Diuretics Flashcards
Rate the Diuretic classes from least to greatest in terms of efficacy
Least - Carbonic Anhydrase Inhibitors
Middle - aldosterone antagonists and Na channel blockers, thiazides, loop diuretics
Most - Loop of henle (not counting the double whammy of loop + thiazide)
What do the 5 different diuretic classes do to potassium levels?
Most Wasting = Loop + Thiazide combination
Wasting (least-greatest) = thiazides, carbonic anhydrase inhibitors, loop of henle agents
SAVING = aldosterone antagonists and sodium channel blockers
What do the 5 different diuretic classes do in terms of H+ handling?
The carbonic anhydrase inhibitors and aldosterone antagonists/Na channel blockers have no H+ effect
H+ decrease (least-greatest) = thiazides, loop agents, combo
What diuretic agents mess with calcium levels?
Loop of henle agents sharply DECREASE calcium levels
Thiazides sharply INCREASE calcium levels
Loop + thiazide combo keeps things about equal in/out
Which diuretic classes affect magnesium levels?
Only loop of henle agents have an appreciable effect on magnesium levels in the serum
Which diuretics function by inhibiting processes in the proximal convoluted tubule?
Mannitol (osmotic) and Acetazolamide (CA inhibitor)
*they also work in proximal straight tubule
Which diuretics function by inhibiting cells in the TALH?
TALH = thick ascending loop of henle
- Furosemide
- Bumetanide
- ethacrynic Acid
which diuretics work after the loop of henle in the proximal portion of the distal convoluted tubule?
- thiazides
* metolazone
Which diuretics act at the level of the cortical collecting duct?
Amiloride (sodium channel blocker), spironolactone (aldosterone inhibitor), Triamterene
What is the job of the proximal convoluted tubule?
70-80% of the reabsorption of water, electrolytes, short peptides and small molecules in plasma filtrate
- there is secretion of orgainic acids and bases here, which is how diuretics get to their site of action
- bicarb is re-generated and reabsorbed here
How does mannitol work?
Mannitol is an osmotic diuretic that is not metabolized or reabsorped in the proximal tubule
- end result is osmotic retention of water in the urine and stuff that freely flows with the water
- induces diuresis by elevating the osmolarity of the glomerular filtrate
- excretion of sodium and chloride is increased
What are the pharmacokinetics of mannitol?
Administered IV, distributes in ECF, excreted by glomerular filtration
When do you use mannitol?
Prevention of acute kidney injury secondary to major vascular surgery
Glaucoma (decrease intraocular pressure)
Preservation of renal function in rhabdomyolysis
Elevated intracranial pressure
What are the adverse effects of mannitol?
acute increase in ECF volume, nausea/headache, in prolonged use, can cause severe water loss and hypernatremia, heart failure (volume expansion)
What does Acetazolamide do?
It inhibits tubular Carbonic Anhydrase, which messes with the tubular reabsorption of bicarbonate
- causes a metabolic acidosis, so it loses effectiveness if a pt is already acidotic
- because of lack of bicarb, lack of sodium reabsorption, leads to a tiny bit of diuresis
- mostly used to prevent HACE and HAPE now
What is Acetazolamide used for?
Glaucoma, Metabolic alkalosis, Mountain sickness/altitude sickness
What are the adverse effects of Acetazolamide?
metabolic acidosis, drowsiness, fatigue, CNS depression, parasthesias
What are the 4 Loop diuretics we talked about?
Furosemide, bumetanide, torsemide, ethacrynic acid
What are the different absorbance percentages through the nephron for water?
Proximal convoluted tubule = 70%
Loop of Henle = 15%
Distal convoluted tubule and collecting duct = 14%
What are the different absorbance percentages for sodium through the nephron?
proximal convoluted tubule = 70%
Loop of Henle = 25%
Distal convoluted tubule and collecting duct = 4.5%
What channel do loop diuretics inhibit?
Na/K/2Cl co-transporter in the TALH
- decreases tonicity of medullary interstitium and therefore inhibits reabsorption of water in collecting duct
- 15-25% excretion of filtered sodium
How is Furosemide administered?
can be administered oral or IV. It binds well to plasma proteins and has a rapid onset of action
*both metabolized and renally eliminated
How is ethacrynic acid administered?
IV. It binds plasma proteins extensively, is metabolized AND renally eliminated. Rapid onset of action
What are loop diuretics used for?
HTN, edema by CV, renal or hepatic diseases.
*also used in hypercalcemia and pulmonary edema
DO NOT USE when there is edema caused by calcium channel blockers
What are the adverse effects of loop diuretics?
Hearing loss (ototoxicity), Rapid onset of action, Hypokalemia, metabolic alkalosis (by way of potassium), Hyponatremia, Hypocalcemia, uric acid retention, sulfa allergy
What are the 4 thiazide diuretics we talked about?
Hydrochlorothiazide, chlorthalidone, metolazone, indapamide
What do the thiazide diuretics do?
Inhibit Na/Cl co-transporter in proximal part of distal convoluted tubule
*only moderate diuresis because of max 5% sodium affect
What is the more potent thiazide?
Metolazone can increase sodium excretion even with lowered GFR (less than 30ml/min)
*used in combo with furosemide for lots of diuresis
How are thiazides administered?
orally. they are secreted into proximal tubule and NOT metabolized
What are thiazides used for?
HTN, edema (metolazone)
What are the adverse effects of the thiazides?
Hypokalemia, hypomagnesemia, uric acid retention (gout), hyponatremia, hypochloremia, hyperglycemia and lipid abnormalities, hypercalcemia, sexual dysfunction, sulfa allergy
What are the two aldosterone antagonists we talked about?
spironolactone and eplerenone (this is the selective one)
What do aldosterone antagonists do?
antagonise the binding of aldosterone receptors at the aldosterone-dependent sodium-potassium exchange sites in the distal convoluted renal tubule
- reduces reabsorption of sodium and secretion/excretion of potassium
- also inhibits free testosterone from binding to androgen receptors in the cytoplasm of breast cells
- eplerenone is the mineralocorticoid selective antagonist
How are the aldosterone antagonists administered?
orally. Metabolized to active state, renal and biliary excretion. Slow onset of action and long half-life
What are aldosterone antagonists used for?
Resistant HTN, Heart Failure, Hyperaldosteronism (but adminster with other diuretics that act on water as this is a potassium saver)
What are the adverse effects of the aldosterone antagonists?
Hyperkalemia (don’t use in proggessive renal failure like under 30ml/min GFR), Gynecomastia (not eplerenone), Amenorrhea
What does the AT1 angiotensin II receptor do?
Vasoconstriction, hypertrophy, proliferation.
Increases: norepinephrine, thirst, sodium retention, PAI-I, oxidation
What does AT2 angiotensin II receptor do?
releases NO, sends an antiproliferation signal, vasodilates
What do ARB’s block?
They block angiotensin II from binding its receptor. They also block the action of the AT1 receptor (which is an angiotensin II receptor)
What do MRAs block?
MRAs block Aldosterone binding to the mineralocorticoid receptor.
- KIDNEY = blocks mineralocorticoid (aldosterone)-dependent sodium retention, potassium depletion, and lastly blocks increased microalbuminuria
- VESSELS/HEART = blocks increased NADPH, ROS, NF-kB and AP1 (eventually blocks inflammation and fibrosis)
- CNS/ANS = blocks central sympathetic drive hypertension, blocks the decreased heart rate variability, decreases myocardial NE uptake
What do MRAs do in the CNS/ANS?
*CNS/ANS = blocks central sympathetic drive hypertension, blocks the decreased heart rate variability, decreases myocardial NE uptake
What do MRAs do in the vessels/heart?
*VESSELS/HEART = blocks increased NADPH, ROS, NF-kB and AP1 (eventually blocks inflammation and fibrosis)
what do MRAs do in the kidney?
*KIDNEY = blocks mineralocorticoid (aldosterone)-dependent sodium retention, potassium depletion, and lastly blocks increased microalbuminuria
What are the two sodium channel blockers we talked about?
Triamterene and Amiloride
How does Amiloride work?
blocks luminal sodium channels and decreases the driving force for potassium secretion/excretion
*indirectly decreases hydrogen ion secretion
How are sodium channel blockers (kidney) administered?
Orally. secreted as organic bases. Metabolized in liver and both renal and biliary excretion
When do you use sodium channel blockers (kidney)?
In combo with other diuretics. They are synergistic with others and help spare some potassium
What are the adverse effects of sodium channel blocker use (kidney)?
Hyperkalemia, hyperuricemia, glucos intolerance in diabetes (amiloride in particular)
In diabetic patients, what diuretic are you concerned about using?
Amiloride, as it can make diabetic patients glucose intolerant
