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72 Cards in this Set

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Based on glutamine metabolism, where is the major nephron site of ammonia production
proximal tubule
What is the major mechanism of luminal sodium transportation in the proximal tubule
Na-H exchange and co-transport glucose, amino acids, phophate, and organic solutes
Name two diuretics acting at the proximal tubule
acetazolamide
mannitol
What is the major mechanism of luminal sodium entry in the thick ascending limb
active NaCl transport: Na-K-2Cl co-transport
Name three diuretics acting at the thick ascending limb
furosemide
bumetanide
ethacrynic acid
Where does PTH work to cause Ca excretion
distal tubule
What is the major mechanism of luminal sodium entry in the distal tubule
Na-Cl co-transport
Name four diuretics acting at the distal tubule
thiazides
metolazone
chlorthalidone
indapamide
Where is the site of final modification of urine
collecting tubule
What do the principal cells do in the collecting tubule
absorb Na and Cl and secrete K (partial aldosterone influence)
What do the intercalated cells do in the collecting tubule
secrete H, reabsorption and secretion of K, and in metabolic alkalosis secrete HCO3
the collecting tubule reabsorbs water and urea relative to what hormone
ADH
What is the major mechanism of luminal sodium entry in the collecting tubule
Na channels
Name three drugs that act at the collecting tubule
spironolactone
triamterene
amiloride
How much of the renal carbonic anhydrase must be inhibited by acetazolamide before diuresis is apparent?
more than 99%
How much of an oral dose of acetazolamide is excreted in the urine unchanged
80% of an oral dose
What happens after several days of acetazolamide administration
a mild hyperchloremic acidosis terminates the diuretic action even with continued administration
Name four therapeutic affects of acetazolamide
1. edematous patients with metabolic alkalosis
2. urinary alkalization
3. decrease aqueous humor production
4. acute motion sickness (dec CSF production and pH)
When is acetazolamide contraindicated? (1)
hepatic cirrhosis (NH4 accumulation)
What is the most commonly used osmotic diuretic
mannitol
What is increased in excretion, aside from urine flow, with mannitol administration
sodium
potassium
chloride
bicarbonate
calcium
magnesium
what does administration of isotonic or hypertonic solutions of mannitol in patients with increased renal vascular resistance do?
lowers resistance and increases total renal plasma flow
Name three therapeutic effects of mannitol
increased urine volume
reduced intracranial pressure
reduced intraocular pressure
what is another name for loop diuretics
high ceiling diuretics
what are the most potent diuretic agents available
loop diuretics
What is the clinical importance of furosemide and ethacrynic acid affecting proximal sodium reabsorption
minimal
they shine in the thick ascending loop
what do loop diuretics do to...
pH
Na
K
HCO3
Cl
Ca
Mg
pH <->
Na inc inc inc
K inc inc
HCO3 <->
Cl inc inc inc
Ca inc
Mg inc
What side of the tubule to loop diuretics work from
luminal side
what is the special problem with furosemide
there is a problem with equivalence of generic products
In which population is the half life of furosemide increased
elderly
When do you use loop diuretics (4)
in patients with
kidney problems,
refractory edema,
acute pulmonary edema or hypertensive crises
the rapid effects of loop diuretics may be life saving in which condition
acute pulmonary edema
are loop diuretics indicated as single agent therapy for hypertension
no
what's worse at causing hyponatremia, loop or thiazide diuretic
thiazide
what three drugs cause hyperglycemia
HCTZ > F> EA
name two drugs that cause ototoxicity (and GI bleeding)
EA > F
Name the three loop diuretic drugs
furosemide
bumetanide
ethacrynic acid
name two distal tubule acting drugs
the thiazides!
chlorothiazide
hydrochlorothiazide
how do thiazides differ from acetazolamide in terms of effectiveness in acid base balance
thiazides are effective at both extremes of acid base balance
acetazolamide is only affective in metabolic alkalosis
is thiazide action additive to any drugs
yes, EA and F
Name four drugs that are not benzothiazdiazines but have diuretic properties that are similar to thiazides
metolazone
chlorthalidone
indapamide
quindathazone
How do thiazides effect...
pH
Na
K
HCO3
Cl
uric acid
Ca
pH inc
Na inc inc
K inc inc
HCO3 inc
Cl inc inc
uric acid inc
Ca DEC
what is the duration of action of thiazides related to
plasma protein binding
do thiazides cross the placenta
yes
what is the preferred initial diuretic when renal function is normal
thiazides
in what population are thiazides usually ineffective
patients with impaired renal function
what is the first agent used in essential hypertension
thiazides
Name 5 therepeutic indications for thiazides
1. hypertension- initial therapy and treatment
2. CHF- initial therapy
3. edematous disorders
4. idiopathic hypercalciuria
5. nephrogenic diabetes insipidus
What are the two classes of drugs acting at the collecting tubules
1. aldosterone antagonist = spironolactone
2. potassium sparing diuretics = triamterene and amiloride
What is the major use of collecting tubule drugs
with thiazides or loop diuretics to reduce potassium excretion, minimize alkalosis and to produce an additive diuretic effect
What ration of spironolatone to Aldosterone is required for inhibition of aldosterone-induced sodium retention
1000:1
Where else does spironolactone work?
other aldosterone action sites: sweat glands, salivary glands, large intestine
When are triamterene and amiloride especially effective
in the adrenalectomized animal (good to know, huh?)
Which side of the lumen does triamterene work and what does it do to the transbasolateral potential difference?
it works on the peritubular side and IRREVERSIBLY inhibits the transbasolateral potential difference
Which side of the lumen does amiloride work and what does it do to the transbasolateral potential difference?
it works on the luminal side and REVERSIBLY inhibits the development of transluminal potential difference
What is an important toxicity spironolactone, triamterene and amiloride
hyperkalemia! more so than potassium supplements, especially with impaired renal function
yes or no for thiazide diuretics:
hypokalemic, hypochloremic alkalosis
hyperkalemia
azotemia
hyponatremia
hyperglycemia
hyperuricemia
hypercalcemia
thiazide diuretics:
hypokalemic, hypochloremic alkalosis - YES
hyperkalemia- NO
azotemia- YES
hyponatremia- YES
hyperglycemia- YES
hyperuricemia- YES
hypercalcemia- YES
yes or no for loop diuretics:
hypokalemic, hypochloremic alkalosis
hyperkalemia
azotemia
hyponatremia
hyperglycemia
hyperuricemia
hypercalcemia
loop diuretics:
hypokalemic, hypochloremic alkalosis- YES
hyperkalemia- NO
azotemia- YES
hyponatremia- RARE
hyperglycemia- YES!
hyperuricemia- YES
hypercalcemia- NO
yes or no for potassium sparing diuretics:
hypokalemic, hypochloremic alkalosis
hyperkalemia
azotemia
hyponatremia
hyperglycemia
hyperuricemia
hypercalcemia
hypokalemic, hypochloremic alkalosis- NO
hyperkalemia- YES
azotemia- YES
hyponatremia- NO
hyperglycemia- RARE
hyperuricemia- RARE
hypercalcemia- NO
what happens when adrenal corticosteroids are given with thiazide or loop diuretics
enhanced hypokalemia
what happens when aminoglycosides are given with loop diuretics
increased ototoxicity and nephrotoxicity
What happens when ACE inhibitors are given with K sparing diuretics
hyperkalemia
what happens when beta blockers are given with thiazides or potassium sparing diuretics
increased effect on lipids, urate, glucose, hyperkalemia
what happens when digitalis is given with thiazides or loop diuretics
increased digitalis toxicity
what happens when indomethacin is given with potassium sparing diuretics
hyperkalemia, acute renal failure
what happens when indomethacin is given with loop diuretic
decreased natriuretic effect
what happens when lithium is given with thiazides
increased serum lithium
what happens when vitamin D, or calcium is given with thiazides
hypercalcemia
Is resistance to diuretics common
yes- decrease in effectiveness of carbonic anhydrase inhibitors occurs with development of a progressive metabolic acidosis
What is acute tolerance due to
marked increase in proximal tubule sodium reabsorption, with the possibility of and increase in the distal tubule and collecting duct --> DECREASING natriuretic effects
Why does rebound sodium retention within a dosing schedule occur
loop diuretics have short durations of action
What does chronic therapy with loop diuretics cause
increased sodium delivery to distal sites -> hypertrophy of distal nephrons -> increase in reabsorptive capability -> DECREASED sodium loss