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Flashcards in Steroid Drugs Deck (26):
1

What are the layers of adrenal gland and their hormones

Cortex:
Zona glomerulosa - mineralocortocoid
Zona fasciculata - glucocorticoid
Zona reticularis - sex steroid

Medulla - catecholamines

2

What are corticosteroids

Hormones synthesised in adrenal cortex, synthesised from cholesterol

3

What is control mechanism of glucocorticoid synthesis

HPA axis and negative feedback:
Hypothalamus - CRH
Anterior pituitary - ACTH
Adrenal cortex - Cortisol

4

What is the action of cortisol

Gluconeogenesis and glycogenolysis
Hyperglycaemia
Proteolysis
Lipolysis
Lipid deposition (high conc)
Lipid redistribution (abdomen, neck)

5

What are the effects of cortisol deficiency

Hypoglycaemia
Weight loss, reduced appetite
Hypotension

6

What are effects of cortisol excess

Hyperglycaemia
Weight gain, increased appetite
Cushing’s syndrome
Hypertension

7

What are effects of aldosterone deficiency

Hypotension
Hyponatraemia
Hyperkalaemia
Dehydration

8

What are effects of aldosterone excess

Hypertension
Hypernatraemia
Hypokalaemia

9

What does cross over mean

GC can have MC like activity by binding to MC receptors
Due to similar structures of MC and GC receptors

10

What determines level of cross over activity

Level of selectivity of hormone for GC and MC receptors

11

What are the different selectivities of different corticosteroids

Fludrocortisone: High MC, Low GC
Hydrocortisone: MC = GC
Prednisolone: Low MC, High GC
Betamethasone: minimal MC, v High GC
Dexamethasone: minimal MC, v High GC

12

What are the potencies of different corticosteroids

Hydrocortisone: 20mg
Prednisolone: 5mg
Dexamethasone: 750 mcg
Betamethasone: 750mcg

13

What are the routes of admin of corticosteroids

Systemic:
Oral
IV

Local:
Inhaled
Intra articular
Topical

14

What is cellular mechanism of action of steroids

Inhibit B + T cell responses
Inhibit NF-kB (inflammatory signalling molecule)
Reduced phagocyte function
Reduced inflammatory cytokine synthesis
Reduced cell adhesion molecule synthesis

15

What is molecular mechanism of action of steroids

Corticosteroids are lipophillic, freely cross cell membrane
Bind to intracellular GC receptors
HSP bound to receptor dissociates on hormone binding
Hormone-receptor complex binds to hormone responsive element on DNA
Control gene transcription
Transactiation: upregulation of gene expression of genes in anti-inflammatory pathway - e.g. Annexin
Transrepression: down regulation of gene expression of genes in inflammatory pathway - e.g. NF-kB
Cisrepression: genes outside inflammatory pathway affected - POMC, Osteocalcin, Keratin

16

What are clinical indications of corticosteroids

Inflammatory disease
Malignancy
Immunosuppression
Diagnosis of Cushing’s disease - dexamethasone suppression test
Adrenal insufficiency
Preterm birth

17

What corticosteroids are used for replacement therapy in adrenal insufficiency

Fludrocortisone - replace MC
Hydrocortisone - replace GC

18

Why do you give steroids in preterm birth

Given to women at risk of pre term birth
Single dose in antenatal period
To reduce risk of respiratory distress syndrome
Steroids stimulate T2 pneumocytes

19

What corticosteroids are used in preterm birth

Betamethasone
Dexamethasone

20

What are MC side effects of corticosteroids

Hypertension
Hypokalaemia
Fluid retention

21

What are GC side effects of corticosteroids

Endocrine: hyperglycaemia, hyperlipidaemia, weight gain/appetite, hirsuitism
Cushing’s syndrome: moon face, buffalo hump, striae
MSK: proximal myopathy, AVN of femoral head, osteoporosis
Immunosuppression: risk of severe infection, TB reactivation
GI: peptic ulcer, acute pancreatitis
Psych: insomnia, depression, mania, psychosis
Eye: cataracts, glaucoma, papilloedema
Intracranial hypertension
Growth disturbance in children
Fever, raised WCC

22

Why do you get osteoporosis with corticosteroids

Inhibit osteocalcin synthesis - reduced osteoblast formation
Increased osteoclasts proliferation
Reduced Ca absorption from gut
Reduced sex steroid synthesis

23

Why do you get adrenal suppression with corticosteroids

LT CS therapy mimics high dose of cortisol for long period
Suppress HPA axis by negative feedback
Suppress cortisol synthesis

24

When do you get adrenal suppression

Prolonged/High dose CS therapy:
>3 weeks
>40mg of prednisolone daily for 1week

25

How do you manage patients on long term corticosteroids

Carry steroid card
Increase dose during intercurrent illness/before surgery
Gradual withdrawal if: >3wks or >40mg pred for a week

26

What occurs in hypoadrenal crisis

Hypoglycaemia
Hyponatraemia
Hypotension
Hyperkalaemia
Severe dehydration
Death