Urinary excretion

Drugs and poisons are excreted into the urine by glomerular filtration and active tubular secretion (see Chapter 28); they can be reabsorbed into the blood if they are in a lipid-soluble form that will penetrate the tubule or if there is an active mechanism for their transport.

There are no methods known to accelerate the active transport of poisons into urine, and enhancement of glomerular filtration is not a practical means to facilitate elimination of toxicants. However, passive reabsorption from the tubular lumen can be altered. Diuretics inhibit reabsorption by decreasing the concentration gradient of the drug from the lumen to the tubular cell and by increasing flow through the tubule. Furosemide is used most often, but osmotic diuretics also are employed (see Chapter 28). Forced diuresis should be used with caution, especially in patients with renal, cardiac, or pulmonary complications.

Nonionized compounds are reabsorbed far more rapidly than ionized polar molecules; therefore, a shift from the nonionized to the ionized species of the toxicant by alteration of the pH of the tubular fluid may hasten elimination (see Chapter 1). Acidic compounds such as phenobarbital and salicylates are cleared much more rapidly in alkaline than in acidic urine. Clinical toxicologists have issued a position paper on the use of urine alkalinization in treatment of acute poisoning. Urine alkalinization increases the urine elimination of chlorpropamide, 2,4-dichlorophenoxyacetic acid, diflunisal, fluoride, mecoprop, methotrexate, phenobarbital, and salicylate. However, urine alkalinization is recommended as first-line treatment only for patients with moderately severe salicylate poisoning who do not meet the criteria for hemodialysis. Urine alkalinization and high urine flow (approximately 600 mL/h) should also be considered in patients with severe 2,4-dichlorophenoxyacetic acid and mecoprop poisoning. Urine alkalinization is not recommended as first-line treatment in cases of phenobarbital poisoning because multiple-dose activated charcoal has been shown to be superior. Urine alkalinization is contraindicated in the case of compromised renal function or failure. Hypokalemia is the most common complication but can be corrected by giving potassium supplements. Intravenous sodium bicarbonate is used to alkalinize the urine.

Renal excretion of basic drugs such as amphetamine theoretically can be enhanced by acidification of the urine. Acidification can be accomplished by the administration of ammonium chloride or ascorbic acid. Urinary excretion of an acidic compound is particularly sensitive to changes in urinary pH if its p^a is within the range of 3.0-7.5; for bases, the corresponding pH range is 7.5-10.5.

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