Chapter 10 endocrine system - adrenal hormones Flashcards
cortisol
- glucocorticoid released by adrenal gland which helps maintain homeostasis by regulating numerous enzymes throughout body
- during stress plays role in inc blood glucose levels and elevate BP
indication:
1) immunosuppressive properties
2) adrenal deficiencies
synthesis:
limib system => regulate release of corticotorpin releasing hormone (CRH) from hypothalamus via serotoniergic, dopaminergic and cholinergic neurons
* CRH stimulate adrenocorticotrophic hormone (ACTH) from anterior pituitary => ACTH activates adenylate cyclase in adrenal cortex => CMP activates prokinase which enhacnes cholesterol esterase activity => this enzymes inc available cholesterol to mitochondria => l/t to production of cortisone (from the cholesterol)
* ALSO ACTH stimulates conversion of cholesterol to pregenolone (1st step in steroid synthesis — testosterone, DHEA, estradiol, cortisol and progesterone)
transport to tissues:
cortisol secreted into bloodstream where 90% bound to cortisol-binding globulin (CBG) and albumin
* active cortisol (10% remaining) freely diffuse into cells where it exerts its action via intracellular recepters (regulate delivery and clearance via CBG)
metabolism
* cortisol becomes => dihydro- and tetrahydro-derivatives which are subsequntly conjugated with glucuronic acid of sulfates
* conjugates water soluble and rapidly excreted by kidneys
* LIVER failure => less metaoblism of CBG + synthesis of it
* resulting in more active (unbound) cortisol present in blood => hypercortism
* similarly, renal failure inc half life of cortisol
indications
* adrenocortical insufficiency
* salt-losing forms of cogenital arenal hyperplasia
* auto immune diseases
* arthritis
* asthma
* dermatitis
* cancer
* sarcoidosis ( inflammatory disease in which the immune system overreacts, causing groups of cells to form clusters of inflamed tissue called “granulomas” in one or more organs of the body)
effects
* adrenal suppression (insuffiency upon withdrawal)
* cushing’s syndrome
1) osteoporosis
2) skin atropy
3) central fat distribution
4) abnormal glucose intolerance
5) BH abnormalities
* suppression of somatic growth
* osteopenia +bone fractures
adrenocorticosteroid hypersecretion
Cushing’s syndrome
- excess glucocorticoids
- caused by
1) overmedication
2) adrenal hypersecretion d/t tumor
3) excessive ACTH release (pituitary adenoma or metastatic tumors)
effects
* osteoporosis
* skin atrophy (decreased thickness of the dermis)
* abnormal fat distribution
* abnormal glucose intolerance
* BH abnormalities + euphoria
Primary hyperaldosteronism
* caused vy adrenal adenoma which secretes aldosterone
* l/t HTN, hypokalemia, metabolic alkalosis (body rebalance body by secreting more K+ in exchange for H+), suppressed renin
Drug example — aminogluthimide (cytadren) — reduce synthesis of adrenal hormones by blocking conversion of cholesterol to pregnealone (precursor steroid…?!)
Mineralocorticoids and androgens
- these two other kinds of steroids are produced in adrenal glands
1) aldosterone (renin-angiotensin pathway)
2) dehydroepiandrosterone and androstenedione are principal androgens
* little masculine fx for men
* BUT for women – metabolized to testosterone => resulting in development of public hair + libido
Actions of glucocorticoids
protein metabolism:
1) inc catabolism, but dec anabolism
carbohydrate metabolism:
1) inc gluconeogenesis, dec insulin bind to receptors
fat distribution
1) redistribute fat towards trunchal obesity
electrolytes
* inc Na+ retention, inc K+ sec + metoblic alkalosis
* dec GI ca++ absorption
Immune sys
* dec antibody production
* dec inflammatory rxn
* dec immunocompetent lymphocytes
* dec antigen processing
bloody cytology
* inc erythropoesis + neutrophils
* dec lymphocytes
Water
* inc water clearance
brain
* dec electrical excitation
GI tract
* inc acid and pepsin secretion thining of mucus..?
hydrocoritsone
cortisone derivative
Chemically identical to cortisol produced by adrenal glands
- preferred for replacement therapy (PO/IV/IM/Top)
- weak nimeralocoritocid effects
- short acting
prednisone
cortisone derivative
PO
- glucocorticoid effects are 4x more potent (than hydrocortisone) and minieralocorticoid effects are half as potent
drug of choice
* for tx of acute asthmatic attack (administered IV)
tramcinolone (aritocort)
cortisone derivative
- compared to hydrocortisone
- 30x more potent than above w/ no mineralocorticoid effects
dexmethasone (decadron)
cortisone derivative
- PV/IV/IM/Inh
- reduce elevated intracranial pressure
- few mineralocorticoid effects
- Dexamethasone suppression test — test whether hypothalamus + pituitary can be suppressed by glucorticoids; if plasma cortisol level is <5 u g/dl eight hrs after receiving 1 gm of dextamethasone => cushing’s syndrome is ruled out
fludrocoritsone (florinef)
cortisone derivative
- PO
- halogenated derivative w/ potent mineralcorticoid effects
- inappropriate for use as an antiinflammatory agent
Mitotane (lysodren)
inhibitors of adrenal hormone synthesis + actions
- destroy adrenocortical cells
indication
* palliative tx of metastatic adrenal carcinoma
metyrapone (metopirone)
inhibitors of adrenal hormone synthesis and actions
- blocks 11b-hydroxylase activity
- l/t inhibition of steroid synthesis
indication:
investigation for cushing’s
aminoglutethamide (cytadren)
inhibitors of adrenal hormone synthesis and actions
- blocks conversin of cholesterol to pregneolone (1st step in steroid synthesis)
indication
* cushing’s disease
* adjunct to irradiation in preparing pt for adrenlectomy (surgical procedure to remove the adrenal gland if it is cancerous and/or producing too much hormone)
* tx adrenal, breast, and ACTH producing tumors
cyprophetadine (periactin)
inhibitors of adrenal hormone synthesis and actions
serotonin and cholinergic antagonist
* which may inhibit ACTH secretion from pituitary microadenoma cells
indication
* experimental for ACTH hypersecretion and cushing’s disease
spironolacton (Aldactone)
inhibitors of adrenal hormone synthesis and actions
- antagonist of aldosterone,
- inhibits Na+ retention
indication
* tx hyperaldosteronism => K+ retention
