Adrenal Physiology & Pharmacology Flashcards
What are the adrenal hormones?
- Mineralocorticoids (aldosterone) –> Zona Glomerulosa
- Glucocorticoids (cortisol) –> Zona Fasciculata
- Sex hormones –> Zona Reticularis
- Epinephrine –> Adrenal Medulla
What is apart of the Hypothalamus-Pituitary-Adrenal Axis?
Hypothalamus:
1. Corticotropin-releasing hormone (CRH)
Pituitary:
2. Adrenocorticotropic hormone corticotropin (ACTH)
Adrenal:
3. Cortisol
What are the adrenocorticosteroid receptors?
- Glucocorticoid r –> associated proteins
- Mineralocorticoid r
- GPCR –> 2nd messenger cascades
What is the role of the hypothalamus in stress response (SHORT TERM)?
- Increased HR
- Increased BP
- Liver converts glycogen to glucose & releases glucose to blood
- Dilation of bronchioles
- Changes in BF patterns leading to increased alertness & decreased digestive & kidney activity
- Increased metabolic rate
What is the role of the hypothalamus in stress response (LONG TERM)?
Mineralocorticoids:
1. Retention of sodium & water by kidneys
- Increased BV & BP
Glucocorticoids:
1. Proteins & fat converted to glucose or broken down for energy
- Increased blood sugar
- Suppression of immune system
What is cortisol’s rhythm?
a dinurnal rhythm - tapers out & is lower at bedtime & then elevates in morning when you wake up
What is Cortisol?
a Glucocorticoid
What are the functions of Cortisol (a Glucocorticoid)?
- Modulates carbohydrate metabolism
- Increased resistance to stress
- Alters blood cell levels in plasma
- Anti-inflammatory & immunosuppressive actions
- Affects other body-wide systems
How do Glucocorticoids enhance metabolism?
Favour gluconeogenesis
- increase AA uptake by the liver & kidneys
- more gluconeogenic enzymes
Stimulate protein catabolism & lipolysis
Glucocorticoid insufficiency may result in HYPOglycemia (particularly during stressful periods of fasting)
How do Glucocorticoids increase resistance to stress?
Provides body w/ energy to combat stress caused by fright, trauma, disease, etc.
Cause a modest rise in BP by enhancing the vasoconstrictor action of adrenergic stimuli on vessels
How do Glucocorticoids alter blood cell levels in plasma?
Decreases eosinophils, basophils, monocytes, & lymphocytes by redistributing them from the circulation to lymphoid tissue
- imp. in tx of leukemia
Increases blood levels of hemoglobin, erythrocytes, platelets
How do Glucocorticoids have an anti-inflammatory & immunosuppressive action?
*Most imp. therapeutic property of glucocorticoids
Decrease peripheral immune cells and inflammatory cytokines
* Less cytokines means decreased T-cell activation, less inflammatory cell migration, etc.
Indirect inhibition of phospholipase A2 and arachidonic acid synthesis which is needed for prostaglandin production
COX-2 synthesis is reduced
Interference with mast cell histamine release
What are ex’s of INCREASED transcriptional changes by glucocorticoids?
- β2 adrenoreceptors
- Anti-inflammatory cytokines (IL-10, IL-12, etc.)
What are ex’s of DECREASED transcriptional changes by glucocorticoids?
- Proinflammatory cytokines (TNFα, IL-1, etc.) and chemokines * Inflammatory enzymes (COX-2)
What other system effects do Glucocorticoids have?
Adequate cortisol levels are needed for glomerular filtration
High levels of glucocorticoids stimulate gastric acid and pepsin production (ulcers)
Effect CNS and mental status (insomnia= short term, depression = long term)
Cortisol inhibits bone formation
Production of fetal lung surfactant
(helps maturation)
What are Corticosteroid pharmacokinetics?
- Transcortin (plasma protein) binds about 90% of circulating cortisol
- Hepatic metabolism
- Renal excretion
- T1/2 = 60-90 mins
- Cortisol levels increased by:
- stress
- hypothyroidism
- liver disease
What is Aldosterone (a Mineralocorticoid)?
modulation of water balance, promotion of Na+/ K+ transport
What are Aldosterone (a Mineralocorticoid) functions?
- promotes Na+ uptake in kidney tubular epithelial cells
- decreases reabsorption of K+ and causes H+ loss in urine
- control of water reabsorption
- increases blood volume and pressure
- secreted only during periods of stress
What are adrenal hormones (glucocorticoids) indicated for therapeutically?
- replacement therapy for adrenal insufficiency (ADDISON’S DISEASE or hypothalamic/pituitary problems)
- arthritis
- skin conditions
- allergies
- asthma
- renal disease
- autoimmune disease (ex: Lupus)
- ulcerative colitis & Crohn’s Disease
- organ transplants
- anaemias, thrombocytopenias
- shock (ex: septic shock)
- cerebral edema & increased intracranial pressure
- FETAL LUNG MATURATION (<34 WEEKS GESTATION)
What are some diff routes of therapeutic glucocorticoids?
- oral
- intralesional
- opthalmic
- intravenous
- intramuscular, inhaled, topical intranasal
- topical
What do Corticosteroid therapies vary in?
Vary in their anti-inflammatory potency, their duration of action, and the degree to which they cause sodium retention
What is Addison’s Disease?
↓ secretion of glucocorticoids and sometimes aldosterone
What are Addison’s Disease sx’s?
- fatigue
- syncope
- G.I. upset
- CNS effects
- joint/muscle pain
- hyperpigmentation(↑ACTH)
What does Severe adrenal insufficiency (Addison’s crisis) result in?
- hyponatremia
- hyperkalemia
- hypercalcemia
- convulsions
- fever
- death
