Diuretics increase urine output by blocking sodium (and chloride) reabsorption at different parts of the nephron — water follows sodium. The site of action predicts both the strength and the electrolyte effect.

Why loop and thiazide diuretics lower potassium: more sodium reaches the collecting duct, where it is exchanged for potassium (and hydrogen ions) — so K⁺ is lost and a metabolic alkalosis can develop.

Calcium: loop diuretics increase calcium excretion (used in hypercalcemia); thiazides decrease it (can raise serum calcium; help prevent calcium kidney stones).

Current guidance

• Hypertension (2025 AHA/ACC): thiazide-type diuretics are one of four first-line classes; stage 2 hypertension usually starts with two drugs of different classes, preferably in a single pill (e.g., an ACE inhibitor or ARB plus a thiazide).
• Heart failure: loop diuretics relieve congestion but do not reduce mortality; MRAs (spironolactone, eplerenone) are one of the four HFrEF pillars (see Heart Failure Drugs).

Boxed warning (furosemide, bumetanide): these potent diuretics can cause profound water and electrolyte depletion — dose and monitoring must be individualized.

Contraindications and cautions

• Anuria (all diuretics); severe dehydration or hypovolemia; hepatic coma or precoma (risk of encephalopathy from hypokalemia and alkalosis)
• Potassium-sparing: serum K⁺ above 5.0 mEq/L (mmol/L) at the start (MRAs in HF are not started if K⁺ ≥ 5.0 mEq/L or eGFR ≤ 30 mL/min/1.73 m²), severe kidney impairment, Addison disease; never with potassium supplements unless specifically ordered and monitored
• Thiazides: gout, hyponatremia, hypercalcemia; less effective at eGFR below about 30 mL/min/1.73 m² (chlorthalidone is an exception in some studies)
• Mannitol: anuria, severe HF or pulmonary edema, severe dehydration, active intracranial bleeding (except during craniotomy)
• Sulfonamide allergy: loops (except ethacrynic acid), thiazides, and acetazolamide are sulfonamides; cross-reactivity with antibiotic sulfonamides is uncommon — ask about the reaction type and follow the prescriber's decision
• Diabetes (thiazides and loops can raise glucose); older adults (falls, hyponatremia)

Pregnancy and lactation: diuretics are not used to treat edema of pregnancy or preeclampsia (they reduce plasma volume). Thiazides may be continued for chronic hypertension under specialist care. Spironolactone and other MRAs are avoided (antiandrogen effects on a male fetus; the 2025 hypertension guideline lists MRAs among drugs to avoid). High-dose diuretics can suppress lactation.

Major interactions

• Digoxin + loop or thiazide: hypokalemia and hypomagnesemia → digoxin toxicity
• Lithium: thiazides and loops raise lithium levels → toxicity
• Aminoglycosides, cisplatin, vancomycin + loops: additive ototoxicity and nephrotoxicity
• NSAIDs: blunt diuresis and BP lowering; NSAID + diuretic + ACE inhibitor/ARB ("triple whammy") → AKI
• Potassium-sparing + ACE inhibitor, ARB, ARNI, potassium supplements, salt substitutes, trimethoprim → dangerous hyperkalemia
• Corticosteroids, amphotericin B, stimulant laxatives, and beta-2 agonists add to hypokalemia
• Other antihypertensives and alcohol add to orthostatic hypotension
• Eplerenone and finerenone with strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir) → hyperkalemia; the combination is contraindicated

Listed in priority order.

1. Fluid status and perfusion
   • Daily weight — same time, same scale, same clothing, after voiding (best indicator of fluid change; 1 kg ≈ 1 L of fluid)
   • Strict intake and output; lung sounds, edema, JVD, dyspnea (response in HF)
   • BP including orthostatic readings; signs of dehydration (thirst, dry mucosa, poor skin turgor, dizziness, rising BUN)
   • Hold and notify for systolic BP < 90 mmHg or signs of hypovolemia, per order
2. Electrolytes and kidney function (baseline, then regularly — more often with IV or high doses)

1. Signs of electrolyte imbalance
   • Hypokalemia: muscle weakness, leg cramps, fatigue, constipation, flattened T waves, U waves, dysrhythmias
   • Hyperkalemia: weakness, paresthesia, peaked T waves, bradycardia, dysrhythmias
2. Administration
   • Give once-daily diuretics in the morning (second dose, if ordered, by mid-afternoon) to avoid nocturia and falls
   • IV furosemide: slowly (about 4 mg/min or slower at high doses); assess hearing and tinnitus
   • IV potassium replacement: never IV push, always by pump; common peripheral maximum 10 mEq/h; confirm urine output
   • Mannitol: in-line filter; inspect for crystals; monitor urine output hourly, osmolality, and lung sounds
3. Safety — fall precautions (urgency, orthostasis), especially in older adults at night; bedside commode or urinal

• Take the diuretic in the morning; plan outings around the peak effect
• Weigh yourself every morning after voiding, before breakfast; report a gain of 2–3 lb (about 1 kg) in a day or 5 lb (about 2 kg) in a week, or a large loss with dizziness
• Rise slowly; sit if dizzy; avoid hot baths and heavy alcohol use
• Loop or thiazide: eat potassium-rich foods if allowed (bananas, oranges, potatoes, tomatoes, beans, leafy greens, dried fruit); take any prescribed potassium supplement with food and a full glass of water
• Potassium-sparing (spironolactone, eplerenone, amiloride): avoid salt substitutes and potassium supplements unless prescribed; do not overload on high-potassium foods
• Report muscle weakness, cramps, palpitations, ringing in the ears, severe thirst, or very low urine output
• Thiazides: use sunscreen and check the skin regularly; report joint pain (gout) or sudden eye pain
• Sick-day advice: during vomiting, diarrhea, or poor fluid intake, contact the prescriber — the diuretic may need to be held temporarily
• Avoid NSAIDs (ibuprofen, naproxen) unless the prescriber approves
• Diabetes: check glucose more often after starting a thiazide or loop diuretic

There is no specific antidote for diuretics. Overdose or overuse causes:

• Loop (furosemide) = most potent; thiazides = first-line for hypertension; potassium-sparing = weak, raise K⁺
• Loop and thiazide → ↓K⁺, ↓Mg²⁺, ↓Na⁺, metabolic alkalosis, ↑uric acid, ↑glucose
• Loop ↓calcium; thiazide ↑calcium
• Normal K⁺ 3.5–5.0 mEq/L (mmol/L); hypokalemia + digoxin = toxicity
• Furosemide: ototoxicity — give high IV doses slowly (about 4 mg/min)
• Spironolactone: hyperkalemia, gynecomastia; no salt substitutes
• Daily weight is the best measure of response; give in the morning
• Diuretics raise lithium levels; NSAIDs blunt diuretics
• Mannitol: raised ICP; monitor osmolality; contraindicated in anuria and pulmonary edema
• Acetazolamide → metabolic acidosis; loops and thiazides → metabolic alkalosis