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BLOCK B - RESPIRATION > Pharmacology - Corticosteroids > Flashcards

Pharmacology - Corticosteroids Flashcards

1
Q

Why can’t we abruptly stop administering corticosteroid drugs to a patient?

A
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2
Q

Endocrine glands function

A

Making and secreting hormones

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3
Q

What are hormones?

A

Chemical messengers made in one organ (cell) that travel via the bloodstream to affect the activity of other organs (cells).

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4
Q

Name the main components of the endocrine system

A
  • pineal gland
  • hypothalamus
  • pituitary gland
  • thyroid gland
  • thymus
  • pancreas
  • adrenal glands
  • testes/ovaries
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5
Q

Many but not all endocrine glands are controlled by the brain. Describe this process

A

Hypothalamus - portal vein - pituitary (Add!!!)

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6
Q

Describe the pituitary (hypophyseal) portal system

A

Anterior pituitary (adenhypophysis)
Posterior pituitary (neurohypophysis) - brain matter

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7
Q

What happens at the median eminance

A

Peptides are released on the primary capillary plexus and travels to the anterior pituitary gland

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8
Q

What are hypothalamic pituitary (HPA) target organ axes?

A

Hypothalamus releases peptides that stimulate the anterior pituitary, which itself releases peptides that stimulates endocrine glands to produce steroid or steroid-like hormones, whoch will feed back on the pituitary and hypothalamus.

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9
Q

WHat is the paraventricular nucleus?

A

?? makes and secretes a hormone called CRH (corticotropin releasing hormone)

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10
Q

What does CRH do?

A

CRH stimulates the corticotrope cell, which will start producing ACTH

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11
Q

What does ACTH do?

A

?

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12
Q

Descrie the two types ofregulation in the HPA axis?

A
  • can be regulated by circadian rhythm
  • can be regulated by stress ( psychological, physical, emotional, cold exposure, hypoglycemia, pain)
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13
Q

Describe circadian regulation of the HPA axis

A

Morning:
Afternoon:

As you decrease glucose levels s you go through the day…???

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14
Q

How are hormones released?
a) continuously
b) in pulses

A

b) in pulses

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15
Q

ACTH is a type of…

A

glucocorticoid

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16
Q

What is CRH? Where is it expressed? How is it produced?

A

Corticotropin-releasing hormone
- Expressed in paraventricular nucleus (PVN) of the hypothalamus
- CRH gene encodes 196 amino acid pre-pro-CRH
- C-terminal 41 amino acids encode CRH
- CRH neurons in PVN project to median eminance
- stimulates synthesis/secretion of ACTH by pituitary corticotrope cells

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17
Q

What type of cell releases ACTH?

A

Pituitary corticotrope cells

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18
Q

Where is CRH released?

A

From the paraventricular nucleus (PVN)

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19
Q

What is ACTH? Where and how is it produced?

A

Adrenocorticotropic hormone
- corticotropin
- produced in pituitary corticotropes
- produced as a 39. a.a. peptide derived from the pro-opiomelanocortin (POMC) precursosr (cleaved by prohormone convertase 1)

20
Q

After ACTH enters systemic circulation, where does it bind?

A

??? receptor on the adrenal gland

21
Q

Describe the outside and inside of the adrenal gland

A

Cortex: outside layer
Medulla: inside layer (where epinephrine is released)

22
Q

Name the three types of adrenocortical steroids (corticosteroids)

A
  • mineralocorticoids (e.g. aldosterone)
  • glucocorticoids (e.g. cortisol, corticosterone)
  • androgens (e.g. DHEA)
23
Q

Describe mineralocorticoids

24
Q

Describe glucocorticoids

25
Describe androgens
26
All steroids are derived from a precursor molecule called...
cholesterol (different enzymes and pathways will convert it into various end products (classes of steroids), like aldosterone, testosterone, estradiol)
27
Describe the mechanisms of ACTH stimulated cortisol synthesis. What is the rate limiting step?
Rate limiting step: movement of steroids from outside to the inside of mitochondria 1. Cholesterol enters the mitochondria 2. Cholesterol is converted to pregnenolone 3.....
28
What are the functions of glucocorticoids ?
Pleiotropic effects - inhibit CRH and POMC/ACTH synthesis and secretion (negative feedback) - Maintain blood glucose (esp. in a fasted state) - Mobilize amino acids from extrahepatic sources - Stimulate lypolysis in adipose tissue (increased FA and glycerol release) - Catabolic and anti-anabolic effects in bone - Inhibit immune function - Inhibit inflammation
29
What are the therapeutic effects of glucocoricoids (administered as drugs). What are the side effects?
30
Describe glucocorticoid receptors
- Part of the nuclear receptor superfamily - Two types: Mineralocorticoid receptor (MR) and Glucocorticoid receptor - ...
31
Describe the basic structure of nuclear receptors
32
Where are hydrophobic molecules buried?
33
Describe glucocorticoid action
Hydrophobic molecules cross the membrane... dimerization of receptors Dimers move to the nucleus and interact with the DNA via their DNA-binding domain to alter transcription
34
What are the primary uses of glucocorticoid analogues (clinically)?
- To treat adrenal insufficiency (e.g. Addison's disease) - Anti-inflammation (e.g. asthma, COPD) - Immunosuppression - Adjuvant to chemotherapy - Lung development
35
Describe the differences between primary, secondary and tertiary insufficiency
Primary: adrenal disorder Secondary: pituitary disorder Tertiary: hypothalamic disorder
36
What is Addison's disease?
- Primary adrenal insufficiency - Relatively rare (prevalence 40-6 per 1,000,000)
37
What are the symptoms of Addison's disease?
- muscular weakness - low blood pressure - depression - weight loss - hyperpigmentation - hypoglycemia
38
What is the etiology of Addison's disease? How is it treated
autoimmune (autoimmune system is attacking an enzyme involved in the production ogf?) Treatment:
39
Describe some anti-inflammatory uses of glucocrticoids?
- rheumatoid arthritis - ...
40
Because of the brad distribution of the glucocrticoid receptors, the ....?? (anti-inflammatory actions of corticosteroids in asthma) Why are these drugs so potent at anti0inflammation
41
Corticosteroids can increase beta-2 receptors which...
42
What are the toxic (side) effects of glucocorticoids?
- impacted glucose utilization - induction of siabetic state - redistribution of fat - osteoporosis - impaired wound healing - adrenal insufficiency - iatrogenoc Cushing's syndrome
43
What is Addison's crisis?
44
What is iatrogenic Cushing's syndrome?
45
What are symptoms of Cushing's syndrome?
- thin arms and legs - increased fat in face, trunk, across shoulder b;lades, base of the neck - moon face (swollen face) - thinning and reddening of skin
46
What are the causes of Cushing's syndrome?
- Prolonged exposure to GCs (e.g. during treatment of asthma, arthritis, lupus...) - Pituitary adenomas (Cushing's disease) - Ectopic ACTH syndrome - Adrenal adenomas (or carcinomas)

BLOCK B - RESPIRATION (31 decks)

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