Pharmacology

Diuretics are medications used to promote the excretion of excess fluids in animals by increasing urine production. They are crucial in managing conditions like edema, heart failure, and certain electrolyte imbalances. These drugs are categorized based on their action mechanisms and sites within the kidneys: loop diuretics, thiazide diuretics, potassium-sparing diuretics, carbonic anhydrase inhibitors, and osmotic diuretics. Each class has distinct effects, complications, and indications. For example, loop diuretics are potent for rapid fluid removal, while potassium-sparing diuretics help conserve potassium. Diuretics can cause dehydration, electrolyte imbalances, and, in some cases, adverse reactions with other medications.

Furosemide, a commonly used loop diuretic in veterinary medicine, inhibits sodium and chloride reabsorption in the kidneys, leading to increased urine production. It causes vasodilation that enhances renal blood flow and decreases fluid retention, with effects peaking shortly after administration. Furosemide is highly protein-bound and primarily cleared through renal secretion. It's dosed based on effect, with major adverse reactions including volume depletion and electrolyte imbalances. Additionally, it may interact with other medications, such as digitalis glycosides and NSAIDs, affecting their efficacy and safety.

Torsemide is a potent loop diuretic used in veterinary medicine, effective in lower doses compared to furosemide. It maintains efficacy over time without the tolerance observed with furosemide, offering higher oral bioavailability in dogs. Additionally, torsemide has antialdosterone, antihypertensive, and antifibrotic effects, making it particularly beneficial for treating congestive heart failure in dogs. Its drug interactions are likely similar to those of furosemide.

Thiazide diuretics like hydrochlorothiazide are less potent and less commonly used in veterinary medicine than loop diuretics. They inhibit sodium reabsorption in the distal convoluted tubule, promoting potassium excretion, and can be combined with other diuretics for refractory fluid retention. However, they're not recommended for azotemic patients or those with hypercalcemia due to their effects on renal blood flow and calcium excretion.

Potassium-sparing diuretics like spironolactone, amiloride, and triamterene, with spironolactone being the most used in veterinary medicine, act as mineralocorticoid receptor antagonists, leading to mild diuresis and potassium retention. Spironolactone, particularly effective in congestive heart failure where aldosterone levels are high, is absorbed well orally and metabolized in the liver. It's usually combined with other diuretics for heart failure management but requires cautious use to avoid hyperkalemia, especially when used with potassium supplements or ACE inhibitors.

Carbonic anhydrase inhibitors like acetazolamide decrease carbonic acid formation in the proximal tubule, leading to less hydrogen ion production. This increases sodium and bicarbonate excretion, causing diuresis and potential systemic acidosis while also enhancing potassium excretion due to intracellular potassium substituting for hydrogen ions.

Osmotic diuretics, like mannitol and DMSO, are used in veterinary medicine to initiate osmotic diuresis and manage edema. Mannitol is preferred for small animals due to cost but has a rapid onset. DMSO, used in large animals, acts also as an anti-inflammatory and penetrates tissues, carrying other chemicals with it. Both have specific dosing protocols to minimize risks and ensure effectiveness, with mannitol's diuretic response guiding subsequent doses and DMSO's use being limited by its odor and potential for hemolysis at high concentrations.

References:

Merck Veterinary Manual - Diuretics