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INTRODUCTION

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Toxic substances include therapeutic agents as well as agricultural and industrial chemicals that have no medical applications. Most chemicals are capable of causing toxic effects when given in excessive dosage; even for therapeutic drugs, the difference between a therapeutic action and a toxic one is most often a matter of dose. Many toxic effects of therapeutic agents have been discussed in previous chapters. Common toxic syndromes associated with major drug groups are summarized in this chapter. This chapter also reviews the principles of management of the poisoned patient.

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TOXICOKINETICS, TOXICODYNAMICS, & CAUSE OF DEATH

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A. Toxicokinetics
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This term denotes the disposition of poisons in the body (ie, their pharmacokinetics). Knowledge of a toxin’s absorption, distribution, and elimination permits assessment of the value of procedures designed to remove it from the skin or gastrointestinal tract. For example, drugs with large apparent volumes of distribution, such as antidepressants and antimalarials, are not amenable to dialysis procedures for drug removal. Drugs with low volumes of distribution, including lithium, phenytoin, and salicylates, are more readily removed by dialysis and diuresis procedures. In some cases, renal elimination of weak acids can be accelerated by urinary alkalinization, whereas renal elimination of some weak bases can be accelerated by urinary acidification. Acidification of urine can be achieved by NH4Cl, vitamin C, or cranberry juice, whereas sodium bicarbonate will alkalinize the urine. The clearance of drugs may be different at toxic concentrations than at therapeutic concentrations. For example, in overdoses of phenytoin or salicylates, the capacity of the liver to metabolize the drugs is usually exceeded, and elimination changes from first-order (constant half-life) to zero-order (variable half-life) kinetics.

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B. Toxicodynamics
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Toxicodynamics denotes the injurious effects of toxins (pharmacodynamic effects). Knowledge of toxicodynamics can be useful in the diagnosis and management of poisoning. For example, hypertension and tachycardia are typically seen in overdoses with amphetamines, cocaine, and antimuscarinic drugs. Hypotension with bradycardia occurs with overdoses of calcium channel blockers, β blockers, and sedative-hypnotics. Hypotension with tachycardia occurs with tricyclic antidepressants, phenothiazines, and theophylline. Hyperthermia is most frequently a result of overdose of drugs with antimuscarinic actions, the salicylates, or sympathomimetics. Hypothermia is more likely to occur with toxic doses of ethanol and other central nervous system (CNS) depressants. Increased respiratory rate is often a feature of overdose with carbon monoxide, salicylates, and other drugs that cause metabolic acidosis or cellular asphyxia. Overdoses of agents that depress the heart are likely to affect the functions of all organ systems that are critically dependent on blood flow, including the brain, liver, and kidney.

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C. Cause of Death in Intoxicated Patients
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The most common causes of death from drug overdose reflect the drug groups most often selected for abuse or for suicide. Sedative-hypnotics and opioids cause respiratory depression, coma, aspiration of gastric contents, and other respiratory malfunctions. ...

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