Impaired renal function

The dosage of flucytosine is 150—200 mg/kg orally in four portions every six hours. A 1% flucytosine solution has been developed for intravenous adrninistration. In some countries, a 10% ointment is also available. In patients with normal renal function, flucytosine is seldom toxic, but occasionally severe toxicity may be observed (leukopenia and thrombocytopenia). Plasma levels should be determined and the dose in patients with impaired renal function should be checked. Liver function tests (transaininases and alkaline phosphatase) should be performed regularly. In some patients with high flucytosine plasma levels, hepatic disorders have been observed (24). 

In vitro studies in human liver fractions indicated that azacitidine may be metabolized by the liver. Azacitidine and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. 

Renal—hematuria, cystitis, elevated blood urea nitrogen, polyuria, dysuria, oliguria, and acute renal failure in those with impaired renal function... 

Angina is a common problem in older adults When an older adult requires an antianginal drug, the dosage maybe reduced to compensate for impaired renal function or heart disease. Older patients are at increased risk for postural hypotension. Blood pressure and ability to ambulate should be monitored closely. 

Significant increases in serum urea nitrogen and serum creatinine levels (which may be indicative of impaired renal function) were observed in Pasteurella-infected rabbits exposed to 2,875 or 5,750 mg/kg/day of Fyrquel 220 for an intermediate duration (MacEwen and Vemot 1983). The results of the histological examination were not reported, and the renal effects of the infection were not discussed. 

The results also showed that the age-related increase in serum creatinine was earlier and faster and more linear among subjects in the highest quartile than among those in the lowest quartile. Based on the results, Kim et al. (1996a) concluded that low-level exposure to lead may impair renal function in middle-aged and older men however, the biological significance of a 0.08 mg/dL increase in serum creatinine is unknown. 

The filtration coefficient is determined by the surface area and permeability of the filtration barrier. An increase in the filtration coefficient leads to an increase in GFR if the filtration coefficient decreases, then GFR decreases. However, this factor does not play a role in the daily regulation of GFR because its value is relatively constant under normal physiological conditions. On the other hand, chronic, uncontrolled hypertension and diabetes mellitus lead to gradual thickening of the basement membrane and therefore to a decrease in the filtration coefficient and GFR, and impaired renal function. 

The potent antidiuretic hormone AVP orchestrates the regulation of free water absorption, body fluid osmolality, cell contraction, blood volume, and blood pressure through stimulation of three G-protein-coupled receptor subtypes Vi-vascular types a and b, V2-renal, and V3-pituitary. Increased AVP secretion is the trademark of several pathophysiological disorders, including heart failure, impaired renal function, liver cirrhosis, and SIADH. As a consequence, these patients experience excess water retention or inadequate free-water excretion, which results in the dilution of sodium concentrations, frequently manifesting as clinical hyponatremia (serum sodium concentration <135mmol/L). This electrolyte imbalance increases mortality rates by 60-fold. Selective antagonism of the AVP V2 receptor promotes water... 

BUN) levels This is of clinical importance in patients with impaired renal function. With the exception of cl oxycy cline, tetracyclines should not be used in patients that are anuric. Doxycycline is excreted by the G1 tract under these conditions, and it will not accumulate in the serum of patients with renal insufficiency... 

Allopurinol is the antihyperuricemic drug of choice in patients with a history of urinary stones or impaired renal function, in patients who have lymphoproliferative or myeloproliferative disorders and need pretreatment with a xanthine oxidase inhibitor before initiation of cytotoxic therapy to protect against acute uric acid nephropathy, and in patients with gout who are overproducers of uric acid. 

The major side effects associated with uricosuric therapy are GI irritation, rash and hypersensitivity, precipitation of acute gouty arthritis, and stone formation. These drugs are contraindicated in patients who are allergic to them and in patients with impaired renal function (CLcr <50 mL/min) or a history of renal calculi, and in patients who are overproducers of uric acid. 

Unlike thiazides, loop diuretics maintain their effectiveness in the presence of impaired renal function, although higher doses may be necessary. 

Potassium-sparing diuretics may cause hyperkalemia, especially in patients with chronic kidney disease or diabetes, and in patients receiving concurrent treatment with an ACE inhibitor, ARB, NSAID, or potassium supplement. Eplerenone has an increased risk for hyperkalemia and is contraindicated in patients with impaired renal function or type 2 diabetes with proteinuria. Spironolactone may cause gynecomastia in up to 10% of patients, but this effect occurs rarely with eplerenone. 

Bioavailability decreases with increasing doses. It is eliminated exclusively renally, and dosage adjustment is necessary in patients with impaired renal function. 

Renal elimination of unchanged drug accounts for 66% of drug clearance, and the dose should be adjusted for impaired renal function. The role of therapeutic drag monitoring is unknown. It has linear pharmacokinetics and is metabolized in blood by nonhepatic enzymatic hydrolysis. 

Metabolic acidosis is characterized by decreased pH and serum HC03 concentrations, which can result from adding organic acid to extracellular fluid (e.g., lactic acid, ketoacids), loss of HC03 stores (e.g., diarrhea), or accumulation of endogenous acids due to impaired renal function (e.g., phosphates, sulfates). 

There is little quantitative information regarding influence of impaired renal function on drug absorption and bioavailability. 

The ratio (Q) of the estimated elimination rate constant or total body clearance relative to normal renal function is used to determine the dose or dosing interval alterations needed (CLfaii is the clearance with impaired renal function). 

Hypercalcemic crisis and symptomatic hypercalcemia are medical emergencies requiring immediate treatment. Rehydration with normal saline followed by loop diuretics can be used in patients with normal to moderately impaired renal function. Initiate treatment with calcitonin in patients in whom saline hydration is contraindicated (Table 78-3). 

Lithium is used in the prophylaxis and treatment of mania and in the prophylaxis of bipolar disorders and recurrent depression. Lithium should be stopped 24 hours before major surgery but the normal dose can be continued for minor surgery, with careful monitoring of fluids and electrolytes. After major surgery, renal function is reduced and this may compromise clearance of lithium. Lithium is a drug with a narrow therapeutic index and it should be avoided if possible in patients with renal impairment. Renal function should be tested before initiating treatment. If lithium is given to patients with renal impairment, a reduced dose should be used and serum lithium concentrations should be monitored closely. 

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. 

Angiotensin-converting enzyme inhibitors should be used with caution in patients taking diuretics because of an enhanced hypotensive effect. Angiotensin-converting enzyme inhibitors should also be used with caution in patients with renal impairment. Renal function needs to be monitored in patients with renovascular disease. 

Liver damage can be avoided if the thiol group donor, N-acetylcysteine, is given intravenously within 6-8 h after ingestion of an excessive dose of acetaminophen. Whether chronic regular intake of acetaminophen leads to impaired renal function remains a matter of debate. 

Digoxin is excreted in the urine largely unchanged, and in patients on long-term therapy approximately 30% of the total body content of digoxin is excreted by this route each day (M5). The proportion is decreased in patients with impaired renal function (D8). Biliary and fecal... 

Correlation between the daily dose of digoxin and plasma digoxin levels in randomly selected patients (E8) is poor, but it is improved if only those with normal renal function are considered (C4, R4). The difference is consistent with the primary role played by the kidneys in the excretion of digoxin and the likelihood that many patients treated with digoxin are elderly and infirm and have impaired renal function (B6). 

R3. Rasmussen, K., Jervell, J., Stonstein, L., and Fjerdriim, K., Digitoxiu kinetics in patients with impaired renal function. Clin. Pharmacol. Ther. 13, 6-14 (1972). 

Elderly Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 g in 48 hours. Monitor serum magnesium in such patients. 

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