Corticosteroids: Physiology, therapeutic uses, side effects Flashcards
What are the 3 classes of steroids that are synthesised from cholestrol?
Cholesterol reacts in 3 different metabolic pathways to mineralocorticoids, glucocorticoids, sex steroids oestrogens and androgens
What is the main form of glucocorticoids in the body?
Cortisol
What is the main form of mineralocorticoids in the body?
Aldosterone
What is the main form of androgens in the body?
Testosterone
What type of physiological mechanism regulates cortisol levels?
Negative feedback loop of cortisol
What does mental/physical stress increase release of, and form which brain region is this substance released?
increases release of corticotropin-releasing hormone (CRH) from the hypothalamus
After CRH is released from the hypothalamus due to stress, what brain region is the CRH transported to and what is the resulting physiological effect?
CRH carried in hypophysioportal vessels to anterior pituitary gland
CRH stimulates release of adrenocorticotropic hormone (ACTH) from pituitary gland
Where is ACTH transported to from the pituitary gland, and what does ACTH stimulate?
ACTH transported to adrenal cortex to increase steroid hormone cortisol production
What are the 2 physiological effects of increased levels of cortisol?
increases body response to stress
exerts feedback inhibition on hypothalamus and pituitary gland to inhibit release of CRH and ACTH
Why are cortisol and other glucocorticoids described as feedback inhibitors?
They inhibit release of CRH and ACTH by hypothalamus and pituitary gland, which stops the negative feedback loop from changing cortisol levels
What rhythm do cortisol levels fluctuate in, and when are peak and lowest levels reached?
circadian rhythm: Peak level within first hour after waking then decreases during day so that lowest level is reached at night
How does cortisol affect fat and protein?
Breakdown fats and proteins
How does cortisol modulate the immune system?
Suppresses inflammation
Give 2 ways in which cortisol affects bone metabolism?
Increases bone resorption
Decreases bone formation
How does cortisol affect blood glucose levels?
Increases blood glucose level
How does cortisol affect the concentrations of potassium and sodium?
Increases potassium excretion, therefore decreases potassium levels
Increases sodium reabsorption in kidneys, therefore increases sodium levels
How does cortisol affect energy levels and mood?
Can cause energised state with disruption to sleep cycle
What is the pathophysiology of Addison’s disease?
Adrenal glands produce insufficient amount of cortisol
Who discovered Addison’s disease, in what year did this discovery occur?
Discovered by physician Thomas Addison in 1855
Why can patients with Addison’s disease present with vitiligo?
Hyperpigmentation of some skin occurred as melanin (brownish pigment) is a byproduct of the reaction that tries to stimulate adrenal gland function
Causes appearance of skin as bronze with white patches
Give 8 clinical features of Addison’s disease?
low bp
fatigue
hyperpigmentation
vitiligo
hypoglycemia
low sodium
high potassium
nausea
vomiting
muscle weakness
What is an Addisonian crisis?
Life-threatening episode of acute adrenal insufficiency due to very low cortisol level, which can result in physiological collapse and death
How is Addison’s disease treated, and how was this discovered?
Glucocorticoid treatment
discovered when pregnant women produced more cortisol so blood samples given to rheumatoid patients and they improved
German scientists isolated hormones from urine of lamb and found cortisol, gave to patient with addison’s disease and the patient strengthened
Why does Cushing’s disease occur?
Adrenal glands produce excessive amount of cortisol
Give 8 clinical features of Cushing’s disease?
Moon face
truncal obesity
purple striae
hypertension (due to increased sodium reabsorption)
hirsutism
osteoporosis
diabetes
Give 6 ways in which corticosteroids can be administered?
orally
topically (eye drops)
cream
intravenously if acute
directly into joint
inhaled
If a drug has both glucocorticoid and mineralocorticoid properties, what drug characteristic does this affect, and how does this affect administration of the drug in 2 ways?
Affects biological half life of drug, which affects dosage and time to take drug
According to database indications, what 2 types of ailment are steroid drugs mostly used to treat?
Respiratory
Musculoskeletal
What kind of corticosteroid receptor primarily mediates anti-inflammatory effects?
Glucocorticoid receptors
What is the mechanism of action of glucocorticoids in initiating anti-inflammatory effects?
Glucocorticoids bind to receptors in cytoplasm and move to nucleus then bind to genes to block transcription of inflammatory cytokines and increase transcription of anti-inflammatory proteins
Give 2 ways in which glucocorticoids affect immune cells in order to provide anti-inflammatory effects?
Reduce concentration of circulating eosinophils, basophils, monocytes
Suppress T-cell activation
What is the relationship between dosage and development of side effects of corticosteroids?
Adverse effects develop quicker is dose is higher, so use lowest dose possible
Give 2 reasons why there is an increased risk of infection when taking corticosteroids?
phagocytosis inhibition
suppression of COX-2 synthesis
How can an corticosteroid overdose affect mood?
Cortisol provides energised state, in overdose this can cause euphoria, mania, psychosis
Why is sleep disturbance a side effect of corticosteroid use?
Increased cortisol level due to glucocorticoid increases energy level, which causes sleep disturbance
What side effect of corticosteroid overdose occurs in the head due to hypertension?
Benign intracranial hypertension (pressure build up around brain that causes headaches and vision problems)
What side effect of corticosteroid overdose affects children in particular, and how does this affect them in the future?
Growth retardation in children which can lead to stunted growth in teenagers
What systems do corticosteroid overdoses upregulate, and what are the 3 effects of this that overall cause myopathy?
Proteolysis systems are upregulated so there is:
increased proteolysis of myofibrils
induced myocyte apoptosis
inhibition of myogenesis
What is osteonecrosis, and why is osteonecrosis a side effect of corticosteroid overdose?
death of living bony tissue/cells
occurs as steroids promote:
osteoblast and osteocyte apoptosis
inhibiting osteoblast and osteoclast function and osteoclastogenesis
What side of effect of corticosteroids includes the stomach, and how can this affect the stomach lining if not treated?
Peptic ulcer (open sore) formation, which can lead to stomach lining perforation (split open which forms hole)
What are the 2 ophthalmic side effects of corticosteroid overdose?
Cataracts (lens develops cloudy patches)
glaucoma (damage to optic nerve)
What 2 effects of corticosteroids can cause osteoporosis?
Increased bone resorption
Antagonistic effect against vitamin D calcium absorption
What 2 inflammatory conditions can arise in the GI system due to corticosteroid overdose?
acute pancreatitis
steatohepatitis (inflammation of liver due to excess fat cells within)
Which method of administration of corticosteroids can cause arrythmia?
IV
Give 3 cardiovascular side effects of corticosteroid overdose?
fluid retention
high cholesterol
accelerated atherosclerosis
Give 5 dermatological side effects of corticosteroid overdose?
purple striae, acne, alopecia, bruising, skin atrophy
Why can corticosteroid overdose cause hyperglycemia?
Corticosteroids containing cortisol increase blood glucose levels
How can corticosteroid affect the liver in a way that causes steroid-induced diabetes?
Steroids make liver less sensitive to insulin, so liver continues to release glucose despite insulin released from pancreas
Insulin resistance develops, eventually causes diabetes
How can corticosteroid overdose cause high bp?
Excessive potassium excretion
Excessive sodium reabsorption in kidneys
Why can corticosteroid overdose increase the risk of fractures in men, and how can this be reduced again?
Corticosteroids disrupt biosynthesis pathway which causes decrease in serum testosterone level, which increases risk of hip and vertebral fractures in men
Risk is reduced when glucocorticoids are stopped
How can corticosteroid overdose affect tendons?
Cause tendon degeneration and eventual rupture
What are the 3 primary uses of mineralocorticoid drugs?
Replacement therapy of adrenal insufficiency
Adrenogenital syndromes
Regulate bp
