1.Steroids Flashcards
What is cortisol?
Where is it formed?
Cortisol- a glucocorticoid (steroid)
- Precursor is cholesterol
Synthesised by zone fasciculata of adrenal gland (located above kidney)
What are the 4 products of cholesterol metabolism?
Cortisol
Aldosterone- helps regulate b.p & renal salt & water reabsorption
Dihydrotestosterone- sex hormone
Estradiol- sex hormone
What is the hypothalamic-pituitary-adrenal axis i.e. how is cortisol synthesised naturally ?
- The hypothalamus produces CRH (corticotrophic releasing hormone).
- This stimulates the pituitary gland to produce ACTH (andrencorticotrophic hormone).
- ACTH stimulates the adrenal cortex in the adrenal glands to synthesise & release glucocorticoids, such as cortisol.
- High Cortisol levels inhibit the hypothalamus so less CRH is produced & pituitary gland isn’t stimulated = less ACTH. This is negative feedback.
- Stress has the opposite effect and increases the production of CRH. Cortisol restores homeostasis after stress.
How does cortisol levels vary throughout the day?
- Highest when we get out of bed in the morning.
- Levels fall throughout the day.
- Lowest at bedtime = allows you to fall asleep.
- Levels increase during the night.
What are the psychological effects of cortisol?
- Modulates the immune system - high levels can lead to immunocompromisation & more infections.
- Reduces bone formation & enhances resorbtion
- Increases gluconeogenesis & causes insulin resistance
- Effects mood - by decreasing seratonin when cortisol is high.
How do steroids reduce inflammation & relive pain (mechanism)
Mentioned in hormones in biochem!
ADD:
- blocks transcription of cytokines & adhesion molecules= cortisol reduced inflammation
suppress COX2 synthesis
Inhibits phagocytosis= increased risk of infection
What is Addisons disease?
Symptoms?
What is addisonian crisis?
Caused due to low levels of cortisol
Symptoms:
- Hyperpigmentation - because hyperthalamus & pituitary are working hard to increase cortisol. But they release lots of melatonin = more pigment.
- Low blood pressure
- Fatigue
- Low Na+ & raised K+
- Anaemia
Addisonian crisis:
- life-threatening condition that results in low blood pressure, low blood levels of sugar & high blood levels of potassium:
- Collapse- cardiovascular collapse
- Hypogylcaemia
- Abdominal pain
- Diarrhoea & vomiting
What is Cushing’s syndrome? Caused by? Symptoms?
When there is too much cortisol (hypercortisolism)
Caused by:
- Long-term use of glucocorticoids
- Prolonged exposure to endogenous glucocorticoids
- Benign tumor in pituitary gland or adrenal gland
- Some areas of lung tumours
Symptoms:
- -runcal obesity - big bodies but skinny arms & legs
- Moon face
- Striae - purple stretch marks
- Hypertension
- Hirsutism - hairyness
- Osteoporosis - bone thinning due to an increase in bone reabsorption.
Difference between Cushing’d disease & Cushing’s syndrome?
Cushing’s disease is where the symptoms are caused by a ACTH-producing pituitary tumour, whereas Cushing’s syndrome is the name for the set of symptoms that occur when there is excess cortisol in the body. You can have Cushing’s syndrome as part of Cushing’s disease but not vice versa.
Where are steroids most commonly used?
Most common to least common
Respiratory system
Skin & subcutaneous tissue
MSK & connective tissue
Properties of steroids?
Gluccorticoids:
- Anti-inflammatory e.g. dexamethasone
- Immunosupressive
Retaining sodium or changing blood pressure e.g. cortisone & prednisolone
What are the side effects of high doses of steroids?
Infection risk increases:
- less phagocytosis
- increase in transcription of anti-inflammatory proteins
- Suppress COX 2 & prostaglandin synthesis.
MSK:
- Myopathy
- Osteoporosis
- Tendon rupture
- Osteonecrosis
Appearance changes:
- Truncal obesity
- Moon face
- Buffalo hump
Metabolic changes:
- Hyperglycaemia
- Insulin resistence
- Protein catabolism
- Electrolyte imbalance (Low Na+ & raised K+)
Gastrointestinal:
- Peptic ulcer disease
- Pancreatitis
- Perforation
- Steatohepatitis (fatty liver)
Ophthalmic:
- Cataracts
- Glaucoma (increased pressure within the eye)
CNS:
- Psychosis,
- Depression
- Mood & sleep disturbance
- Benign intracranial hypertension
Dermatologic:
- Acne
- Striae
- Alopecia
- Bruising (easier to tear blood vessels)
- Skin atrophy
Growth restriction in children:
- Inhibits linear growth
- Delayed epiphyseal closure
- Suppression of growth hormone secretion
Cardiovascular:
- Fluid retention
- Altered lipid profiles
- Arrthymias
- Accelerated atherosclerosis
Why should you not immediately stop use of steroids? How to reduce side effects risk?
Never stop steroids suddenly if it is after 3 weeks of use:
- Addisonian crisis!
- Relapse of condition your taking steroids for e.g poly myalgia rheumatica
Lowest dose for shortest time
Check guidelines
try non-drug interventions first
Routes of admission of steroids?
orally
topically
IV
