This cheat sheet summarizes the major diuretic drug classes used to change renal sodium and water handling. College medical science students need it to connect nephron anatomy, transporter targets, clinical uses, and adverse effects. It is especially useful for comparing drugs that can look similar but act at different nephron sites.
The goal is to make class selection, electrolyte effects, and safety risks easier to review quickly.
The core idea is that diuretics increase urine output by blocking solute reabsorption or changing tubular osmotic forces. Loop diuretics block NKCC2 in the thick ascending limb, while thiazides block NCC in the distal convoluted tubule. Potassium-sparing diuretics act in the collecting duct by blocking ENaC or aldosterone effects.
Carbonic anhydrase inhibitors reduce bicarbonate reabsorption, and osmotic diuretics increase filtrate osmolality to pull water into the tubule.
Key Facts
- Loop diuretics such as furosemide inhibit NKCC2 in the thick ascending limb, increasing Na+, K+, Cl-, Ca2+, Mg2+, and water excretion.
- Thiazide diuretics such as hydrochlorothiazide inhibit NCC in the distal convoluted tubule, increasing NaCl and water excretion but increasing Ca2+ reabsorption.
- Potassium-sparing diuretics reduce K+ secretion in the collecting duct by blocking ENaC with amiloride or triamterene, or by blocking aldosterone receptors with spironolactone or eplerenone.
- Carbonic anhydrase inhibitors such as acetazolamide decrease HCO3- reabsorption in the proximal tubule, causing alkaline urine and possible metabolic acidosis.
- Osmotic diuretics such as mannitol are filtered but poorly reabsorbed, so they raise tubular fluid osmolality and increase water excretion.
- Fractional excretion of sodium can be estimated as FENa = (urine Na+ x plasma creatinine) / (plasma Na+ x urine creatinine) x 100%.
- Loop diuretics are high-ceiling diuretics because larger doses can produce large increases in sodium and water excretion until the maximal response is reached.
- Common electrolyte risks include hypokalemia with loop and thiazide diuretics, hyperkalemia with potassium-sparing diuretics, and metabolic acidosis with carbonic anhydrase inhibitors.
Vocabulary
- Diuretic
- A drug that increases urine production by reducing renal reabsorption of sodium, water, or other solutes.
- Nephron
- The functional unit of the kidney that filters blood and modifies filtrate to form urine.
- NKCC2
- A sodium-potassium-chloride cotransporter in the thick ascending limb that is inhibited by loop diuretics.
- NCC
- A sodium-chloride cotransporter in the distal convoluted tubule that is inhibited by thiazide diuretics.
- ENaC
- An epithelial sodium channel in the collecting duct that promotes sodium reabsorption and indirectly increases potassium secretion.
- Aldosterone
- A steroid hormone that increases sodium reabsorption and potassium secretion in the collecting duct.
Common Mistakes to Avoid
- Confusing loop and thiazide calcium effects is wrong because loop diuretics increase Ca2+ excretion, while thiazides usually decrease Ca2+ excretion.
- Assuming all diuretics cause hypokalemia is wrong because potassium-sparing diuretics can cause dangerous hyperkalemia, especially with ACE inhibitors, ARBs, or kidney disease.
- Placing thiazides in the loop of Henle is wrong because thiazides act mainly on NCC in the distal convoluted tubule.
- Using mannitol for pulmonary edema without careful assessment is wrong because osmotic expansion of extracellular fluid can worsen congestion before diuresis occurs.
- Ignoring acid-base effects is wrong because acetazolamide can cause metabolic acidosis, while loop and thiazide diuretics commonly contribute to metabolic alkalosis.
Practice Questions
- 1 A patient has urine Na+ = 60 mEq/L, plasma creatinine = 2 mg/dL, plasma Na+ = 140 mEq/L, and urine creatinine = 50 mg/dL. Calculate FENa using FENa = (urine Na+ x plasma creatinine) / (plasma Na+ x urine creatinine) x 100%.
- 2 A patient taking furosemide has serum K+ of 3.0 mEq/L. If the normal lower limit is 3.5 mEq/L, by how many mEq/L is the potassium below the lower limit?
- 3 A 70 kg patient receives mannitol at 0.5 g/kg. How many grams of mannitol are given?
- 4 Explain why spironolactone can reduce edema while increasing the risk of hyperkalemia.
Understanding Diuretics Classes Reference
The amount of sodium that reaches each nephron segment helps explain why drug effects differ. The early tubule reabsorbs most filtered sodium, so a drug acting there leaves a large fluid load for later segments. The thick ascending limb normally helps build the concentrated medullary environment needed to conserve water.
When this gradient is weakened, the kidney has more difficulty producing concentrated urine. This is one reason loop drugs can work even when kidney function is reduced. Their effect can be limited when little drug reaches the tubular fluid, such as in severe kidney impairment or poor absorption from gut swelling.
Electrolyte changes are not just side effects to memorize. They follow from altered flow and electrical forces in the nephron. Extra sodium arriving at the collecting duct promotes sodium uptake there.
This process encourages potassium secretion into urine. Increased tubular flow can further increase potassium loss. Low potassium may cause weakness, constipation, muscle cramps, or dangerous heart rhythm changes.
Loop drugs can lower magnesium, which can make low potassium harder to correct. Thiazides tend to retain calcium, so they may be useful for some patients with recurrent calcium kidney stones. Loop drugs increase calcium loss, which matters in patients prone to low calcium.
Potassium-sparing drugs have a smaller effect on total urine volume than loop drugs, but they are important in combinations. They can reduce potassium loss caused by other diuretics. The tradeoff is high blood potassium, especially in people with reduced kidney function or those taking drugs that lower aldosterone activity.
Spironolactone can cause breast tenderness, breast enlargement in males, and menstrual changes because it can affect steroid hormone receptors. Eplerenone causes fewer of these hormone related effects. Amiloride has a useful role in lithium related nephrogenic diabetes insipidus because it reduces lithium entry into collecting duct cells.
Clinical use depends on the body problem, not only on how much urine a drug produces. Rapid fluid removal is often needed in pulmonary edema, where fluid enters lung tissue and makes breathing difficult. Thiazides are common choices for long term blood pressure control.
Acetazolamide can lower fluid production in the eye, help prevent acute mountain sickness, and correct some metabolic alkalosis states. Mannitol can reduce brain swelling or eye pressure in selected settings, yet it can initially expand blood volume and worsen pulmonary edema or heart failure. Students should connect each class to urine sodium, potassium, bicarbonate, calcium, magnesium, acid base status, blood pressure, and volume status.
Safe prescribing requires checking kidney function, body weight, blood pressure, and repeated blood electrolyte measurements. A rising creatinine level may reflect reduced kidney perfusion, though the full clinical picture determines whether a change is harmful.