3.2 Steroid Drugs

Question 1

What are the 3 layers of the adrenal coretx and what is secreted from each?

Answer 1

Zona Gomerulosa: mineralocorticoids (aldosterone)

Zona Fasciula: glucocorticoids (cortisol)

Zona Reticularis: androgens/ sex steroids (DHEA)

Question 2

Corticosteroids are derived from what?

Answer 2

cholesterol

Question 3

Cortisol = endogenous glucocorticoid

What is the name given to the SAME structure when it is given pharmacologically (exogenous)

Answer 3

Hydrocortisone

Question 4

Give 2 other glucocorticoids (not cortisol)

Answer 4

Dexamethazone and Prednisolone

Question 5

Explain the HPA axis

Answer 5

Question 6

Give 3 metabolic actions of glucocorticoids

Answer 6

1) glycogenolysis and gluconeogenesis ➞ hyperglycaemia and proteinolysis
2) Lipolysis (at low conc)
3) Lipid deposition (at high conc) ➞ Redistribution of fat

Question 7

Give 4 effects of a glucocorticoid deficiency

Answer 7

1. Hypoglycaemia
2. Weight loss
3. Nausea
4. Hypotension
5. Underweight

Question 8

Give 4 effects of a glucocorticoid excess

Answer 8

1. Hyperglycaemia
2. Weight gain
3. Increased appetite
4. Hypertension
5. Cushingoid

Question 9

When considering the effect of glucocorticoids, what else MUST we consider and why?

Answer 9

Mineralocorticoid effect!

Glucocorticoids can bind to mineralocorticoid receptors due to their structural similary. This may cause patients to present with symptoms associated with mineralocorticoids AND corticoids

Question 10

Give 4 effects of a mineralocorticoid deficiency

Answer 10

1. Hyponatraemia
2. Dehydration
3. Hypotension
4. Hyperkalaemia

Question 11

Give 3 effects of a mineralocorticoid excess

Answer 11

1. Hypernatraemia
2. Hypertension
3. Hypokalaemia

Question 12

Explain what the image below shows

Answer 12

The relative action of specific corticosteroid drugs on the glucocorticoid and mineralocorticoid receptors

Hydrocortisone = 1

➞ normalised effect on both receptors which is used to compare the other drugs

Question 13

What does the image below show?

Answer 13

Equivalent anti-inflammatory doses of corticosteroids (potency) compared to a 5mg dose of Prednisolone

This table takes no account of mineralocorticoid effects, nor does it take account of variations in duration of action

Question 14

What 3 similarities can be said about most corticosteroids

Answer 14

1) When taken orally, steroids have similar bioavailability
2) Most metabolised hepatically and cleared renally (renal clearance)
3) Ability for clearance with all steroids, decreases with age

Question 15

Give 5 routes of administration for corticosteroids and an example of a drug used in each

Answer 15

Question 16

Give 4 effects of corticosteroids on the immune system

Answer 16

1. Inhibition of B and T cell responses
2. Inhibition of NF-κB
3. Reduced transcription of cytokines
4. Reduced expression of cell adhesion molecules
5. Reduced phagocytic function
6. Immunosuppression
7. Reduced inflammation

Question 17

Steroids are ______ soluble and ______ cross the cell membrane

Answer 17

lipid, can

Question 18

Steroid diffuses into cell and binds to hormone receptors either in the ______ or the ________.

They then _______ and act as either ______ or ______ of hormone response elements by regulating gene ________.

Answer 18

cytoplasm, nucleus, dimerise, enhancers, inhibitors, transcription

Question 19

What does HSP and HRE stand for?

Answer 19

HSP – heat shock protein

HRE – hormone response element

Question 20

What is the role of NF-κB?

Answer 20

Good modulator of the inflammatory response

Question 21

Give 2 things that occur when a corticosteroid binds to the glucocorticoid receptor

Answer 21

1) transactivation ➞ regulates Annexin 1 which inhibits leukocyte inflammation events
2) transrepression ➞ upregulates CBP which is the inhibtor of NF-κB

These stimulate anti-inflammatory gene transcription

Question 22

Give 3 negative side effects of glucocorticoids and state why?

Answer 22

1) Repression of gene expression by down regulation of HPA axis
2) Downregulation of osteocalcin ➞ important for osteoblast activity
3) Reduces the amount of keratin ➞ skin thinning

Question 23

What is CBP and its relevance in corticosteroids? (non-genetic effect)

Answer 23

CBP: cAMP response element binding protein

This is a coactivator molecule. Corticosteroid can bind to this which attacts and complexes to NF-κB. This holds NF-κB in an inactive form which reduces its inflammatory effect.

(Note: this is in additon to the upregulation of NF-κB inhibtors)

Question 24

Give 4 clinical uses of steroid drugs

Answer 24

• Inflammatory disease
• Immuno-suppression
• Malignancy
• Adrenal insufficiency
• Cushing’s disease diagnosis

Question 25

Give 3 instances when corticosteroids may be used for replacement therapy

Answer 25

1. Deficiency 2. Addison’s disease 3. Adrenolectomy

Question 26

What are the 2 main corticosteroids and their dosage used in replacement therapy?

Answer 26

Hydrocortisone 20 – 30 mg daily Fludrocortisone 50 – 300 μg daily

Question 27

Give 4 Inflammatory diseases we can use corticosteroids to treat/manage

Answer 27

1. Asthma 2. GI diseases 3. Inflammatory skin conditions 4. Nephrotic syndrome 5. Rheumatoid arthritis 6. Cerebral oedema

Question 28

What is the use of steroids in preterm birth? Who are they offered too and when?

Answer 28

Steroid are used to enhance lung maturation. They can cross the placenta and stimulate surfactant production of immature lungs. This reduces the symptoms of respiratory distress syndrome A single course of antenatal corticosteroids are offered to women, who are at risk of preterm birth, between 24 and 34 weeks of gestation.

Question 29

Give 2 examples of steroids that can be used for preterm births (incl doses)

Answer 29

Betamethasone 12 mg given IM in two doses OR Dexamethasone 6 mg given IM in four doses

Question 30

Give 3 Mineralocorticoid side-effects (ADRs)

Answer 30

1. Fluid retention 2. Hypertension 3. Hypokalaemia

Question 31

Give 6 Glucocorticoid side effects

Answer 31

Question 32

Give 2 Cushingoid features in terms of fat distribution

Answer 32

1) Central obesity 2) Dorso-cervical fat pad

Question 33

Give 5 Corticosteroid effects on bone

Answer 33

1. Inhibition of osteoblast formation 2. Increased osteoclast proliferation 3. Reduced calcium absorption in gut 4. Reduced sex steroid production 5. Osteoporosis

Question 34

All steroid drugs mimic what endogenous steroid hormone? What is the major risk factor of this for patients?

Answer 34

Cortisol Adrenal suppression (may persist for years if patient is on long term treatment). Abrupt withdrawal may lead to hypo-adrenal crisis

Question 35

How long does it take for supression of the HPA axis to occur? Give an example of a specific drug and dosage that will do this

Answer 35

Suppression of HPA axis occurs after 3 weeks Prednisolone \> 20mg will suppress HPA axis

Question 36

Give ALL 6 main features/ risks of a Hypoadrenal crisis

Answer 36

1. Hypotension 2. Hypoglycaemia 3. Hyponatraemia 4. Hyperkalaemia 5. Severe dehydration 6. Death if untreated

Question 37

If a patient who has been on long term prednisolone requires surgery what MUST we do?

Answer 37

**Gradually** withdraw them off oral prednisolone

Question 38

How can we identify if a patient is on long term steroids when they are admitted into hospital?

Answer 38

Most will carry a steroid treatment card