Aminoglycosides renal function

INEFFECTIVE TISSUE PERFUSION RENAL The patient taking an aminoglycoside is at risk for nephrotoxicity. The nurse measures and records the intake and output and notifies the primary health care provider if the output is less than 750 ml/day. It is important to keep a record of the fluid intake and output as well as a daily weight to assess hydration and renal function. The nurse encourages fluid intake to 2000 ml/day (if the patient s condition permits). Any changes in the intake and output ratio or in the appearance of the urine may indicate nephrotoxicity. The nurse reports these types of changes to the primary health care provider promptly. The primary health care provider may order daily laboratory tests (ie, serum creatinine and blood urea nitrogen [BUN]) to monitor renal function. The nurse reports any elevation in the creatinine or BUN level to tiie primary health care provider because an elevation may indicate renal dysfunction. 

Although most CF patients have shorter half-lives and larger volumes of distribution than non-CF patients, some patients exhibit decreased clearance. Possible causes include concomitant use of nephrotoxic medications, presence of diabetic nephropathy, history of transplantation (with immunosuppressant use and/or procedural hypoxic injury), and age-related decline in renal function in older adult patients. Additionally, CF patients are repeatedly exposed to multiple courses of IV aminoglycosides, which can result in decreased renal function. Evaluation of previous pharmacokinetic parameters and trends, along with incorporation of new health information, is key to providing appropriate dosage recommendations. 

Obtain serum drug levels for aminoglycosides and/or vancomycin and perform pharmacokinetic analysis. Adjust the dose, if needed, according to the parameters in Table 13-2. Obtain follow-up trough levels at weekly intervals or sooner if renal function is unstable. Follow serum creatinine levels if renal function is unstable. Hearing tests may be scheduled yearly or per patient preference. 

Vancomycin Infusion related toxicity (phlebitis, red man syndrome) Potential for additive renal toxicity if being coadministered with a nephrotoxic agent (e.g., aminoglycoside) monitor renal function (BUN/SCr) weekly in stable patients Consider vancomycin troughs to ensure therapeutic concentrations ... 

Nephrotoxins (N) orototoxins (0) (eg., amphotericin B (N), cisplatin (N/0), cyclosporine (N), furosemide (0), NSAIDs (N), radio contrast (N), vancomycin (N) Additive adverse effects Monitor aminoglycoside SDC and renal function... 

Amphotericin B Azoles Nephrotoxins (e.g, aminoglycosides, cidofovir, cyclosporine, foscarnet, pentamidine) See Chap. 125 in Pharmacotherapy A Pathophysiologic Approach, seventh edition, page 1998. Additive adverse effects Monitor renal function... 

Gentamicin is an aminoglycoside. All aminoglycosides tend to be nephrotoxic and ototoxic. The dose must be reduced and serum concentrations must be monitored in patients with impaired renal function. Concomitant administration of aminoglycosides and other nephrotoxic drugs, such as certain diuretics, ciclosporin, teicoplanin and vancomycin should be avoided. 

Toxicity Aminoglycosides are associated with significant nephrotoxicity or ototoxicity. These agents are excreted primarily by glomerular filtration thus, the serum half-life will be prolonged and significant accumulation will occur in patients with impaired renal function. Toxicity may develop even with conventional doses, particularly in prerenal azotemia or impaired renal function. 

Dosing interval Preliminary evidence indicates that aminoglycosides may be administered on a once-daily basis without compromising efficacy and without increasing the potential for nephrotoxicity and ototoxicity. It is possible that the incidence of nephrotoxicity may even be decreased. Elderly Elderly patients may have reduced renal function that is not evident in the results of routine screening tests, such as BUN or serum creatinine. A Ccr determination may be more useful. 

As with other aminoglycosides, reduce dosage in impaired renal function. 

Cephalosporins are the agents of choice in renal failure. They attain adequate urine concentrations despite severely impaired renal function and toxicity remains low with increased plasma levels. Quinolones are preferred over aminoglycosides due to aminoglycoside-related ototoxicity. 

Answer Ototoxicity and nephrotoxicity are common adverse effects of aminoglycoside therapy, particularly when administered orally. You immediately arrange to check renal function and fortunately discover that renal function is not significantly impaired in this patient. You inform the patient that the hearing loss is probably permanent and that he should carefully check with pharmacists and physicians in the future to be certain that any prescriptions drugs that he might receive do not further aggravate this condition. 

Foscarnet should not be used in combination with drugs that cause renal toxicity (e.g., acyclovir, aminoglycosides, amphotericin B, NSAIDs). Abnormal renal function has been noted when foscarnet is used with ritonavir or ritonavir and saquinavir. Pentamidine may increase the risk of nephrotoxicity, hypocalcemia, and... 

Abnormal clearance may be anticipated when there is major impairment of the function of the kidney, liver, or heart. Creatinine clearance is a useful quantitative indicator of renal function. Conversely, drug clearance may be a useful indicator of the functional consequences of heart, kidney, or liver failure, often with greater precision than clinical findings or other laboratory tests. For example, when renal function is changing rapidly, estimation of the clearance of aminoglycoside antibiotics may be a more accurate indicator of glomerular filtration than serum creatinine. 

Loop diuretics occasionally cause dose-related hearing loss that is usually reversible. It is most common in patients who have diminished renal function or who are also receiving other ototoxic agents such as aminoglycoside antibiotics. 

The normal half-life of aminoglycosides in serum is 2-3 hours, increasing to 24-48 hours in patients with significant impairment of renal function. Aminoglycosides are only partially and irregularly removed by hemodialysis—eg, 40-60% for gentamicin—and even less effectively by peritoneal dialysis. 

Streptomycin is ototoxic and nephrotoxic. Vertigo and hearing loss are the most common adverse effects and may be permanent. Toxicity is dose-related, and the risk is increased in the elderly. As with all aminoglycosides, the dose must be adjusted according to renal function (see Chapter 45). Toxicity can be reduced by limiting therapy to no more than 6 months whenever possible. 

Answer The patient s high serum creatinine indicates compromised renal function. The aminoglycosides can be nephrotoxic and thus the drug was not employed. However, tobramycin might have been used together with ceftazidime if the dose were adjusted for renal function. 

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