Impaired renal function

Progression of liver disease may result in hepatorenal syndrome. This is characterized by reduced glomerular filtration rate, hyponatremia with water intoxication, and almost complete sodium reabsorption. Since the main role of the kidney is excretion, the first dose of drugs used in renal failure is usually unchanged; again, it is subsequent doses that may need modification. One exception is suxamethonium which should be used with extreme caution in acute renal failure because of the risk of hyperkalemia. Other effects of renal disease may also change drug effects. These may include the following:

1. disturbances of acid-base balance affecting drug activity and patient sensitivity;

2. altered fluid balance affecting drug distribution;

3. altering molecular states of metabolites (morphine-6-glucuronide becomes lipophilic);

4. uremia displacing drugs from binding sites on plasma proteins, such as albumin globulins and lipoproteins.

Renal function can be assessed in many ways, and the estimates of the doses of drugs required based on the results. However, these methods are not without pitfalls and so clinical monitoring remains important. Measurement of serum urea is affected by both renal and hepatic function. Similarly, creatinine levels vary with age and muscle bulk. Creatinine clearance may give a good assessment of glomerular filtration rate, allowing prediction of the secretion of some drugs such as the aminoglycosides. However, other drugs, such as the penicillins, are secreted by tubular mechanisms. Their excretion may be preserved until the creatinine clearance is very low.

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