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PHAR222 > L13 Cortocosteroids > Flashcards

L13 Cortocosteroids Flashcards

1
Q

Corticosteroids are a member of what type of hormones

A

Steroid

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2
Q

Corticosteroids are secreted by what

A

the cortex of the adrenal gland

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3
Q

Where are the adrenal glands located?

A

Above the kidney

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4
Q

What are the major regions of the adrenal gland

A

Capsule
Adrenal cortex
Adrenal Medulla

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5
Q

There are two major types of corticosteroids

A

Mineralocorticoids and glucocorticoids
Like aldosterone and cortisol

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6
Q

What are mineralocorticoids’ functions

A
  • regulate water and electrolyte balance
  • Principal endogenous mineralocorticoids
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7
Q

What are glucocorticoid functions

A
  • Regulate carbohydrate and protein metabolism
  • are principal endogenous glucocorticoids
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8
Q

What effect do mineralocorticoids have with glucocorticoids

A

Some glucocorticoids, such as cortisol and several synthetic derivatives (drugs), also exert some mineralocorticoid activity due to incomplete receptor selectivity

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9
Q

Why are glucocorticoids important?

A
  • endogenous cortisol promotes metabolic changes that
    allow us to adapt to physiological stresses
  • Synthetic glucocorticoids suppress inflammation, allergy
    & immune responses
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10
Q

What controls the production of cortisol from glucocorticoids

A

The HPA (hypothalamic pituitary adrenal) axis

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11
Q

Corticotrophin-releasing hormone from what stimulates release of what and from where

A

(CRH) from the hypothalamus stimulates the release of corticotrophin (ACTH) from the anterior pituitary gland

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12
Q

Corticotrophin stimulates _____ production by the adrenal cortex

A

Cortisol

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13
Q

Cortisol exerts physiological effects on many tissues and also inhibits ____ and CRH via a negative feedback loop

A

corticotrophin

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14
Q

Synthesis of endogenous cortisol

A
  • glucocorticoids are not stored preformed, but synthesized and released as needed.
  • cholesterol, is converted to pregnenolone, in a rate-limiting step regulated by corticotrophin
  • Pregnenolone is converted by a series of enzymatic steps to cortisol
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15
Q

Diagram of cortisol production from cholesterol

A

Cholesterol
↓
Pregnenolone
↓
Cortisol (has ketone and OH groups)

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16
Q

Ketoconazole

A

an anti-fungal drug, blocks cortisol synthesis by inhibiting cholesterol side-chain convertase

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17
Q

What does stress do to cortisol

A

Increase cortisol levels

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18
Q

Diagram of the actions of cortisol

A

Stress
↓
HPA
↓
Cortisol
↓
bind to cortisol-binding globulin in blood and go to tissues
↓
Will bind to cytosolic glucocorticoid receptor
↓
Translocate to cell nucleus
↓
Transcription of glucocorticoid-responsive genes
↓
Protein translation
↓
Effects metabolism

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19
Q

Metabolism (glucocorticoid effect)

A
  • ↓ uptake and utilization of glucose by peripheral tissues,
  • ↑ synthesis of glucose by liver (gluconeogenesis)
  • ↑ breakdown of fat and muscle
  • ↑ glycogen formation,- ’creating a stockpile of glucose’
    ⇒ tendency to hyperglycaemia
20
Q

At physiological levels, the effects of cortisol on water & electrolyte balance (mineralocorticoid effect) & on organ systems (e.g. ↓ vasodilatation, ↑ breakdown of bone) is relatively minor.

A
21
Q

Too much endogenous cortisol production causes

A

Cushings disease

22
Q

Cushing’s disease is often
due to an ACTH-secreting
tumor of

A

pituitary gland

23
Q

Cushing disease features in ppl

A
  • Buffalo hump
  • Moon face
  • increase abdominal fat
  • Thin skin
  • Thin arms and legs
  • easy bruising and poor wound healing
24
Q

Cushing disease treatment

A

y surgery (to remove tumour), but pharmacologic therapy can be considered

25
Q

pasireotide

A

– a somatostatin receptor agonist that inhibits ACTH release from pituitary  reduces cortisol synthesis by adrenal glands

26
Q

Too little endogenous cortisol production

A

Addisons disease
-Weight loss, fatigue, painful muscles & joints

27
Q

Addison disease treatment

A

Treatment involves replacement therapy. Physiologic doses of natural glucocorticoids (cortisol* hydrocortisone) are given daily in split doses: 2/3 in the morning & 1/3 in the evening to mimic natural pattern of hormone secretion.

28
Q

Major pharmacological effects of glucocorticoids

A
  • Cortisol deficiency treatment mimics normal levels and patterns of secretino and action
  • Given in supraphysiological doses (has pos and neg effects)
29
Q

supraphysiologic doses, which can produce positive and negative effects:

A
  • General effects on metabolism, water & electrolyte balance & organ
    systems (blood pressure, bones etc.)
  • Negative feedback effects on hypothalamus/pituitary –> atrophy of adrenal gland
  • Anti-inflammatory and immunosuppressive effects
30
Q

Clinical uses of glucocorticoids list

A
  1. Replacement therapy,
  2. To inhibit inflammation associated with (what)
  3. To suppress the immune system
  4. As an adjunct therapy in cancer
  5. To stimulate lung development in the fetus (dexamethasone*)
31
Q
  1. Replacement therapy,
A

where the goal is to mimic the physiologic patterns of cortisol action. cortisol
Low, physiologic doses used for long periods -> minimal side-effects

32
Q
  1. To inhibit inflammation associated with
A

 asthma beclomethasone*
 inflammatory bowel disease, arthritis
 various conditions of the skin (eczema), eye (allergic conjunctivitis), nose (rhinitis)
High doses used, but given locally -> some localised side-effects
 allergic reactions (to drugs, insect venoms, etc.)cortisol, prednisolone etc
High oral doses used, but for a short period  minimal side-effects

33
Q

Note: Glucocorticoids inhibit inflammatory reactions, by altering transcription of a wide range of genes involved in the inflammatory process.

A
34
Q
  1. To suppress the immune system
A

 in organ or bone marrow transplantation
 in autoimmune diseases (prednisolone)
 in asthma (beclomethasone)
High, oral doses used for long periods -> significant side-effects

35
Q
  1. As an adjunct therapy in cancer
A

 given with cytotoxic drugs to treat specific cancers (inhibit lymphocyte proliferation)
 to decrease chemotherapy-induced nausea and vomiting
 to reduce swelling in brain tumors (dexamethasone*)
High, oral doses used for long periods -> significant side-effects

36
Q
  1. To stimulate lung development in the fetus (dexamethasone*)
A

given at 24-34 weeks gestation if birth expected within 7 days
High, oral doses used for short periods  minimal side-effects

37
Q

Note: Glucocorticoids can be given by variety of routes: Some are active ______ (i.m. or i.v). Some are given____ (aerosol, eye-drops, creams, injected intra-articularly) to reduce side-effects.

A

orally and systemically
topically

38
Q

Serious adverse effects of Glucocorticoids (GCs)

A
  1. high, oral dosing of GCs for long periods, e.g. immunosuppressive therapy, cancer
  2. Cushing’s disease

include reductions in:
- response to infection,
- wound healing,
- capacity to synthesize
corticosteroids, etc.

39
Q

Endogenous (e.g. cortisol) and
exogenous (e.g. dexamethasone)
glucocorticoids inhibit secretion
of ___ ____ _____

A

CRF, corticotrophin & cortisol

40
Q

Exogenous glucocorticoids inhibit
the secretion of endogenous
glucocorticoids, causing____ of the adrenal gland

A

atrophy

41
Q

rapid withdrawal of glucocorticoids is associated with
acute adrenal insufficiency
(low production of cortisol)

A

Decrease resistance to stress & infections

42
Q

Cortisone and Cortisol

A
  • Anti-inflammatory
  • Na+ retaining
  • Short DoA (8-12hr)
  • Replacement and emergencies
  • Cortisone is inactive then converted to active cortisol

Natural

43
Q

Prednisone and Prednisolone

A
  • Anti-inflammatory
  • Some Na+ retaining
  • Medium DoA (12-36 hr)
  • Used as anti-in and immunosuppressive agents
  • Sone inactive until converted to prenisolone
44
Q

Dexamethasone

A
  • Anti-inflammatory
  • Minor Na+ retaining
  • Long DoA (36-72 hr)
  • Potent anti-in and immunosuppressive agents
  • When water rentention is undesirable
45
Q

Beclomethasone

A
  • Anti-inflammatory
  • Not Na+ retaining
  • Longer DoA (72+ hr)
  • Poorly absorbed
  • Usually topically for rhinitis and inhaled for asthma

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