Renal dysfunction drug therapy

H Risk factors for ototoxicity include preexisting renal dysfunction, prolonged therapy, and concomitant receipt of other ototoxic drugs such as f urosemide. Because KC is only 45 years old, age is not a risk factor. Beta-lactam antibiotics and ACE inhibitors are not typically ototoxic and would not contribute to KC s otoxoticity. 

Monitoring Before initiation of therapy and at least annually thereafter, assess renal function. In patients at risk of renal dysfunction, assess renal function more frequently and discontinue the drug if renal impairment is present. 

Nitrofurantoin is administered orally and is rapidly and almost completely absorbed from the small intestine only low levels of activity are achieved in serum because the drug is rapidly metabolized. Relatively high protein binding (about 70%) also affects serum levels, reducing potential for systemic toxicity and alteration of intestinal flora. Relative tissue penetration is much lower than other antimicrobials for UTIs, and therefore, nitrofurantoin is not indicated in the therapy of infections such as pyelonephritis and renal cortical or perinephric abscesses. Nitrofurantoin is rapidly excreted by glomerular filtration and tubular secretion to yield effective urinary levels. In moderate to severe renal dysfunction, toxic blood levels may occur while urinary levels may be inadequate. The drug is inactivated in the liver. 

Compared with previously available therapy, the adverse effects associated with cyclosporine are much less severe but still worthy of concern. Nephrotoxicity, which can occur in up to 75% of patients, ranges from severe tubular necrosis to chronic interstitial nephropathy. This effect is generally reversible with dosage reduction. Vasoconstriction appears to be an important aspect of cyclosporine-induced nephrotoxicity. Hypertension occurs in 25% of the patients and more frequently in patients with some degree of renal dysfunction the concomitant use of antihypertensive drugs may prove useful. Hyperglycemia, hyperlipidemia, transient liver dysfunction, and unwanted hair growth are also observed. 

Gastrointestinal complaints (eg, nausea, diarrhea, vomiting, flatulence) are the most common adverse effects but rarely require discontinuation of therapy. Other potential adverse effects include headache and asthenia. Tenofbvir-associated proximal renal tubulopathy causes excessive renal phosphate and calcium losses and 1-hydroxylation defects of vitamin D, and preclinical studies in several animal species have demonstrated bone toxicity (eg, osteomalacia). Monitoring of bone mineral density should be considered with long-term use in those with risk factors for or with known osteoporosis, as well as in children. Reduction of renal function over time, as well as cases of acute renal failure and Fanconi s syndrome, have been reported in patients receiving tenofovir alone or in combination with emtricitabine. For this reason, tenofovir should be used with caution in patients at risk for renal dysfunction. Tenofovir may compete with other drugs that are actively secreted by the kidneys, such as cidofovir, acyclovir, and ganciclovir. 

Serum drug concentrations should be monitored for drugs with narrow therapeutic indices and ehminated largely by the kidney (e.g., aminoglycosides and vancomycin) to optimize therapy in pediatric patients with renal dysfunction. For drugs with wide therapeutic ranges (e.g., penicillins and cephalosporins), dosage adjustment may be necessary only in moderate to severe renal failure. 

Functional renal insufficiency is manifested as increases in serum creatinine and blood urea nitrogen. As cardiac output and renal blood flow decline, renal perfusion is maintained by the vasoconstrictor effect of angiotensin II on the efferent arteriole. Patients most dependent on this system for maintenance of renal perfusion (and therefore most likely to develop functional renal insufficiency with ACE inhibitors) are those with severe heart failure, hypotension, hyponatremia, volume depletion, and concomitant use of NSAIDs. - Sodium depletion (usually secondary to diuretic therapy) is the most important factor in the development of functional renal insufficiency with ACE inhibitor therapy. Renal insufficiency therefore can be minimized in many cases by reduction in diuretic dosage or liberalization of sodium intake. In some patients, the serum creatinine concentration will return to baseline levels without a reduction in ACE inhibitor dose. Since renal dysfunction with ACE inhibitors is secondary to alterations in renal hemodynamics, it is almost always reversible on discontinuation of the drug. ... 

Drug therapy may also cause renal insufficiency due to lower urinary tract obstruction. Ureteral obstruction can be caused by calculi or retroperitoneal fibrosis. Bladder dysfunction with urinary outflow obstruction can result, particularly in males with prostatic hypertrophy, from anticholinergic drugs including tricyclic antidepressants and disopyramide. Bladder outlet and ureteral obstruction may result from bladder fibrosis following hemorrhagic cystitis with cyclophosphamide or ifosfamide therapy. Concurrent treatment with mesna can prevent cystitis and this complication. 

In patients with vitamin D deficiency, oral vitamin D 50,000 units daily for 10 days or once weekly for 8 weeks, or 50,000 to 500,000 units intramuscularly is recommended. Serum calcium and 25(OH) vitamin D should be monitored periodically. Once replete, daily intakes of 600 to 1000 units are usually required. In the community or nursing home, vitamin D 100,000 units once per quarter is reasonable. In patients with vitamin D malabsorption (e.g., gluten-sensitive celiac sprue), 25(OH) vitamin D (calcidiol) administration is needed. In patients with severe hepatic or renal disease, calcitriol therapy may be required. This drug requires careful titration and serum calcium and creatinine monitoring because of its hypercalcemic potential and the limited calciuric ability of the dysfunctional kidney. 

Studies on the pathogenesis of aminoglycosides are largely carried out in otherwise normal animals while clinically these drugs are administered to patients with serious infections and associated co-morbidities. Based on clinical observations, there appear to be a variety of factors that predispose to the development of renal dysfunction with aminoglycoside therapy [8] (Table 1). 

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