PHARM FINAL Flashcards
(53 cards)
The hypothalamic - pituitary - adrenal Axis
Is our bodies response to stress (fight or flight)
Stimuli = stress
Leads to hippocampus activates the hypothalamus
Hypothalamus releases vasopressin and corticoid releasing factor
CRF travels to the pituitary gland which releases adrendocorticotropic hormone to the blood to the adrenal cortex
Adrenal cortex releases cortisol
Cortisol is a negative feedback to pituitary and hypothalamus to reduce further stimulation of the system
Discuss the anatomy of the adrenal glands
Most superficial
Zone glomerulosa = secretes aldosterone
Zone fasciculata = secretes cortisol and androgens
Zone reticularis = secretes cortisol and androgens
Adrenal medulla = secretes epinephrine and norepinephrine
Most deep
Why are there different expression of enzymes in different zones of the adrenal glands?
Most superficial
Zona Glomerulosa = CYP11B2 which lead to aldosterone
Zona Fasciculata / reticularis = CYP11B1 and CYP17 to lead to cortisol & corticosterone
Medulla = CYP17 to lead to DHEA & androstenedione
What is the Maastricht acute stress test for humans?
This test measures the levels of cortisol in humans that respond to stress when they did their hand in cold water and try to do arithmetic
-males have high release of stress and faster
-women have a slower and nit as high release
What is diurnal cycle of serum glucocorticoids?
-Is the lowest in the middle of the night, but peaks in the morning (probably;y have something to do with waking)
-maybe anti - inflammatory because melatonin is pro inflammatory
- there is no average difference between males and females, age puberty but there is a lot of variance in individual levels of glucocorticoids
Why does stress increase glucocorticoid release into the blood and what can this result in?
- there are big differences fro individual to individual
-inappropriate stress response can result in too much and too long which can lead to a weaker HPA axis response
What is habituation?
-Repeated stressor can lead to habituation
-Chronic stressors (server pains, hypoglycemia) can lead to NO habituation
-both cases a novel stress can cause HYPER response of the HPA axis
What do corticosteroids do?
-regulate energy metabolism
-increase short term memory
-maintain BP
-inhibit inflammation
-help with fetal lung development
What does it mean when you have corticosteroids deficiency?
Addison’s disease
-causes low blood sugar
-low BP
-weakness
-muscle and joint pain
-skin darkening or vitiligo
-salt craving (reduce salt, increase potassium)
-nausea/diarrhea
-depression
What does it mean when you have corticosteroid overload?
Cushing;s syndrome
-skin thinning
-depression/mood swings
-memory loss/learning disability
-muscle wasting
-poor wound healing / suppression immune system
-hypertension
-diabetes
-osteoporosis
-anovulation
What are clinical causes of Addison’s disease?
Adrenal glands not functioning leads to hypocortsiol and hypo aldosterone
Hypo cortisol leads to decrease liver function & creased stomach digestive enzymes -> low blood sugar & vomiting diarrhea -> brain coma & death
Hypo aldosterone - kidney and water sodium loss -> low fluid volume -> low p=blood pressure -> shock -> Brian coma & death
What are clinical causes Cushing’s syndrome?
Hyper tension,
Buffalo hump,
Skin ulcers from poor wound healing,
Thinking of skin, moon face,
Osteoporosis
What is cortisone?
Isolated in the 1940’s and used for rheumatoid arthritis for the first time in 1948 and quickly become a widely sued drug
Who are Hench, Kendall and Reichstien?
Received the Nobel price in 1950 for discoveries related to hormones of the adrenal cortex
What are therapeutic uses of corticosteroids?
Allergic reactions = asthma, angioedema
Inflammation of bones/joints = arthritis, bursitis
Skin diseases = atopic dermatitis
thyroid disease = malignant exophthalmos
Miscellaneous= hypercalcemia
List some therapeutic verse adverse effects of glucocorticoids use (Dose and length of treatment)
Therapeutic effects= anti inflammatory effect and immunosuppression will decrease pain, swelling, stiffness, and physical disability
Adverse = infections, myopathy, osteoporosis, weight gain, increase CDV risk
How do synthetic glucocorticoids compare to non synthetic glucocorticoids?
Synthetic glucocorticoids that are stronger anti-inflammatories and can be used topically. Most do not have the salt retention properties that cortisol dose. Although some (Dexamethansone) have dramatically longer half lives compared to hydrocortisone
How do glucocorticoids regulate the gene in your body?
-10-20% of the genes in your body regulate your genes by binding to glucocorticoids receptors (GR) inside cells - can be alpha (active) or beta (blocks alpha)
-Because they have great affinity to corticosteroid binding globulin (CBG) in plasma but not very well to albumin
-regulation of genes by the GR can either invites transaction of the target genes or transrespression (messes up other transcription factor)
How do glucocorticoids work in a cell?
Glucocorticoids bind to their receptor which cause dimerization, translocation to the nucleons and bind to DNA to regulate transcription of target genes
What is the net result of glucocorticoids regulating your genes in your body?
The net results in increase anti-inflammatory gene expression, decrease in pro-inflammatory gene
What do glucocorticoids do
Affect metabolism and immune function because secrete cortisol
-in blood and binds to CBG
what do mineral corticosteroids do?
Salt retaking from secreting aldosterone
-causes sodium reabsportion in distal renal tubule, sweat glands, salivary glands and GI
-when it binds to mineralcorticoid receptor it increases the expression of sodium / postassium ATPase and epithelial sodium channel in the collecting duct in kidneys
What is insulin and where is it produced?
Insulin is a peptide h romaine produced by the beta cells of the pancreas and is central for regulating carbohydrate and fat metabolism
What is glycogen and where is it produced?
Glycogen is a polysaccharide and is produced in the liver and ,uncles
