Diuretics Flashcards
mannitol
osmotic
Acetazolamide
Carbonic Anhydrase Inhibitor
furosemide
loop diuretic, renal elimination, 1.5 hour half life, small potency
bumetanide
loop diuretic- most potent, when furosemide is maxed out, a banned agent for athletes who need to meet a certain weight, renal elimination
torsemide
loop diuretic- 3 and 1/2 hour half life because it undergoes extensive metabolism, metabolic elimination, 2nd largest potency
ethacrynic acid
loop diuretic, 100% bioavailability, 1 hour half life, renal elimination
HCTZ
thiazide, eliminated renally, 70% bioavailability, 2.5 hour half life, least potent
chlorthalidone
thiazide, mostly renally eliminated, least potent, 47 hour half life (largest half life)
indapamide
thiazide, metabolic elimination, most potent, 65% bioavailability, 14 hour half life
metolazone
thiazide, more potent than chlorthalidone and HCTZ, less potent than indapamide, mostly renally excreted and a little biliary and metabolic, 8-14 hour half life
amiloride
collecting duct diuretic, longest half life, 15-25% bioavailability, most potent, diarrhea and headache
triamterene
collecting duct diuretic, 50% bioavailability, 4 hour half life, 10x less potent than triamterene, causes leg cramps and dizziness
eplerenone
collecting duct diuretic
spironolactone
collecting duct diuretic, 65% bioavailability, 1.6 hours half life, diarrhea gastritis, peptic ulcers, drowsiness/lethargy
diuretics effect on ECF volume and weight
decreases
pros of diuretics
decreases blood pressure, helps edema
cons of diuretics
too much of a decrease, SNS, RAAS
what does a diuretic do
decrease NaCl, decrease H2O
Excretion is greater than intake
Na excretion increases, Na stops going down and is a steady state,
excrete to much what is the consequence
hypoatremia
CA inhibitors site of action and MOA
site of action: proximal tubule
plays a role in bicarbonate reabsorption (Bicarbonate is tied to Na+)
these agents reduce Na+ by preventing reabsorption of bicarbonate - by preventing Na+ reabsorption, the water will follow H2O and so water will go out of the body with the HCO3- and Na+
What happens to k+ in CA inhibitors?
Increases excretion, RAAS System
What happens to urinary pH with CA inhibitors?
Urine becomes more basic- causes metabolic acidosis and decreases the pH (why some people take acetezolamide - they have acidosis)
Use of CA inhibitors
Glaucoma (aqueous humor in the eye has a lot of bicarbonate and topical formulation lowers the pressure causing less volume)
ICU treating metabolic alkalosis caused by excessive use of loop diuretics
Osmotic diuretics MOA and site of action
Freely filtered at the glomerulus, exerts an osmotic force in the tubule reducing the movement, reduce the movement of water out of the tubule into the interstitial space
Site of action: loop of Henle/ proximal tubule
Increase osmolarity if you increase the filtrate
Use of osmotic diuretics
Head trauma - pulls water out of the cell so it lowers the osmolarity and lowers the pressure
Reduction of excessively high intraocular pressure
CA inhibitors what happens to
urinary excretion:
increase the volume of urine
CA inhibitors what happens to
K+ excretion:
increases K+ - nothing to do with transporters - RAAS secretes K+
CA inhibitors what happens to
urinary pH:
increases pH, basic
CA inhibitors what happens to
Metabolic _______
acidosis, pH decreases
loop diuretic site of action and MOA
in the thick ascending limb of loop of henle they transport Na+ out of the filtrate, and dilute it before it is delivered to the distal convoluted tubule, TAL is impermeable to water and reabsorbs Na, K, Cl, so the filtrate is less dilute, competitive and reversible inhibition, highly efficacious- high ceiling diuretics
Cl- flow and K+ flow in loops
Cl- flow: comes in apical side and leaves the basolateral side
K+ flow: comes in basolateral and leaves apical
apical side of the cell is positive and basolateral is negative
blocking the symporter in loop diuretics
increases Na+/Cl-/K+ excretion
loop diuretics effect on Ca2+ and Mg2+ excretion
there is an absence of the transepithelial potential difference increases Ca2+ and Mg2+ excretion. they usually want to follow the negative charge and be reabsorbed but because Cl- is in the filtrate they want to stay in the filtrate
main effects of loop diuretics
decreases volume
renin release stimulated with aggressive loop diuretic- need to give an ACE inhibitor to prevent RAAS
drugs that affect renal blood flow such as NSAIDS decrease loop effectiveness (nsaids block PGE and PGE inhibits Na reabsorption)
major differences between the four loops
half life and potency- all 60-90 half life except torsemide
structure of loops and why is this important?
furosemide, bumetanide, and torsemide are sulfonamides or sulfonylureas - do not give to patients with a sulfa allergy
adverse effects and drug interactions with loops
hyponatremia and volume depletion - hypokalemia causes arrhythmias and hypomagnesia causes arrhythmias, ototoxicity is rare and higher doses electrolytes imbalance in the inner ear
use of loops
edema (associated with heart failure) - not controlled well, is BP in the range that you want it to be?
hypertension
acute renal failure (poor flow through kidney speeds up fluid in nephron and increases movement of filtrate and increases renal function
thiazide diuretics MOA and site of action
inhibits sodium-chloride cotransporter on the apical side of the cell, increased excretion of na and cl results in h2o excretion
thiazide diuretics effect on Na and Cl excretion
increase
thiazide diuretics effect on Ca2+ reabsorption
increase, triggers osteoblast formation
effectiveness of thiazide diuretics
good, not as good as loops
adverse effects of thiazide diuretics
decreased glucose intolerance (low K+ levels)
arrhythmias (low K+ levels)
decreased LDL and TGs 2-15%
thiazide drug interactions
potentially lethal thiazide and quinidine due to hypokalemia and the reduced elimination of quinidine - will get toxic levels of quinidine in the body and will prolong the QT interval, this will be an irreversible situation
therapeutic indications of thiazide diuretics
ineffective at GFR < 30-40 mL/min (indapamide may be an option) - additive effects with hypertensive agents
use of thiazide diuretics
hypertension (vasodialtory properties to help relax and dialate the vessels, alters the pressure, body realizes as pressure increases it needs to bring it down) and heart failure (better outcomes for patients who are on a thiazide
structure of thiazide
sulfer- do not give to a patient with a sulfur allergy
potassium sparing diuretic site of action and MOA
inhibit the ENaC Na+ channel (competitive- by inhibiting the reabsorption of Na+ in the CD, K+ excretion is reduced (Na+ is “balanced” by K+ excretion) slow Na+ and K+ excretion
used in conjunction with another diuretic
potassium vs loop charge
opposite efect of loop because it is flipped the other way
thiazide effects on ions
increases in Na+/Cl- excretion and decreases in K+, H+, Ca2+, Mg2+ excretion
Adverse effects of potassium sparing diuretics
hyperkalemia- who should not take these?? arrhythmias, K+ imbalance, other K+ sparing drugs (drugs that target RAAS like ACE)
use of potassium sparing diuretics
hypertension, increased efficacy when used in combo and never used solo
triamterene/HCTZ
maxzide, dyazide, combo therapy with potassium sparing diuretic
amiloride/HCTZ
moduretic, combo therapy with potassium sparing diuretic
diuretic resistance
edema that is refractory to a given diuretic - good to give low dose loop diuretic, compensatory increases in sodium reabsorption in the nephron are not blocked by the diuretic, move to a more potent drug like thiazide to loop
how do diuretics help heart failure and hypertension
thiazides are best, reduce extracellular volume, reduces blood pressure to treat hypertension, heart failure patients experience edema and diuretics speed up the removal of excess fluid
3 things that thiazides do
decrease volume, alter pressure curve helps sense pressure change, vasodilatory
