Chapter 58

A 62-year-old woman with a history of depression is found in her apartment in a lethargic state. An empty bottle of bupropion is on the bedside table. In the emergency department, she is unresponsive to verbal and painful stimuli. She has a brief generalized seizure, followed by a respiratory arrest. The emergency physician performs endotracheal intubation and administers a drug intravenously, followed by another substance via a nasogastric tube. The patient is admitted to the intensive care unit for continued supportive care and recovers the next morning. What drug might be used intravenously to prevent further seizures? What substance is commonly used to adsorb drugs still present in the gastrointestinal tract?

Over 1 million cases of acute poisoning occur in the USA each year, although only a small number are fatal. Most deaths are due to intentional suicidal overdose by an adolescent or adult. Childhood deaths due to accidental ingestion of a drug or toxic household product have been markedly reduced in the last 40 years as a result of safety packaging and effective poisoning prevention education.

Even with a serious exposure, poisoning is rarely fatal if the victim receives prompt medical attention and good supportive care. Careful management of respiratory failure, hypotension, seizures, and thermoregulatory disturbances has resulted in improved survival of patients who reach the hospital alive.

This chapter reviews the basic principles of poisoning, initial management, and specialized treatment of poisoning, including methods of increasing the elimination of drugs and toxins.

The term toxicokinetics denotes the absorption, distribution, excretion, and metabolism of toxins, toxic doses of therapeutic agents, and their metabolites. The term toxicodynamics is used to denote the injurious effects of these substances on body functions. Although many similarities exist between the pharmacokinetics and toxicokinetics of most substances, there are also important differences. The same caution applies to pharmacodynamics and toxicodynamics.

### Special Aspects of Toxicokinetics

#### Volume of Distribution

The volume of distribution (Vd) is defined as the apparent volume into which a substance is distributed in the body (see Chapter 3). A large Vd implies that the drug is not readily accessible to measures aimed at purifying the blood, such as hemodialysis. Examples of drugs with large volumes of distribution (> 5 L/kg) include antidepressants, antipsychotics, antimalarials, opioids, propranolol, and verapamil. Drugs with a relatively small Vd (< 1 L/kg) include salicylate, ethanol, phenobarbital, lithium, valproic acid, and phenytoin (see Table 3–1).

#### Clearance

Clearance is a measure of the volume of plasma that is cleared of drug per unit time (see Chapter 3). The total clearance for most drugs is the sum of clearances via excretion by the kidneys and metabolism by the liver. In planning a detoxification strategy, it is important to know the contribution of each organ to total clearance. For example, if a drug is 95% cleared ...

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