Basic and Clinical Pharmacology, 13th Ed.

Management of the Poisoned Patient

Kent R. Olson, MD


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.


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 V 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 V (< 1 L/kg) include salicylate, ethanol, phenobarbital, lithium, valproic acid, and phenytoin (see Table 3–1).


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 by liver metabolism and only 5% cleared by renal excretion, even a dramatic increase in urinary concentration of the drug will have little effect on overall elimination.

Overdosage of a drug can alter the usual pharmacokinetic processes, and this must be considered when applying kinetics to poisoned patients. For example, dissolution of tablets or gastric emptying time may be slowed so that absorption and peak toxic effects are delayed. Drugs may injure the epithelial barrier of the gastrointestinal tract and thereby increase absorption. If the capacity of the liver to metabolize a drug is exceeded, the first-pass effect will be reduced and more drug will be delivered to the circulation. With a dramatic increase in the concentration of drug in the blood, protein-binding capacity may be exceeded, resulting in an increased fraction of free drug and greater toxic effect. At normal dosage, most drugs are eliminated at a rate proportional to the plasma concentration (first-order kinetics). If the plasma concentration is very high and normal metabolism is saturated, the rate of elimination may become fixed (zero-order kinetics). This change in kinetics may markedly prolong the apparent serum half-life and increase toxicity.


The general dose-response principles described in Chapter 2 are relevant when estimating the potential severity of an intoxication. When considering quantal dose-response data, both the therapeutic index and the overlap of therapeutic and toxic response curves must be considered. For instance, two drugs may have the same therapeutic index but unequal safe dosing ranges if the slopes of their dose-response curves are not the same. For some drugs, eg, sedative-hypnotics, the major toxic effect is a direct extension of the therapeutic action, as shown by their graded dose-response curve (see Figure 22–1). In the case of a drug with a linear dose-response curve (drug A), lethal effects may occur at 10 times the normal therapeutic dose. In contrast, a drug with a curve that reaches a plateau (drug B) may not be lethal at 100 times the normal dose.

For many drugs, at least part of the toxic effect may be different from the therapeutic action. For example, intoxication with drugs that have atropine-like effects (eg, tricyclic antidepressants) reduces sweating, making it more difficult to dissipate heat. In tricyclic antidepressant intoxication, there may also be increased muscular activity or seizures; the body’s production of heat is thus enhanced, and lethal hyperpyrexia may result. Overdoses of drugs that depress the cardiovascular system, eg, β blockers or calcium channel blockers, can profoundly alter not only cardiac function but all functions that are dependent on blood flow. These include renal and hepatic elimination of the toxin and that of any other drugs that may be given.



An understanding of common mechanisms of death due to poisoning can help prepare the care-giver to treat patients effectively. Many toxins depress the central nervous system (CNS), resulting in obtundation or coma. Comatose patients frequently lose their airway protective reflexes and their respiratory drive. Thus, they may die as a result of airway obstruction by the flaccid tongue, aspiration of gastric contents into the tracheobronchial tree, or respiratory arrest. These are the most common causes of death due to overdoses of narcotics and sedative-hypnotic drugs (eg, barbiturates and alcohol).

Cardiovascular toxicity is also frequently encountered in poisoning. Hypotension may be due to depression of cardiac contractility; hypovolemia resulting from vomiting, diarrhea, or fluid sequestration; peripheral vascular collapse due to blockade of α-adrenoceptor-mediated vascular tone; or cardiac arrhythmias. Hypothermia or hyperthermia due to exposure as well as the temperature-dysregulating effects of many drugs can also produce hypotension. Lethal arrhythmias such as ventricular tachycardia and fibrillation can occur with overdoses of many cardioactive drugs such as ephedrine, amphetamines, cocaine, digitalis, and theophylline; and drugs not usually considered cardioactive, such as tricyclic antidepressants, antihistamines, and some opioid analogs.

Cellular hypoxia may occur in spite of adequate ventilation and oxygen administration when poisoning is due to cyanide, hydrogen sulfide, carbon monoxide, and other poisons that interfere with transport or utilization of oxygen. Such patients may not be cyanotic, but cellular hypoxia is evident by the development of tachycardia, hypotension, severe lactic acidosis, and signs of ischemia on the electrocardiogram.

Seizures, muscular hyperactivity, and rigidity may result in death. Seizures may cause pulmonary aspiration, hypoxia, and brain damage. Hyperthermia may result from sustained muscular hyperactivity and can lead to muscle breakdown and myoglobinuria, renal failure, lactic acidosis, and hyperkalemia. Drugs and poisons that often cause seizures include antidepressants, isoniazid (INH), diphenhydramine, cocaine, and amphetamines.

Other organ system damage may occur after poisoning and is sometimes delayed in onset. Paraquat attacks lung tissue, resulting in pulmonary fibrosis, beginning several days after ingestion. Massive hepatic necrosis due to poisoning by acetaminophen or certain mushrooms results in hepatic encephalopathy and death 48–72 hours or longer after ingestion.

Finally, some patients may die before hospitalization because the behavioral effects of the ingested drug may result in traumatic injury. Intoxication with alcohol and other sedative-hypnotic drugs is a common contributing factor to motor vehicle accidents. Patients under the influence of hallucinogens such as phencyclidine (PCP) or lysergic acid diethylamide (LSD) may suffer trauma when they become combative or fall from a height.


The initial management of a patient with coma, seizures, or otherwise altered mental status should follow the same approach regardless of the poison involved: supportive measures are the basics (“ABCDs”) of poisoning treatment.

First, the airway should be cleared of vomitus or any other obstruction and an oral airway or endotracheal tube inserted if needed. For many patients, simple positioning in the lateral, leftside-down position is sufficient to move the flaccid tongue out of the airway. Breathing should be assessed by observation and pulse oximetry and, if in doubt, by measuring arterial blood gases. Patients with respiratory insufficiency should be intubated and mechanically ventilated. The circulation should be assessed by continuous monitoring of pulse rate, blood pressure, urinary output, and evaluation of peripheral perfusion. An intravenous line should be placed and blood drawn for serum glucose and other routine determinations.

At this point, every patient with altered mental status should receive a challenge with concentrated dextrose, unless a rapid bedside blood glucose test demonstrates that the patient is not hypoglycemic. Adults are given 25 g (50 mL of 50% dextrose solution) intravenously, children 0.5 g/kg (2 mL/kg of 25% dextrose). Hypoglycemic patients may appear to be intoxicated, and there is no rapid and reliable way to distinguish them from poisoned patients. Alcoholic or malnourished patients should also receive 100 mg of thiamine intramuscularly or in the intravenous infusion solution at this time to prevent Wernicke’s syndrome.

The opioid antagonist naloxone may be given in a dose of 0.4–2 mg intravenously. Naloxone reverses respiratory and CNS depression due to all varieties of opioid drugs (see Chapter 31). It is useful to remember that these drugs cause death primarily by respiratory depression; therefore, if airway and breathing assistance have already been instituted, naloxone may not be necessary. Larger doses of naloxone may be needed for patients with overdose involving propoxyphene, codeine, and some other opioids. The benzodiazepine antagonist flumazenil (see Chapter 22) may be of value in patients with suspected benzodiazepine overdose, but it should not be used if there is a history of tricyclic antidepressant overdose or a seizure disorder, as it can induce convulsions in such patients.

History & Physical Examination

Once the essential initial ABCD interventions have been instituted, one can begin a more detailed evaluation to make a specific diagnosis. This includes gathering any available history and performing a toxicologically oriented physical examination. Other causes of coma or seizures such as head trauma, meningitis, or metabolic abnormalities should be sought and treated. Some common intoxications are described under Common Toxic Syndromes.

A. History

Oral statements about the amount and even the type of drug ingested in toxic emergencies may be unreliable. Even so, family members, police, and fire department or paramedical personnel should be asked to describe the environment in which the toxic emergency occurred and should bring to the emergency department any syringes, empty bottles, household products, or over-the-counter medications in the immediate vicinity of the possibly poisoned patient.

B. Physical Examination

A brief examination should be performed, emphasizing those areas most likely to give clues to the toxicologic diagnosis. These include vital signs, eyes and mouth, skin, abdomen, and nervous system.

1. Vital signs—Careful evaluation of vital signs (blood pressure, pulse, respirations, and temperature) is essential in all toxicologic emergencies. Hypertension and tachycardia are typical with amphetamines, cocaine, and antimuscarinic (anticholinergic) drugs. Hypotension and bradycardia are characteristic features of overdose with calcium channel blockers, β blockers, clonidine, and sedative hypnotics. Hypotension with tachycardia is common with tricyclic antidepressants, trazodone, quetiapine, vasodilators, and β agonists. Rapid respirations are typical of salicylates, carbon monoxide, and other toxins that produce metabolic acidosis or cellular asphyxia. Hyperthermia may be associated with sympathomimetics, anticholinergics, salicylates, and drugs producing seizures or muscular rigidity. Hypothermia can be caused by any CNS-depressant drug, especially when accompanied by exposure to a cold environment.

2. Eyes—The eyes are a valuable source of toxicologic information. Constriction of the pupils (miosis) is typical of opioids, clonidine, phenothiazines, and cholinesterase inhibitors (eg, organophosphate insecticides), and deep coma due to sedative drugs. Dilation of the pupils (mydriasis) is common with amphetamines, cocaine, LSD, and atropine and other anticholinergic drugs. Horizontal nystagmus is characteristic of intoxication with phenytoin, alcohol, barbiturates, and other sedative drugs. The presence of both vertical and horizontal nystagmus is strongly suggestive of phencyclidine poisoning. Ptosis and ophthalmoplegia are characteristic features of botulism.

3. Mouth—The mouth may show signs of burns due to corrosive substances, or soot from smoke inhalation. Typical odors of alcohol, hydrocarbon solvents, or ammonia may be noted. Poisoning due to cyanide can be recognized by some examiners as an odor like bitter almonds.

4. Skin—The skin often appears flushed, hot, and dry in poisoning with atropine and other antimuscarinics. Excessive sweating occurs with organophosphates, nicotine, and sympathomimetic drugs. Cyanosis may be caused by hypoxemia or by methemoglobinemia. Icterus may suggest hepatic necrosis due to acetaminophen or Amanita phalloides mushroom poisoning.

5. Abdomen—Abdominal examination may reveal ileus, which is typical of poisoning with antimuscarinic, opioid, and sedative drugs. Hyperactive bowel sounds, abdominal cramping, and diarrhea are common in poisoning with organophosphates, iron, arsenic, theophylline, A phalloides, and A muscaria.

6. Nervous system—A careful neurologic examination is essential. Focal seizures or motor deficits suggest a structural lesion (eg, intracranial hemorrhage due to trauma) rather than toxic or metabolic encephalopathy. Nystagmus, dysarthria, and ataxia are typical of phenytoin, carbamazepine, alcohol, and other sedative intoxication. Twitching and muscular hyperactivity are common with atropine and other anticholinergic agents, and cocaine and other sympathomimetic drugs. Muscular rigidity can be caused by haloperidol and other antipsychotic agents, and by strychnine or by tetanus. Generalized hypertonicity of muscles and lower extremity clonus are typical of serotonin syndrome. Seizures are often caused by overdose with antidepressants (especially tricyclic antidepressants and bupropion [as in the case study]), cocaine, amphetamines, theophylline, isoniazid, and diphenhydramine. Flaccid coma with absent reflexes and even an isoelectric electroencephalogram may be seen with deep coma due to sedative-hypnotic or other CNS depressant intoxication and may be mistaken for brain death.

Laboratory & Imaging Procedures

A. Arterial Blood Gases

Hypoventilation results in an elevated PCO2 (hypercapnia) and a low PO2 (hypoxia). The PO2 may also be low in a patient with aspiration pneumonia or drug-induced pulmonary edema. Poor tissue oxygenation due to hypoxia, hypotension, or cyanide poisoning will result in metabolic acidosis. The PO2 measures only oxygen dissolved in the plasma and not total blood oxygen content or oxyhemoglobin saturation and may appear normal in patients with severe carbon monoxide poisoning. Pulse oximetry may also give falsely normal results in carbon monoxide intoxication.

B. Electrolytes

Sodium, potassium, chloride, and bicarbonate should be measured. The anion gap is then calculated by subtracting the measured anions from cations:

Anion gap = (Na+ + K+) – (HCO3 + Cl)

Normally, the sum of the cations exceeds the sum of the anions by no more than 12–16 mEq/L (or 8–12 mEq/L if the formula used for estimating the anion gap omits the potassium level). A larger than expected anion gap is caused by the presence of unmeasured anions (lactate, etc) accompanying metabolic acidosis. This may occur with numerous conditions, such as diabetic ketoacidosis, renal failure, or shock-induced lactic acidosis. Drugs that may induce an elevated anion gap metabolic acidosis (Table 58–1) include aspirin, metformin, methanol, ethylene glycol, isoniazid, and iron.

TABLE 58–1 Examples of drug-induced anion gap acidosis.


Alterations in the serum potassium level are hazardous because they can result in cardiac arrhythmias. Drugs that may cause hyperkalemia despite normal renal function include potassium itself, β blockers, digitalis glycosides, potassium-sparing diuretics, and fluoride. Drugs associated with hypokalemia include barium, β agonists, caffeine, theophylline, and thiazide and loop diuretics.

C. Renal Function Tests

Some toxins have direct nephrotoxic effects; in other cases, renal failure is due to shock or myoglobinuria. Blood urea nitrogen and creatinine levels should be measured and urinalysis performed. Elevated serum creatine kinase (CK) and myoglobin in the urine suggest muscle necrosis due to seizures or muscular rigidity. Oxalate crystals in large numbers in the urine suggest ethylene glycol poisoning.

D. Serum Osmolality

The calculated serum osmolality is dependent mainly on the serum sodium and glucose and the blood urea nitrogen and can be estimated from the following formula:


This calculated value is normally 280–290 mOsm/L. Ethanol and other alcohols may contribute significantly to the measured serum osmolality but, since they are not included in the calculation, cause an osmol gap:


Table 58–2 lists the concentration and expected contribution to the serum osmolality in ethanol, methanol, ethylene glycol, and isopropanol poisonings.

TABLE 58–2 Some substances that can cause an osmol gap.


E. Electrocardiogram

Widening of the QRS complex duration (to more than 100 milliseconds) is typical of tricyclic antidepressant and quinidine overdoses (Figure 58–1). The QTc interval may be prolonged (to more than 440 milliseconds) in many poisonings, including quinidine, antidepressants and antipsychotics, lithium, and arsenic (see also Variable atrioventricular (AV) block and a variety of atrial and ventricular arrhythmias are common with poisoning by digoxin and other cardiac glycosides. Hypoxemia due to carbon monoxide poisoning may result in ischemic changes on the electrocardiogram.


FIGURE 58–1 Changes in the electrocardiogram in tricyclic antidepressant overdosage. A: Slowed intraventricular conduction results in prolonged QRS interval (0.18 s; normal, 0.08 s). B and C:Supraventricular tachycardia with progressive widening of QRS complexes mimics ventricular tachycardia. (Reproduced, with permission, from Benowitz NL, Goldschlager N: Cardiac disturbances. In: Haddad LM, Shannon MW, Winchester JF [editors]. Clinical Management of Poisoning and Drug Overdose, 3rd ed. WB Saunders, 1998. © Elsevier.)

F. Imaging Findings

A plain film of the abdomen may be useful because some tablets, particularly iron and potassium, may be radiopaque. Chest radiographs may reveal aspiration pneumonia, hydrocarbon pneumonia, or pulmonary edema. When head trauma is suspected, a computed tomography (CT) scan is recommended.

Toxicology Screening Tests

It is a common misconception that a broad toxicology “screen” is the best way to diagnose and manage an acute poisoning. Unfortunately, comprehensive toxicology screening is time-consuming and expensive and results of tests may not be available for days. Moreover, many highly toxic drugs such as calcium channel blockers, β blockers, and isoniazid are not included in the screening process. The clinical examination of the patient and selected routine laboratory tests are usually sufficient to generate a tentative diagnosis and an appropriate treatment plan. Although screening tests may be helpful in confirming a suspected intoxication or for ruling out intoxication as a cause of apparent brain death, they should not delay needed treatment.

When a specific antidote or other treatment is under consideration, quantitative laboratory testing may be indicated. For example, determination of the acetaminophen level is useful in assessing the need for antidotal therapy with acetylcysteine. Serum levels of salicylate (aspirin), ethylene glycol, methanol, theophylline, carbamazepine, lithium, valproic acid, and other drugs and poisons may indicate the need for hemodialysis (Table 58–3).

TABLE 58–3 Hemodialysis in drug overdose and poisoning.1



Decontamination procedures should be undertaken simultaneously with initial stabilization, diagnostic assessment, and laboratory evaluation. Decontamination involves removing toxins from the skin or gastrointestinal tract.

A. Skin

Contaminated clothing should be completely removed and double-bagged to prevent illness in health care providers and for possible laboratory analysis. Wash contaminated skin with soap and water.

B. Gastrointestinal Tract

Controversy remains regarding the efficacy of gut emptying by emesis or gastric lavage, especially when treatment is initiated more than 1 hour after ingestion. For most ingestions, clinical toxicologists recommend simple administration of activated charcoal to bind ingested poisons in the gut before they can be absorbed (as in the case study). In unusual circumstances, induced emesis or gastric lavage may also be used.

1. Emesis—Emesis can be induced with ipecac syrup (never extract of ipecac), and this method was previously used to treat some childhood ingestions at home under telephone supervision of a physician or poison control center personnel. However, the risks involved with inappropriate use outweighed the unproven benefits, and this treatment is rarely used in the home or hospital. Ipecac should not be used if the suspected intoxicant is a corrosive agent, a petroleum distillate, or a rapid-acting convulsant. Previously popular methods of inducing emesis such as fingertip stimulation of the pharynx, salt water, and apomorphine are ineffective or dangerous and should not be used.

2. Gastric lavage—If the patient is awake or if the airway is protected by an endotracheal tube, gastric lavage may be performed using an orogastric or nasogastric tube—as large a tube as possible. Lavage solutions (usually 0.9% saline) should be at body temperature to prevent hypothermia.

3. Activated charcoal—Owing to its large surface area, activated charcoal can adsorb many drugs and poisons. It is most effective if given in a ratio of at least 10:1 of charcoal to estimated dose of toxin by weight. Charcoal does not bind iron, lithium, or potassium, and it binds alcohols and cyanide only poorly. It does not appear to be useful in poisoning due to corrosive mineral acids and alkali. Studies suggest that oral activated charcoal given alone may be just as effective as gut emptying (eg, ipecac-induced emesis or gastric lavage) followed by charcoal. Repeated doses of oral activated charcoal may enhance systemic elimination of some drugs (including carbamazepine, dapsone, and theophylline) by a mechanism referred to as “gut dialysis,” although the clinical benefit is unproved.

4. Cathartics—Administration of a cathartic (laxative) agent may hasten removal of toxins from the gastrointestinal tract and reduce absorption, although no controlled studies have been done. Whole bowel irrigation with a balanced polyethylene glycol-electrolyte solution (GoLYTELY, CoLyte) can enhance gut decontamination after ingestion of iron tablets, enteric-coated medicines, illicit drug-filled packets, and foreign bodies. The solution is administered orally at 1–2 L/h (500 mL/h in children) for several hours until the rectal effluent is clear.

Specific Antidotes

There is a popular misconception that there is an antidote for every poison. Actually, selective antidotes are available for only a few classes of toxins. The major antidotes and their characteristics are listed in Table 58–4.

TABLE 58–4 Examples of specific antidotes.


Methods of Enhancing Elimination of Toxins

After appropriate diagnostic and decontamination procedures and administration of antidotes, it is important to consider whether measures for enhancing elimination, such as hemodialysis or urinary alkalinization, can improve the clinical outcome. Table 58–3 lists intoxications for which dialysis may be beneficial.

A. Dialysis Procedures

1. Peritoneal dialysisAlthough it is a relatively simple and available technique, peritoneal dialysis is inefficient in removing most drugs.

2. HemodialysisHemodialysis is more efficient than peritoneal dialysis and has been well studied. It assists in correction of fluid and electrolyte imbalance and may also enhance removal of toxic metabolites (eg, formic acid in methanol poisoning; oxalic and glycolic acids in ethylene glycol poisoning). The efficiency of both peritoneal dialysis and hemodialysis is a function of the molecular weight, water solubility, protein binding, endogenous clearance, and distribution in the body of the specific toxin. Hemodialysis is especially useful in overdose cases in which the precipitating drug can be removed and fluid and electrolyte imbalances are present and can be corrected (eg, salicylate intoxication).

B. Forced Diuresis and Urinary pH Manipulation

Previously popular but of unproved value, forced diuresis may cause volume overload and electrolyte abnormalities and is not recommended. Renal elimination of a few toxins can be enhanced by alteration of urinary pH. For example, urinary alkalinization is useful in cases of salicylate overdose. Acidification may increase the urine concentration of drugs such as phencyclidine and amphetamines but is not advised because it may worsen renal complications from rhabdomyolysis, which often accompanies the intoxication.



Acetaminophen is one of the drugs commonly involved in suicide attempts and accidental poisonings, both as the sole agent and in combination with other drugs. Acute ingestion of more than 150–200 mg/kg (children) or 7 g total (adults) is considered potentially toxic. A highly toxic metabolite is produced in the liver (see Figure 4–5).

Initially, the patient is asymptomatic or has mild gastrointestinal upset (nausea, vomiting). After 24–36 hours, evidence of liver injury appears, with elevated aminotransferase levels and hypoprothrombinemia. In severe cases, fulminant liver failure occurs, leading to hepatic encephalopathy and death. Renal failure may also occur.

The severity of poisoning is estimated from a serum acetaminophen concentration measurement. If the level is greater than 150–200 mg/L approximately 4 hours after ingestion, the patient is at risk for liver injury. (Chronic alcoholics or patients taking drugs that enhance P450 production of toxic metabolites are at risk with lower levels.) The antidote acetylcysteine acts as a glutathione substitute, binding the toxic metabolite as it is produced. It is most effective when given early and should be started within 8–10 hours if possible. Liver transplantation may be required for patients with fulminant hepatic failure.


Stimulant drugs commonly abused in the USA include methamphetamine (“crank,” “crystal”), methylenedioxymethamphetamine (MDMA, “ecstasy”), and cocaine (“crack”) as well as pharmaceuticals such as pseudoephedrine (Sudafed) and ephedrine (as such and in the herbal agent Ma-huang) (see Chapter 32). Caffeine is often added to dietary supplements sold as “metabolic enhancers” or “fat-burners.” Newer synthetic analogs of amphetamines such as 3,4-methylenedioxypyrovalerone (MDPV) and various derivatives of methcathinone are becoming popular drugs of abuse, often sold on the street as “bath salts” with names like “Ivory Wave,” “Bounce,” “Bubbles,” “Mad Cow,” and “Meow Meow.”

At the doses usually used by stimulant abusers, euphoria and wakefulness are accompanied by a sense of power and well-being. At higher doses, restlessness, agitation, and acute psychosis may occur, accompanied by hypertension and tachycardia. Prolonged muscular hyperactivity or seizures may contribute to hyperthermia and rhabdomyolysis. Body temperatures as high as 42°C (107.6°F) have been recorded. Hyperthermia can cause brain damage, hypotension, coagulopathy, and renal failure.

Treatment for stimulant toxicity includes general supportive measures as outlined earlier. There is no specific antidote. Seizures and hyperthermia are the most dangerous manifestations and must be treated aggressively. Seizures are usually managed with intravenous benzodiazepines (eg, lorazepam). Temperature is reduced by removing clothing, spraying with tepid water, and encouraging evaporative cooling with fanning. For very high body temperatures (eg, > 40–41°C [104–105.8°F]), neuromuscular paralysis is used to abolish muscle activity quickly.


A large number of prescription and nonprescription drugs, as well as a variety of plants and mushrooms, can inhibit the effects of acetylcholine at muscarinic receptors. Some drugs used for other purposes (eg, antihistamines) also have anticholinergic effects, in addition to other potentially toxic actions. For example, antihistamines such as diphenhydramine can cause seizures; tricyclic antidepressants, which have anticholinergic, quinidine-like, and α-blocking effects, can cause severe cardiovascular toxicity.

The classic anticholinergic (technically, “antimuscarinic”) syndrome is remembered as “red as a beet” (skin flushed), “hot as a hare” (hyperthermia), “dry as a bone” (dry mucous membranes, no sweating), “blind as a bat” (blurred vision, cycloplegia), and “mad as a hatter” (confusion, delirium). Patients usually have sinus tachycardia, and the pupils are usually dilated (see Chapter 8). Agitated delirium or coma may be present. Muscle twitching is common, but seizures are unusual unless the patient has ingested an antihistamine or a tricyclic antidepressant. Urinary retention is common, especially in older men.

Treatment for anticholinergic syndrome is largely supportive. Agitated patients may require sedation with a benzodiazepine or an antipsychotic agent (eg, haloperidol). The specific antidote for peripheral and central anticholinergic syndrome is physostigmine, which has a prompt and dramatic effect and is especially useful for patients who are very agitated. Physostigmine is given in small intravenous doses (0.5–1 mg) with careful monitoring, because it can cause bradycardia and seizures if given too rapidly. Physostigmine should not be given to a patient with suspected tricyclic antidepressant overdose because it can aggravate cardiotoxicity, resulting in heart block or asystole. Catheterization may be needed to prevent excessive distention of the bladder.


Tricyclic antidepressants (eg, amitriptyline, desipramine, doxepin, many others; see Chapter 30) are among the most common prescription drugs involved in life-threatening drug overdose. Ingestion of more than 1 g of a tricyclic (or about 15–20 mg/kg) is considered potentially lethal.

Tricyclic antidepressants are competitive antagonists at muscarinic cholinergic receptors, and anticholinergic findings (tachycardia, dilated pupils, dry mouth) are common even at moderate doses. Some tricyclics are also strong α blockers, which can lead to vasodilation. Centrally mediated agitation and seizures may be followed by depression and hypotension. Most important is the fact that tricyclics have quinidine-like depressant effects on the cardiac sodium channel that cause slowed conduction with a wide QRS interval and depressed cardiac contractility. This cardiac toxicity may result in serious arrhythmias (Figure 58–1), including ventricular conduction block and ventricular tachycardia.

Treatment of tricyclic antidepressant overdose includes general supportive care as outlined earlier. Endotracheal intubation and assisted ventilation may be needed. Intravenous fluids are given for hypotension, and dopamine or norepinephrine is added if necessary. Many toxicologists recommend norepinephrine as the initial drug of choice for tricyclic-induced hypotension. The antidote for quinidine-like cardiac toxicity (manifested by a wide QRS complex) is sodium bicarbonate: a bolus of 50–100 mEq (or 1–2 mEq/kg) provides a rapid increase in extracellular sodium that helps overcome sodium channel blockade. Do not use physostigmine! Although physostigmine does effectively reverse anticholinergic symptoms, it can aggravate depression of cardiac conduction and cause seizures.

Monoamine oxidase inhibitors (eg, tranylcypromine, phenelzine) are older antidepressants that are occasionally used for resistant depression. They can cause severe hypertensive reactions when interacting foods or drugs are taken (see Chapters 9 and 30), and they can interact with the selective serotonin reuptake inhibitors (SSRIs).

Newer antidepressants (eg, fluoxetine, paroxetine, citalopram, venlafaxine) are mostly SSRIs and are generally safer than the tricyclic antidepressants and monoamine oxidase inhibitors, although they can cause seizures. Bupropion (not an SSRI) has caused seizures even in therapeutic doses. Some antidepressants have been associated with QT prolongation and torsades de pointes arrhythmia. SSRIs may interact with each other or especially with monoamine oxidase inhibitors to cause the serotonin syndrome, characterized by agitation, muscle hyperactivity, and hyperthermia (see Chapter 16).


Antipsychotic drugs include the older phenothiazines and butyrophenones, as well as newer atypical drugs. All of these can cause CNS depression, seizures, and hypotension. Some can cause QT prolongation. The potent dopamine D2 blockers are also associated with parkinsonian movement disorders (dystonic reactions) and in rare cases with the neuroleptic malignant syndrome, characterized by “lead-pipe” rigidity, hyperthermia, and autonomic instability (see Chapters 16 and 29).


Salicylate poisoning (see Chapter 36) is a much less common cause of childhood poisoning deaths since the introduction of child-resistant containers and the reduced use of children’s aspirin. It still accounts for numerous suicidal and accidental poisonings. Acute ingestion of more than 200 mg/kg is likely to produce intoxication. Poisoning can also result from chronic overmedication; this occurs most commonly in elderly patients using salicylates for chronic pain who become confused about their dosing. Poisoning causes uncoupling of oxidative phosphorylation and disruption of normal cellular metabolism.

The first sign of salicylate toxicity is often hyperventilation and respiratory alkalosis due to medullary stimulation. Metabolic acidosis follows, and an increased anion gap results from accumulation of lactate as well as excretion of bicarbonate by the kidney to compensate for respiratory alkalosis. Arterial blood gas testing often reveals a mixed respiratory alkalosis and metabolic acidosis. Body temperature may be elevated owing to uncoupling of oxidative phosphorylation. Severe hyperthermia may occur in serious cases. Vomiting and hyperpnea as well as hyperthermia contribute to fluid loss and dehydration. With very severe poisoning, profound metabolic acidosis, seizures, coma, pulmonary edema, and cardiovascular collapse may occur. Absorption of salicylate and signs of toxicity may be delayed after very large overdoses or ingestion of enteric coated tablets.

General supportive care is essential. After massive aspirin ingestions (eg, more than 100 tablets), aggressive gut decontamination is advisable, including gastric lavage, repeated doses of activated charcoal, and consideration of whole bowel irrigation. Intravenous fluids are used to replace fluid losses caused by tachypnea, vomiting, and fever. For moderate intoxications, intravenous sodium bicarbonate is given to alkalinize the urine and promote salicylate excretion by trapping the salicylate in its ionized, polar form. For severe poisoning (eg, patients with severe acidosis, coma, and serum salicylate level > 100 mg/dL), emergency hemodialysis is performed to remove the salicylate more quickly and restore acid-base balance and fluid status.


In overdose, β blockers inhibit both β1 and β2 adrenoceptors; selectivity, if any, is lost at high dosage. The most toxic β blocker is propranolol. As little as two to three times the therapeutic dose can cause serious toxicity. This may be because propranolol in high doses may cause sodium channel blocking effects similar to those seen with quinidine-like drugs, and it is lipophilic, allowing it to enter the CNS (see Chapter 10).

Bradycardia and hypotension are the most common manifestations of toxicity. Agents with partial agonist activity (eg, pindolol) can cause tachycardia and hypertension. Seizures and cardiac conduction block (wide QRS complex) may be seen with propranolol overdose.

General supportive care should be provided as outlined earlier. The usual measures used to raise the blood pressure and heart rate, such as intravenous fluids, β-agonist drugs, and atropine, are generally ineffective. Glucagon is a useful antidote that—like β agonists—acts on cardiac cells to raise intracellular cAMP but does so independent of β adrenoceptors. It can improve heart rate and blood pressure when given in high doses (5–20 mg intravenously).


Calcium antagonists can cause serious toxicity or death with relatively small overdoses. These channel blockers depress sinus node automaticity and slow AV node conduction (see Chapter 12). They also reduce cardiac output and blood pressure. Serious hypotension is mainly seen with nifedipine and related dihydropyridines, but in severe overdose all of the listed cardiovascular effects can occur with any of the calcium channel blockers.

Treatment requires general supportive care. Since most ingested calcium antagonists are in sustained-release form, it may be possible to expel them before they are completely absorbed; initiate whole bowel irrigation and oral activated charcoal as soon as possible, before calcium antagonist-induced ileus intervenes. Calcium, given intravenously in doses of 2–10 g, is a useful antidote for depressed cardiac contractility but less effective for nodal block or peripheral vascular collapse. Other treatments reported to be helpful in managing hypotension associated with calcium channel blocker poisoning include glucagon and high-dose insulin (0.5–1 unit/kg/h) plus glucose supplementation to maintain euglycemia. Recently case reports have suggested benefit from administration of lipid emulsion (Intralipid, normally used as an intravenous dietary fat supplement) for severe verapamil overdose.


Carbon monoxide (CO) is a colorless, odorless gas that is ubiquitous because it is created whenever carbon-containing materials are burned. Carbon monoxide poisoning is the leading cause of death due to poisoning in the USA. Most cases occur in victims of fires, but accidental and suicidal exposures are also common. The diagnosis and treatment of carbon monoxide poisoning are described in Chapter 56. Many other toxic gases are produced in fires or released in industrial accidents (Table 58–5).

TABLE 58–5 Characteristics of poisoning with some gases.



Organophosphate and carbamate cholinesterase inhibitors (see Chapter 7) are widely used to kill insects and other pests. Most cases of serious organophosphate or carbamate poisoning result from intentional ingestion by a suicidal person, but poisoning has also occurred at work (pesticide application or packaging) or, rarely, as a result of food contamination or terrorist attack (eg, release of the chemical warfare nerve agent sarin in the Tokyo subway system in 1995).

Stimulation of muscarinic receptors causes abdominal cramps, diarrhea, excessive salivation, sweating, urinary frequency, and increased bronchial secretions (see Chapters 6 and 7). Stimulation of nicotinic receptors causes generalized ganglionic activation, which can lead to hypertension and either tachycardia or bradycardia. Muscle twitching and fasciculations may progress to weakness and respiratory muscle paralysis. CNS effects include agitation, confusion, and seizures. The mnemonic DUMBELS (diarrhea, urination, miosis and muscle weakness, bronchospasm, excitation, lacrimation, and seizures, sweating, and salivation) helps recall the common findings. Blood testing may be used to document depressed activity of red blood cell (acetylcholinesterase) and plasma (butyrylcholinesterase) enzymes, which provide an indirect estimate of synaptic cholinesterase activity.

General supportive care should be provided as outlined above. Precautions should be taken to ensure that rescuers and health care providers are not poisoned themselves by exposure to contaminated clothing or skin. This is especially critical for the most potent substances such as parathion or nerve gas agents. Antidotal treatment consists of atropine and pralidoxime (see Table 58–4). Atropine is an effective competitive inhibitor at muscarinic sites but has no effect at nicotinic sites. Pralidoxime given early enough may be capable of restoring the cholinesterase activity and is active at both muscarinic and nicotinic sites.


Cyanide (CN) salts and hydrogen cyanide (HCN) are highly toxic chemicals used in chemical synthesis, as rodenticides (eg, “gopher getter”), formerly as a method of execution, and as agents of suicide or homicide. Hydrogen cyanide is formed from the burning of plastics, wool, and many other synthetic and natural products. Cyanide is also released after ingestion of various plants (eg, cassava) and seeds (eg, apple, peach, and apricot).

Cyanide binds readily to cytochrome oxidase, inhibiting oxygen utilization within the cell and leading to cellular hypoxia and lactic acidosis. Symptoms of cyanide poisoning include shortness of breath, agitation, and tachycardia followed by seizures, coma, hypotension, and death. Severe metabolic acidosis is characteristic. The venous oxygen content may be elevated because oxygen is not being taken up by cells.

Treatment of cyanide poisoning includes rapid administration of activated charcoal (although charcoal binds cyanide poorly, it can reduce absorption) and general supportive care. The conventional antidote kit available in the USA includes two forms of nitrite (amyl nitrite and sodium nitrite) and sodium thiosulfate. The nitrites induce methemoglobinemia, which binds CN, creating the less toxic cyanomethemoglobin; thiosulfate is a cofactor in the enzymatic conversion of CN to the much less toxic thiocyanate (SCN).

In 2006 the FDA approved a new cyanide antidote, a concentrated form of hydroxocobalamin, which is now available as the Cyanokit (EMD Pharmaceuticals, Durham, North Carolina). Hydroxocobalamin (one form of vitamin B12) combines rapidly with CN to form nontoxic cyanocobalamin (another form of vitamin B12).


Digitalis and other cardiac glycosides and cardenolides are found in many plants (see Chapter 13) and in the skin of some toads. Toxicity may occur as a result of acute overdose or from accumulation of digoxin in a patient with renal insufficiency or from taking a drug that interferes with digoxin elimination. Patients receiving long-term digoxin treatment are often also taking diuretics, which can lead to electrolyte depletion (especially potassium).

Vomiting is common in patients with digitalis overdose. Hyperkalemia may be caused by acute digitalis overdose or severe poisoning, whereas hypokalemia may be present in patients as a result of long-term diuretic treatment. (Digitalis does not cause hypokalemia.) A variety of cardiac rhythm disturbances may occur, including sinus bradycardia, AV block, atrial tachycardia with block, accelerated junctional rhythm, premature ventricular beats, bidirectional ventricular tachycardia, and other ventricular arrhythmias.

General supportive care should be provided. Atropine is often effective for bradycardia or AV block. The use of digoxin antibodies (see Chapter 13) has revolutionized the treatment of digoxin toxicity; they should be administered intravenously in the dosage indicated in the package insert. Symptoms usually improve within 30–60 minutes after antibody administration. Digoxin antibodies may also be tried in cases of poisoning by other cardiac glycosides (eg, digitoxin, oleander), although larger doses may be needed due to incomplete cross-reactivity.


Overdosage with ethanol and sedative-hypnotic drugs (eg, benzodiazepines, barbiturates, γ-hydroxybutyrate [GHB], carisoprodol [Soma]; see Chapters 22 and 23) occurs frequently because of their common availability and use.

Patients with ethanol or other sedative-hypnotic overdose may be euphoric and rowdy (“drunk”) or in a state of stupor or coma (“dead drunk”). Comatose patients often have depressed respiratory drive. Depression of protective airway reflexes may result in pulmonary aspiration of gastric contents, leading to pneumonia. Hypothermia may be present because of environmental exposure and depressed shivering. Ethanol blood levels greater than 300 mg/dL usually cause deep coma, but regular users are often tolerant to the effects of ethanol and may be ambulatory despite even higher levels. Patients with GHB overdose are often deeply comatose for 3–4 hours and then awaken fully in a matter of minutes.

General supportive care should be provided. With careful attention to protecting the airway (including endotracheal intubation) and assisting ventilation, most patients recover as the drug effects wear off. Hypotension usually responds to intravenous fluids, body warming if cold, and, if needed, dopamine. Patients with isolated benzodiazepine overdose may awaken after intravenous flumazenil, a benzodiazepine antagonist. However, this drug is not widely used as empiric therapy for drug overdose because it may precipitate seizures in patients who are addicted to benzodiazepines or who have ingested a convulsant drug (eg, a tricyclic antidepressant). There are no antidotes for ethanol, barbiturates, or most other sedative-hypnotics.


Ethylene glycol and methanol are alcohols that are important toxins because of their metabolism to highly toxic organic acids (see Chapter 23). They are capable of causing CNS depression and a drunken state similar to ethanol overdose. In addition, their products of metabolism—formic acid (from methanol) or hippuric, oxalic, and glycolic acids (from ethylene glycol)—cause a severe metabolic acidosis and can lead to coma and blindness (in the case of formic acid) or renal failure (from oxalic acid and glycolic acid). Initially, the patient appears drunk, but after a delay of up to several hours, a severe anion gap metabolic acidosis becomes apparent, accompanied by hyperventilation and altered mental status. Patients with methanol poisoning may have visual disturbances ranging from blurred vision to blindness.

Metabolism of ethylene glycol and methanol to their toxic products can be blocked by inhibiting the enzyme alcohol dehydrogenase with a competing drug, such as fomepizole (4-methylpyrazole). Ethanol is also an effective antidote, but it can be difficult to achieve a safe and effective blood level.


Iron is widely used in over-the-counter vitamin preparations and is a leading cause of childhood poisoning deaths. As few as 10–12 prenatal multivitamins with iron may cause serious illness in a small child. Poisoning with other metals (lead, mercury, arsenic) is also important, especially in industry. See Chapters 3356, and 57 for detailed discussions of poisoning by iron and other metals.


Opioids (opium, morphine, heroin, meperidine, methadone, etc) are common drugs of abuse (see Chapters 31 and 32), and overdose is a common result of using the poorly standardized preparations sold on the street. See Chapter 31for a detailed discussion of opioid overdose and its treatment.


In the USA, rattlesnakes are the most common venomous reptiles. Bites are rarely fatal, and 20% do not involve envenomation. However, about 60% of bites cause significant morbidity due to the destructive digestive enzymes found in the venom. Evidence of rattlesnake envenomation includes severe pain, swelling, bruising, hemorrhagic bleb formation, and obvious fang marks. Systemic effects include nausea, vomiting, muscle fasciculations, tingling and metallic taste in the mouth, shock, and systemic coagulopathy with prolonged clotting time and reduced platelet count.

Studies have shown that emergency field remedies such as incision and suction, tourniquets, and ice packs are far more damaging than useful. Avoidance of unnecessary motion, on the other hand, does help to limit the spread of the venom. Definitive therapy relies on intravenous antivenom (also known as antivenin) and this should be started as soon as possible.


Although it has been largely replaced by inhaled β agonists, theophylline continues to be used for the treatment of bronchospasm by some patients with asthma and bronchitis (see Chapter 20). A dose of 20–30 tablets can cause serious or fatal poisoning. Chronic or subacute theophylline poisoning can also occur as a result of accidental overmedication or use of a drug that interferes with theophylline metabolism (eg, cimetidine, ciprofloxacin, erythromycin; see Chapter 4).

In addition to sinus tachycardia and tremor, vomiting is common after overdose. Hypotension, tachycardia, hypokalemia, and hyperglycemia may occur, probably owing to β2-adrenergic activation. The cause of this activation is not fully understood, but the effects can be ameliorated by β blockers (see below). Cardiac arrhythmias include atrial tachycardias, premature ventricular contractions, and ventricular tachycardia. In severe poisoning (eg, acute overdose with serum level > 100 mg/L), seizures often occur and are usually resistant to common anticonvulsants. Toxicity may be delayed in onset for many hours after ingestion of sustained-release tablet formulations.

General supportive care should be provided. Aggressive gut decontamination should be carried out using repeated doses of activated charcoal and whole bowel irrigation. Propranolol or other β blockers (eg, esmolol) are useful antidotes for β-mediated hypotension and tachycardia. Phenobarbital is preferred over phenytoin for convulsions; most anticonvulsants are ineffective. Hemodialysis is indicated for serum concentrations greater than 100 mg/L and for intractable seizures in patients with lower levels.


Dart RD (editor): Medical Toxicology, 3rd ed. Lippincott Williams & Wilkins, 2004.

Goldfrank LR et al (editors): Goldfrank’s Toxicologic Emergencies, 9th ed. McGraw-Hill, 2010.

Olson KR et al (editors): Poisoning & Drug Overdose, 6th ed. McGraw-Hill, 2011.

POISINDEX. (Revised Quarterly.) Thomson/Micromedex.


Overdose of bupropion can cause seizures that are often recurrent or prolonged. Drug-induced seizures are treated with an intravenous benzodiazepine such as lorazepam or diazepam. If this is not effective, phenobarbital or another more potent central nervous system depressant may be used. To prevent ingested drugs and poisons from being absorbed systemically, a slurry of activated charcoal is often given orally or by nasogastric tube.