Endocrine Pharmacology, Pt. 2 Flashcards
What are mineralocorticoids responsible for? What 3 are most common?
regulate electrolytes and water balance
- aldosterone
- deoxycorticosterone pivalate (DOCP)
- fludrocortisone (aldosterone analog)
What are the main actions of mineralocorticoids in the kidneys, brain, and heart?
KIDNEYS: increases Na+ reabsorption in to the blood and excretion of K+ and H+ into the urine
BRAIN: stimulates the production of ADH (vasopressin)
HEART: enhances renin-angiotensin-aldosterone system to increase Na++ and blood pressure (hypertension)
What is the cellular mechanism of action of mineralocorticoids?
mineralocorticoids bind to intracellular MR and is transported into the nucleus where it binds to HRE and induces DNA transcription
What is the mineralocorticoid affinity for MR?
deoxycorticosterone > corticosterone (rodents) > aldosterone > cortisol (mammals)
What corticosteroid is able to bind to both mineralocorticoid and glucocorticoid receptors?
fludrocortisone
What are the 2 results of aldosterone deficiency?
- decreased Na+ and Cl- concentration —> decreased ECF volume —> decreased blood volume —> cardiac dysfunction
- increased K+ in ECF —> cardiac toxicity —> arrhythmia —> cardiac death
(all lead to death)
What 3 aldosterone agonists are used to treat aldosterone deficiency?
- aldosterone
- deoxycorticosterone
- fludrocortisone (aldosterone analog)
What are the 3 functions of aldosterone agonists?
- increase Na+ resorption into the blood
- promote excretion of K+ and H+ into the urine
- regulate blood pressure
What are aldosterone agonists commonly used to treat?
Addison’s (hypoadrenocorticism) in dogs and cats
What is the main result of aldosterone excess?
reabsorption of excess Na+ and water from renal tubules increases arterial blood pressure, leading to pressure diuresis
excretion of Na+ and water in the urine causing hypokalemia, muscle weakness, spasms, paralysis, and decreased ECF
What is spironolactone? How does it work? What 2 effects does it have?
aldosterone agonist that acts as a competitive antagonist
- decreases Na+ reabsorption and K+ excretion
- has effects on RAAS
What is canrenone?
aldosterone antagonist that is a diuretic metabolite of spironolactone
What is eplerenone? Why is it unique?
aldosterone antagonist that binds the MR (not PR or AR)
specificity for MR gives it a more specific effect
What 3 things are aldosterone antagonists used to treat?
- hypertension
- CHF
- other conditions where the body retains excess fluid (edematous state)
Glucocorticoid vs. mineralocorticoid effects:
some conditions require both effects
What stimulates the thyroid gland to excrete its hormones?
- hypothalamus releases thyroid-releasing hormone (TRH)
- this stimulated the pituitary gland to release thyroid-stimulating hormone (TSH, thyrotropin)
- this stimulates the thyroid to release triiodothyronine (T3) and thyroxine (T4)
What body functions do T3 and T4 control?
- heart rate
- temperature
- metabolism (Ca++)
- brain development
- bone maintenance
What ion is an essential component of T3 and T4?
iodine - correct functioning of thyroid relies of the proper supply from the diet
How do T3 and T4 compare? How do they become active?
T3 = more biologically active form that has a high binding affinity to TH receptor
T4 = inactive form that has a higher binding affinity to plasma proteins and converts into T3 on cell entry
diodinase enzymes convert inactive T4 into active T3
How do T3 and T4 compare in plasma protein binding? What 3 plasma proteins are used for transport?
T3 = 0.3% unbound (active!)
T4 = 0.03% unbound (inactive!)
- thyroxine-binding protein (70%)
- transthyretin/pre-albumin (<15%)
- albumin (15%)
How does protein-binding affinity of T4 compare amount animal species?
PROTEIN-BOUND = primates > goats > horses > dogs > cats, rodents, birds
FREE = cats, rodents, birds > dogs > primates, horses, goats
What 4 genomic effects does T3 have? 1 non-genomic effect?
- metabolic rate (enzymes, fat, protein, gluconeogenesis)
- neurological development (myelination, neuron signaling)
- skeletal development (bone formation and remodeling)
- muscle development
- TR metabolites may be coupled to Na+ channels, Na+,K+ ATPase to affect electrolyte balance