Nephrotoxicity drugs

An additive nephrotoxicity develops when pentamidine isethionate is administered with other nephrotoxic drugs (eg, aminoglycosides, vancomycin, or amphotericin B). An additive bone marrow depression occurs when the drug is administered with antineoplastic drugs or when the patient lias received radiation therapy recently. 

Human immune globulin intravenous (IGIV) products have been associated with renal impairment, acute renal failure, osmotic nephros s and death. Individuals with a predication to acute renal failure, such as those with preexisting renal disease, diabetes mellitus individuals older than 65 years or patients receiving nephrotoxic drugs should not be given human IGIV products... 

A primary goal of therapy is ameliorating any identifiable underlying causes of ARF such as hypovolemia, nephrotoxic drug administration, or ureter obstruction. Prerenal and... 

Amphotericin B-induced ARF occurs in as many as 40% to 65% of patients treated with the conventional desoxycholate formulation.30 Nephrotoxicity is due to renal arterial vasoconstriction and distal renal tubule cell damage. Risk factors include high doses, treatment for at least 7 days, preexisting kidney dysfunction, and concomitant use of other nephrotoxic drugs.31 Three lipid-based formulations of amphotericin B have been developed in an attempt to decrease the incidence of ARF amphotericin B lipid complex, amphotericin colloidal dispersion, and liposomal amphotericin B. The range of... 

Cyclosporine and tacrolimus are calcineurin inhibitors that are administered as part of immunosuppressive regimens in kidney, liver, heart, lung, and bone marrow transplant recipients. In addition, they are used in autoimmune disorders such as psoriasis and multiple sclerosis. The pathophysiologic mechanism for ARF is renal vascular vasoconstriction.41 It often occurs within the first 6 to 12 months of treatment, and can be reversible with dose reduction or drug discontinuation. Risk factors include high dose, elevated trough blood concentrations, increased age, and concomitant therapy with other nephrotoxic drugs.41 Cyclosporine and tacrolimus are extensively metabolized by... 

ARF is a potentially life-threatening condition that can lead to significant morbidity and mortality. Supportive therapy, prompt correction of hypo- or hypervolemia, treatment of underlying conditions, and avoidance of nephrotoxic drugs is essential. 

Nephrotoxicity IDV potentially TDF Onset IDV—months after therapy TDF—weeks to months after therapy Symptoms IDV—asymptomatic rarely develop end-stage renal disease TDF—asymptomatic to symptoms of nephrogenic diabetes insipidus, Fanconi syndrome 1. History of renal disease 2. Concomitant use of nephrotoxic drugs Avoid use of other nephrotoxic drugs adequate hydration if on IDV monitor creatinine, urinalysis, serum potassium and phosphorus in patients at risk D/C offending agent, generally reversible supportive care electrolyte replacement as indicated... 

The answer is d, (Hardman, p 1200. Katzung, p 830.) Nephrotoxicity and symptomatic hypocalcemia are major toxicities associated with foscar-net Underlying renal disease, concomitant use of nephrotoxic drugs, dehydration, and rapid infusion of high doses increase the risk. 

In patients who cannot tolerate voriconazole, amphotericin B can be used. Full doses (1 to 1.5 mg/kg/day) are generally recommended, with response measured by defervescence and radiographic clearing. The lipid-based formulations may be preferred as initial therapy in patients with marginal renal function or in patients receiving other nephrotoxic drugs. The optimal duration of treatment is unknown. 

Medications Avoid concurrent use of potentially nephrotoxic drugs (e.g., nonsteroidal antiinflammatory drugs, aminoglycosides) A-2... 

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. 

Hypercalcemia Carefully monitor standard hypercalcemia-related metabolic parameters, such as serum levels of calcium, phosphate, and magnesium, as well as serum creatinine. Do not use loop diuretics until the patient is adequately rehydrated use with caution in combination with zoledronic acid in order to avoid hypocalcemia. Use zoledronic acid with caution with other nephrotoxic drugs. Concomitant use with estrogen/hormone replacement therapy (alendronate) Two clinical studies have shown that the degree of suppression of bone turnover (as assessed by mineralizing surface) was significantly greater with the combination than with either component alone. 

Nephrotoxicity The risk of toxicity may be appreciably increased by high serum concentrations or prolonged therapy. Factors that may increase the risk of nephrotoxicity include use in elderly and neonatal patients and concomitant use with other nephrotoxic drugs. 

Avoid concurrent or sequential use of other neurotoxic and/or nephrotoxic drugs with streptomycin sulfate, including neomycin, kanamycin, gentamicin, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, tobramycin, and cyclosporine. 

Drugs that may interact with foscarnet include nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine), pentamidine, and zidovudine. Foscarnet decreases serum levels of ionized calcium. Exercise particular caution when other drugs known to influence serum calcium levels are used concurrently. 

Drugs that may affect ganciclovir include imipenem-cilastatin, nephrotoxic drugs. 

Drugs that may affect valganciclovir include didanosine, imipenem-cilastin, nephrotoxic drugs, probenecid, trimethoprim, zalcitabine, and zidovudine. Drugs that may be affected by valganciclovir include cytotoxic drugs, didanosine, and zidovudine. 

Nephrotoxic drugs Care should be taken in using cyclosporine with nephrotoxic drugs. 

The most clinically significant adverse effect of foscarnet is renal impairment. Nephrotoxicity is most likely to occur during the second week of induction therapy but may occur at any time during induction or maintenance therapy. Serum creatinine levels may be elevated in up to 33 to 50% of patients this effect is usually reversible upon drug discontinuation. Dehydration, previous renal impairment, and concurrent administration of other nephrotoxic drugs increase the risk of renal toxicity. Infusion of fluids along with foscarnet decreases the likelihood of renal impairment to about 12%. Dosage adjustment is required for patients with renal insufficiency. 

Contraindications Concurrent use of other ototoxic or nephrotoxic drugs, hypersensitivity to capreomycin... 

Nephrotoxicity, especially with concurrent/sequential use of other nephrotoxic drugs, renal impairment, concurrent/sequential use of muscle relaxants. 

However, the nephrotoxicity involves more than this accumulation, as other cephalosporins such as cephalexin, which is not nephrotoxic, also accumulate and reach similar concentrations, although these are not sustained. Cephaloglycin is another nephrotoxic drug of the same class this drug accumulates initially, but is also not sustained. So, clearly, other factors are also important. 

Nagai J, Takano M. Molecular aspects of renal handling of aminoglycosides and strategies for preventing the nephrotoxicity. Drug Metab Pharmacokinet. 2004 19 159-170. 

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