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tvpjournal.com | January/February 2016 | Today's VeTerinary PracTice PracTicaL TecHniQUes FroM THe naVc insTiTUTe Peer reviewed 101 Torsemide appears to be less affected by resistance, but a mechanism for this characteristic has not been identifed. TORSEMIDE Torsemide, like furosemide, is a very potent diuretic. In the Literature although not studied as thoroughly as would be desirable in animals, torsemide's profle in humans suggests that quality of life and survival are enhanced when compared with furosemide. 1,9,10 There are no large clinical trials published to date in veterinary medicine; however: • a study of 7 dogs with clinically stable cHF demonstrated that replacement of furosemide with torsemide was both safe and effective. 11 • another small case series suggested that duration and quality of life in 3 dogs with advanced refractory cHF were prolonged and improved, respectively, with torsemide. 12 • one feline and several canine laboratory studies 13-15 demonstrated drug traits that could potentially make use of torsemide advantageous in treating cHF in veterinary patients (Table 2). Pharmacokinetics & Pharmacodynamics diuretics exert their diuretic action at the nephron, and duration of diuretic action is related to urinary excretion rate. The pharmacokinetic and pharmacodynamic characteristics of torsemide (when compared with furosemide, Table 2) include, slower release from the plasma to the renal tubular fuid and resultant slower urinary excretion rate. The slower transfer rate of torsemide is hypothesized to be due to inherent properties of torsemide (it is less acidic and less of it exists in an anionic form, as compared with furosemide). The result is greater, smoother, and longer-acting diuresis (Figure 2). 13-15 Two veterinary studies have addressed torsemide pharmacodynamics, each showing superior diuresis when compared with furosemide (Figures 2 and 3 , page 102), at substantially lower dosage. 13,15 in addition, furosemide begins to lose effcacy (diuretic resistance) at 14 days of oral therapy in healthy dogs (Figure 3, page 102), while torsemide is less affected. 7 The relevance of the latter fnding in clinical cases remains to be seen. Furosemide versus Torsemide Furosemide is the diuretic of choice for everyday use because it is potent, rapid in onset, relatively inexpensive, and enjoys a comfort level with clinicians based on years of clinical experience. However, its rapid onset but short duration of action and association with diuretic resistance supports consideration of alternative loop diuretics, such as torsemide. TAblE 2. Treatment of congestive heart Failure: Torsemide compared With Furosemide 13-15 advanTages oF Torsemide • b etter diuresis (greater water loss/mg prescribed); potentially a disadvantage if administration results in excessive diuresis and electrolyte loss • l onger-acting diuresis (longer effective half-life) • Smoother diuresis (once daily torsemide provides constant, slowly declining thera- peutic level) ( Figures 2, 3, and 6, page 103) P o T en T ial advan Tages o F T orsemide • Improvement in cardiac function a • Reduced myocardial collagen content (fbrosis) a • Survival beneft over furosemide a,b • Fewer hospitalizations for CHF a,b • less affected by food intake a,b • l ess potassium loss in urine b • Aldosterone receptor blocker: Inconclusive data; if this does not occur or occurs minimally, then the elevated aldosterone levels seen in some studies are undesirable b a. Data from human studies b. Unproven or contradictory results in canine or other veterinary patients Note: Almost all the adverse effects seen with furosemide can occur with torsemide. FIGURE 2. Urine production in control animals, those receiving standard-dose furosemide, and those receiving torsemide orally. Note the similar peak effect between agents and the brisk and longer-acting diuresis with torsemide. These studies were performed in normal dogs.