Thiazides work primarily at the distal convoluted tubules (DCT) to inhibit Na⁺ and Cl^– reabsorption, which leads to greater Na⁺ and Cl⁻ delivery to more distal portions of the nephron. Water “follows the salt,” and urine output is thus increased.

As with all diuretics, hypovolemia can occur. For thiazides in specific, one must be aware of possible hypokalemic–hypochloremic metabolic alkalosis, hyponatremia, hypomagnesemia, hypercalcemia (increased calcium reabsorption in the distal tubules), hyperglycemia, and hyperuricemia. Idiosyncratic acute angle glaucoma after thiazide administration has been reported.

Thiazides, given orally, are commonly used as first-line agents for treatment of hypertension. Thiazides may also be used for volume overload situations (e.g., pulmonary edema, congestive heart failure). Thiazides may be used for treatment of nephrogenic diabetes insipidus. Metolazone and loop diuretics (often bumetanide) together have a synergistic effect that may produce profound diuresis in patients resistant to diuresis with single agent therapy. One must be aware of implications related to thiazide side effects. Hypovolemia may complicate blood pressure management and tissue perfusion. Electrolyte imbalances (especially hypokalemia) may prolong nondepolarizing neuromuscular blockade and exacerbate skeletal muscle weakness.

Loop diuretics work at the medullary portion of the ascending loop of Henle, blocking the Na⁺/K⁺/2Cl⁻ transporter, limiting Na⁺ reabsorption, and thus delivering more Na⁺ and Cl⁻ to the distal portions of the nephron. Of note, furosemide has a prostaglandin-stimulating action within the kidney, which increases renal blood flow, further promoting diuresis. Loop diuretics also increase the excretion of calcium and magnesium.

As with all diuretics, hypovolemia can occur. For loop diuretics in specific, one must be aware of hypokalemic–hypochloremic metabolic alkalosis, hyponatremia, hypomagnesemia, and hyperuricemia (increased urate reabsorption). Reversible hearing loss is rare but has been reported, especially in patients on high doses of loop diuretics. Loop diuretics, with the exception of ethacrynic acid, contain a sulfonamide nucleus and should be used cautiously in patients with sulfa-/sulfonamide allergies.

Loop diuretics are commonly used in an oral form to help reduce volume overload in patients with renal dysfunction, CHF, or liver dysfunction. Loop diuretics can be useful for treatment of increased intracranial pressure, rapid correction of hyponatremia, treatment of hypertension in combination with a thiazide diuretic, or as supplemental treatment of hypercalcemia or hyperkalemia. Note that furosemide can be given as an oral form or IV form; the oral to IV dose ratio is 3:1. Bumetanide may be paired with metolazone (a thiazide diuretic) to produce profound, prolonged diuresis in patients refractory to single agent diuretic therapy. One must be aware of implications related to loop side effects. Hypovolemia may complicate blood pressure management and tissue perfusion. Electrolyte imbalances (especially hypokalemia, hypocalcemia) may prolong nondepolarizing neuromuscular blockade and exacerbate skeletal muscle weakness.

Carbonic anhydrase inhibitors cause noncompetitive inhibition of the carbonic anhydrase enzyme; carbonic anhydrase is used to catalyze the reactions between water, carbon dioxide, carbonic acid, and bicarbonate. In the proximal tubule (PT) of the kidney, inhibition of carbonic anhydrase causes an increase in renal bicarbonate excretion (alkalinization of urine). In the eye, acetazolamide inhibits aqueous humor production, which reduces intraocular pressure.

Acetazolamide may cause mild hyperchloremic metabolic acidosis, which is related to increased renal excretion of bicarbonate.

Acetazolamide is prescribed for treatment of glaucoma or altitude sickness. One must be aware of implications related to carbonic anhydrase side effects. Hypovolemia may complicate blood pressure management and tissue perfusion. When encountered, the metabolic acidosis may alter the function of other anesthetic medications or create an additive acidosis in the setting of concomitant respiratory acidosis. Perioperative normal saline administration may worsen hyperchloremic acidosis as well.