3.A-Diuretics Flashcards
True or false: hypertension is usually a multifactorial problem
true
How can the kidney play a role in hypertension?
fail to eliminate enough fluid–>fluid builds up in vessels–>blood pressure increase
If you were to explain to someone with zero knowledge about diuretics, how would you explain diuretics to them?
diuretics increase urine production to help reduce blood pressure
they block the reabsorption of sodium
more Na in the urine=more fluid excreted
Which parts of the nephron are responsible for Na+ reabsorption? (state the % of Na+ reabsorbed in each part)
proximal tubule (65%)
ascending loop of Henle (25%)
distal tubule (very little)
What is the major driver of fluid retention?
sodium reabsorption
True or false: the kidney filters 120ml/min, makes urine at 1ml/min, thus 99% of filtered fluid is reabsorbed
true
What structure connects the afferent arteriole and ascending loop of Henle? What does this structure do?
macula densa
it senses Na+ concentrations in the nephron
Describe tubuloglomerular feedback.
occurs at the macula densa cells
an increased concentration of Na at the macula densa cell causes vasoconstriction at the afferent arteriole
(high Na will decrease renal blood flow)
True or false: all diuretics have impact on blood pressure
false
List the classes of diuretics.
loop diuretics
thiazide diuretics
potassium-sparing diuretics
carbonic anhydrase diuretics
osmotic diuretics
Where do loop diuretics act?
ascending loop of Henle (Na-K-2Cl symport inhibitors)
True or false: loop diuretics block the reabsorption of Na only
false
they block the reabsorption of Na and Cl
What is the significance of blocking the reabsorption of Cl with loop diuretics?
less Cl in the interstitial space means less force to draw in Ca and Mg
What are some undesirable actions of loop diuretics?
Ca and Mg loss due to loss of electrical gradient that is normally causing by the reabsorption of Cl
K loss in urine due to RAAS
uric acid retention in blood
What are the loop diuretics listed in the Sask Formulary?
furosemide
bumetanide
ethacrynic acid
Why are loop diuretics not ideal for bp control?
short half life
potent stimulator of kidney activation
-RAAS activation
-single dose can result in over correction
Normally loop diuretics are not ideal for bp control, what is the exception?
patients with poor kidney function
-half life is prolonged
-blood pressure effect is more stable
Where do thiazide diuretics act?
distal tubule (Na-Cl symport inhibitors)
True or false: thiazide diuretics are weaker than loop diuretics because there is less Na reabsorbed in the distal tubule
true
location of action matters!!!
What are some differences that thiazides have compared to loops in regards to how they effect ions and blood pressure?
thiazides:
-Ca can increase with long term use
-Mg loss occurs but less likely than loops
-better for bp control
What are the thiazide diuretics listed in the Sask Formulary?
chlorthalidone
hydrochlorothiazide
indapamide
metolazone
At what GFR should thiazide diuretics not be used?
<30-40ml/min
List off the common uses of TZD and loop diuretics.
high blood pressure: thiazides
high blood pressure in ppl with kidney disease: loops
heart failure: loop and thiazides
What are the electrolyte problems with Na blocking diuretics?
hypokalemia (low K)
hyponatremia (low Na)
hypochloremia (low Cl)
hypomagnesemia (low Mg)
calcium (increases with TZDs, decreases with loops)
What are the impacts on plasma metabolites and hemodynamics with Na blocking diuretics?
plasma metabolites:
-hyperuricemia (increased risk for gout)
-decreased glucose tolerance=increased blood glucose
hemodynamic effects:
-hypotension (cause of dizziness)
-reduced renal perfusion
-increased activity of RAAS
Hypokalemia is known to be the most common electrolyte imbalance with Na blocking diuretics, what else can increase the risk for hypokalemia?
low K intake
receiving other K depleting drugs
accelerated loss (vomiting/diarrhea)
Where do K-sparing diuretics act?
late distal tubule and collecting duct (inhibit ENaCs)
-decreased Na absorption exaggerates the polarization of the
epithelial membrane
-discourages K excretion
How are K sparing diuretics mainly used in practice?
to prevent K decreased during diuretic therapy
commonly combined with a loop or TZD
What are the K sparing diuretics listed in the Sask Formulary?
triamterine
amiloride
Describe carbonic anhydrase inhibitors.
not effective diuretics
typically used for glaucoma
prevent the reabsorption of NaHCO3
Describe osmotic diuretics.
freely filtered with little reabsorption
create an osmotic effect to keep water in urine
typically only used in hospital
What are the agents used as osmotic diuretics?
glycerin
mannitol
urea
What rate (ml/min) does the kidney filter at?
filters 120ml/min
makes urine at 1ml/min
Which diuretic acts at the proximal tubule?
there are none that act at the proximal tubule
Why are certain diuretics used to lower blood pressure?
high blood pressure often involves increased blood volume
What is the most common electrolyte deficiency with Na blocking diuretics?
hypokalemia
How strong is the diuretic effect of K sparing diuretics?
very weak (little Na is reabsorbed by the distal tubule)
What is the main benefit of the carbonic anhydrase pathway?
enables re-absorption of HCO3- (critical buffer)
