Kidney Pharmacology

Abstract

Critical illness and impaired renal function alters drug pharmacokinetics and pharmacodynamics, potentially changing drug efficacy and increasing the likelihood of unwanted effects. Drugs that are most affected are those that are mostly excreted through renal elimination (≥30 %) and those that contain active or toxic metabolites that are excreted through renal elimination. To evaluate the effect of kidney failure on the drug disposition, a comparison among different dosing guidelines must be carried out. A loading dose may be required when it is important to rapidly achieve target plasma drug concentrations. To adjust the maintenance dosage, the interval extension method or the decreasing doses method or both can be used. Extra caution is warranted when prescribing drugs with a narrow therapeutic index in children with renal dysfunction. The correct application of pharmacokinetic principles may be useful in handling drug therapy during continuous renal replacement therapy. Drug elimination in children receiving a renal replacement therapy is a composite of non-renal drug elimination, residual kidney function, and the added elimination provided by the extracorporeal therapy. The efficiency to eliminate drugs depends on the physiochemical characteristics of the drug and the mode and intensity of the dialysis procedure. Six possible approaches for drug dosing during continuous renal replacement therapy have been proposed on the basis of the available references. This chapter also introduces the most common diuretics used in children. Continuous infusion of a loop diuretic is more efficient than intermittent high doses and this method diminishes toxicity and resistance.