Toxicokinetics in Clinical Toxicology

Jaeger, Albert; Sauder, P; Kopferschmitt,; Dahlet, M.

doi:10.1080/17843286.1990.11718122

Cited by 12 publications

(2 citation statements)

References 7 publications

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“…After drug overdose, the pharmacokinetic characteristics of the drug may undergo clinically significant alterations which result in a prolonged, cyclic or unexpectedly severe course, rendering clinical management much more difficult (Jaeger et al 1990;Platt 1990). However, the clinician familiar with these toxicokinetic alterations may exploit them to provide effective therapeutic interventions for the intoxicated patient (table II).…”

Section: Clinical Implications Of Toxicokineticsmentioning

confidence: 98%

Pharmacokinetics of Drugs in Overdose

Sue

Shannon

1992

Clinical Pharmacokinetics

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The pharmacokinetics of drugs may be altered following an overdose. The degree of absorption depends on the physical characteristics of the drug; the rate of dissolution may delay or broaden peak serum concentrations. The pathophysiological effects of a drug may also limit or augment absorption. Altered distribution of drugs in overdose results from changes in the extent of protein binding and size of the volume of distribution. Saturation of hepatic enzyme systems in overdose is manifested by delayed metabolism or elimination of many drugs; renal elimination of unchanged drug may take on greater importance in this instance. Familiarity with the toxicokinetic profile of a given drug enables the physician to exploit these principles in order to limit toxicity. Delayed or prolonged absorption allows for late decontamination. Multiple doses of activated charcoal are effective in interrupting both entero-enteric and enterohepatic recirculation. Alkalinisation-induced ion trapping enhances renal elimination of unchanged drugs which normally undergo hepatic transformation. For several drugs, chronic overdose due to altered distribution is associated with a greater severity of toxic manifestations despite relatively low serum drug concentrations. Conversely, with some drugs, induction of metabolic pathways may lead to more rapid drug elimination in chronic overdose. Knowledge of the pharmacokinetic alterations which occur in drug overdose enables the physician to predict toxicity with greater accuracy and to institute optimum therapy in a timely manner.

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Section: Clinical Implications Of Toxicokineticsmentioning

confidence: 98%

Pharmacokinetics of Drugs in Overdose

Sue

Shannon

1992

Clinical Pharmacokinetics

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“…However, the toxicokinetic requirements for an efficient toxin removal do not differ between the two techniques: small volume of distribution (<1 liter per kg), low endogenous clearance (<4 ml/min/kg), and an extraction ratio exceeding endogenous elimination. 7 The phenomenon of rebound must be considered in the evaluation of removal of drugs. Depending on the volume of distribution of a particular drug, a large quantity may be protein bound or stored intracellularly, as in muscle or adipose tissue.…”

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confidence: 99%

Extracorporeal removal of toxins

Tyagi

Winchester

Feinfeld

2008

Kidney International

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Holubek et al. reviewed data on extracorporeal removal (ECR) of toxins from the Toxic Exposure Surveillance System (TESS) from 1985 to 2005. Hemodialysis use increased, but hemoperfusion nearly disappeared. Lithium, ethylene glycol, salicylate, and, increasingly, acetaminophen still often necessitate hemodialysis; ECR for theophylline has disappeared. TESS data do not separate continuous renal replacement therapy from hemodialysis, and not all poisonings were reported in this system. Nonetheless, these trends are useful to the nephrology community.

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