Acid diuresis, forced

If the drug taken in overdose is a base, for example, a benzodiazepine tranquilliser or an antihistamine, excretion should be favoured by acidification of the urine. Agents that may be used to achieve this include ammonium chloride, NH Cl- (an acidic salt by partial hydrolysis) and ascorbic acid (vitamin C). If the pH of the urine is artificially lowered, the technique is called forced acid diuresis. 

Forced diuresis by furosemide, mannitol etc. and altering the urinary pH- increasing the pH of urine favours ionisation of acidic drugs like salicylates, phenobarbital etc. whereas reducing the pH favours ionisation of basic drugs like pethidine, amphetamine etc. 

Enhanced renal excretion is usually achieved by fluid diuresis, in which excess fluid is administered to increase urine flow. Forced diuresis is generally reserved for cases of mild to moderate severity. In some cases, fluid diuresis is supplemented by ionized diuresis (discussed previously in Chapter 3). By the appropriate raising or lowering of urine pH, the degree of ionization of acidic and basic drugs, respectively, is increased and they can be trapped in the urine. 

The same strategy - artificial alkalization or acidification of the urine - is quite commonly employed in the clinical treatment of poisonings. However, if the poison (drug) is neither acidic nor basic, the only option is to increase the urine volume. In this case, the amount of the drug (assuming it to be membrane-permeant, as many are) eliminated will simply be proportional to the volume of urine produced. This strategy is called forced diuresis . Another, more effective but also more involved method for the accelerated elimination of hydrophobic drugs such as barbi-... 

When a dmg is in its unionised form it will more readily diffuse from the urine to the blood. In an acidic urine, acidic drugs will diffuse back into the blood from the urine. Acidic compounds such as nitrofurantoin are excreted faster when the urinary pH is alkaline. Amfetamine, imipramine and amitriptyline are excreted more rapidly in acidic urine. The control of urinary pH in studies of pharmacokinetics is thus vital. It is difficult, however, to find compounds to use by the oral route for deliberate adjustment of urinary pH. Sodium bicarbonate and ammonium chloride may be used but are unpalatable. Intravenous administration of acidifying salt solutions presents one approach, especially for the forced diuresis of basic dmgs in cases of poisoning. 

Teshima D et al Usefulness of forced diuresis for acute boric add poisoning in an aduit. J Clin Pharm Thar 2001 26(5) 387-390. [PM ID 11679030] (In this case report, 3.25 L of IV fluid and 100 mg of furosemide were given over 4 hours, and the measured urinary elimination of borale was reported to be equal to that reported with hemodialysis. The authors suggest that this procedure be considered in patients with massive boric acid ingestion.)... 

Aspirin is encountered frequently in the laboratory in overdose cases. It directly stimulates the respiratory centre in the brain causing hyperventilation and a resultant respiratory alkalosis. Later, a metabolic acidosis is superimposed on this and the acid-base picture becomes more complex. Potassium levels should therefore be monitored closely. Removal ofthedrugfrom the circulation is encouraged by forced alkaline diuresis. 

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