Forced diuresis

Forced diuresis (increased urine formation by diuretics and fluid) may enhance the excretion of certain drugs in urine and is used to treat drug overdose or poisoning of these drugs and hemorrhagic cystitis.

Most of the drugs are either weak acids or weak bases. When urine is made alkaline, elimination of acidic drugs in urine is increased. The converse applies for alkaline drugs.

This method is only of therapeutic significance where the drug is excreted in active form in urine and where the pH of urine can be adjusted to levels above or below the pK value of the active form of drug. For acidic drugs, urine pH should be above the pK value of that drug, and converse for the basic drugs. It is because the ionization of acidic drug is increased in alkaline urine and ionized drugs can not easily cross plasma membrane so cannot re-enter blood from kidney tubules. This method is ineffective for drugs which are strongly protein bound (eg tricyclics) or which have a large apparent volume of distribution (eg paracetamol, tricyclics).

Forced alkaline diuresis has been used to increase the excretion of acidic drugs like salicylates and phenobarbitone, while forced acid diuresis has been used to enhance the elimination of amphetamine, quinine, quinidine, and strychnine when poisoning by theses drugs has occurred.

For forced alkaline diuresis, a diuretic like frusemide is given intravenously and sodium bicarbonate is added to the infusion fluid to make blood and, in turn, urine alkaline. Potassium replacement becomes of utmost importance in this setting because potassium is usually also lost in urine and hypokalemia promotes bicarbonate ion retention and prevents bicarbonate excretion, thus interfering with alkalinization of the urine.

For forced acid diuresis, ascorbic acid (vitamin C) is used. Ammonium chloride has also been used for forced acid diuresis but it is a toxic compound. Usually however, this technique produces only slight increase in the renal clearance of the drug. Forced acid diuresis is rarely done in practice.

Forced alkaline diuresis is also recommended for rhabdomyolysis.