Term
| are the kidneys primarily responsible for regulating long term BP? |
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Definition
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Term
| what do the kidneys regulate? |
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Definition
| fluid/electrolyte balance and acid/base balance |
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Term
| what is the functional unit of the kidney? what is this unit composed of? |
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Definition
| the nephron, which is composed of a glomerulus and tubule which forms a U-shaped tube - the loop of henle and terminates as a collecting duct |
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Term
| how much of the blood goes to the kidneys? |
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Definition
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Term
| what is tubular reabsorption? |
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Definition
| how the water and solutes are reabsorbed from the tubule lumen back into the blood vessels that align right alongside the nephron |
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Term
| what is tubular secretion? |
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Definition
| how drugs (organic acids - diuretics, PCN, uric acid, bases and K+ ions) are eliminated through the tubule lumen -> urine |
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Term
| what is the tubuloglomerular feed back reflex? |
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Definition
| macula densa cells at the juncture of the ascending limb/distal tubule sense increased Na+ loss and a chemical signal is sent to the afferent arteriole to vasoconstrict - decreasing RBF/GFR to protect salt/water wasting. the decreased RBF activates the RAA system to generate angiotensin II to vasoconstrict and release aldosterone/ADH (from adrenal cortex) -> which increases Na/water retention in the distal portion of the distal tubule and collecting ducts. (ADH is the only way water can be retained in the collecting tubule) |
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Term
| how is the tubuloglomerular feed back reflex also a way to void extra K+? |
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Definition
| whenever you absorbing Na, you are excreting K+ |
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Term
| what does the kidney secrete whenever it senses a decrease in blood flow (via the macula densa)? |
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Definition
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Term
| what is the mechanism of action for carbonic anhydrase inhibitors as diuretics? |
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Definition
| carbonic anhydrase helps make H+ ions (by making carbonic acid, which becomes bicarb and H+) available for exchange w/Na+ and H2O in the proximal tubules, but CAIs block this action and prevent this exchange. if H+ is not broken from bicarb, then it can't be used to exchange for Na+ (which usually comes back from the urine) |
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Term
| what is the mechanism of action for carbonic anhydrase inhibitors as urine alkylating agents? |
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Definition
| CAIs inhibit CA from making carbonic acid from CO2 and H2O. carbonic acid is the precursor to bicarb, so if if the CAs in the PCT lining cells can't make carbonic acid, which becomes bicarb, that bicarb can't get back into the blood. the trapped bicarb is urinated out and the blood is denied the bicarb that it usually would have recieved - therefore the blood is more acidic - which can lead to metabolic acidosis |
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Term
| what is the carbonic anhydrase inhibitor we need to know? what is its mechanism of action? effect? |
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Definition
| acetazolamide, whose sulfonamide group inhibits carbonic anhydrase. it inhibits carbonic anhydrase which leads to increased loss of bicarb (HCO3-) and Na+. it functions as a weak diuretic that alkalinizes the urine, and causes blood acidosis |
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Term
| what is acetazolamide used for? |
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Definition
| acetazolamide is used for glaucoma (decreases aqueous humor formation), for metabolic alkalosis tx, and to produce alkalinization of urine |
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Term
| what are ADRs associated with acetazolamide? |
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Definition
| b/c it has a sulfa group, possible allergy/rash, also GI n-v, CNS depression, parasthesias, and it is teratogenic |
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Term
| what is mannitol? where is it's main site of action? |
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Definition
| an osmotic diuretic (induces diuresis b/c it is not reabsorbed in the renal tubule, thereby increasing the osmolality of the glomerular filtrate, facilitating excretion of water, and inhibiting the renal tubular reabsorption of sodium, chloride, and other solutes). its main site of action is the PCT. |
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Term
| how is mannitol administered? why? |
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Definition
| IV b/c it is not reabsorbed from the GI tract |
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Term
| why is mannitol not helpful in CHF? |
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Definition
| b/c mannitol works in the extracellular fluid, pulling out intracellular fluid. CHF is a condition where the heart is drowning in extracelluar fluid, so mannitol exacerbates that (expands the extracellular fluid compartment) |
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Term
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Definition
| mannitol is used to promote diuresis/urine flow in low urine states eg drug OD and nephrotoxic drugs |
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Term
| what are ADRs for mannitol? |
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Definition
| hyperatremia, hyperkalemia, volume depletion |
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Term
| what is the mechanism of action for the loop diuretics? |
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Definition
| loop diuretics such as furosemide inhibit the Na/K/2Cl carrier (which usually brings those ions back into bloodstream from the ascending limb), but when those ions are "wasted" the water follows them. Mg and Ca are also lost, b/c the K gradient created by the carrier usually pushes K out and brings Mg and Ca in |
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Term
| how much of the Na load do loop diuretics affect? |
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Definition
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Term
| what do loop diuretics, such as furosemide increase excretion of? |
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Definition
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Term
| what are loop diuretics, such as furosemide used to treat? |
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Definition
| acute CHF/pulm edema, acute/chronic renal failure, and hypercalcemia |
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Term
| what are ADRs associated with loop diuretics? |
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Definition
| loop diuretics, such as furosemide can increase cholesterol/triglycerides, otoxicity (ethacrynic acid highest incidence), pain, vertigo, tinnitus, and hearing loss. furosemide, bumetanide, and torsemide are all sulfonamide derivativese - therefore they can cause *sulfa allergy rxns. also - the adverse H's |
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Term
| what are the adverse H's associated with loop diuretics? |
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Definition
| hyponatremia (excessive diuretic effect), hypotension (loss of fluid volume), hypokalemia (cardiac arrhythmias), hypocalcemia (muscular excitability/tetany), hypomagnesemia (twitching/convulsions), hypochloremic alkalosis (excessive loss of Cl), hyperuricemia (completes with tubular secretion uric acid), and hyperglycemia (interferes with the release of insulin - related to hypokalemia) |
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Term
| what is the difference between loop diuretics and thiazides in terms of Ca? |
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Definition
| loop diuretics will promote loss of Ca, while thiazides do not - therefore they do not promote osteoporosis |
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Term
| what are the mechanisms of most of the diuretics dependent on? |
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Definition
| the concentration gradient set up be the Na/K ATPase, which pumps Na into the blood and K into the cells of the DCT |
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Term
| what is the M/A of thiazides/hydrochlorothiazide? |
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Definition
| the thiazides inhibit the Na/Cl cotransporter, which usually affects about 5-10% of the Na load - drawing less water into the urine |
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Term
| what does hydrochlorothiazide administration increase excretion of? |
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Definition
| Na, K, Cl, Mg, water volume - *not Ca* (Ca is actively reabsorbed via PTH) |
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Term
| what are ADRs for the thiazides/hydrochlorothiazide? |
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Definition
| the H's except for hypocalcemia, can incresae plasma LDL-cholesterol/triglycerides, and they are sulfa derivatives *allergy* |
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Term
| what are thiazides/hydrochlorothiazide used for? |
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Definition
| edema/pulm edema, HTN, CHF, renal failre, diabetes insipidus, Ca dysfunction - to increase serum CA, and in hypercalciuria/*kidney stones* to decrease urinary Ca |
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Term
| what are the mechanisms of action of spironolactone/amiloride? what kind of diuretics are they considered? |
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Definition
| aldosterone activates a mechanism that brings Na+ in from the urine and kicks K+ out. spironolactone blocks the receptor for this mechanism and amiloride blocks the protein that brings K in. they are considered to be K+ sparing diuretics |
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Term
| what does spironolactone do? |
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Definition
| a competitive agonist of aldosterone (which normally stimulates reaborbtion of Na in exhanges for K), but spironolactone causes Na loss and K retention by acting on the collecting ducts and late distal tubule |
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Term
| what is the diuretic action of spironolactone? |
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Definition
| limited, only 2-5% of Na load - dependent on level of aldosterone activity |
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Term
| when is spironolactone used? |
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Definition
| in mineralocorticoid excess, conn's sydrome (excessive aldosterone secretion and K wasting), secondary aldosteronism from CHF, cirrhosis, and nephrotic syndrome |
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Term
| what are ADRs associated with spironolactone? |
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Definition
| nausea, gastric ulceration, drowiness, *hyperkalemia, antiandrogenic effects (gynecomastia/male impotence) |
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Term
| how does amiloride compare to spironolactone? |
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Definition
| amiloride blocks the sodium channel of the Na/K exchange mechanism that aldosterone controls, inhibiting that exchange mechanism and promoting K retention |
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Term
| what is amiloride used for? |
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Definition
| amiloride is used with other diuretics, maybe loop diuretics to prevent hypokalemia |
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Term
| what are ADRs associated with amiloride? |
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Definition
| GI (n-v-d), rash, headache, *hyperkalemia* (esp with ACEIs, angiotensin blockers, or K supplementation) |
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Term
| what is the mechanism of action for conivaptan/demeclocycline? |
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Definition
| these drugs work in the collecting duct, which is usually impermeable to water, but if the V2 receptor is stimulated by ADH (anti diuretic hormone), G protein -> cyclic AMP stimulate porins to open up and bring water back from the urine. however, conivaptan blocks the V2 receptor, keeping that H2O reabsorption from ever happening |
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Term
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Definition
| conivaptan is an ADH receptor blocker that decreases water reaborption by inhibiting the V2 receptor. it also blocks the vasoconstrictive effects of V1A receptors, and may be used for heart failure |
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Term
| what is conivaptan indicated for? |
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Definition
| syndrome of inappropriate ADH, hypothyroidism, and adrenal insufficiency |
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Term
| what are ADRs associated with conivaptan? |
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Definition
| hypokalemia, injection site rxns w/IV use |
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Term
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Definition
| a tetracycline that antagonizes ADH by inhibiting cAMP concentrations in the collecting tubules. |
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Term
| what is demeclocycline indicated for? |
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Definition
| SIADH, can be used orally |
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Term
| what are ADRs associated with demeclocycline? |
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Definition
| nephrogenic diabetes insipidus, renal failure, contraindicated in children under 12 |
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