Diuretics Flashcards
Are most diuretics more dependent on glomerular filtration or on tubular secretion?
More dependent on tubular secretion.
4 main sites of sodium reabsorption in the nephron?
Proximal tubule (PT) - 50-70% .
Thick ascending loop of Henle (tALH) - 25%.
Distal convoluted tubule (DCT) - 5%.
Collecting duct (CD) - 3%.
Which class of diuretics targets proximal tubule?
Carbonic anhydrase inhibitor.
How do carbonic anhydrase inhibitors produce a diuretic effect?
How do they affect HCO3-, Na+, and K+ excretion?
Reabsorption of HCO3- is blocked, and it doesn’t have a chance to be absorbed in the distal nephron, since usually bicarb is really low by then. (Osmotic diuresis from increased HCO3-?)
Increased HCO3- excretion.
Not much affect on Na+.
Increased K+ secretion in distal tubule (probs due to increased neg. charge in lumen).
Clinical utility of carbonic anhydrase inhibitors?
Correction of alkalosis. (this… makes a lot of sense)
Last-ditch correction of hyperkalemia.
(Altitude sickness and glaucoma too… but I wouldn’t worry about that.)
4 examples of loop diuretics? (probably the first one, which you already know, is most important to know)
Furosemide (Lasix)
Bumetanide
Torsemide
Ethacrynic acid
Target of loop diuretics?
NKCC2 in the tALH.
3 conditions for which loop diuretics are used?
Hypervolemia / Na+ retention (“edematous disorders”).
Hyperkalemia.
Hypercalcemia. (rarely.. for bone-lysing tumors.)
4 potentially deleterious solute perturbations that can result from loop diuretics?
Hypokalemia.
Hypocalcemia / hypercalciuria.
Hypomagnesemia.
Hyperuricemia (-> gout).
2 non-renal adverse effects of loop diuretics?
Ototoxicity (worse with ethacrynic acid). Sulfa allergy (doesn't apply to ethacrynic acid).
Given ethacrynic acid has a worse side effect profile than other loop diuretics, why would one ever use it?
All the other loop diuretics have a sulfa moeity.
If you have a sulfa allergy, and need a loop diuretic, you have to use ethacrynic acid.
What is the “braking phenomenon” for loop diuretics?
After a few days, nephron will increase Na+ absorption at other sites, returning total body Na+ to a new, lower steady state.
This is good… you don’t want to lose all your volume.
What drugs inhibit Na+ reabsorption in the distal tubule?
What’s the molecular target?
Thiazide diuretics inhibit the Na/Cl cotransporter.
How do thiazide diuretics affect Ca++?
Reabsorption of Ca++ is increased.
In the DCT Ca++ is reabsorbed via the Ca++/Na+ antiporter on the basolateral membrane. Apparently the activity of the Ca++/Na+ antiporter (Na+ into cell, Ca++ out to blood) is increased due to decreased intracellular Na+ (which is a bit counterintuitive, but I guess the cell wants to maintain Na+ levels).
4 clinical uses of thiazide diuretics?
First line Tx for HTN.
Edematous states (with a loop diuretic).
Idiopathic hypocalciuria.
Hyperkalemia.
Effect of thiazide diuretics on K+ handling?
K+ secretion is increased.
(Why? There will be increased Na+ in the collecting duct, and Na+ reabsorption there is coupled to K+ secretion. Wasn’t mentioned in lecture… but this didn’t make sense to me.)
4 solute-related side effects of thiazide diuretics?
Hypokalemia.
Hyponatremia.
Hyperuricemia.
Increased Ca++ reabsorption.
1 non-renal side effects of thiazide diuretics?
Impaired insulin release / diminished use of glucose.
Loop diuretics and thiazide diuretics have a lot of similar effects. What are two ways that they’re different?
Loop diuretics increase Ca++ excretion, thiazides increase Ca++ reabsorption.
Loop diuretics decrease ability to concentrate urine, by destroying the medullary tonicity gradient; thiazides don’t inhibit the ability to concentrate urine.
Which is more likely to cause hyponatremia: a thiazide or a loop diuretic? Why?
Thiazide.
Because the ability to concentrate urine is preserved when taking thiazides, if ADH is present, free water can be reabsorbed in the collecting duct.
Not so with loop diuretics - even if ADH is present, water can’t be reabsorbed well in the collecting duct.
What type of diuretic is “potassium sparing”? What is the molecular target, where in the nephron does it act, and why does it spare K+?
Inhibitors of aldosterone or of ENaC in the collecting duct spare potassium.
If Na+ is not absorbed in the collecting duct, the electrochemical gradient does not favor K+ secretion into the lumen.
Review: Which cells in the collecting duct express ENaC?
Principal cells.
2 examples of ENaC blockers?
Amelioride and triamterene.
2 examples of aldosterone antagonists?
Spironolactone and eplerenone.
Clinical utility of K+ sparing diuretics?
They’re not very potent natriuretics (recall only 3-5% of filtered Na+ is reabsorbed in the collecting duct), but they can be used in combo with other diuretics to help prevent hypokalemia.
Advantage of spironolactone vs. other K+ diuretics?
There are several… but notably it doesn’t require tubular secretion, and works at low EABV.
(making it quite good for CHF)
Side effects of K+ sparing diuretics?
Intuitively, hyperkalemia in those predisposed to it.
Spironolactone can cause gynecomastia.
2 major sites where osmotic diuretics cause a different in water absorption?
Proximal tubule, loop of Henle.
Do osmotic diuretics cause more Na+ or water diuresis?
They cause loss of both, but more water than Na+, potentially leading to hypernatremia.
(but it’s complicated. Remember HHNK.)
Review: How do you inhibit ADH?
With a “-vaptan”. But these haven’t yet been shown to improve mortality.
