Therapeutic Use of Adrenal Steroids Flashcards

1
Q

Name the three parts of the adrenal cortex and the steroids that each produces.

A

Zona Glomerulosa – Aldosterone
Zona Fasciculata – Cortisol
Zona Reticularis – Sex Steroids

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2
Q

What hormone controls the production of adrenal sex steroids?

A

ACTH

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3
Q

What controls the production of aldosterone?

A

Angiotensin II

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4
Q

State four triggers of aldosterone release

A

Hyperkalaemia
Hyponatraemia
Drop in renal blood flow
Beta-1 stimulation

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5
Q

What is the principle action of aldosterone?

A

Increases Na+ reabsorption

Increases K+ excretion

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6
Q

State three differences between glucocorticoid receptors and mineralocorticoid receptors.

A

GRs are widely distributed; MRs have a discrete distribution
GRs are selective for glucocorticoids; MRs cannot distinguish between cortisol and aldosterone
GRs have a low affinity for cortisol; MRs have a high affinity for cortisol

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7
Q

Describe how MRs are protected from cortisol stimulation.

A

There is an enzyme called 11-beta hydroxysteroid dehydrogenase-2, which converts cortisol to the inactive cortisone to prevent it from interacting with mineralocorticoid receptors. NOTE: 11-beta-HSD-1 converts cortisone back to cortisol

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8
Q

Why do you get hypokalaemia in Cushing’s syndrome?

A

In Cushing’s syndrome there is so much cortisol that it overloads the 11-beta-HSD-2 system so the cortisol binds to the mineralocorticoid receptors and has mineralocorticoid effects.

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9
Q

Name three glucocorticoid drugs in order of decreasing mineralocorticoid activity.

A

Hydrocortisone (highest mineralocorticoid activity)
Prednisolone
Dexamethasone

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10
Q

What does prednisolone tend to be used for?

A

Immunosuppression

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11
Q

What does dexamethasone tend to be used for?

A

Acute anti-oedema

E.g. used clinically for things like brain metastases where there is a lot of oedema

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12
Q

Name an aldosterone analogue.

A

Fludrocortisone

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13
Q

How are all these drugs administered?

A

Orally

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14
Q

Describe the extent of plasma protein binding in each of these four drugs.

A

They bind to plasma proteins – corticosteroid binding globulin + albumin
Hydrocortisone is extremely plasma protein bound –90-95% Prednisolone is less bound
Dexamethasone and fludrocortisone are even less bound
Fludrocortisone only binds to albumin

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15
Q

Where are the corticosteroid drugs metabolised and how are they excreted?

A

Hepatic metabolism

Excreted in the bile and urine

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16
Q

Describe the half-lives of the four drugs.

A

In order of increasing half-life (shortest half-life first):
 Hydrocortisone + Fludrocortisone (1 hr duration)
 Prednisolone (12 hour duration)
 Dexamethasone (40 hour duration)

17
Q

State five reasons for giving corticosteroid replacement therapy

A
Primary adrenocortical failure  
Secondary adrenocortical failure  
Acute adrenocortical failure  
Congenital adrenal hyperplasia 
Iatrogenic adrenocortical failure
18
Q

State two causes of primary adrenocortical failure.

A

Addison’s disease

Chronic adrenal insufficiency

19
Q

What is the usual treatment for primary adrenocortical failure?

A

There is a lack of cortisol and aldosterone so you must replace both
Hydrocortisone
Fludrocortisone

20
Q

What is secondary adrenocortical failure?

A

The adrenal gland itself is fine but there is a problem with the pituitary gland (ACTH deficiency)
There is NORMAL aldosterone production (because aldosterone isn’t dependent on ACTH)
So only cortisol needs to be replaced

21
Q

Describe the treatment of secondary adrenocortical failure.

A

HYDROCORTISONE (titrate the dose to mimic normal physiology)

22
Q

What is the treatment for acute adrenocortical failure (Addisonian Crisis)?

A
IV saline (because they are suffering from a salt losing crisis) 
High dose hydrocortisone  
Dextrose (if they are hypoglycaemic) 
NOTE: don’t normally need dextrose because the hydrocortisone will increase blood glucose anyway
23
Q

What is the most common cause of congenital adrenal hyperplasia?

A

21-hydroxylase deficiency

24
Q

Describe the ACTH levels in CAH and explain the effect this has on steroid synthesis.

A

High ACTH – because no cortisol is being produced so there is no negative feedback on the hypothalamo-pituitary axis
High ACTH means that the sex steroid synthesis pathway is turned on – there is an increase in adrenal sex steroids

25
Q

What are the consequences of CAH in childhood?

A

CAH caused by partial enzyme deficiency can result in virilisation and precocious puberty

26
Q

How do you treat CAH?

A

Replace cortisol with high dose hydrocortisone (2-3/day) or dexamethasone (1/day)
Replace aldosterone with fludrocortisone
This is to replace cortisol and to suppress the ACTH axis to reduce adrenal sex steroid production

27
Q

How do you monitor CAH?

A

Measure 17a-hydroxyprogesterone levels

Monitor them clinically – are they complaining of hirsuitism/acne or cushingoid symptoms?

28
Q

When would you change the dose of hydrocortisone in CAH?

A

If they are under any particular stress such as illness

29
Q

What is iatrogenic adrenocortical failure?

A

Long-term, high dose glucocorticoid therapy can suppress the HPA axis and hence suppress adrenal function so that they no longer produce cortisol by themselves
They need to keep a steroid dependence bracelet