Alkaline diuresis

Alkaline diuresis promotes elimination of weak acids (eg, barbiturates, salicylates) and is accomplished by the administration of IV sodium bicarbonate. 

The mechanisms by which cresols produce toxic effects are unknown, and the toxicokinetics of these compounds are not well understood. Procedures that might decrease the toxicity of cresols present in the bloodstream have not been identified. Although supporting data were not located, it is possible that elimination of cresols from the blood would be enhanced by alkaline diuresis, which would increase the proportion of cresols existing in the ionized state, thereby reducing reabsorption of cresols by the kidney tubules. 

Alkalinisation of urine (alkaline diuresis) is effective for salicylates and phenoxyacetate herbicides. 

Carbonic anhydrase inhibitors were the forerunners of modern diuretics. They were discovered when it was found that bacteriostatic sulfonamides caused an alkaline diuresis and hyperchloremic metabolic acidosis. With the development of newer agents, carbonic anhydrase inhibitors are now rarely used as diuretics, but they still have several specific applications that are discussed below. The prototypical carbonic anhydrase inhibitor is acetazolamide. 

Changes in plasma pH may also affect the distribution of toxic compounds by altering the proportion of the substance in the nonionized form, which will cause movement of the compound into or out of tissues. This may be of particular importance in the treatment of salicylate poisoning (see chap. 7) and barbiturate poisoning, for instance. Thus, the distribution of phenobarbital, a weak acid (pKa 7.2), shifts between the brain and other tissues and the plasma, with changes in plasma pH (Fig. 3.22). Consequently, the depth of anesthesia varies depending on the amount of phenobarbital in the brain. Alkalosis, which increases plasma pH, causes plasma phenobarbital to become more ionized, alters the equilibrium between plasma and brain, and causes phenobarbital to diffuse back into the plasma (Fig. 3.22). Acidosis will cause the opposite shift in distribution. Administration of bicarbonate is therefore used to treat overdoses of phenobarbital. This treatment will also cause alkaline diuresis and therefore facilitate excretion of phenobarbital into the urine (see below). 

Correction of the metabolic acidosis with intravenous bicarbonate. This will also increase urine flow and cause it to become more alkaline (alkaline diuresis) and therefore facilitate excretion of salicylic acid and its conjugated metabolites. As the blood pH rises, the ionization of the salicylic acid increases, causing a change in the equilibrium and distribution of salicylate, which diffuses out of the CNS (Fig. 7.59). 

Massive doses of sulfanilamide, as well as of other sulfonamides, caused alkaline diuresis as a side effect. From 1940 onwards, the mechanism of this side effect was further investigated it was confirmed that carbonic anhydrase inhibition was responsible for the diuresis. Presenting the whole story of the development of... 

The method does not distinguish between the common 5,5-substituted barbiturates. If the physician proposes to institute a forced alkaline diuresis or haemodialysis, it is essential to confirm the presence of a long-acting barbiturate (e.g, barbitone, phenobarbitone) by thin-layer chromatog-raphy or gas chromatography. 

The effect of varying urinary pH has been used in the treatment of drug overdose by applying forced alkaline diuresis as an adjunct to the treatment of salicylate or phenobarbitone poisoning. The success of the treatment is limited by the extent to which these drugs are distributed, and by the presence of... 

Two patients (aged 31 and 38 years) with cutaneous leishmaniasis given intramuscular pentamidine 600 mg twice in 48 hours developed rhabdomyolysis (12). They recovered with fluid replacement and alkaline diuresis. 

Alkaline diuresis will favor the excretion of weak acids (anions) such as salicylate or phenobarbital. Indeed, the more the drug is ionized, the more it is trapped in the tubular lumen and consequently is not reabsorbed, hence eliminated in the urine. This mechanism can play a role in the treatment of severe intoxications. The reverse being true for weak bases (cations) such as methadone. Acidification of the urine facilitates the reahsorption of weak acids and will re-... 

Chyka PA, Seger D, Krenzelok EP, et al. Position paper Single-dose activated charcoal. Clin Toxicol(Phila). 2005 43 61-87 Proudfoot AT, Krenzelok EP, Vale JA, et al. Position Paper on urine alkalinization.JTox/co/C/m Toxicol. 2004 42 1-26 Garrettson LK Geller RJ. Acid and alkaline diuresis. When are they of value in the treatment of poisoning Drug Serf 1990 5 220-232... 

Phenobarbitai 50-100 mg q. 8-12 hr Flepatic (renal) q. 8-12 hr q. 8-12 hr q. 12-16 hr Up to 50% unchanged drug excreted with urine with alkaline diuresis Dose after dialysis hale normal dose Dose for GFR 10-50 ml/min... 

There are no clinical procedures specific for dioxin intoxication, but clinical management for acute intoxication by dioxin-containing chemicals such as 2,4-D and 2,4,5-T may be applied. Basically, these procedures include decontamination of the gut and/ or skin and possibly alkaline diuresis for severe overdose situations. 

Dimereaprol, 2,3-dhnercaptosuccinic acid, n-penicillamine Charcoal heraoperfusion, multiple-dose oral activated charcoal, alkaline diuresis (phenobarbital only)... 

Treatment for salicylate intoxication is directed toward (1) decreasing further absorption, (2) increasing elimination, and (3) correcting add-base and electrolyte disturbances. Activated charcoal binds aspirin and prevents its absorption. Elimination of salicylate may be enhanced by alkaline diuresis and in severe cases by hemodialysis." Sodium bicarbonate may be given to alleviate metabolic acidosis. Indications for hemodialysis include serum salicylate >1000 mg/L, severe CNS depression, intractable metabolic acidosis, hepatic failure with coagulopathy, and renal failure. ... 

The principal site of excretion that is liable to drag interactions is in the kidney. The classic example is forced alkaline diuresis using intravenous sodium... 

Hefi ier and Sahn, 1981). In the case of salicylate-induced edema, drug levels can be lowered with forced alkaline diuresis and then pulmonary edema clears quickly. 

Salicylates Confusion, lethargy, coma, seizures, hyperventilation, hyperthermia, dehydration, hypotelemia. anion gap metabolic acidosis Correct acidosis and fluid and electrolyte imbalance. Provide alkaline diuresis or hemodialysis to aid elimination... 

D. Enhancement of Elimination Enhancement of elimination is possible for a number of toxins, including manipulation of urine pH to accelerate renal excretion of weak acids and bases. For example, alkaline diuresis is effective in toxicity due to fluoride, isoniazid, fluoroquinolones, phenobarbital, and salicylates. Urinary acidiflcation may be useful in toxicity due to weak bases, including amphetamines, nicotine, and phencyclidine, but care must be taken to avoid acidosis and renal failure in rhabdomyolysis. Hemodialysis or hemoperfusion enhances the elimination of many toxic compounds, including acetaminophen, ethylene glycol, formaldehyde, lithium, methanol, procainamide, quinidine, salicylates, and theophylline. Cathartics such as sorbitol (70%) may decrease absorption and hasten removal of toxins from the gastrointestinal tract. 

Treat salicylate intoxication (see p 331) with alkaline diuresis and hemodialysis. 

D. Enhanced elimination. There is no proven role for these procedures, although alkalinization of the urine may promote excretion of 2,4-D. (As with other weak acids, alkalinization would be expected to promote ionization of the phenoxy acid and decrease reabsorption from the renal tubules.) Hemodialysis has been recommended based on limited clinical data showing clearances similar to alkaline diuresis. Plasmapheresis was reported effective in a pediatric case report involving polyneuropathy associated with 2,4-D ingestion. 

Treat massive hemolysis with blood transfusions if needed, and prevent hemoglobin deposition in the kidney tubules by alkaline diuresis (as for rhabdomyolysis see p 27). 

Another patient with HGPRTase deficiency and minimal neurological signs presented with intractable gout at the age of 35 years and developed an episode of acute renal failure when his fluid intake was reduced below 3 litres/2U hours. This was attributed to the formation of uric acid crystals within his renal tubules so that an intense alkaline diuresis was instituted, resulting in a urine volume which, over one 2k hour period, exceeded 15 litres. This succeeded, however, in completely reversing his acute renal insufficiency and, when a regular urine volume of 5 litres/day was maintained, his renal function returned to normal. His usual 2k hour urinary urate excretion exceeded 2.5 g. Thus, an acute deterioration of renal function may occur in urate overproduction, which may be completely reversed by an intense diuresis (Observation k). 

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. 

Push fluids. Severe toxicity needs IV hydration + forced pressure alkaline diuresis or... 

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