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PMCOL 200 Final > Corticosteroids > Flashcards

Corticosteroids Flashcards

(45 cards)

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1
Q

What are the two parts of the Adrenal Gland

A

Medulla

Cortext

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2
Q

What is the adrenal gland

A

Apex of kidney

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3
Q

What does the medulla produce

A

Adrenaline

Catecholamine / amino acid hormone

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4
Q

What does the cortex produce

A

Steroid hormones

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5
Q

Layers of the Cortex

A

Zona Glomerulosa
Zona Fasciculata
Zona Reticularis

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6
Q

Mineralocorticoids
- Function
- Example
- Produced Where

A

Mediate Salt balance
Ex. Aldosterone

Produced by Zona Glomerulosa

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7
Q

Glucocorticoids
- Function
- Example
- Produced Where

A

Metabolic (how body uses sugars) and immune effects
Ex. Cortisol

Zona Fasciculata

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8
Q

Androgens
- Function
- Example
- Produced Where

A

Precursors for strong androgens
Responsible for sex hormones like
Testosterone and
Estrogens
Ex. DHEA

Zona Retucularis

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9
Q

What does HPA Axis control

A

Cortisol release from Zona Fasciculata

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10
Q

Describe main pathway of HPA Axis

A

Hypothalamus controls synthesis of Corticotropin Releasing Factors (CRF/CRH), hormones which controls ACTH production by the anterior pituitary

ACTH (Anterior Pituitary) stimulates steroid production, cortisol in synthesized in the adrenal cortex

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11
Q

Describe Negative Feedback in the HPA Axis

A

Cortisol has a negative feedback on
CRH production (Hypothalamus)
ACTH (Anterior Pituitary)

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12
Q

Why is cortisol important

A

Suppresses stress response and acts on glucocorticoid tissues, catabolism, and immuno surpression

Lack of cortisol can causes hyperproduction of certain products

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13
Q

What is Aldosterone

A

Mineralocorticoid Response

Targets kidneys promoting Na+/Water reabsorption and K+ excretion

Increases blood volume and pressure

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14
Q

Describe the generalized mechanism of steroid hormone action

A

Steroid hormone diffuses into plasma membrane

Cytoplasmic unliganded receptor forms a complex with Hsp90

Hormone binds to cytoplasmic receptor, dissociates from Hsp
Forms a Steroid-receptor dimer (activated state)

Dimerized receptors interact with DNA and influence transcription of target genes: Glucocorticoid receptors

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15
Q

Define spectrum in the context of steroids

A

Drugs can be designed to have different affinities for Glucocorticoid receptors or Mineralocorticoids receptors

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16
Q

What are glucocorticoid target tissues

A

Adipose (body fat), muscle, liver

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17
Q

What kind of steroid do glucocorticoid target tissues express

A

11beta-hydroxysteroid dehydrogenase, type 1

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18
Q

What does 11beta-hydroxysteroid dehydrogenase, type 1 do?

A

Activates Cortisol

Converts cortisone to Cortisol (Type 1)
Ketone to Alcohol group

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19
Q

What causes corticosteroid specificity

Study These Flashcards
A

Affinity of compound/receptor and metabolism in target tissues

20
Q

Prednisone

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A

Prodrug

Orally taken and metabolized to prednisolone in the liver and in important glucocorticoid target tissues

21
Q

Prednisolone

Study These Flashcards
A

Strong topical effect (applied on skin)

Active form of prednisone

22
Q

What does cortisol activate

Study These Flashcards
A

Glucocorticoid receptors
Mineralocorticoid receptors

23
Q

What weak effect does cortisol have

Study These Flashcards
A

Weak mineralocorticoid effects in vivo

24
Q

What does 11beta-hydroxysteroid dehydrogenase, type 2 do?

Study These Flashcards
A

Inactivates Cortisol

Converts Cortisol to Cortisone
Alcohol to Ketone group

25
What is Pseudohyperaldosteronism
Excess cortisol can have an effect on aldosterone target tissues (kindeys), increasing blood pressure through water/Na+ reabsorption Licorice contains an inhibitor of 11beta-hydroxysteroid dehydrogenase, type 2. Preventing inactivation of cortisol
26
How does Pseudohyperaldosteronism occur
Licorice contains an inhibitor of 11beta-hydroxysteroid dehydrogenase, type 2. Preventing inactivation of cortisol
27
What is Apparent Minceralocorticoid Exess
Looks like an excess of mineralocorticoid but isn't Caused by mutations to 11beta hydroxysteroid dehydrogenase, type 2 gene Inhibits conversion of cortisol to cortisone Cortisol then acts act aldosterone tissue
28
Glucocorticoid effect on Carbohydrate Metabolism
Increases circulating glucose
29
Effect of Glucocorticoid on Fat/Lipid Balance
Catabolic breakdown of fat Loss of muscle and bone mass in limbs Fat accumulation in viscera and trunk (Skinny Fat)
30
Describe pathway of glucocorticoid effects (Initial)
Food is consumed, calories are transferred to selected sites (Adipose Tissues) Adipose Tissues: Triglycerides are broken down by lipolytic hormones into free fatty acids (Short term loss of fat) (High insulin from desensitization to glucose spike)
31
Describe pathway of glucocorticoid effects (Liver)
Glucose inhibits insulin production in muscles Muscle proteins are broken down to form amino acids which are carried to the liver to be used as glucose precursors Glucose is formed and is used to inhibit insulin in adipose tissue
32
Cyclooxygenase-2 function and role
COX-2 is an inflammatory mediator Arachidonic acid conversion to different prostanoids depending on cell type (Prostaglandins and Thromboxane)
33
Glucocorticoids relationship with COX-2
Glucocorticoids suppress transcription of the COX-2 gene
34
What are the effects of inhibiting COX-2
Affects all downstream products like PGI2,TXA2 PGF2, PGD2, PGE2
35
What is Annexin A1
Lipocortin/Annexin with very powerful and broad anti-inflammatory effects Effects are very early in inflammatory response
36
What are the two effects of Annexin A1
1. Directly effecting Leukocytes and inhibiting their ability to infiltrate tissue 2. Suppressing phospholipase A2 activity, prevents formation of arachidonic acid, thus, preventing all downstream prostanoids
37
What is Addison's Disease Symptoms
Insufficient glucocorticoid production (and often mineralocorticoids) Lack of glucose causes fatigue, salt + sugar balance issues, skin discolouration
38
How is Addison's Disease treated
Hydrocortisone Glucocorticoid / Mineralocorticoid supplements can treat hormone deficiency
39
What is Cushing's Syndrome Symptoms
Excessive cortisol from adrenal overactivity Round face and fat deposition in trunk Muscle loss and osteoporosis (Protein and bone catabolism) Resembles side effects of therapeutic doses of GCs
40
What causes Cushing's Syndrome
Adrenal Tumours (Produces cortisol) Pituitary Tumours (Produces ACTH, stimulates adrenal cortex) Drug-Induced (High dose GC) Ectopic Tumour (Produces ACTH, stimulate adrenal cortex)
41
How is Cushing's Syndrome treated
Resection of adrenal / pituitary tumours Adjustment of doses of cortisol
42
Side Effects of Synthetic Glucocorticoids
Metabolic: Glucose produces high blood sugar - Hyperglycemia Immunosuppressive Catabolic: Osteoporosis, muscle wasting Anti-Inflammatory: Affects cell division, slow wound healing, ulcerations Hypertension caused by non-specific MC effects of GCs Psychosis: Especially in elderly
43
Why should Glucocorticoid treatments not be stopped abruptly
GC acts as cortisol and negatively inhibits ACTH and CRH production. Body grows dependent on GC and can't make its own cortisol Body needs time to synthesize its own cortisol
44
Effects of abruptly stopping GC treatment
Addisonian Crisis: Hypoglycemia (Low Glucose) Hyponatremia (Low Sodium) Hyperkalemia (High Potassium)
45
What is Tapering Treatment
Slowly reducing a treatment to prevent an abrupt stop Used in stopping long term glucocorticoid treatments

PMCOL 200 Final (5 decks)

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