Today's Veterinary Practice provides comprehensive information to keep every small animal practitioner up to date on companion animal medicine and surgery as well as practice building and management.
Issue link: http://todaysveterinarypractice.epubxp.com/i/619503
Today's VeTerinary PracTice | January/February 2016 | tvpjournal.com PracTicaL TecHniQUes FroM THe naVc insTiTUTe Peer reviewed 100 • Vasodilators: angiotensin-converting enzyme (ace) inhibitors, amlodipine, hydralazine, or nitroprusside • Antiarrhythmic agents: Lidocaine, sotalol, or amiodarone. Adverse Effects Furosemide's popularity is deserved, and most experienced clinicians are comfortable administering this drug. However, negative effects are associated with any potent diuretic (Table 1), which include: • Production of electrolyte disturbances (notably hypokalemia and hypomagnesemia), which may contribute to muscular weakness and arrhythmias • activation of the raas due to reduced renal blood flow and sodium loss (Figure 1), which produces adverse effects in the heart, vessels, and kidneys. 3,4,5 aldosterone and angiotensin ii contribute to congestion and hypertension via sodium retention and vasoconstriction, respectively. excessive, chronic production of these 2 hormones, therefore, further increases the workload on an already failing heart. additionally, the activated raas stimulates the sympathetic nervous system, which is toxic to cardiac myocytes and increases heart rate, produces vasoconstriction, and predisposes to cardiac arrhythmias. 6 Pharmacokinetics Furosemide's rapid onset of action makes it indispensable in the emergent treatment of cardiogenic pulmonary edema. it does, however, have a relatively short duration of action, which often necessitates repeated bolus dosing in the emergency setting and, at home, up to 3 to 4 times per day dosing in patients with advanced cHF. This characteristic—multiple peaks and valleys in serum drug concentrations—may enhance furosemide's stimulation of the sympathetic nervous system and raas, contributing to diuretic resistance. 7 increasing dosages are required over time and, in many cases, other diuretics are added to maintain patient comfort. Resistance diuretic resistance is multifactorial, resulting from neurohormonal activation as well as: 1. enhanced sodium and solute reabsorption at the proximal tubule in response to diuretic-induced contraction of the extracellular fuid volume 2. nephron hypertrophy in response to increased solute delivery to distal nephron segments 3. decreased renal responsiveness to natriuretic peptides. 8 TAblE 1. Potential adverse effects of Furosemide & Torsemide in congestive heart Failure • Dehydration • Hypotension • Hypokalemia and hypomagnesemia (resulting in arrhythmias and muscular weakness) • Reduced cardiac output (reduced preload with dehydration) • Azotemia, and possibly exacerbation of acute or chronic renal disease • Activation of the RAAS; associated with: » Increased aldosterone secretion and myocardial collagen deposition » Myocardial fbrosis » Sympathetic nervous system activation (arrhythmia, vasoconstriction) » Vasoconstriction (angiotensin II) and increased afterload » baroreceptor dysfunction » Arrhythmias » Sodium and fuid retention (signs of congestion) » Potassium and magnesium wasting • Ototoxicity is uncommonly, if ever, recognized in dogs and cats Note: Data in normal dogs show signifcantly higher plasma aldosterone spot concentrations with torsemide, compared to furosemide, administration. This result may indicate that torsemide has a greater RAAS stimulatory effect than furosemide, torsemide has some mineralocorticoid blocking effects, or both. More studies are indicated. FIGURE 1. Mean urine aldosterone-to-creatinine ratio (A:Cr) in 12 normal dogs challenged with furosemide at 2 mg/kg Q 12 H. At day 5 and 10, the RAAS is activated and, with continuous treatment, stays activated for at least 10 days. The urine A:Cr ratio indicates the amount of aldosterone found in the urine over 24 hours and refects RAAS activation.