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Pharmacology > Corticosteroids: Physiology, therapeutic uses, side effects > Flashcards

Corticosteroids: Physiology, therapeutic uses, side effects Flashcards

1
Q

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

A

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

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2
Q

What is the main form of glucocorticoids in the body?

A

Cortisol

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3
Q

What is the main form of mineralocorticoids in the body?

A

Aldosterone

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4
Q

What is the main form of androgens in the body?

A

Testosterone

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5
Q

What type of physiological mechanism regulates cortisol levels?

A

Negative feedback loop of cortisol

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6
Q

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

A

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

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7
Q

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?

A

CRH carried in hypophysioportal vessels to anterior pituitary gland

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

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8
Q

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

A

ACTH transported to adrenal cortex to increase steroid hormone cortisol production

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9
Q

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

A

increases body response to stress

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

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10
Q

Why are cortisol and other glucocorticoids described as feedback inhibitors?

A

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

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11
Q

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

A

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

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12
Q

How does cortisol affect fat and protein?

A

Breakdown fats and proteins

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13
Q

How does cortisol modulate the immune system?

A

Suppresses inflammation

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14
Q

Give 2 ways in which cortisol affects bone metabolism?

A

Increases bone resorption

Decreases bone formation

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15
Q

How does cortisol affect blood glucose levels?

A

Increases blood glucose level

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16
Q

How does cortisol affect the concentrations of potassium and sodium?

A

Increases potassium excretion, therefore decreases potassium levels

Increases sodium reabsorption in kidneys, therefore increases sodium levels

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17
Q

How does cortisol affect energy levels and mood?

A

Can cause energised state with disruption to sleep cycle

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18
Q

What is the pathophysiology of Addison’s disease?

A

Adrenal glands produce insufficient amount of cortisol

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19
Q

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

A

Discovered by physician Thomas Addison in 1855

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20
Q

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

A

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

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21
Q

Give 8 clinical features of Addison’s disease?

A

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

22
Q

What is an Addisonian crisis?

A

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

23
Q

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

A

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

24
Q

Why does Cushing’s disease occur?

A

Adrenal glands produce excessive amount of cortisol

25
Q

Give 8 clinical features of Cushing’s disease?

A

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

26
Q

Give 6 ways in which corticosteroids can be administered?

A

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

27
Q

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?

A

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

28
Q

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

A

Respiratory
Musculoskeletal

29
Q

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

A

Glucocorticoid receptors

30
Q

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

A

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

31
Q

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

A

Reduce concentration of circulating eosinophils, basophils, monocytes

Suppress T-cell activation

32
Q

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

A

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

33
Q

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

A

phagocytosis inhibition

suppression of COX-2 synthesis

34
Q

How can an corticosteroid overdose affect mood?

A

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

35
Q

Why is sleep disturbance a side effect of corticosteroid use?

A

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

36
Q

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

A

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

37
Q

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

A

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

38
Q

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

A

Proteolysis systems are upregulated so there is:

increased proteolysis of myofibrils

induced myocyte apoptosis

inhibition of myogenesis

39
Q

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

A

death of living bony tissue/cells

occurs as steroids promote:
osteoblast and osteocyte apoptosis

inhibiting osteoblast and osteoclast function and osteoclastogenesis

40
Q

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

A

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

41
Q

What are the 2 ophthalmic side effects of corticosteroid overdose?

A

Cataracts (lens develops cloudy patches)

glaucoma (damage to optic nerve)

42
Q

What 2 effects of corticosteroids can cause osteoporosis?

A

Increased bone resorption

Antagonistic effect against vitamin D calcium absorption

43
Q

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

A

acute pancreatitis

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

44
Q

Which method of administration of corticosteroids can cause arrythmia?

A

IV

45
Q

Give 3 cardiovascular side effects of corticosteroid overdose?

A

fluid retention

high cholesterol

accelerated atherosclerosis

46
Q

Give 5 dermatological side effects of corticosteroid overdose?

A

purple striae, acne, alopecia, bruising, skin atrophy

47
Q

Why can corticosteroid overdose cause hyperglycemia?

A

Corticosteroids containing cortisol increase blood glucose levels

48
Q

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

A

Steroids make liver less sensitive to insulin, so liver continues to release glucose despite insulin released from pancreas

Insulin resistance develops, eventually causes diabetes

49
Q

How can corticosteroid overdose cause high bp?

A

Excessive potassium excretion

Excessive sodium reabsorption in kidneys

50
Q

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

A

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

51
Q

How can corticosteroid overdose affect tendons?

A

Cause tendon degeneration and eventual rupture

52
Q

What are the 3 primary uses of mineralocorticoid drugs?

A

Replacement therapy of adrenal insufficiency

Adrenogenital syndromes

Regulate bp

Pharmacology (11 decks)

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