Therapeutic use of adrenal steroids

Question 1

What are the triggers for aldosterone release?

Answer 1

Hyperkalaemia
Hyponatraemia
Low renal blood flow
Beta 1 adrenoceptor stimulation

Question 2

What is the difference between the distribution of glucocorticoid receptors and mineralocorticoid receptors?

Answer 2

GR wide distribution but MR has a discrete distribution that is mainly in the kidney

Question 3

What is the difference between the selectivity of glucocorticoid receptors and mineralocorticoid receptors?

Answer 3

GR selective for glucocorticoids

MR does not distinguish between aldosterone and cortisol

Question 4

What is the difference between the affinity of glucocorticoid receptors and mineralocorticoid receptors?

Answer 4

GR low affinity for cortisol

MR high affinity for cortisol

Question 5

Why does cortisol not bind to MR all the time?

Answer 5

11 beta hydroxysteroid dehydrogenase (11betaHSD) inactivates cortisol into cortisone

Question 6

What is a problem with 11 beta HSD in cushings

Answer 6

TOO much cortisol so 11betaHSD overwhelmed therefore cortisol binds to MR and Na+ in K+ out and makes hypokalaemia

Question 7

What does hydrocortisone do?

Answer 7

It is a glucocorticoid with mineralocorticoid activity at high doses - treat for addisons

Question 8

What does prednisolone do?

Answer 8

Glucocorticoid with weak mineralocorticoid activity

- Immunosupressant, asthma, arthritis

Question 9

What does dexamethasone do?

Answer 9

Synthetic glucocorticoid with no mineralocorticoid activity

Question 10

What is fludrocortisone

Answer 10

Used to replace aldosterone - it is an aldosterone analogue

Question 11

What are the drugs used to replace cortisol in adrenocortical failure?

Answer 11

Normally use hydrocortisone but there is also prednisolone and dexamethasone

Question 12

What are routes of administration of corticosteroids?

Answer 12

Oral - hydrcortisone, prednisolone, dexamethasone, fludrocortisone
Parenteral (iv./im.) -hydrocortisone, dexamethasone - done if needed high dose fast

Question 13

How are the adrenal steroid drugs distributed around the body

Answer 13

Bind to plasma proteins eg cortisol binding globulin and albumin like cortisol does

Question 14

What is the duration of action of hydrocortisone?

Answer 14

8h

Question 15

What is the duration of action of prednisolone?

Answer 15

12h

Question 16

What is the duration of action of dexamethasone?

Answer 16

40h

Question 17

What do you do to a patient with addisons disease in A&E

Answer 17

1. resussitate patient with 0.9% NaCl to give back salt, and iv. hydrocortisone
2. hydrocortisone and fludrocortisone by oral when they go home

Question 18

What does a large dose of iv. hydrocortisone do?

Answer 18

Bind to GR and so much of it so it overwhelms 11betaHSD so the hydrocortisone binds to MR as well

Question 19

What is different with secondary adrenocorticol failure compared to primary?

Answer 19

Patients lack cortisol but aldosterone is normal bc problem with pituitary

Question 20

How do you treat secondary adrenocorticol failure?

Answer 20

Only give hydrocortisone because their aldosterone count is normal

Question 21

How do you treat acute adrenocortical failure aka addisonian crisis?

Answer 21

1. iv 0.9% NaCl to rehydrate patient
2. High dose hydrocortisone iv infusion or im every 6h
3. 5% dextrose if hypoglycaemic

Question 22

What are the objectives of therapy for congenital adrenal hyperplasia?

Answer 22

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

Question 23

How to treat congenital adrenal hyperplasia?

Answer 23

Big dose of glucocorticoid eg dexamethasone 1/ day pm or hydrocortisone 2-3/ day pm and fludrocortisone
Monitor/optimise therapy by measuring 17 OH progesterone

Question 24

Why is treating congenital adrenal hyperplasia difficult to manage?

Answer 24

Too much glucocorticoid - cushings

Too little - addisons

Question 25

How does cortisol production change when someone is ill?

Answer 25

Stress causes cortisol to increase by 10x the amount and it helps you get better

Question 26

Why do patients die with addisons disease?

Answer 26

Because they forget when they are ill to increase the dose of cortisol in your body - minor illness needs 2x normal dose until feeling ill
- surgery needs hydrocortisone i.m with premed and 6-8hr intervals (if nil by mouth) and oral once eating and drinking

Question 27

What must you tell patients with adrenocortical failure?

Answer 27

They have to wear a steroid alert card and wear a MedicAlert bracelet/necklace so that emergency services can give them cortisol if they collapse on the street