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Mpharm 1 > PH1124 - corticosteroids > Flashcards

PH1124 - corticosteroids Flashcards

1
Q

what are the two steroids synthesized within the adrenal cortex? (2)

A
  • corticosteroids

- androgens

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2
Q

what are the two types of corticosteroids? (2)

A
  • glucocorticoids (cortisol)

- mineralocorticoids (aldosterone)

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3
Q

what are synthesized in the adrenal medulla?

A
  • catecholamines (noradrenaline and adrenaline)
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4
Q

what are the layers of the adrenal gland? (outside to inside) (3)

A
  • zona glomerulosa
  • zona fasiculata
  • zona reticularis
    (adrenal medulla)
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5
Q

what is the role of the zona reticularis?

A
  • secretes glucocorticoids and some sex steroids
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6
Q

what is the role of the zona fasiculata?

A
  • widest region that secretes glucocorticoids and some sex steroids
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7
Q

what is the role of the zona glomerulosa?

A
  • secrete aldosterone (lacks 17-α-hydroxylase)
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8
Q

what are the two pathways of corticosteroid synthesis? (2)

A
  • glucocorticoid pathway (17-hydroxylated corticosteroids)

- mineralocorticoid pathway (17-deoxycorticosteroids)

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9
Q

what is the structure of corticosteroids? (3)

A
  • 21 carbon skeleton
  • cyclohexane rings A, B and C in ‘chair’ conformation
  • cyclopentane ring D
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10
Q

what is the synthesis of corticosteroids like in the adrenal cortex? (2)

A
  • only produces steroids as required

- produces sufficient steroids for only a few minutes secretion

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11
Q

what stimulates the transport of cholesterol into cells?

A
  • adrenocorticotrophin
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12
Q

what is cholesterol transported by in the blood?

A
  • LDL (low density lipoprotein)
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13
Q

why is cholesterol important in the synthesis of corticosteroids?

A
  • it is an important precursor when corticosteroid production is stimulated
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14
Q

where does cholesterol come from? (3)

A
  • 60-80% comes from your blood
  • stored in the adrenal cortex
  • made in cells from acetate and acetylcoenzyme A
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15
Q

how is cortisol transported in the blood? (2)

A
  • 90% corticosteroid-binding proteins by transcortin and albumin (majority is bound to transcortin)
  • 10% free plasma glucocorticoids are biologically active
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16
Q

what are the differences in capacity and affinity for the corticosteroid-binding proteins? (2)

A
  • transcortin has a low capacity but high affinity

- albumin has a high capacity but low affinity

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17
Q

how are cortisol, corticosterone and aldosterone metabolised and excreted? (4)

A
  • metabolised in the liver
  • reduction of 4,5 double bond and the C3 and C20 keto groups
  • resultant derivatives conjugated with glucuronic acid or sulphate at C3 hydroxyl group
  • excretion in urine
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18
Q

what is the regulation of corticosteroid biosynthesis?

A
  • glucocorticoids (in ZF and ZR) cause negative feedback loop causing the anterior pituitary to stop producing ACTH
  • the glucocorticoids stop the hypothalamus releasing CRH which also inhibits the production of the glucocorticoids
  • the release of ACTH also causes a short negative feedback loop to the hypothalamus to stop the production of CRH
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19
Q

what does CRH stand for?

A
  • corticotropin releasing hormone
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20
Q

what is CRH?

A
  • causes the anterior pituitary gland to release more ACTH which causes the release of glucocorticoids
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21
Q

where is CRH released from and when?

A
  • hypothalamus
  • in response to emotional or traumatic stress and the sleep-wake cycle
  • release potentiated by vasopressin, oxytocin, adrenaline and cytokines
22
Q

what does CRH act on?

A

pituitary corticotroph cells

23
Q

what is ACTH?

A
  • adrenocorticotropic hormone
24
Q

what is the release of ACTH regulated by? (2)

A
  • CRH

- glucocorticoids

25
Q

when is ACTH released?

A
  • response to the sleep-wake cycle, stress, psychiatric disturbances, neurotransmitters and peptides
26
Q

what is the secretion of ACTH stimulated by?

A
  • vasopressin
27
Q

what is diurnal variation? (3)

A
  • natural rhythm for the release of CTH and glucocorticoids
  • adapts of changes in sleep-wake patterns
  • rhythm controlled by CRH
28
Q

what are steroid receptors?

A
  • located inside the cell (intracellular) and belong to a gene superfamily of nuclear recepotrs
  • they interact with nuclear DNA to modulate transcription of specific genes
29
Q

what are the steroid receptors found in the cytoplasm? (2)

A
  • glucocorticoids

- mineralocorticoids

30
Q

what are the steroid receptors found in the nucleus? (3)

A
  • androgen
  • oestrogen
  • progesterone
31
Q

what is the molecular mechanism of the action of steroids? (3)

A
  • steroids enter the cytoplasm of the cell to bind to a receptor to make a substrate receptor complex
  • two of the complexes form to make a dimer
  • this enters the nucleus of the cell and can either up/down regulate the transcription of a gene by the zinc fingers it contains
32
Q

what are the physiological actions of corticosteroids? (7)

A
  • carbohydrate and protein metabolism
  • fat metabolism
  • central nervous system effects
  • effects on bone
  • mineralocorticoid effects
  • permissive effects
  • anti-inflammatory and immunosupressive effects
33
Q

what is the role of corticosteroids in carbohydrate and protein metabolism? (2)

A
  • they antagonise the action of insulin on glucose uptake increasing blood glucose
  • increase protein breakdown and reduce protein synthesis
34
Q

what would happen to an individual is there were no corticosteroids present?

A
  • if subjected to a shortage of food or extensive exercise they may have hypoglycaemic episodes
35
Q

what would prolonged high doses of corticosteroids cause to an individual?

A
  • hyperglycaemia, wasting of muscle with thinning of capillary walls and loss of the bone matrix
36
Q

how do corticosteroids control fat metabolism?

A
  • they stimulate fat breakdown (lipolysis) and inhibit fat synthesis
37
Q

what do high levels of corticosteroids do to body fat?

A
  • causes redistribution of body fat to the neck shoulders and cheeks with loss of fat from the limbs
38
Q

how do corticosteroids affect the central nervous system? (2)

A
  • involved in the neuronal development in the foetal and neonatal brain
  • development of the CRH-ACTH axis
39
Q

how do corticosteroids effect bone? (2)

A
  • leads to a net decrease in plasma calcium as it is regulated by calcium metabolism
  • prolonged doses of glucocorticoid steroids leads to osteoporosis
40
Q

what are the mineralocorticoid effects from corticosteroids?

A
  • increased Na+ reabsorption in exchange for K+ excretion

- increased water retention

41
Q

what are the permissive effects of corticosteroids? (2)

A
  • allow other hormones to exert effects

- helps the body to maintain its temperature and respond to stress

42
Q

what leads to increased cortisol?

A
  • stress
43
Q

how does stress protection work?

A
  • prevents stress-induced defense reactions from getting out of control
44
Q

what are the some of the anti-inflammatory effects caused by corticosteroids? (4)

A
  • decreased vasodilation and fluid exudation by direct vasoconstriction on small blood vessels
  • decreases fibroblast function so less chronic inflammation
  • decrease generation of pro-inflammatory mediators and increases the production of anti-inflammatory mediator
  • stabilises mast cells and lysosomal membranes
45
Q

how does corticosteroids cause immunosuppressive effects? (5)

A
  • decreases the action of T helper cells and reduce clonal proliferation of T cells due to the decreases interleukin production
  • reduce the numbers of circulating T and B lymphocytes and antibody production
  • impairs recognition responses in antigen presentation
  • reduces numbers of toxic radicals produced by macrophages
  • reduces phagocytic activity of macrophages
46
Q

what happens at the cellular site of action of corticosteroids? (4)

A
  • antigen recognition
  • stimulation of IL-1
  • expression of IL-2 and other cytokines
  • proliferation and differentiation
47
Q

what controls the secretion of aldosterone?

A
  • controlled mainly by the renin-angiotensin system but hyperkalaemia and ACTH increase release
48
Q

where are the aldosterone receptors found?

A
  • distal and convoluted tubules and collecting duct in the kidney, bladder, colon, sweat and salivary glands
49
Q

what is the main action of aldosterone?

A
  • retain Na+ and lose K+ therefore water is retained because it follows Na+
50
Q

what is the mechanism of action of aldosterone? (3)

A
  • increased production of the Na+ transporter in luminal membrane
  • pumps Na+ out of the luminal fluid into the tubular cells
  • increases Na+/K+ ATPase pump to pump Na+ out of tubular cells into the plasma increasing the blood volume
51
Q

what is cushings disease/syndrome?

A
  • increased ACTH (adrenocorticotropic hormone) causes increased cortisol
52
Q

what are the symptoms of cushings disease? (6)

A
  • muscle weakness and wasting
  • easily bruised
  • redistribution of body fat
  • prominent abdomen
  • diabetes
  • high levels of plasma and urine cortisol

Mpharm 1 (59 decks)

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