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.
Diuretics Most diuretic drugs are either
weak acids or
weak bases. When urine is made
alkaline, elimination of acidic drugs in the 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 cannot easily cross a
plasma membrane so cannot re-enter blood from
kidney tubules. This method is ineffective for drugs that are strongly protein bound (e.g.,
tricyclic antidepressants) or which have a large apparent
volume of distribution (e.g.
paracetamol, tricyclic antidepressants). For
forced alkaline diuresis,
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 lost in urine. If blood levels of potassium are depleted below normal levels, then
hypokalemia occurs, which promotes bicarbonate ion retention and prevents bicarbonate excretion, thus interfering with alkalinization of the urine. Forced alkaline diuresis has been used to increase the excretion of acidic drugs like
salicylates and
phenobarbitone, and is recommended for
rhabdomyolysis. For
forced acid diuresis,
ascorbic acid (
vitamin C) is sometimes used.
Ammonium chloride has also been used for forced acid diuresis, but it is a
toxic compound. Usually, however, this technique only produces a slight increase in the
renal clearance of the drug. Forced acid diuresis is rarely done in practice, but can be used to enhance the elimination of
cocaine,
amphetamine,
quinine,
quinidine,
atropine and
strychnine when poisoning by these drugs has occurred. ==Rebound diuresis==