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Ther 201 2nd Exam > Glucocorticoids and Mineralocorticoids > Flashcards

Glucocorticoids and Mineralocorticoids Flashcards

1
Q

2 Main parts of Adrenal Gland and the substances they produce

A

Adrenal Cortex = Corticosteroids

Adrenal Medulla = Catecholamines

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2
Q

3 Main types of Corticosteroids, their site of production and their stucture

Mnemonic: MGA GFR (outer to inner).

A

From outer to inner layer:
Zona Glomerulosa - Mineralocorticoids (21 C)
Zona Fasciculata - Glucocorticoids (21 C)
Zona Reticularis - Androgens (19 C)

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3
Q

What are the fight or flight hormones?

A

Adrenal Medula secretion –> Catecholamines:
Epinephrine/ Adrenaline
Norepinephrine/Noradrenaline

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4
Q

What is the precursor of all steroid hormones, glucocorticoids, mineralocorticoids and sex hormones?

A

Cholesterol!

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5
Q

All the products derived from cholesterol are steroids (T/F)

A

T. Pero preferred lang tawagin na cortisol at glucocorticoid

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6
Q

Mineralocorticoids:

What is the Major mineralocorticoid produced? Function?

A

Aldosterone.
Acts on the DISTAL PORTION of convoluted tubule to promote Na reabsorption and K excretion.

Basta MINERALocorticoid = aldosterone = Na and K (Mineral —> ions …ewan, basta)

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7
Q

What controls secretion of aldosterone?

A

Primarily: RAAS
Secondary: ACTH

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8
Q

Mineralocortioid Receptor is highly specific. (T/F)

A

F. It can also bind with glucocorticoids (ex. cortisol)

Why? Since Mineralo- and Gluco- are higly similar in structure.

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9
Q

When administering doses of cortisol, its possible to observe hypertension and hypokalemia. (T/F)

A

T.

Hypertension and hypokalemia is caused by high doses of aldosterone which is almost similar, in structure, to cortisol

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10
Q

Blood levels of Cortisol is 2000x higher than Aldosterone. How can aldosterone stimulate SPECIFIC biological effects?

A

Target cells for aldosterone has an enzyme which can target cortisol and convert it into cortisone (has lesser affinity to Mineralo- Receptor). With this, aldosterone can now easily bind to Mineralo- Receptor

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11
Q

Mineralocorticoids:
What are its effects on the body?
[Think about Na+ and K+]

A

[Na+] Sodium Retention —> leads to hypertension, edema and heart failure

[K+] Potassium Excretion —> Hypokalemia —> leads to muscle weakness and metabolic alkalosis.

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12
Q

FLUDROCORTISONE is a distinct mineralocorticoid agonist only for mineralocorticoid receptors. (T/F)

A

F.
FIRST, it is a actually a glucocorticoid.
It has glucocorticoid activity when given at high concentrations and mineralocorticoid activity at low concentrations.

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13
Q

At what dose should you administer Fludrocortisone for it to exhibit a salt-retaining activity (bale mineralocorticoid activity)? Does this dose have significant anti-inflamm effects?

A

0.1 mg given 2-7 times per week.

The dosage is too small to have significant inflammatory effects.

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14
Q

Glucocorticoids Characteristics:

When does blood conc of glucocorticoids increase?

A

During stress (mental, emotional, etc)

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15
Q

Glucocorticoids Characteristics:

Do glucocorticoids have immunosuppressive, metabolic and anti-inflammatory effects?

A

Yes. For metabolic, the inc. glycogenolysis, gluconeogenesis, proteolysis and lipolysis.
They also reduce the activity of the innate and acquired immune systems.

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16
Q

Glucocorticoids Characteristics:

What is the Permissive Effect?

A

Catecholamines causes vasoconstriction. The presence of glucocorticoids further enhance the vasoconstrictive effects of catecholamine such that it can reverse hypotension.

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17
Q

Glucocorticoids Characteristics:

What is the main endogenous glucocorticoid? How much of it is physiologically secreted by the body per day?

A

Cortisol (a.k.a. Hydrocortisone)

~20mg/day (15-30mg/day)

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18
Q

Glucocorticoids Characteristics:

Describe the chain of events that lead to cortisol production.

A

Stress —> stimulate Hypothalamus to secrete Corticotropin releasing hormone —> signals Ant. Pituitary gland to release Adrenocorticotropic Hormone —> tells adrenal gland to secrete cortisol

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19
Q

Glucocorticoids Characteristics:

When are cortisol levels highest? lowest?

A

Highest in the morning (give you enough energy to start the day).
Lowest at midnight.

20
Q

Glucocorticoids Characteristics:

What are the carrier proteins of cortisol?

A
  1. Transcortin (main)

2. Albumin

21
Q

Glucocorticoids Characteristics:

Name the 2 hormones that affect the binding of Cortisol to its carrier proteins? What are their effects?

A
  1. Estrogen: causes the inc. in serum conc. of transcortin thus inc. the total amount of cortisol WITHOUT changing the level of free cortisol
  2. Progesterone: has great affinity for transcortin and can displace bound cortisol resulting into an inc. in active free cortisol
22
Q

Glucocorticoids Characteristics:

Name 2 states wherein there is an increase in the level of binding proteins in the serum.

A
  1. Pregnancy (due to inc. in estrogen)

2. Hyperthyroidism

23
Q

Glucocorticoids Characteristics:

Name 2 factors that regulate ACTH secretion.

A
  1. Free cortisol inhibits ACTH (negative feedback)

2. CRH secreted by Hypothalamus promote ACTH secretion by ant. pituitary gland.

24
Q

Glucocorticoids Characteristics:

What is the plasma half life of cortisol?

A

80 minutes

25
Q

Glucocorticoids Characteristics:

There are 2 types of negative feedback mechanism that stops cortisol production. What are they?

A
  1. Short loop mechanism: free cortisol signals Ant. Pituitary gland to stop ACTH production
  2. Long loop mechanism: free cortisol signals the hypothalamus to stop CRH production
26
Q

Glucocorticoids Characteristics:

Describe the general mechanism of glucocorticoid receptor regulation.

A

Ligand enter cell —> bind to cytoplasmic receptor —> receptor dissociates from HSP90 —> ligand-receptor complex transported into the nucleus —> interacts with DNA and nuclear proteins —> mRNA transcription —> mRNA transported to cytoplasm —> cellular changes

27
Q

Glucocorticoids Characteristics:

What are the 2 genes of glucocorticoid receptor?

A
  1. hGR-alpha

2 hGR-beta

28
Q

How does INFLAMMATION and STEROIDS affect chromatic structure?

A

Inflammation —> Histone acetylation —> transcriptional activation

Steroids —> Histone deacetylation —> gene silencing

29
Q

Glucocorticoids Characteristics:

It is one of the famous secondary messengers of the anti-inflammatory action of glucocorticoid.

A

Lipocortin-1

30
Q

Effects of Glucocorticoids:

What are the main effects of glucocorticoids?

A

(1) Metabolic, (2) Skeletal, (3) Fat cell, (4) Connective tissue and bone, (5) Anti-inflammatory effects

31
Q

Metabolic Effects: Inc or Dec?

  1. Glycogenolysis? Gluconeogenesis?
  2. Protein synthesis?
  3. Lipolysis
  4. Osteoclast activity? Osteoblast?
  5. Vit D?
A
  1. Inc, Inc - results in hyperglycemia
  2. Dec -results in muscle weakness & atrophy
  3. Inc - lipolysis and fat redistribution (Cushing)
  4. Inc, Dec. - results in osteoporosis
  5. Dec conversion of Vit D2 to active vit. D -resuts in dec. Ca2+ absorption from GIT
32
Q

Skeletal Effects:

  1. Muscles mass (Inc or Dec?)
  2. Protein catabolism is greatest for the _____ derivatives.
A
  1. It will dec. due to decreased protein synthesis

2. Fluorinated derivatives

33
Q

Fat Cell Effects:

  1. Synthesis of Long chain FA (inc or dec?)
  2. Stimulate the effects of what lipolytic hormones?
A
  1. dec or inhibited

2. catecholamins, glucagon, GH

34
Q

Connective Tissue & Bone effects: (inc/dec?)

  1. Bone formation?
  2. Ca2+ absorption
  3. Parathyroid hormone (PTH) secretion?
  4. Bone resorption and remodeling?
A
  1. dec
  2. dec
  3. inc, due to decreased plasma levels of Ca2+ (compensartory mechanism)
  4. Inc, due to release of PTH

All of the 4 Factors lead to OSTEOPOROSIS

35
Q

Anti-inflammatory Effects:

What are the 3 Major Mechanisms?

A
  1. Interference w/ Leukocyte Migration
  2. Inhibition of Arachidonic acid cascade
  3. Permissive effect o catecholamine activity
36
Q

Anti-inflammatory Effects:

Inhibition of Arachidonic acid cascade results into?

A

decreased production of Prostaglandins, Interleukins and Cytokines

These are derived from the degradation of Arachidonic acid due to the action of Phospholipase 2

37
Q

Anti-inflammatory Effects:

What are the cellular changes that are involved?

A
  1. Dec.in prolif and migration of Agranulocytes
  2. Reduced number of Eosinophils and Basophils
  3. Neutrophils INCREASE in number
38
Q 
Glucocorticoids can be used in Therapy.
Give some examples of diseases in these areas that could be managed by cortisol:
1. Dermatologic 
2. Allergic disease
3. Rheumatologic
4. Asthma
A
  1. Atopic Dermatitis. Eczema
  2. allergic rhinitis, urticaria
  3. Systemic Lupus Erythematosus
39
Q

Glucocorticoids could serve as a replacement therapy in Adrenal Insufficiency.
Describe how is this possible.

A
  1. Post adrenalectomy,
  2. Hypopituitarism,
  3. Withdraw of prolonged drug use
40
Q

Glucocoricoids can be divided into classes using what factors/characteristics?

A
  1. Potencies in Na+ retention
  2. effect on Carb metabolism
  3. Anti-inflammatory effects
41
Q

Structure-Activity Relationship:

  1. Effect of C6 methylation?
  2. Effect of C9 Fluorination?
A
  1. Inc in anti-inflamm. activity and improves pulmonary penetration (ex. methylprednisolone)
  2. Inc anti-inflamm effect w/ pronounced catabolic effect. (ex. dexamethasone)
42
Q

Commonly Used Glucocorticoids:
Give examples of 2 short-acting drugs.
When are they used?

A

Hydrocortisone and Cortisone.

  • potencies are close to the normal endogenous cortisol of the body
  • HIGH MINERALOID potencies.
  • used during shock because it can raise BP
43
Q

Commonly Used Glucocorticoids:

Give examples of 4 intermediate acting drugs. What are their characteristics?

A

Methylprednisolone, Prednisone, Prednisolone, Triamcinolone.

  • high anti-inflamm potency
  • low mineralocorticoid potency
44
Q

Commonly Used Glucocorticoids:

Give 2 examples of Long acting drugs. What are their characteristics?

A

Betamethasone and Dexamethasone

  • they are fluorinated
  • very high anti inflamm potency
  • very low mineralocorticoid potency
  • causes the GREATEST effect on glucose Metab
45
Q

Adverse effects:
At what dose will the use of glucocorticoid for more than 1 week result into HPA axis suppression?
What are its know adverse effects?

A 
7.5 mg
Causes Cushing syndrome (persistent lipolysis)
Suppressed Immune system
Peptic Ulcer
Growth suppression, Osteoporosis.
46
Q

Should nasal steroid be lipophilic or hydrophilic?

A

Lipophilic
Faster uptake by nasal mucosa
Greater retention within the tissue
Enhanced glucocoricoid receptor binding

Ther 201 2nd Exam (6 decks)

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