Steroid Drugs Flashcards
What are the layers of adrenal gland and their hormones
Cortex:
Zona glomerulosa - mineralocortocoid
Zona fasciculata - glucocorticoid
Zona reticularis - sex steroid
Medulla - catecholamines
What are corticosteroids
Hormones synthesised in adrenal cortex, synthesised from cholesterol
What is control mechanism of glucocorticoid synthesis
HPA axis and negative feedback:
Hypothalamus - CRH
Anterior pituitary - ACTH
Adrenal cortex - Cortisol
What is the action of cortisol
Gluconeogenesis and glycogenolysis Hyperglycaemia Proteolysis Lipolysis Lipid deposition (high conc) Lipid redistribution (abdomen, neck)
What are the effects of cortisol deficiency
Hypoglycaemia
Weight loss, reduced appetite
Hypotension
What are effects of cortisol excess
Hyperglycaemia
Weight gain, increased appetite
Cushing’s syndrome
Hypertension
What are effects of aldosterone deficiency
Hypotension
Hyponatraemia
Hyperkalaemia
Dehydration
What are effects of aldosterone excess
Hypertension
Hypernatraemia
Hypokalaemia
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
What determines level of cross over activity
Level of selectivity of hormone for GC and MC receptors
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
What are the potencies of different corticosteroids
Hydrocortisone: 20mg
Prednisolone: 5mg
Dexamethasone: 750 mcg
Betamethasone: 750mcg
What are the routes of admin of corticosteroids
Systemic:
Oral
IV
Local:
Inhaled
Intra articular
Topical
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
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
What are clinical indications of corticosteroids
Inflammatory disease Malignancy Immunosuppression Diagnosis of Cushing’s disease - dexamethasone suppression test Adrenal insufficiency Preterm birth
What corticosteroids are used for replacement therapy in adrenal insufficiency
Fludrocortisone - replace MC
Hydrocortisone - replace GC
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
What corticosteroids are used in preterm birth
Betamethasone
Dexamethasone
What are MC side effects of corticosteroids
Hypertension
Hypokalaemia
Fluid retention
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
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
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
When do you get adrenal suppression
Prolonged/High dose CS therapy:
>3 weeks
>40mg of prednisolone daily for 1week
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
What occurs in hypoadrenal crisis
Hypoglycaemia Hyponatraemia Hypotension Hyperkalaemia Severe dehydration Death
