Renal function dose-related toxicity

A related issue is the patient s ability to metabolize and eliminate drugs adequately. For example, lithium is excreted entirely by the kidneys, and if a patient suffers from significantly impaired renal function, high, potentially toxic levels could develop on standard doses. Although the dose could be adjusted to compensate for the decrease in drug clearance, it might be more appropriate to choose another mood stabilizer such as valproate or carbamazepine, because they are primarily metabolized through the liver. 

Dose-Related Toxicity Often Occurs When Impaired Renal Function is Unrecognized... 

It is incumbent on health professionals to avoid toxic drugs whenever possible. Antibiotics associated with CNS toxicities, usually when not dose-adjusted for renal function, include penicillins, cephalosporins, quinolones, and imipenem. Hematologic toxicities generally are manifested with prolonged use of nafcillin (neutropenia), piperacillin (platelet dysfunction), cefotetan (hypoprothrombinemia), chloramphenicol (bone marrow suppression, both idiosyncratic and dose-related toxicity), and trimethoprim (megaloblastic anemia). Reversible nephrotoxicity classically is associated with aminoglycosides... 

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. 

PLATINUM COMPOUNDS AMINOGLYCOSIDES, CAPREOMYCIN, COLISTIN, STREPTOMYCIN, VANCOMYCIN t risk of renal toxicity and renal failure and of ototoxicity. The ototoxicity tends to occur when cisplatin is administered early during the course of aminoglycoside therapy Additive renal toxicity Monitor renal function prior to and during therapy, and ensure an intake of at least 2 L of fluid daily. Monitor serum potassium and magnesium and correct any deficiencies. Most side-effects of aminoglycosides are dose-related, and it is necessary to t interval between doses and 1 dose of aminoglycoside if there is impaired renal function... 

Ocular effects, including optic neuritis, papilledema, and retrobulbar neuritis, are uncommon adverse effects of cisplatin-containing cancer chemotherapy. The risk of retinal toxicity is restricted to high-dose cisplatin therapy (for example 200 mg/m over 5 days) and can result in blurred vision and altered color perception, which can persist for several months. In contrast to cisplatin, carbo-platin is seldom involved in drug-induced visual disturbances. In two cases there was a relation between the administration of carboplatin (800-1200 mg/m ) and the occurrence of chnical cortical blindness (122). However, both patients had impaired renal function before the start of therapy with carboplatin. 

Acyclovir is the drug of choice for herpes simplex encephalitis. In patients with normal renal function, acyclovir is usually administered as 10 mg/kg intravenously every 8 hours for 2 to 3 weeks. Herpes virus resistance to acyclovir has been reported with increasing incidence, particularly from immunocompromised patients with prior or chronic exposures to acyclovir. The alternative treatment for acyclovir-resistant herpes simplex virus is foscarnet. The major toxicity of foscarnet is renal impairment, and doses must be individualized for renal function. The dose for patients with normal renal function is 40 mg/kg infused over 1 hour every 8 to 12 hours for 2 to 3 weeks. Ensuring adequate hydration is imperative. In addition, patients receiving foscarnet should be monitored for seizures related to alterations in plasma electrolyte levels. 

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