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THER 201 Therapeutics > Glucocorticoids > Flashcards

Glucocorticoids Flashcards

1
Q

CORTICOSTEROIDS

A
  • Glucocorticoids and mineralocorticoids (21C)

- Androgens (19C)

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2
Q

Outer cortex of the adrenal gland secretes…

A

Corticosteroids

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3
Q

Inner medulla of the adrenal gland secretes…

A

Catecholamines

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4
Q

Catecholamines

A

Epinephrine, norepinephrine
Adrenaline, noradrenaline

Fight or flight hormones
Prepare the body for extra effort in danger, stress, difficult tasks

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5
Q

Exogenous intake of glucocorticoids (as drugs) can lead to…

A
  • Suppression of endogenous function of the adrenal gland
  • Atrophy of zona glomerulosa, fasciculata, reticularis

ZG - mineralocorticoids (aldosterone)
ZF - glucocorticoids (cortisol)
ZR - androgens (androstenedione)

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6
Q

Precursor of steoid synthesis

A

Cholesterol

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7
Q

Receptors involved in steroid synthesos do dot exhibit much specificity because…

A

Receptors involved in steroid synthesis do not exhibit much specificity because…

Many enzymatic steps with similar pathways and final structures are involved in hormone synthesis

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8
Q

Drugs with a similar molecular structure to a parent cmpd, apart from some functional groups

A

Analogues are drugs with a similar molecular structure to a parent cmpd, apart from some functional groups

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9
Q

Major mineralocorticoid produced by adrenal cortex

A

Aldosterone is the major mineralocorticoid produced by adrenal cortex

  • FLUDROCORTISONE - main pharmacologic equivalent (fluorinated aldosterone)
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10
Q

Aldosterone acts at the distal convoluted tubule to promote… ___ reabsorption and __ excretion

A

Aldosterone acts at the distal convoluted tubule to promote… Na+ reabsorption and K+ excretion

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11
Q

Retention of more Na+ –> Water retention –> BP increases

A

Hyperaldosteronism

  • Retention of more Na+ –> Water retention –> BP increases
  • Manifests as hypertension and hypokalemia
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12
Q

Aldosterone secretion is controlled by…

A

RAAS

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13
Q

(Mineralocorticoids effects)

Sodium retention manifests as…

A

(Mineralocorticoids effects)

Sodium retention manifests as…

Hypertension
Edema
Cardiac failure (chronic)

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14
Q

(Mineralocorticoids effects)

Potassium excretion results to __________ and manifests as _______ and _______

A

(Mineralocorticoids effects)

Potassium excretion results to HYPOKALEMIA and manifests as MUSCLE WEAKNESS and METABOLIC ALKALOSIS

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15
Q

Fludrocortisone has both glucocorticoid (at high/low conc) and mineralocorticoid activity (at high/low conc)

A

Fludrocortisone has both glucocorticoid (at HIGH conc) and mineralocorticoid activity (at LOW conc)

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16
Q

At very low levels, glucocorticoid activity (will/will not) manifest

A

At very low levels, glucocorticoid activity WILL NOT manifest

17
Q

At high levels, glucocorticoid activity will manifest

A

Anti-inflammatory
Glucose elevating effect

At high levels, glucocorticoid activity will manifest

18
Q

Main endogenous glucocorticoid

A

Cortisol is the main endogenous glucocorticoid

Hydrocortisone - main pharmacologic equivalent

19
Q

Cortisol has metabolic (glucose, protein, lipid metab), anti-inflammatory, and immunosuppressive effects

A

Anti-inflammatory and immunosuppressive effects - clinically relevant

20
Q

One of the most impt effects of glucocorticoids

Maintains normal BP

A

Permissive effect

In the presence of glucocorticoids, the vasoconstriction effects of catecholamines can reverse hypotension (ie synergism of cortisol and catecholamines)

21
Q

Cortisol production is controlled by __________ mainly via _____

A

Cortisol production is controlled by HPA AXIS mainly via ACTH

*hypothalamic-pituitary-adrenal axis

22
Q

Average secretion of cortisol

A

25-30 umol/m2 per day

9-11 mg/day

23
Q

Cortical secretion follows a 24-hr biological rhythm

Highest plasm conc: ?
Lowest plasma conc: ?

A

Cortical secretion follows a 24-hr biological rhythm

Highest plasm conc: AM
Dips in the afternoon
Lowest plasma conc: PM

24
Q

(long/short acting) potent agents are NOT prefered because they make cortisol levels high all day

A

LONG ACTING potent agents are NOT prefered because they make cortisol levels high all day

Normal ACTH secretion will be suppressed –> adrenal hypertrophy

25
Q

(long/short acting) potent agents are prefered because they can be divided into two doses – higher dose (AM) and lower dose (afternoon, not in the evening)

A

Short acting potent agents are prefered because they can be divided into two doses – higher dose (AM) and lower dose (afternoon, not in the evening)

Dosing cortisol in the evening will suppress its usual drop and prevent rise of ACTH levels

26
Q

Plasma half-life of cortisol

A

80 min

27
Q

Carrier protein of cortisol (or hydrocortisone)

A

Transcortin

If bound non-specifically, albumin

28
Q

Malnourished people –> very low albumin level (hypoalbuminemia) –> lots of unbound steroids

What is the consequence of greater systemic bioavailability?

A

ADR

29
Q

Binding proteins of cortisol are increased in what states?

A

Pregnancy and hyperthyroidism

- increased cortisol binding proteins

30
Q

Bound cortisol, biologically inactive, but may be affected by… (give 2)

A

Estrogens and Progestogen affect the activity of bound cortisol

31
Q

Estrogen effect on bound cortisol

A

Estrogen increases serum conc of transcortin –> rise in cortisol without chsnging the level of free cortisl

32
Q

Progestogen effect on bound cortisol

A

Progestogen has great affinity of transcortin, can displace cortisol bound to transcortin, leads to increased free cortisol

Unbound/free cortisol acts as mineralocorticoid –> water retention –> edema

33
Q

(genes of the Glucocorticoid Receptor)

_______ modulates the expression of glucocorticoid responsive genes

A

(genes of the Glucocorticoid Receptor)

hGR-a modulates the expression of glucocorticoid responsive genes

34
Q

(genes of the Glucocorticoid Receptor)

_______ is transcriptionally inactive, but inhibits hGR-a mediated transactivation of target genes in a dose-dependent manner

A

(genes of the Glucocorticoid Receptor)

hGR-b is transcriptionally inactive, but inhibits hGR-a mediated transactivation of target genes in a dose-dependent manner

35
Q

__________ and _________ leads to the anti-inflammatory and immunosuppressive actions of glucocorticoids

A

TRANSREPRESSION and TRANSACTIVATION leads to the anti-inflammatory and immunosuppressive actions of glucocorticoids (~transcription)

THER 201 Therapeutics (7 decks)

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