Term
| what type of secretion does cortisol undergo? |
|
Definition
|
|
Term
| when are levels of cortisol highest? |
|
Definition
| at about 8 am in the morning |
|
|
Term
| what stimulates cortisol secretion? |
|
Definition
| stimulated by ACTH on the adrenal gland |
|
|
Term
| what is the hypothalamic hormone that stimulates release of cortisol? |
|
Definition
|
|
Term
| what is the effect of CRH on the pituitary? |
|
Definition
| stimulate ACTH release from corticotrophs in the anterior pituitary |
|
|
Term
| what is the effect of ACTH on the adrenal gland? |
|
Definition
| stimulate receptors in the zona fasciculata stimulates cortisol synthesis and secretion |
|
|
Term
| how is cortisol negatively controlled? |
|
Definition
| negative feedback by circulating cortisol |
|
|
Term
| what is necessary in the regulation of circulating cortisol? |
|
Definition
| negative feedback shuts off endogenous production of corticosteroids |
|
|
Term
| steroid hormone biosynthesis as a whole uses a variety of different what? |
|
Definition
|
|
Term
| why is it important that adrenocortical hormone biosynthesis is dependent on many different cytochrome p450s? |
|
Definition
| because they can be regulated and affected by a number of different agents |
|
|
Term
| what is the precursor of steroid hormones? |
|
Definition
|
|
Term
| what is the main site of regulation of steroid hormone synthesis? |
|
Definition
first enzyme - 20,22-desmolase or cholesterol side chain cleavage
converts cholesterol |
|
|
Term
| what determines what hormone is made from cholesterol precursor? |
|
Definition
| which enzymes are present |
|
|
Term
| cytochrome p450 systems use what 2 things for their reactions? |
|
Definition
| molecular oxygen and NADPH |
|
|
Term
| what is the importance of knowing that steroid hormone synthesis is dependent on cytochrome p450 systems? |
|
Definition
| they are inducible and inhibitable by other drugs |
|
|
Term
| steroid hormone state in plasma? |
|
Definition
| avidly bound in circulation by binding globulins |
|
|
Term
| can steroid hormones cross the plasma membrane? |
|
Definition
YES
they are highly lipophilic |
|
|
Term
| what is true about a steroid hormone that can enter a cell and bind to its receptor? |
|
Definition
| it has to be in free form (not bound to plasma binding globulin) |
|
|
Term
| what are the 3 components of steroid receptors? |
|
Definition
1. N terminal region - transcriptional activation domain
2. DNA binding region - central region that binds the receptor to the response element on DNA
3. ligand binding region - where hormone binds |
|
|
Term
| what is the state of steroid receptors in the cytoplasm or nucleus before they are bound by their hormone? |
|
Definition
| they are associated with chaperones |
|
|
Term
| what is the function of chaperones associated with steroid hormone receptors? |
|
Definition
| they maintain the receptor in a high affinity state |
|
|
Term
| what are the 3 chaperones for cortisol receptor? |
|
Definition
1. HSP70
2. HSP90
3. IP - immunophilin |
|
|
Term
| how do steroid receptors elicit a response in the cell? |
|
Definition
| they act as transcription factors activating genes through specific response elements |
|
|
Term
| what binds cortisol in the blood? |
|
Definition
| corticosteroid binding globulin (CBG) or transportin |
|
|
Term
| all steroid hormones have what underlying structure? |
|
Definition
|
|
Term
| what is the structure of cortisol? |
|
Definition
| its a C-21 steroid with 4 rings |
|
|
Term
| how is cortisol metabolized? |
|
Definition
by successive reduction in the A ring
reduced in 3 steps |
|
|
Term
| what is the purpose of cortisol metabolism? |
|
Definition
it makes a more water soluble metabolite that can be excreted in the urine
happens with all steroids |
|
|
Term
| what are the 3 MAJOR metabolic effects of adrenal steroids? |
|
Definition
1. CHO, protein, and fat metabolism - increase gluconeogenesis
2. electrolyte and water metabolism
3. anti-inflammatory and immunosuppressive effects |
|
|
Term
| what happens to plasma glucose levels with adrenal steroids administration? |
|
Definition
increase
can cause hyperglycemia |
|
|
Term
| what happens to amino acids with adrenal steroids administration? |
|
Definition
| they are mobilized from tissues |
|
|
Term
| what happens to glucose uptake with adrenal steroids administration? |
|
Definition
| it is inhibited in fat cells |
|
|
Term
| what can be an effect of long term use of adrenal steroids on muscle? |
|
Definition
| can lead to breakdown of muscle and muscle wasting |
|
|
Term
| how do adrenal steroids affect electrolyte and water metabolism? |
|
Definition
1. increases Na reabsorption
2. increases K secretion/excretion
3. inhibits Ca absorption from intestine |
|
|
Term
| how do adrenal steroids inhibit Ca absorption from the intestine? |
|
Definition
act as an antagonist of vitamin D activity in the gut - vitamin D is normally involved in Ca absorption
leads to an increase Ca loss in feces |
|
|
Term
| what 3 ways do adrenal steroids act as anti-inflammatory and immunosuppressive agents? |
|
Definition
1. inhibition of arachidonic acid and its metabolites
2. inhibit cytokine production and release
3. inhibit production of adhesion molecules |
|
|
Term
| what 2 enzymes in the arachidonic acid pathway do adrenal steroids inhibit? |
|
Definition
| COX2 and phospholipase A2 |
|
|
Term
| what is the function of COX 2 in the arachidonic acid pathway? |
|
Definition
normally converts AA to PGE
inhibited by adrenal steroids |
|
|
Term
| what is the function of phospholipase A2 in the arachidonic acid pathway? |
|
Definition
normally responsible for synthesis of AA
inhibited by adrenal steroids |
|
|
Term
| how do adrenal steroids inhibit cytokine production and release? |
|
Definition
| block NF Kappa B which is needed for interleukins |
|
|
Term
| what adhesion molecules are inhibited by adrenal steroids? |
|
Definition
|
|
Term
| where does inhibition of adhesion molecules with adrenal steroids occur? |
|
Definition
|
|
Term
| what effects of adrenal steroids are seen at physiological concentrations of corticosteroids? |
|
Definition
1. carbohydrate, protein, and fat metabolism
2. electrolyte and water metabolism |
|
|
Term
| when are the anti-inflammatory and immunosuppressive effects of adrenal steroids seen? |
|
Definition
| only at higher than physiological concentrations of corticosteroids |
|
|
Term
| how are adrenal steroids involved in the response to tissue injury? |
|
Definition
| inhibit the response to injury by blocking the mediators of the response |
|
|
Term
| what are some clinical uses of synthetic glucocorticoids? |
|
Definition
allergic reactions
collagen-vascular disorders
eye diseases
GI disease
heme disorders
infections
inflammatory conditions of bones and joints
neurologic disorders
organ transplants
pulmonary disease
renal disorders
skin diseases
thyroid disease
hypercalcemia
mountain sickness |
|
|
Term
| forms of glucocorticoid administration? |
|
Definition
| many different ways - injected into joints, inhalants, topically, orally |
|
|
Term
what is the the only thing synthetic glucocorticoids are used to treat?
why is it used in so many other disorders? |
|
Definition
adrenal insufficiency
it is used to alleviate the symptoms of other disorder |
|
|
Term
| what are the 2 goals of synthetic products of cortisol? |
|
Definition
1. reduce the salt retaining activity
2. make a longer acting and more potent glucocorticoid |
|
|
Term
| what are the 3 main categories of glucocorticoids? |
|
Definition
1. short acting
2. intermediate acting
3. long acting |
|
|
Term
| 2 short acting glucocorticoids? |
|
Definition
1. hydrocortisone
2. prednisone |
|
|
Term
| how does hydrocortisone compare to endogenous cortisol? |
|
Definition
|
|
Term
| how does prednisone compare to endogenous cortisol? |
|
Definition
4x anti-inflammatory action
1/3 salt retaining activity - avoid HTN
still short acting |
|
|
Term
| what is the intermediate acting glucocorticoid? |
|
Definition
|
|
Term
| how does triamcinosone compare to endogenous cortisol? |
|
Definition
higher anti-inflammatory (5x)
NO salt retaining activity |
|
|
Term
| what are the long acting glucocorticoids? |
|
Definition
1. dexamethasone
2. betamethasone |
|
|
Term
| how does dexamethasone compare to endogenous cortisol? |
|
Definition
very potent anti-inflammatory action (30x)
NO salt retaining activity |
|
|
Term
| what mineralocorticoid is used as a drug? |
|
Definition
|
|
Term
| how does fludrocortisone compare to endogenous cortisol? |
|
Definition
has some anti-inflammatory activity
salt retaining activity is 250x higher |
|
|
Term
| activity of beclomethasone? |
|
Definition
| long to intermediate acting |
|
|
Term
| salt retaining activity of beclomethasone? |
|
Definition
|
|
Term
|
Definition
| for treatment of asthma in inhalant preparations |
|
|
Term
| are synthetic corticosteroids orally active? |
|
Definition
YES
all steroids are orally active
peptide hormones are not |
|
|
Term
| what has to happen to cortisone, prednisone, and methylprednisone before they are effective in the body? |
|
Definition
| they have to be activated in the body |
|
|
Term
| what enzyme is responsible for activation of cortisone, prednisone, and methylprednisone? |
|
Definition
| hepatic 11 beta-hydroxysteroid dehydrogenase 1 |
|
|
Term
| what does hepatic 11 beta-hydroxysteroid dehydrogenase do? |
|
Definition
activates:
methylprednisone to methylprednisolone
prednisone to prednisolone
cortisone to cortisol |
|
|
Term
| activation of cortisone, prednisone, and methylprednisone by hepatic 11 beta-hydroxysteroid dehydrogenase 1 normally occurs how? |
|
Definition
| very rapidly upon oral administration |
|
|
Term
| side effects of corticosteroid therapy (6 main types)? |
|
Definition
1. endocrine-metabolic
2. cardiovascular
3. musculoskeletal
4. nervous disorders - mood disorders
5. increase infections
6. cataracts in children |
|
|
Term
| what are the endocrine side effects of corticosteroid therapy? |
|
Definition
1. hyperglycemia - stimulates gluconeogenesis
2. retarded somatic growth - in children
3. negative N and Ca balance
4. retain Na and water - stimulates aldosterone
5. suppression HPA - significantly endogenous cortisol production |
|
|
Term
| why do you have taper down drug dosage of coricosteroids rather than remove them immediately after use? |
|
Definition
| to allow endogenous mechanisms to recover from the suppression of the HPA axis and endogenous cortisol secretion that can occur |
|
|
Term
| what are the cardiovascular side effects of corticosteroid therapy? |
|
Definition
|
|
Term
| what are the musculoskeletal side effects of corticosteroid therapy? |
|
Definition
myopathy - muscle wasting from amino acid mobilization and conversion to glucose
anti-vitamin D effects can lead to long term Ca loss from bones and osteoporosis |
|
|
Term
| what happens to host defenses as a side effect of corticosteroid therapy? |
|
Definition
| they are decreased and lead to an increased susceptibility to opportunistic infections |
|
|
Term
| what is an important side effect of corticosteroid therapy in children and why? |
|
Definition
| can cause cataracts with parenteral use that are irreversible |
|
|
Term
| use of topical glucocorticoids? |
|
Definition
| for resp, dermatologic (psoriasis, poison ivy) and many other uses |
|
|
Term
| 2 topical glucocorticoids? |
|
Definition
1. budesonide
2. flunisolide
used in metered dose inhalers for asthma |
|
|
Term
| is budesonide absorbed orally? |
|
Definition
| relatively poorly absorbed orally |
|
|
Term
|
Definition
| inflammatory bowel disease |
|
|
Term
| side effects of inhaled steroids? |
|
Definition
| oral candidiasis and dysphonia due to local deposition in the mouth and throat |
|
|
Term
| mechanism of action of aminoglutethimide and ketoconazole? |
|
Definition
| inhibit cortisol (steroid hormone) biosynthesis and decrease cortisol secretion |
|
|
Term
| aminoglutethimide and ketoconazole use? |
|
Definition
in patients with Cushing's
inhibit cortisol biosynthesis and decrease cortisol secretion |
|
|
Term
| what 2 drugs can be used to inhibit cortisol biosynthesis and decrease cortisol secretion in patients with Cushing’s? |
|
Definition
| aminoglutethimide and ketoconazole |
|
|
Term
| what drug can be used in inoperable adrenocortical carcinoma? |
|
Definition
|
|
Term
| mechanism of action of mitotane? |
|
Definition
| causes selective destruction of adrenocortical cells |
|
|
Term
The poorly absorbed synthetic glucocorticoid budesonide taken orally is used to treat inflammatory bowel disease. This reduces the incidence of side effects of long-term therapy with better absorbed corticosteroids such as prednisone. Systemic side effects of oral prednisone include:
a. Hypoglycemia
b. Hypercalcemia
c. Postural hypotension
d. Changes in mood |
|
Definition
|
|
Term
| can topically applied corticosteroids lead to systemic side effects? |
|
Definition
YES
if applied to certain areas of the body with high circulation or absoprtion |
|
|
Term
| what is the best place for absorption of corticosteroids in a man? |
|
Definition
|
|
