Corticosteroids: Physiology, therapeutic uses, side effects

Question 1

What are the 3 classes of steroids that are synthesised from cholestrol?

Answer 1

Cholesterol reacts in 3 different metabolic pathways to mineralocorticoids, glucocorticoids, sex steroids oestrogens and androgens

Question 2

What is the main form of glucocorticoids in the body?

Answer 2

Cortisol

Question 3

What is the main form of mineralocorticoids in the body?

Answer 3

Aldosterone

Question 4

What is the main form of androgens in the body?

Answer 4

Testosterone

Question 5

What type of physiological mechanism regulates cortisol levels?

Answer 5

Negative feedback loop of cortisol

Question 6

What does mental/physical stress increase release of, and form which brain region is this substance released?

Answer 6

increases release of corticotropin-releasing hormone (CRH) from the hypothalamus

Question 7

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?

Answer 7

CRH carried in hypophysioportal vessels to anterior pituitary gland

CRH stimulates release of adrenocorticotropic hormone (ACTH) from pituitary gland

Question 8

Where is ACTH transported to from the pituitary gland, and what does ACTH stimulate?

Answer 8

ACTH transported to adrenal cortex to increase steroid hormone cortisol production

Question 9

What are the 2 physiological effects of increased levels of cortisol?

Answer 9

increases body response to stress

exerts feedback inhibition on hypothalamus and pituitary gland to inhibit release of CRH and ACTH

Question 10

Why are cortisol and other glucocorticoids described as feedback inhibitors?

Answer 10

They inhibit release of CRH and ACTH by hypothalamus and pituitary gland, which stops the negative feedback loop from changing cortisol levels

Question 11

What rhythm do cortisol levels fluctuate in, and when are peak and lowest levels reached?

Answer 11

circadian rhythm: Peak level within first hour after waking then decreases during day so that lowest level is reached at night

Question 12

How does cortisol affect fat and protein?

Answer 12

Breakdown fats and proteins

Question 13

How does cortisol modulate the immune system?

Answer 13

Suppresses inflammation

Question 14

Give 2 ways in which cortisol affects bone metabolism?

Answer 14

Increases bone resorption

Decreases bone formation

Question 15

How does cortisol affect blood glucose levels?

Answer 15

Increases blood glucose level

Question 16

How does cortisol affect the concentrations of potassium and sodium?

Answer 16

Increases potassium excretion, therefore decreases potassium levels

Increases sodium reabsorption in kidneys, therefore increases sodium levels

Question 17

How does cortisol affect energy levels and mood?

Answer 17

Can cause energised state with disruption to sleep cycle

Question 18

What is the pathophysiology of Addison’s disease?

Answer 18

Adrenal glands produce insufficient amount of cortisol

Question 19

Who discovered Addison’s disease, in what year did this discovery occur?

Answer 19

Discovered by physician Thomas Addison in 1855

Question 20

Why can patients with Addison’s disease present with vitiligo?

Answer 20

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

Question 21

Give 8 clinical features of Addison’s disease?

Answer 21

low bp
fatigue
hyperpigmentation
vitiligo
hypoglycemia
low sodium
high potassium
nausea
vomiting
muscle weakness

Question 22

What is an Addisonian crisis?

Answer 22

Life-threatening episode of acute adrenal insufficiency due to very low cortisol level, which can result in physiological collapse and death

Question 23

How is Addison’s disease treated, and how was this discovered?

Answer 23

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

Question 24

Why does Cushing’s disease occur?

Answer 24

Adrenal glands produce excessive amount of cortisol

Question 25

Give 8 clinical features of Cushing's disease?

Answer 25

Moon face truncal obesity purple striae hypertension (due to increased sodium reabsorption) hirsutism osteoporosis diabetes

Question 26

Give 6 ways in which corticosteroids can be administered?

Answer 26

orally topically (eye drops) cream intravenously if acute directly into joint inhaled

Question 27

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?

Answer 27

Affects biological half life of drug, which affects dosage and time to take drug

Question 28

According to database indications, what 2 types of ailment are steroid drugs mostly used to treat?

Answer 28

Respiratory Musculoskeletal

Question 29

What kind of corticosteroid receptor primarily mediates anti-inflammatory effects?

Answer 29

Glucocorticoid receptors

Question 30

What is the mechanism of action of glucocorticoids in initiating anti-inflammatory effects?

Answer 30

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

Question 31

Give 2 ways in which glucocorticoids affect immune cells in order to provide anti-inflammatory effects?

Answer 31

Reduce concentration of circulating eosinophils, basophils, monocytes Suppress T-cell activation

Question 32

What is the relationship between dosage and development of side effects of corticosteroids?

Answer 32

Adverse effects develop quicker is dose is higher, so use lowest dose possible

Question 33

Give 2 reasons why there is an increased risk of infection when taking corticosteroids?

Answer 33

phagocytosis inhibition suppression of COX-2 synthesis

Question 34

How can an corticosteroid overdose affect mood?

Answer 34

Cortisol provides energised state, in overdose this can cause euphoria, mania, psychosis

Question 35

Why is sleep disturbance a side effect of corticosteroid use?

Answer 35

Increased cortisol level due to glucocorticoid increases energy level, which causes sleep disturbance

Question 36

What side effect of corticosteroid overdose occurs in the head due to hypertension?

Answer 36

Benign intracranial hypertension (pressure build up around brain that causes headaches and vision problems)

Question 37

What side effect of corticosteroid overdose affects children in particular, and how does this affect them in the future?

Answer 37

Growth retardation in children which can lead to stunted growth in teenagers

Question 38

What systems do corticosteroid overdoses upregulate, and what are the 3 effects of this that overall cause myopathy?

Answer 38

Proteolysis systems are upregulated so there is: increased proteolysis of myofibrils induced myocyte apoptosis inhibition of myogenesis

Question 39

What is osteonecrosis, and why is osteonecrosis a side effect of corticosteroid overdose?

Answer 39

death of living bony tissue/cells occurs as steroids promote: osteoblast and osteocyte apoptosis inhibiting osteoblast and osteoclast function and osteoclastogenesis

Question 40

What side of effect of corticosteroids includes the stomach, and how can this affect the stomach lining if not treated?

Answer 40

Peptic ulcer (open sore) formation, which can lead to stomach lining perforation (split open which forms hole)

Question 41

What are the 2 ophthalmic side effects of corticosteroid overdose?

Answer 41

Cataracts (lens develops cloudy patches) glaucoma (damage to optic nerve)

Question 42

What 2 effects of corticosteroids can cause osteoporosis?

Answer 42

Increased bone resorption Antagonistic effect against vitamin D calcium absorption

Question 43

What 2 inflammatory conditions can arise in the GI system due to corticosteroid overdose?

Answer 43

acute pancreatitis steatohepatitis (inflammation of liver due to excess fat cells within)

Question 44

Which method of administration of corticosteroids can cause arrythmia?

Answer 44

IV

Question 45

Give 3 cardiovascular side effects of corticosteroid overdose?

Answer 45

fluid retention high cholesterol accelerated atherosclerosis

Question 46

Give 5 dermatological side effects of corticosteroid overdose?

Answer 46

purple striae, acne, alopecia, bruising, skin atrophy

Question 47

Why can corticosteroid overdose cause hyperglycemia?

Answer 47

Corticosteroids containing cortisol increase blood glucose levels

Question 48

How can corticosteroid affect the liver in a way that causes steroid-induced diabetes?

Answer 48

Steroids make liver less sensitive to insulin, so liver continues to release glucose despite insulin released from pancreas Insulin resistance develops, eventually causes diabetes

Question 49

How can corticosteroid overdose cause high bp?

Answer 49

Excessive potassium excretion Excessive sodium reabsorption in kidneys

Question 50

Why can corticosteroid overdose increase the risk of fractures in men, and how can this be reduced again?

Answer 50

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

Question 51

How can corticosteroid overdose affect tendons?

Answer 51

Cause tendon degeneration and eventual rupture

Question 52

What are the 3 primary uses of mineralocorticoid drugs?

Answer 52

Replacement therapy of adrenal insufficiency Adrenogenital syndromes Regulate bp