Corticosteroids Flashcards

1
Q

What are corticosteroids?

A

They are hormones derived from cholesterol and produced in the ADRENAL CORTEX.

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2
Q

What are the main corticosteroids?

A
  • Cortisol

- Aldosterone

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3
Q

What 2 categories of corticosteroids does cortisol and aldosterone split into?

A
Cortisol = Glucocorticoids  
Aldosterone = Mineralcorticoids
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4
Q

What is the purpose of corticosteroids?

A

Lowers inflammation in the body and thus, reduces the immune system activity in the body.

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5
Q

How does cortisol act?

A

Acts via the glucocorticoid receptors.

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6
Q

How does aldosterone act?

A

Acts via the mineralocorticoids receptors.

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7
Q

What does cortisol do?

A

Acts on carbohydrate and protein metabolism.

Regulates host defence mechanisms.

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8
Q

What does aldosterone do?

A

Regulates water and electrolyte balance.

ESSENTIAL = sodium conservation in the kidney and sweat glands.

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9
Q

Where are glucocorticoids made?

A

Zona Fasiciculata

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10
Q

Where are mineralocorticoids made?

A

Zona Glomerulosa

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11
Q

How is glucocorticoid release regulated?

A

It is regulated by the HPA axis and engages with NEGATIVE feedback control.

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12
Q

What is a competitive inhibitor involved with glucocorticoid release?

A

Metyrapone

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13
Q

What is the purpose of metyrapone?

A

Reduces glucocorticoids when there is an OVERLOAD.

This inhibits beta - hydroxylase which INHIBITS cortisol.

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14
Q

What is Cushing’s syndrome?

A

This is a syndrome which occurs due to excessive levels of endogenous glucocorticoids.

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15
Q

What is Addison’s syndrome?

A

This is a syndrome which occurs due to very little levels of corticosteroids in the body.

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16
Q

What is the difference between Cushing’s syndrome and Addison’s syndrome?

A

Cushing’s produces TOO MUCH hormone whereas Addison’s produces TOO LITTLE hormone.

17
Q

What are some symptoms of Cushing’s syndrome?

A

Increased abdominal fat
Easy bruising
Hypertension
Thinning of the skin

18
Q

What are the 2 pathways glucocorticoids can take in terms of mechanism of action?

A

Upregulate transcriptional machinery OR repress the activity of transcription factors.

19
Q

What is the molecular mechanism of action of glucocorticoids?

A

Dimerized glucocorticoids go bind to recognition sites on DNA.

20
Q

What happens regarding up regulating transcriptional machinery?

A

Glucocorticoids BIND to the glucocorticoid receptor = Ligand binding results in a nuclear receptor being activated.

21
Q

What happens regarding repressing the activity of transcription factors?

A

Influences multiple signal transduction.

Switching off multiple activated inflammatory genes via inhibition of HAT and HDAC2.

22
Q

What is gene transrepression?

A

One protein represses the activity of a second protein.

This results in silencing pro inflammatory genes.

23
Q

What is the action which occurs on inflammatory cells?

A

There is a decreased number of neutrophils leaving the blood vessels and reduced activation of neutrophils // macrophages // mast cells.
There is a decreased activation of T - Helper cells.
There is a decreased fibroblast function.

24
Q

What are some examples of synthetic therapeutically used glucocorticoids?

A

Cortisone
Prednisone
Betamethasone
Dexamethasone

25
Q

What are some examples of natural therapeutically used glucocorticoids?

A

Cortisol

26
Q

Which glucocorticoid is the most potent and thus has the least mineralocorticoid activity?

A

Dexamethasone

27
Q

What is the mechanism of synthetic glucocorticoids?

A

They bind to albumin but NOT to transcortin. They are MORE SLOWLY synthesised thus giving them a LONGER DURATION of action.

28
Q

What is the mechanism of cortisol glucocorticoids?

A

Binds to a corticosteroid - binding albumin and thus, is extensively metabolised in the gut wall.

29
Q

What diseases are synthetic glucocorticoids used to treat?

A
Myeloma 
Renal disorders
Bronchial Asthma
Bell's Palsy
Organ transplantation
30
Q

What type of administration is used to deliver glucocorticoids?

A

Topical Administration

31
Q

What are the side effects of glucocorticoid therapy?

A
Cushing's syndrome
Hyperglycaemia
Osteoporosis 
Muscle Wasting
Cataracts // Glaucoma
Easy bruising