to changes in gene expression over a time period of hours to days.
STeroid hormone receptors inside cells = must get inside
Steroids = lipophilic - helps get through membrane

67
Q

Describe glucocorticoid regulation of gene expression

A

Up to 20% of all genes in immune cells are regulated by glucocorticoids
Binds to dna via glucocorticoid receptor

Can induce transactivation = Turn on genes
OR
transrepression

No clear mechanism

68
Q

describe When exposed to glucocorticoids

A

IN CELL = chaperons that complex with steroid and allow it to go into nucleus
Can eventually turn off inflammation = Not just through one mechanism - many different mechanisms
Glucocorticoids can stop cytokine production, replication of t cells, many different immune responses

69
Q

describe effects of glucocorticoids

A

Changes in cell proliferation, survival, differentiation, migration
Decreased pro-inflammatory cytokines, interleukins, prostaglandins
DECREASE INFLAMMATION
Inhibits innate and adaptive

70
Q

describe glucocorticoids and innate immune cells

A

Inhibits innate immune cells
inhibiting these innate immune cells such as eosinophils or mast cells from producing, degranulating and producing lipid mediators such as arachidonic acid or leukotrienes or prostaglandins. But it also stops antigen presentation and proliferation of T cells, as well as the production of specific cytokines

71
Q

describe what else glucocorticoid’s affects

A

Generally transcriptional activation
Metabolic –increase glucose to protect the brain and heart (“fight or flight”)
Increase blood glucose
decreasing fat deposits (increased lipolysis)
increased protein catabolism and decreased synthesis

72
Q

how does glucocorticoids Increase blood glucose

A

increasing glycogen breakdown (glycogenolysis)
increasing glucose synthesis (gluconeogenesis)
Activate system = activate system so have more glucose available - more energy
Can also cause weight gain

73
Q

describe glucocorticoids and oral contraceptives

A

when someone is on oral contraceptives and they need to take glucocorticoids, the dosage would be different than someone who’s not on oral contraceptives.
Since affects biosynthesis pathway

74
Q

describe pharmacokinetics

A

Glucocorticoids are administered through most routes, but local administration is preferred to minimize adverse effects associated with systemic actions
Since drugs can act on whole body

75
Q

describe circulating cortisol

A

Circulating cortisol is 80%–90% bound to plasma proteins with high affinity to corticosteroid-binding globulin (CBG, transcortin), 5%–10% loosely bound to albumin, and 3%–10% as the free, active fraction
Once glucocorticoids in system =can move through system by binding to CBG

76
Q

describe cbg

A

CBG can also bind synthetic glucocorticoids such as prednisone and prednisolone, but not dexamethasone, resulting in almost 100% of plasma dexamethasone bioactive

77
Q

describe cbg - how it works

A

Corticosteroid-binding globulin (CBG) transports glucocorticoids in the blood and thereby modulates the tissue availability of these hormones
If need glucocorticoid to get to tissue - can be difficult if give it the drug iv or orally = First gets into systemic circulation and is bound to CBG and might not get to tissue
Basically, binding to CBG helps transport the hormone but inflammation, stress, induced release of molecules like elastase releases the steroid from the complex

78
Q

describe cbg - when giving glucocorticoid

A

When giving someone a glucocorticoid the CBG binding and loss of bioavailability needs to be considered
EX = mutation in enzyme that allows you to break CBG from corticosteroid, If cannot separate = cannot go into cell

79
Q

describe where glucocorticoids absorbed

A

Most glucocorticoids are absorbed rapidly and readily from the GI tract and from synovial and conjunctival spaces because of their lipophilic character, but they are absorbed very slowly through the skin.
SOME ORgans absorb glucocorticoids easier

80
Q

what do elevated levels of estrogen do to glucocorticoids

A

Elevated concentrations of estrogen, such as occurs in pregnancy, contraceptive use, or hormone replacement therapy, increase the biosynthesis of CBG in the liver, requiring increased plasma cortisol concentrations to maintain an appropriate bioactive fraction
Need to give all info to doctors

81
Q

what else affects glucocorticoids

A

Weight also matters
Since lipophilic
If obese = more fat = more lost from site you want it to go

Circadian rhythm affects the drug
Circadian rhythm is the name given to your body’s 24-hour “internal clock.”
Sleep = glucocorticoids shift up and then go down in morning

82
Q

describe what addition of a fluorine atom at position 9 does - glucocorticoids as drugs

A

enhances glucocorticoid and mineralocorticoid activity
Change at 9th position = Introduction of fluorine enhances mineralocorticoid, glucocorticoid activities

83
Q

describe what addition of a methyl group at position 16 will do - glucocorticoids as drugs

A

as present in betamethasone and dexamethasone increases GR activation and virtually eliminates MR activation, yet does increase the duration of action of these compounds
a methyl group at position 16 of prednisone= increase glucocorticoid activation and eliminate any mineralocorticoid activation and increase duration of drug
Change in 16th position = introduce methyl, minimizes mineralocorticoid activity in 9 alpha-fluoro compounds

84
Q

describe plasma half lives of glucocorticoids as drugs

A

Prednisone, prednisolone, and methylprednisolone have intermediate plasma half-lives, whereas betamethasone and dexamethasone are long acting analogues. - depends on disease
Have been modified so cna last longer in system
Modified also so will not eliminate or turn on production of mineralocorticoids

85
Q

describe ways of administering glucocorticoids

A

Inflammatory diseases of skin = eczema= Creams
Asthma = Inhalation, Stop inflammation in lung (Only in lung)

86
Q

describe Replacement Therapy: Addison’s Disease

A

Adrenal insufficiency occurs when the adrenal glands do not make enough of the hormone cortisol.
The primary kind is known as Addison’s disease.
It is rare

Give glucocorticoids to help, since they cannot produce own cortisol
Good and helps since people are hypoglycemia = not enough sugar absorption

87
Q

describe treatment Addisons disease

A

involve hormone replacement therapy to correct the levels of steroid hormones thebody isn’t producing. Some options for treatment include oral corticosteroids such as:
Hydrocortisone (Cortef), prednisone or methylprednisolone to replace cortisol. These hormones are given on a schedule to mimic the normal 24-hour fluctuation of cortisol levels.
Fludrocortisone acetate to replace aldosterone

88
Q

Describe myeloproliferative disorders

A

type of blood cancer that begin with an abnormal mutation (change) in stem cells in the bone marrow that leads to an overproduction of any combination of white cells, red cells and platelets - immune cells
Reduces the side effects of have excess white blood cells= use glucocorticoids

89
Q

describe Adverse effects of glucocorticoids

A

Side effects = increase of hair, acne, greasy skin, irregular periods
biosynthetic pathways of glucocorticoids are really similar to some of your sex hormones
reduced fertility, tiredness and fatigue.
And then on the other side, you also have increased appetite, weight gain, muscle weakness.
And this is really dependent on if you have too low cortisol or if you have too high cortisol
Psychiatric, neurologic, skin/soft tissue, musculoskeletal system. Developmental, endocrine, cardiovascular, immunologic, ophthalmic

90
Q

describe Pharmacovigilance

A

Adverse Effects of Prolonged Glucocorticoids Therapy=
Osteoporosis and fracture
Glucose intolerance and diabetes
Central obesity
Muscle wasting
Increased risk of infections
Depression
Cataracts

91
Q

describe Pharmacovigilance- osteoporosis and fracture

A

≥ 3 months -increase in fracture risk
Because = taking glucocorticoids increases calcium absorption by gut and reduces it being exported into bones = fractures

92
Q

describe Pharmacovigilance - glucose tolerance and diabetes

A

doubled in rheumatoid arthritis patients taking ≥7.5 mg prednisone
Since glucocorticoids increase glucose absorption

93
Q

what does Long term high dose exogenous steroid lead to

A

shut down of HPA axis and adrenal atrophy
Hypothalamus turns off production of endogenous cortisols = effect body functions

94
Q

name more adverse effects of glucocorticoids

A

Oral candidiasis (thrush)–Rinse mouth after inhalation
Leads to immunosuppression in mouth = changes in salivary glands that protect mouth from infections
HPA axis suppression–Uncommon with low or medium doses
Growth inhibition–Pre-pubertal patients
Decreased bone density
Oral corticosteroids (e.g., prednisone)–Extreme cases–Short duration

95
Q

what is cushings syndrome

A

if on glucocorticoids for prolonged period and high doses

96
Q

describe characteristics of cushings

A

Physical abnormalities
individuals who either had some sort of allergic reaction or have an autoimmune disease that was ineffectively maintained with the specific drugs such as the ones that are blocking the cytokines or the T cell proliferation. So they’re on glucocorticoids for months in high doses, milligram doses.
= moon face, thickening of neck, gain weight - many side effects
But need glucocorticoids to reduce inflammation

97
Q

describe cushings disease - cause

A

Cushing’s disease can be caused by issues with the body’s hormone signalling or from the overuse of steroids.

98
Q

describe HPA axis cushings

A

Have all of it ramped up =
Cortisol Increases hypothalamus to produce more = can be caused by tumour in pituitary that does not stop feedback loop
Cause different = pitautary ACTH dependent cushing syndrome
Same effects as cushing’s syndrome

99
Q

describe HPA axis cushings - ectopic

A

Ectopic ACTH cushing syndrome
External ACTH acts on adrenal and produced more cortisol and acts on hypothalamus

100
Q

describe adrenal adenoma cushings

A

Adrenal adenoma = tumour in adrenal gland = production of more corticosteroids = no way to inhibit cycle

101
Q

how to treat cushings

A

Exogenous glucocorticoids = reduce size of adrenal gland and need more and more hormones = iatrogenic cushing’s syndrome
Causes by exogenous glucocorticoids and loss of function of adrenal gland
Phenotype same so hard to tell which kind of cushings it is

PHAR 300 (22 decks)

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