Kidney unstable function

Saline laxatives containing magnesium, potassium, or phosphates should be used cautiously in persons with reduced kidney function. Monitor appropriate serum electrolyte concentrations in patients with unstable renal function evidenced by changing serum creatinine or creatinine clearance. 

Several equations have been developed to assess unstable kidney function. The Jelliffe equation (Table 22-1) estimates creatinine clearance by considering the change in serum creatinine over a specified time period.11 While it is more mathematically difficult to calculate, it better estimates creatinine clearance in patients with rapidly changing kidney function compared to an equation that only includes a single creatinine concentration. 

Biotin (8.49), a thiophene-lactam, occurs in yeast, liver, kidney, eggs, vegetables, and nuts. It functions as a cocarboxylase in a number of biochemical reactions. It binds COj in the form of an unstable carbamic acid on one of the lactam nitrogens. The carbamate carboxyl is then donated easily. 

FIGURE 16.11 Simplified scheme of procainamide metabolism. In individuals with normal kidney function, renal excretion of unchanged drug accounts for more than half the elimination of a procainamide dose, wdiereas acetylation by NAX2 accounts for only 24% and 17% of elimination in rapid and slowr acetylators, respectively. A small amount is of procainamide is metabolized to a hydroxylamine, wdiich is in equilibrium with a postulated chemically unstable and reactive nitroso compound that is capable of haptenic binding to histone proteins. 

In 1985, the self-inactivating property of thienamycin was overcome by the use of a terminal imino functionality which is less nudeophilic. Imipenem (Fig. 22.32) has a broad spectrum of activity and is administered by deep intramuscular injection or as an intravenous infusion. Renal dehydropeptidase 1, an enzyme present in the kidney, attacks and inactivates imipenem. This problem has been overcome by the co-administration of imipenem with cilastatin, a renal dehydropeptidase 1 inhibitor. Mer-openem (Fig. 22.32), an analogue introduced in 1996, is stable to the action of renal dehydropeptidase 1 and is also administered by deep intramuscular injection or as an intravenous infusion. Since the discovery of thienamycin in 1976, only parenteral analogues have heen successfully used clinically because the carhapenem structure is unstable in both the stomach and intestine. 

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