Furosemide tolerance

Wakelkamp M, Alvan G, Gabrielsson J, Paintaud G. Pharmacodynamic modeling of furosemide tolerance after multiple intravenous administration. Clin Pharmacol Ther 1996 60 75-88. 

Fig. 8. Relationship between natriuresis and furosemide excretion rate. The first observation representing counter-clockwise hysteresis has not been included in the fitting of the sigmoid max model. (From Wakelkamp M. Furosemide dosage input - consequences for diuretic effect, tolerance and efficiency. Diss. Karolinska Institutet, Stockholm 1997.)...

Wakelkamp M. Furosemide dosage input-consequences for diuretic effect, tolerance and efficiency. Diss. Karolinska Institutet, Stockholm 1997. 

Unauthorized use of these diuretics, or the failure to follow label indications for approved use in the cattle, could lead to unacceptable residues in meat and milk destined for human consumption. While there are no official tolerances for these drugs in milk, the Food and Drug Administration (FDA) has established safe levels that range from 7 ppb for trichlormethiazide, to 10 ppb for furosemide, and 67 ppb for the other thiazides (56). Administration of diuretics is associated with potential toxic effects such as bone marrow depression, hyperbilirubinemia. 

Furosemide rarely causes the syndrome of inappropriate antidiuretic hormone secretion (SIADH) (although it has been found useful in treating some patients with SIADH who cannot tolerate water restriction (428)). In furosemide-induced cases (SEDA-7, 246), serum ADH concentrations were raised, total body sodium was normal, total body potassium greatly reduced, and intracellular water raised at the expense of extracellular fluid volume. However, such cases are rare, and no new cases have been published since this complication was reported in SEDA-7. 

Thiazide diuretics are ineffective once the GFR becomes less than 25 mL/min, and loop diuretics are often used at high doses (e.g. furosemide 500 mg to 1 g daily) to gain an effect. Metolazone is effective when combined with a loop diuretic. Potassium-sparing diuretics such as amiloride are not recommended. Spironolactone is not generally used, but is beneficial in low dose for the treatment of heart failure even in patients on dialysis. Beta-blockers and calcium channel blockers are generally well tolerated. Any ankle swelling with calcium channel blockers must not be confused with fluid overload. 

Neither patient had a previous history of drug hypersensitivity. Both patients had previously tolerated furosemide, another sulfonamide derivative. The temporal correlation with torasemide administration suggested a causal relation, but the mechanism was unclear. 

Case Conclusion CC s oncologist decides to stop the interferon therapy and initiate a trial of imatinib mesylate. She tolerated the imatinib well, with minimal complaints of lower extremity edema for which she was prescribed furosemide. Six weeks after starting imatinib, CC s peripheral blood smear appeared normal (hematologic response) and cytogenetic evaluation of her bone marrow revealed disappearance of the Philadelphia chromosome. 

For those patients with normal to moderately impaired renal function, the cornerstone of initial treatment of hypercalcemia is volume expansion to increase urinary calcium excretion (see Table 49-6). Patients with severe renal insufficiency usually do not tolerate volume expansion they may be initiated on therapy with calcitonin. Patients with symptomatic hypercalcemia are often dehydrated secondary to vomiting and polyuria thus rehydration with saline-containing fluids is necessary to interrupt the stimulus for sodium and calcium reabsorption in the renal mbule. ° Rehydration can be accomplished by the infusion of normal saline at rates of 200 to 300 mL/h, depending on concomitant conditions (primarily cardiovascular and renal) and extent of hypercalcemia. Adequacy of hydration is assessed by measuring fluid intake and output or by central venous pressure monitoring. Loop diuretics such as furosemide (40 to 80 mg IV every 1 to 4 hours) or ethacrynic acid (for patients with sulfa allergies) may also be instiffited to increase urinary calcium excretion and to minimize the development of volume overload from the administration of saline (see Table 49-6). Loop diuretics such as furosemide... 

Probenecid but not cidofovir alters zidovudine pharmacokinetics such that zidovudine doses should be reduced when probenecid is present, as should the doses of drugs similarly affected by probenecid fe.g., /i-lactam antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], acyclovir, lorazepam, furosemide, methotrexate, theophylline, and rifampin). Concurrent nephrotoxic agents are contraindicated, and an interval of 1 week before beginning cidofovir treatment is recommended after prior exposure to aminoglycosides, intravenous pentamidine, amphotericin foscamet, NSAIDs, or contrast dye. Cidofovir and oral ganciclovir in combination are poorly tolerated at full doses. 

Ibuprofen (Advil, Medipren, Motrin, Nuprin, Rufen) Better tolerated than aspirin by most patients. Reduces diuretic effects of furosemide and may reduce effectiveness of several antihypertensive agents. 

The risk of ACE inhibitor-induced renal impairment in patients with or without renovascular disease can be potentiated by diuretics. " In an analysis of 74 patients who had been treated with captopril or lisinopril, reversible acute renal failure was more coimnon in those who were also treated with a diuretic (furosemide and/or hydrochlorothiazide) than those who were not (11 of 33 patients compared with 1 of 41 patients). Similarly, in a prescription-event monitoring study, enalapril was associated with raised creatinine or urea in 75 patients and it was thought to have contributed to the deterioration in renal function and subsequent deaths in 10 of these patients. However, 9 of these 10 were also receiving loop or thiazide diuretics, sometimes in high doses. Retrospective analysis of a controlled study in patients with hypertensive nephrosclerosis identified 8 of 34 patients who developed reversible renal impairment when treated with enalapril and various other antihypertensives including a diuretic (furosemide or hydrochlorothiazide). In contrast, 23 patients treated with placebo and various other antihypertensives did not develop renal impairment. Subsequently, enalapril was tolerated by 7 of the 8 patients without deterioration in renal function and 6 of these patients later received diuretics. One patient was again treated with enalapril with recurrence of renal impairment, but discontinuation of the diuretics (furosemide, hydrochlorothiazide, and triamterene) led to an improvement in renal function despite the continuation of enalapril. ... 

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