The Ionization of Acidic Drug is Increased in Alkaline Urine and Ionized Drugs Cannot Easily Cross a Plasma Membrane
We are pleasure to introduce our Journal of Kidney Treatment and Diagnosis covers several clinical areas of renal medicine, such as dialysis, transplantation, diabetes, anaemia, pharmacy nutrition and clinical aspects of kidney care.
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, and strychnine when poisoning by these drugs has occurred.
With Regards,
John Robert
Managing Editor
Journal of Kidney Treatment and Diagnosis