8 - Therapeutic Use of Adrenal Steroids Flashcards by Anisha Malli

What can influence the hypothalamo-pituitary-adrenal axis for cortisol synthesis?

Circadian rhythm

Stress

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Which part of the adrenal cortex synthesises cortisol?

Zona fasciculata

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Which part of the adrenal cortex synthesis aldosterone?

Zona glomerulosa

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What are the 3 arms of adrenal steroid hormone production?

Glucocorticoids (incl. cortisol)

Mineralocorticoids (incl. aldosterone)

Sex Steroids

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What organs are the main source of sex steroids?

Gonads

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How is aldosterone synthesis and release regulated?

Via Renin-Angiotensin System

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What is the pathway to Aldosterone synthesis via renin?

Angiotensinogen (liver)

–> Renin (kidney)

Angiotensin I

–> Angiotensin Converting Enzyme (ACE)

Angiotensin II

Acts on adrenal gland, causes aldosterone synthesis

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What can activate aldosterone synthesis?

Hyperkalaemia

Hyponatraemia

Decreased renal blood flow

Beta-1 adrenoreceptor stimulation

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What are the functions of cortisol?

Has lots of different actions depending on which sort of cells it is acting upon.

controlling the body’s blood sugar levels
regulating metabolism
acting as an anti-inflammatory
influencing memory formation
controlling salt and water balance
influencing blood pressure
helping development of a foetus in utero

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What are the functions of aldosterone?

increase sodium reabsorbed into the bloodstream
increase potassium excreted in the urine
causes water to be reabsorbed along with sodium
increases blood volume
therefore increases blood pressure

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What part of the kidney is sensitive to renal blood flow and measures it?

Juxta-Glomerular Apparatus

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What are the families of receptors called for cortisol and aldosterone?

Glucocorticoid Receptors (GR)

Mineralocorticoid Receptors (MR)

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Which super-family of receptors do MR and GR types belong to?

Nuclear Receptor super-family

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Outline facts about Glucocorticoid Receptors (GR)

Wide distribution

Selective for glucocorticoids

Low affinity for cortisol

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Outline facts about Mineralocorticoid Receptors (MR)

Discrete distribution (kidney)

Do not distinguish between aldosterone and cortisol

High affinity for cortisol

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What is special about cortisol’s ability to bind to receptors?

It can bind to both Glucocorticoid Receptors (GR) and Mineralocorticoid Receptors (MR)

It has a low affinity for GRs and a high affinity for MRs

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Why is cortisol’s ability to bind to Mineralocorticoid Receptors typically not a problem physiologically?

This is because cortisol is very quickly broken down by 11 beta-hydroxysteroid dehydrogenase 2 into cortisone

Cortisone is inactive and can’t bind to the Mineralocorticoid Receptors

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Why is cortisol’s ability to bind to Mineralocorticoid Receptors a problem in Cushing’s Syndrome?

The body makes too much cortisol

Therefore, the enzyme (11 beta-hydroxysteroid dehydrogenase 2) that breaks down cortisol quickly into cortisone is overwhelmed

Some of the cortisol binds to the receptors and acts as aldosterone

This causes hypokalaemia, hypernatraemia and hypertension

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Explain the mechanism of action of Hydrocortisone

Glucocorticoid

Acts in the same way as cortisol

Can bind to Mineralocorticoid receptors but only does so at high doses because otherwise it is broken down by 11 beta-hydroxysteroid dehydrogenase 2 (like cortisol)

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How are people in Addisonian Crisis treated?

Study These Flashcards

Patient has low aldosterone and cortisol
Low aldosterone
- increased sodium excretion
- increased water excretion
- increased potassium retention

I.V. 0.9% NaCl (Normal Saline)

give patient back sodium and water
restore circulating volume

Parenteral high dose of Hydrocortisone

works quickly
acts as cortisol
however, because it’s a large dose, it acts as aldosterone as well by overwhelming 11 beta-hydroxysteroid dehydrogenase 2 and binding to Mineralocorticoid Receptors

5% Dextrose
- given if patient is hypoglycaemic due to lack of cortisol

SEND THEM HOME ON:

Hydrocortisone or Prednisolone
- replace cortisol

Fludrocortisone
- replace aldosterone

Name some Glucocorticoid drugs

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Hydrocortisone

Prednisolone

Dexamethasone

What is Hydrocortisone?

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Glucocorticoid with mineralocorticoid activity at high doses

Oral/Parenteral

What is Prednisolone?

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Glucocorticoid with weak mineralocorticoid activity

Oral

What is Dexamethasone?

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Synthetic glucocorticoid with no mineralocorticoid

Oral/Parenteral

What is Fludrocortisone?

Aldosterone analogue Oral

What receptors can Hydrocortisone bind to?

GR MR

What receptors can Prednisolone bind to?

GR Slightly to MR

What receptors can Fludrocortisone bind to?

What receptors can Dexamethasone bind to?

What does Parenteral mean?

The route of administration of a drug is I.V. or I.M.

Why are people with brain tumours sometimes administered Dexamethasone?

These patients commonly present with oedema Dexamethasone has anti-inflammatory properties and reduces swelling

How does cortisol travel around the body?

Bound to plasma proteins - Cortisol Binding Globulin (CBG) - Albumin Only free hormone is active Other glucocorticoids also bind to plasma proteins

What is the duration of action of Hydrocortisone?

8 hours

What is the duration of action of Prednisolone?

12 hours

What is the duration of action of Dexamethasone?

40 hours

What is another name for Addison's Disease?

Primary Adrenocortical Failure

What is caused by Addison's Disease?

No aldosterone, cortisol or sex steroids ``` Hyperkalaemia (retention of potassium) Hyponatraemia (excretion of sodium) Excretion of water alongside the sodium Low Renal Blood Flow due to low circulating volume Beta-1 adrenoreceptor stimulation ```

How do you treat Addison's Disease?

Hydrocortisone (oral) - replace cortisol Fludrocortisone (oral) - replace aldosterone

What is Secondary Adrenocortical Failure?

ACTH deficiency (most commonly due to a pituitary tumour causing loss of corticotrophs) ``` Lack cortisol Normal aldosterone (because under RAAS system) ``` Treat with hydrocortisone or prednisolone

What is the difference between Primary and Secondary Endocrine Failure?

Primary = the gland itself has stopped working Secondary = problem with pituitary or hypothalamus

What is the difference between oral administration of hydrocortisone compared with prednisolone?

Prednisolone can just be taken once a day Hydrocortisone needs to be taken multiple times a day This is due to their different duration of action times

What is Congenital Adrenal Hyperplasia?

Congential lack of enzymes needed for adrenal steroid synthesis Still Primary Adrenocortical Failure

What are the objectives of therapy for Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency?

Replace cortisol Suppress ACTH (and thus, adrenal androgen production) Replace aldosterone in salt wasting forms

How do you treat Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency?

Hydrocortisone/Prednisolone - replace cortisol Fludrocortisone - replace aldosterone Lower ACTH - Dexamethasone 1x per day OR - Hydrocortisone 2-3x per day

How is therapy monitored/optimised for Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency?

Measure: 17 Hydroxyprogesterone - precursor that builds up in CAH - should start to decrease if treatment is working Clinical Assessment - hirtusim - acne

Why is treatment of Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency difficult to balance?

If patients are given lots of glucocorticoids in an attempt to suppress high levels of ACTH, they may become Cushingoid (due to a high glucocorticoid dose) = IATROGENIC CUSHING'S However if you lower the glucocorticoid dose, then the patient may develop hirsutism again due to ACTH rising again.

What is some additional measures advice that needs to be given to patients with adrenocortical failure?

Tell the patients about "sick day rules" Patient can't make extra cortisol when sick (flu, fever, infection etc)/stressed Therefore, they need to take an increased glucocorticoid dose (double) until they get better

When does a patient with adrenocortical failure need an increase dose of glucocorticoids?

In minor illness (stress) - 2x normal dose Surgery (major acute stressor) - Need big doses of hydrocortisone as the body would normally make with functioning adrenals when undergoing surgery - I.M. hydrocortisone - With pre-meds - at 6-8 hour intervals - Oral hydrocortisone once back to eating and drinking

What must patients with adrenocortical failure wear/carry?

Should carry a steroid alert card and wear a MedicAlert bracelet/necklace

8 - Therapeutic Use of Adrenal Steroids Flashcards

(49 cards)