Poisoning diuresis

A variety of therapies for thallium poisoning have been suggested by neutralising thallium in the intestinal tract, hastening excretion after resorption, or decreasing absorption. Berlin-Blue (fertihexacyanate) and sodium iodide in a 1 wt % solution have been recommended. Forced diuresis hemoperfusion and hemodialysis in combination results in the elimination of up to 40% of the resorbed thaHous sulfate (39). 

A case report of acute arsine poisoning in which a 27-y-old man was exposed to arsine during chemical manufacturing was reported by Pinto (1976). The subject was exposed to arsine as a result of arsine production via a reaction between a galvanized bucket and an arsenic-containing sulfuric acid solution. The exposure (duration not specified) produced toxic effects characterized by abdominal cramping, thoracic discomfort, and hematuria. Over the next week, the patient s hematocrit declined from 42.5 to 27.1 and hemoglobin dropped from 14.1 to 9.5 g/dL even with medical intervention (blood transfusions and mannitol diuresis). Nine hours after exposure, blood arsenic was 159 g/dL and urinary arsenic was 1862 ug/L. 

Mannitol (OsmitroL others) [Osmotic Diuretic] Uses Cerebral edema, T lOP/ICP, renal impair, poisonings Action Osmotic diuretic Dose Test dose 0.2 g/kg/dose IV over 3-5 min if no diuresis w/in 2 h, D/C Oliguria 50-100 g IV over 90 min T lOP 0.5-2 g/kg IV over 30 min Cerebral edema 0.25-1.5 g/kg/dose IV >30 min Caution [C, ] w/ CHF or volume overload Contra Anuria, dehydration, HE, PE Disp Inj SE May exacerbate CHF, N/V/D Interactions t Effects OF cardiac glycosides X effects OF barbiturates, imipramine, Li, salicylates EMS Monitor ECG for hypo-/hyperkalemia (T wave changes) OD May cause dehydration, t urine frequency/amount hypotension and CV collapse symptomatic and supportive... 

Elimination of absorbed substances may be accomplished by administering multiple dose activated charcoal for poisons with entero-hepatic recirculation or by altering urine pH to promote excretion. Forced diuresis, if warranted, should only be done after carefully exercising precautions such as the provision of adequate hydration and maintaining electrolyte balance. 

Drugs and poisons can in principle be removed from the systemic circulation by forced osmotic diuresis. These are theoretical concepts used in the... 

In the management of refractory edema, the high ceiling diuretics may be used in conjunction with other types of diuretics. They are also useful for forced diuresis in hypnotic or other poisonings. 

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). 

Phenobarbitone Sodium Phenobarbitone sodium decomposes in aqueous solutions. Barbiturate poisoning may be treated with stomach wash and administration of activated charcoal. Monitoring respiratory, cardiovascular, and renal functions, hemodialysis, charcoal administration, forced diuresis, symptomatic and supportive therapy, and peritoneal dialysis may be performed. 

If urine flow increases, the time that a drug is exposed to the reabsorptive surface of the kidney is decreased. This principle forms the basis for the treatment of certain extreme cases of acute drug overdose. In these situations patients undergo forced diuresis with large volumes of fluid in order to accelerate drug clearance (e.g., meprobamate poisoning). 

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-... 

Osmotically acting diuretic agents. These are applied in the treatment of intoxication in order to increase the urine volume and accelerate elimination of the poison ( forced diuresis ). The classical example is mannitol. This sugar is quite similar to glucose in structure but does not get metabolized nor reabsorbed from the primary glomerular filtrate in the kidneys. 

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... 

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... 

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. 

Lassen, N. A. Treatment of severe acute barbiturate poisoning by forced diuresis and alkalinisation of the urine. The LancetII, 338 (1960). 

Numerous methods have been used to increase the rate of excretion of poisons from the body. Of these, only diuresis, multiple-dose activated charcoal, and hemodialysis are useful occasionally. These approaches should be considered only if the risks of the procedure are significantly outweighed by the expected benefits or if the recovery of... 

In humans, the symptoms of acetylcholine poisoning resemble on the one hand the syndrome of nicotine poisoning (muscle twitch, excitability, followed by muscular paralysis) and, on the other hand, the syndrome of muscarine poisoning (nausea, pain, exudation, increased diuresis, dyspnoea, pulmonary oedema). Owing to the effect on the central nervous system, the loss of sense of orientation, ataxy, tremor, derangement of consciousness and fainting occur simultaneously. 

Acute barbiturate toxicity is characterized by automatism, or a state of drug-induced confusion, in which patients lose track of how much medication they have taken and take more. Death results from respiratory failure. The treatment of poisoning consists of support respiration, prevention of hypotension, diuresis, hemodialysis and, in the event of phenobarbital poisoning, the administration of sodium bicarbonate. Tolerance does not develop to lethal doses. 

Aspirin poisoning leads to inappropriate vasodilation compounded by volume depletion and acidosis, which worsens vasodilation. Aggressive volume repletion with intravenous fluids should be instituted. The aim is to achieve large-volume diuresis to optimize salicylate elimination. If necessary, vasopressors (e.g., norepinephrine, phenylephrine) are added. 

There are no methods known to accelerate the active transport of poisons into urine, and enhancement of glomerular filtration is not a practical means to facilitate elimination of toxicants. However, passive reabsorption from the tubular lumen can be altered. Diuretics inhibit reabsorption by decreasing the concentration gradient of the drug from the lumen to the tubular cell and by increasing flow through the tubule. Furosemide is used most often, but osmotic diuretics also are employed ("see Chapter 28). Forced diuresis should be used with caution, especially in patients with renal, cardiac, or pulmonary complications. 

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