The five diuretic classes in order down the nephron: where each works, how, how strong it is, what it does to potassium, calcium and magnesium, what else it changes, what it is for, what it causes and what it interacts with.
| Class and examples | Site on the nephron | How it works | Sodium chloride inhibited and urine output | Effect on potassium, calcium, magnesium | Uric acid, glucose, acid-base | Indications | Main adverse effects | Interactions and pearls | Source |
|---|---|---|---|---|---|---|---|---|---|
| Loop diuretics furosemide, bumetanide, torsemide, ethacrynic acid | Thick ascending limb of the loop of Henle (about 25 percent of sodium is reabsorbed there) | Inhibit the sodium-potassium-2 chloride carrier on the luminal membrane | Most potent: inhibit sodium chloride reabsorption by 20 to 25 percent; urine output up to 4 liters per day | Increase potassium excretion (hypokalemia); increase calcium and magnesium excretion | Hyperglycemia; less uric acid excreted (gout); mild metabolic (contraction) alkalosis; mild hyperlipidemia | Pulmonary edema, nephrotic syndrome, cirrhosis with ascites, hypercalcemia (with saline), heart failure, renal failure, hypertension; still work when creatinine clearance is below 30 mL/min | Volume depletion, hypokalemia (arrhythmias), hyperglycemia, contraction alkalosis, gout, ototoxicity, hyponatremia (seizures), rash, photosensitivity, azotemia | NSAIDs (nonsteroidal anti-inflammatory drugs) blunt the natriuretic and blood pressure response; aminoglycosides potentiate ototoxicity; warfarin (protein-binding competition); lithium clearance falls; digoxin arrhythmias with low potassium and magnesium. The vasodilator effect involves prostaglandins. | L9 slide 12 slide 9 slide 13 slide 14 slide 15 slide 16 slide 17 slide 18 slide 19 |
| Thiazide diuretics hydrochlorothiazide, chlorothiazide, chlorthalidone, metolazone, indapamide | Distal convoluted tubule (about 5 percent of sodium is reabsorbed there) | Inhibit the sodium-chloride transporter on the luminal membrane | Inhibit up to 5 percent of filtered sodium chloride; urine output 1 to 2 liters per day | Increase potassium and magnesium excretion; decrease calcium excretion (more is reabsorbed) | Hyperglycemia (less insulin), hyperuricemia and gout, metabolic alkalosis; low-density lipoprotein (LDL) cholesterol rises | Hypertension (low dose preferred; best in elderly patients, African American patients and sodium-retentive states), renal failure, cirrhosis, heart failure, calcium oxalate kidney stones (a small rise in serum calcium is a side effect, but urinary calcium falls) | Volume depletion, hypokalemia, alkalosis, gout, hyperglycemia, hypercalcemia, hyperlipidemia, rash, photosensitivity, dizziness, headache, weakness, sexual dysfunction, constipation | Metolazone stays effective at low creatinine clearance (thiazides in general lose effect at low clearance). NSAIDs block the prostaglandins and weaken the natriuresis. With digoxin, keep potassium above 4.0 mEq/L. Not potent enough for most heart failure. (Added background: newer trial data show chlorthalidone can still work in advanced kidney disease, so the low-clearance cutoff is not absolute.) | L9 slide 21 slide 10 slide 20 slide 22 slide 23 slide 24 slide 25 slide 26 slide 27 slide 28 slide 29 slide 52 |
| Potassium-sparing diuretics amiloride, triamterene (combined with hydrochlorothiazide in Moduretic, Dyazide, Maxzide) | Collecting duct (2 to 3 percent of sodium is reabsorbed there) | Block the luminal sodium channels, which lowers the gradient that drives potassium secretion | Inhibit 2 to 3 percent of sodium chloride reabsorption; modest increase in urine flow | Potassium is held back (hyperkalemia) | Glucose intolerance in diabetes; a modest change in uric acid | Same indications as the other diuretics but much less natriuretic and diuretic effect; used mostly in combination with other diuretics or antihypertensive drugs | Hyperkalemia; glucose intolerance; megaloblastic anemia (triamterene); azotemia (amiloride) | Caution with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and potassium supplements. (Added background: potassium chloride salt substitutes add potassium; both agents carry a boxed warning for hyperkalemia.) | L9 slide 30 slide 11 slide 31 slide 32 slide 33 |
| Aldosterone antagonists spironolactone, eplerenone | Collecting duct (and distal tubule): the aldosterone receptor | Bind the steroid receptor but do not translocate to the nucleus, so no new sodium channels or pumps are made; most effective when aldosterone is high; 30 to 60 minute lag before effect | Block 2 to 3 percent of sodium chloride reabsorption; modest urine production | Hold back potassium (less potassium loss, hyperkalemia) | Modest effect on lipid, glucose and uric acid levels; mild acidosis | Primary aldosteronism, hypertension, heart failure (reduces mortality in advanced heart failure), edema, cirrhosis (secondary hyperaldosteronism), nephrotic syndrome | Hyperkalemia with mild acidosis; nausea, vomiting, gastrointestinal upset; spironolactone: gynecomastia and testicular atrophy in men, menstrual irregularities in women | Eplerenone has less effect on androgen receptors: the switch when those effects occur. Heart failure patients are not eligible when potassium is above 5 or creatinine is high. | L9 slide 36 slide 34 slide 35 slide 37 slide 38 slide 73 |
| Carbonic anhydrase inhibitors acetazolamide, dichlorphenamide, methazolamide | Proximal tubule (60 to 70 percent of the filtrate is reabsorbed there) | Inhibit carbonic anhydrase: bicarbonate absorption falls by 80 to 90 percent, so less hydrogen ion is made and less sodium-hydrogen exchange occurs | Short term, sodium and potassium excretion rise about 5 percent; the effect falls to 1 to 3 percent after 3 to 5 days (a weak, self-limited diuretic) | Potassium depletion | Metabolic acidosis (bicarbonate lost in the urine) | Glaucoma (dorzolamide and brinzolamide in the eye), epilepsy, mountain sickness | Metabolic acidosis, potassium depletion, drowsiness | Unlike every other diuretic class, these acidify the blood rather than causing a contraction alkalosis. The weakest diuretics, used for their other effects. | L9 slide 39 slide 8 slide 40 slide 42 slide 43 |