Effect of furosemide on aminoglycoside-induced nephrotoxicity and auditory toxicity in humans

Smith, Craig R.; Lietman, Paul S.

doi:10.1128/aac.23.1.133

Cited by 32 publications

(9 citation statements)

References 21 publications

(25 reference statements)

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“…We found a significant trend toward a lower ototoxic potential for netilmicin; this has also been found in some experimental models (5,8,14,20,27) and in several, but not all, open and randomized clinical studies (4,10,15,18,21,38,40). Several factors have been identified by univariate statistical techniques as predisposing individuals to auditory toxicity (4,9,13,16,18,22,28,35,37,41). A multivariate approach, however, seems more appropriate since the variables cited in the literature are often very interrelated.…”

Section: Discussionmentioning

confidence: 75%

“…Apart from the aminoglycoside type, we identified age and the presence of an abnormally high trough level as predisposing factors for development of auditory toxicity, and only age was retained in the final logistic model. All of these factors have been cited previously (4,6,9,16,18,22,24,35,37). Conversely, Moore et al (24), also using a multivariate approach, identified a significant association between auditory toxicity and the duration of therapy, presence of shock, dehydration, liver dysfunction, and peak temperature, but age did not reach statistical significance in either the univariate or multivariate analysis.…”

Section: Discussionmentioning

confidence: 88%

“…In this study, patients with auditory toxicity underwent therapy for a longer period, were more likely to be bacteremic, dehydrated, or have an underlying liver dysfunction, and on the average, had a higher temperature than those without auditory toxicity (24). Other predisposing factors such as male sex or advanced age have also been identified in clinical and experimental studies (4,6,9,13,16,22,28,29,35,37,41). A trend toward a lower ototoxic potential for netilmicin has been confirmed in several randomized and open clinical studies (10,15,18,38,40).…”

mentioning

confidence: 81%

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Univariate and multivariate analyses of risk factors predisposing to auditory toxicity in patients receiving aminoglycosides

Gatell

Araujo

et al. 1987

Antimicrob Agents Chemother

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Risk factors predisposing to auditory toxicity of aminoglycosides were analyzed from records of 187 patients enrolled in three prospective randomized trials comparing the toxicity of netilmicin, tobramycin, and amikacin. Patients were eligible if they received three or more days of therapy and at least two serial audiograms were available. The overall auditory toxicity rate was 9.6% (18 of 187). Auditory toxicity was detected in 4.4, 10.8, and 23.5% of patients given netilmicin, tobramycin, and amikacin, respectively (P = 0.05). In the univariate analysis, patients who developed auditory toxicity were significantly older (P = 0.01) and had a significantly higher (P = 0.04) percentage of trough levels of netilmicin or tobramycin above 2 mg/liter or amikacin above 5 mg/liter. In the final logistic regression model, only age was retained as independently influencing the development of auditory toxicity (P < 0.00001). Conversely, factors that did not add significantly to the prediction of auditory toxicity were aminoglycoside serum levels, total aminoglycoside dose, duration of therapy, sex, peak temperature, presence of bacteremia, shock, liver cirrhosis, dehydration, previous otic pathology or renal failure, and development of renal toxicity. At least in certain populations, age is the most important predisposing factor for the development of auditory toxicity in patients receiving aminoglycosides.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 81%

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Univariate and multivariate analyses of risk factors predisposing to auditory toxicity in patients receiving aminoglycosides

Gatell

Araujo

et al. 1987

Antimicrob Agents Chemother

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“…Forced diuresis, however, only slightly enhanced the clearance of metoclopramide (Ell et al 1985). Enhanced toxicity of tobramycin may be caused by a 40% decrease in the volume of distribution following administration of frusemide, resulting in significantly higher trough concentrations of tobramycin (Kaka et al 1984), but no change in tobramycin renal clearance (Smith & Lietman 1983). Furthermore, frusemide may compete with acidic drugs at renal tubular secretion sites with different effects on renal excretion; Kom et al (1986) found no change in the clearance of ceftriaxone in healthy volunteers.…”

Section: Drug Interactionsmentioning

confidence: 88%

Clinical Pharmacokinetic Considerations in the Treatment of Increased Intracranial Pressure

Heinemeyer

1987

Clinical Pharmacokinetics

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Life-threatening increased intracranial pressure can be reversed by a variety of drugs. These compounds all have some disadvantages, producing rebound effects, severe coma or cardiovascular depression and electrolyte imbalance. However, reduction of intracranial pressure is a prerequisite for recovery and the benefits of treatment outweigh the risks. Dexamethasone is rapidly eliminated, the short half-life (about 3 hours) indicating that dosage intervals should be kept small. As yet, however, its therapeutic efficacy has not been clearly demonstrated. Therefore, an association between pharmacokinetics and pharmacodynamics cannot be established. Osmotic diuretics are the most widely used agents for reduction of intracranial pressure. Pharmacokinetics show a very close relationship to changes in serum osmolality, but there are large variations in the clearance. For the use of osmotics, the blood-brain barrier must be intact. Osmotic diuretics may lead to intracerebral oedema or to acute renal failure as serum osmolality increases. Considering the pharmacokinetics of each drug, and the dynamics of intracerebral pressure and osmolality, an intermittent, individually titrated dosage should be administered, with simultaneous monitoring of intracranial pressure. Frusemide (furosemide) can be used as an adjunct, to enhance the effect of osmotic diuretics. Its pharmacokinetics are limited by renal function, depending on age as well as on the extent of renal impairment. Altered renal elimination of concomitantly administered drugs, and electrolyte imbalances should be anticipated when diuretics are used. Barbiturates are certain to decrease intracranial pressure in humans by an as yet unknown mechanism. Their administration is recommended for patients that do not respond to conventional therapy. As barbiturates can result in deep coma, knowledge of their pharmacokinetics is of great importance for recovery. Following single doses, pentobarbitone has a relatively long elimination half-life (about 22 hours). However, after repeated administration for several days, its elimination may be enhanced due to autoinduction. Thiopentone kinetics are characterised by distribution and redistribution into deep peripheral compartments. Administration of high and frequent doses leads to considerably delayed recovery. This is not true for methohexitone, which shows comparable pharmacokinetics after single and multiple dose administration. Elimination depends on liver blood flow. Thus, recovery from methohexitone-coma is rapid. Rapid elimination is also an important characteristic of etomidate and alphaxalone/alphadolone, two non-barbiturate hypnotics.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…Aminoglycosides [204] Gentamicin [203] Kanamycin [216] Tobramycin [217] Additive oto-and nephrotoxicity…”

Section: Loop Diuretics Furosemidementioning

confidence: 99%

Antihypertensive therapy: special focus on drug interactions

Maas

Böger²

2003

Expert Opinion on Drug Safety

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Today, the lifetime risk of patients aged 55-65 years to receive antihypertensive drugs approaches 60%. Yet, recent trials suggest that hypertension is not adequately controlled in the majority of patients. The prevalence of hypertension increases with advancing age, as does the prevalence of comorbid conditions and the total number of medications taken. Multi-drug therapy, advancing age and comorbid conditions are also key risk factors for adverse drug reactions and drug interactions. In this review, the authors evaluate the most frequently used antihypertensive drugs (diuretics, beta-adrenergic blockers, angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor Type 1 blockers and alpha-adrenergic blockers) with special reference to pharmacodynamic and pharmacokinetic drug interactions. As the spectrum of drugs prescribed is constantly changing, safety yesterday does not imply safety today and safety today does not imply safety tomorrow. Furthermore, therapeutic efficacy should not be neglected over concerns regarding drug interactions. Many patients are at risk of clinically relevant drug interactions involving antihypertensive drugs but, presently, even more patients may be at risk of suffering from the consequences of their inadequately treated hypertension. In this respect, the authors discuss controversial viewpoints on the overall clinical relevance of drug interactions occurring at the level of cytochrome P450 metabolism.

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Effect of furosemide on aminoglycoside-induced nephrotoxicity and auditory toxicity in humans

Abstract: We analyzed data from three prospective, controlled, randomized, double-blind clinical trails to determine whether furosemide increases the nephrotoxicity and auditory toxicity of aminoglycosides. All

Cited by 32 publications

References 21 publications

Univariate and multivariate analyses of risk factors predisposing to auditory toxicity in patients receiving aminoglycosides

Univariate and multivariate analyses of risk factors predisposing to auditory toxicity in patients receiving aminoglycosides

Clinical Pharmacokinetic Considerations in the Treatment of Increased Intracranial Pressure

Antihypertensive therapy: special focus on drug interactions

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