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Part 3

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waveurflag's version from 2018-03-29 01:58

Section

Question Answer
Steroids are produced in the cortex of adrenal glands
Zona glomerulosa (outermost) – production of mineralocorticoids
Zona fasciculateproduction of glucocorticoids
Zona reticularis(innermost) – production of adrenal androgens
Medullaproduces catecholamines
Acute Stressmedulla) – membrane receptors, second messengers o "Dog attack" o Shorter time• Doesn’t need to recruit hypothalamus and pituitary – bypasses
Prolonged Stress(cortex) – nuclear steroid receptors o changes your genes and mRNA to make proteins that affect your system o Happens over time
EPI effects on heart, lungs, and blood vessels• Heart  AC/cAMP  inc HR • Lungs  AC/cAMP  bronchodilation • BV  PLC/IP3/DAG  vasoconstriction, inc BP
ACUTE STRESS = GLYCOLYSIS!!!!• Broken down glycogen in body to have glucose available for muscle o Beta receptor activates cAMP to have faster glycolysis
• Cortisol accounts for at least 95% of glucocorticoid activity (most common!!!), and approximately 15 to 20 mg are secreted daily. o Normal, nonstress: peak in the morning to get you up in the morning, decrease at 12 pm
• Corticosteronehas a small amount of activity (less active than cortisol), and approximately 1.5 to 4 mg are secreted daily.
• Cortisone has little activity and is secreted in minute quantities. • In the peripheral tissues, cortisol is converted to cortisone by the enzyme 11-beta-steroid dehydrogenase. • It can be considered an inactive metabolite of cortisol
• 11-B-HSD1 vs 11-B-HSD2Type 2 converts active cortisol into INactive cortisone, and Type 1 is vice versa
Licoricecontains glycyrrhetinic acid, or Carbenoxolone can inhibit 11β-HSD and lead to a • contains glycyrrhetinic acid, or Carbenoxolone can inhibit 11β-HSD and lead to a mineralocorticoid excess syndrome.
If cortisol is not inactivated, the net effect is similar to aldosterone excess
How does our body regulate corticotropin releasing hormone?• Hypothalamus glucocorticoid sensor will sense that there is enough glucocorticoids in the body, sending the signal back to the hypothalamus to shut down the glucocorticoid cascade.
Glucocorticoids canreduce inflammation, but suppress the immune system
Prednisone• 3-Pharmacologic class: Glucocorticoid agonist • Indications: o Asthma o COPD o Rheumatic disorders o Allergic disorders, o Ulcerative colitis o Crohn's disease o Adrenocortical insufficiency o Acts as anti-inflammatory + immunosuppressant
Prednisoloneo Lower mineralocorticoic activity than cortisol o Avoid mineralocorticoid activity to prevent adverse effects with mineralocorticoids (i.e. inc BP). Only want glucocorticoid receptor effects, not BP effects o Addition of one double bond in the ring makes prednisolone more receptive to glucocorticoid than mineralocorticoid.
Prednisolone Effects at the Nuclear Level • Step 1 - Glucocorticoid receptor usually inhibit inflammatory genes when cortisone binds it o Prednisolone will inhibit inflammatory genes • Step 2 - Prednisolone will find GRE (glucocorticoid response element) o Activates anti-inflammatory genes • Steps 3 and 4 - Prednisolone will inhibit: o Transcription factor p65/nf-KB – pro-inflammatory, want to inhibit o cAMP-response elemnt binding protein 1 – also pro-inflammatory, want to inhibit • Step 5 - Activation of histone deacetylase 2 o How do you shut them down? Histone deacetylation o Histone deacetylation prevents opening of histone so DNA cannot be reached
Histone• At N terminus (histone tail) – lysine rich • Lysine is the target of acetylation in histone proteins • Addition/removal of acetyl groups occurs here
HDACprevents DNA from uncoiling and prevents inflammatory protein DNA sequences from being read
Prednisolone (high or sustained doses)bone loss and diabetes
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