injury: a meta-analysis. Int J Tuberc Lung Dis. 2008;12(9):994–1002.
meta-analysis. Mol Biol Rep. 2013;40(5):3591–3596.
Huang YS et al. Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for
antituberculosis drug-induced hepatitis. Hepatology. 2002;35(4):883–889.
children under isoniazid treatment. Int J Clin Pharmacol Ther. 2013;52(4):292–302.
Lexicomp. Warfarin. Copyright 1978–2015. Hudson, OH: Lexicomp. Accessed September 8, 2015.
genotypes and warfarin dosing. Clin Pharmacol Ther. 2011;90(4):625–629.
Van Booven et al. Cytochrome P450 2C9-CYP2C9. Pharmacogenet Genomics. 2010;20(4):277–281.
Drug Dosing. New York, NY: McGraw-Hill; 2015.
Lexicomp. Phenytoin. Copyright 1978–2015. Hudson, OH: Lexicomp. Accessed September 8, 2015.
Caudle KE et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B
genotypes and phenytoin dosing. Clin Pharmacol Ther. 2014;96(5):542–548.
Care. New York, NY: McGraw-Hill; 2009.
Lexicomp. Azathioprine. Copyright 1978–2015. Hudson, OH: Lexicomp. Accessed September 5, 2015.
Rufo PA, Bousvaros A. Current therapy of inflammatory bowel disease in children. Pediatr Drugs.
Relling MV et al. Clinical pharmacogenetics implementation consortium guidelines for thiopurine
methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther. 2011;89:387–391.
Principles of Internal Medicine. 19th ed. New York, NY: McGraw-Hill; 2015.
simvastatin-induced myopathy. Clin Pharmacol Ther. 2012;92(1):112–117.
Ramsey LB et al. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and
simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014;96(4):423–428.
carbamazepine dosing. Clin Pharmacol Ther. 2013;94(3):324–328.
Medicine. 19th ed. New York, NY: McGraw-Hill; 2015.
Med J. 1978;1(6127):1583–1586.
drug hypersensitivity. J Allergy Clin Immunol. 2015;136(2):236–244.
abacavir dosing. Clin Pharmacol Ther. 2012;91(4):734–738.
Ma JD et al. HLA-B*5701 testing to predict abacavir hypersensitivity. PLoS Curr. 2010;2:RRN1203.
MD: National Center for Biotechnology Information; Created: March 26, 2013.
http://www.ncbi.nlm.nih.gov/books/NBK127547/.
Ferrell PB, McLeod HL. Carbamazepine, HLA-B*1502 and risk of Stevens–Johnson syndrome and toxic
epidermal necrolysis: US FDA recommendations. Pharmacogenomics. 2008;9(10):1543–1546.
Lexicomp. Carbamazepine. Copyright 1978–2015. Hudson, OH: Lexicomp. Accessed December 6, 2015.
Hicks JK et al. Clinical pharmacogenetics implementation consortium (CPIC) guideline for CYP2D6 and
Crews KR et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for cytochrome
Lexicomp. Codeine. Copyright 1978–2015. Hudson, OH: Lexicomp. Accessed September 13, 2015.
Zhou SF. Polymorphisms of human cytochrome P450 2D6 and its clinical significance, Part II. Clin
Pharmacokinet. 2009;48(12):761–804.
Abidi MZ et al. CYP2C19*17 genetic polymorphism—an uncommon cause of voriconazole treatment failure.
Diagn Microbiol Infect Dis. 2015;83(1):46–48.
Lexicomp. Voriconazole. Copyright 1978–2015. Hudson, OH: Lexicomp. Accessed September 10, 2015.
EnglJ Med. 2003;349:1157–1167.
Infect Dis J. 2011;30(6):533–534.
Ward RM, Kearns GL. Proton pump inhibitors in pediatrics: mechanism of action, pharmacokinetics,
pharmacogenetics, and pharmacodynamics. Pediatr Drugs. 2013;15(2):119–131.
Koukouritaki SB et al. Developmental expression of human hepatic CYP2C9 and CYP2C19. J Pharmacol Exp
Netzer C, Biller-Andorno N. Pharmacogenetic testing, informed consent and the problem of secondary
information. Bioethics. 2004;18(4):344–360.
Haga SB, LaPointe NMA. The potential impact of pharmacogenetic testing on medication adherence.
Pharmacogenomics J. 2013;13(6):481–483.
Lexicomp. Ivacaftor. Copyright 1978–2015. Hudson, OH: Lexicomp. Accessed September 2, 2015.
mutation. Am J Respir Crit Care Med. 2013;187(11):1219–1225.
site. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm453565.htm. Published July
2, 2015. Accessed September 10, 2015.
Pharmacol Ther. 2012;91(3):450–458.
U.S. Food & Drug Administration. Table of Pharmacogenomic Biomarkers in Drug Labeling.
www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics. Accessed September 8, 2015.
Ehmann F et al. Pharmacogenomic information in drug labels: European Medicines Agency perspective.
Pharmacogenomics J. 2015;15:201–201.
Whirl-Carrillo M et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther.
Med Inform Assoc. 2013;21(e1):e93–e99.
ed. Totowa, NJ: Humana Press; 2011.
sequencing. Genet Med. 2013;15(7):565–574.
Medical Genetics Genomics. Genet Med. 2013;15:664–666.
counselors and pharmacists. Pharmacogenomics. 2013;14(8):957–968.
In 2013, 2.2 million poisonings were reported to the American
Association of Poison Control Centers. Half of these exposures occur in
children younger than 5 years of age and usually involve a single
substance that is found in the home such as personal care items,
analgesics, and cleaning agents. The most common exposures in
descending order include cosmetic/personal care products, household
cleaning agents, analgesics, toys and foreign bodies, and topical
The most important aspect of patient management is to support airway,
breathing, and circulation (the “ABCs”). There is no “cookbook”
method to treat all poisoned patients, so it is important to treat the
patient, not the poison or the laboratory values. The assessment and
treatment of the potentially poisoned patient can be separated into seven
functions: (a) gather history of exposure, (b) evaluate clinical
presentation (i.e., “toxidromes”), (c) evaluate clinical laboratory patient
data, (d) remove the toxic source (e.g., irrigate eyes, decontaminate
exposed skin), (e) consider antidotes and specific treatment, (f) enhance
systemic clearance, and (g) monitor patient outcome.
GASTROINTESTINAL DECONTAMINATION
The most appropriate method for gastrointestinal (GI) tract
decontamination is unclear because sound comparative data for
different methods of GI decontamination are not available. Lavage,
emesis, and cathartics are rarely performed as there is no evidence they
improve patient outcome. Activated charcoal is generally safe to use,
but it should not be administered if the benefit is not greater than the
risk. Whole bowel irrigation using a polyethylene glycol–balanced
electrolyte solution can successfully remove substances (iron, lithium,
sustained-release dosage forms) from the entire GI tract in a period of
An antidote is a drug that neutralizes or reverses the toxicity of another
substance. Some antidotes displace drugs from receptor sites (e.g.,
naloxone for opioids, flumazenil for benzodiazepines), and some can
inhibit the formation of toxic metabolites (e.g., N-acetylcysteine [NAC]
for acetaminophen, fomepizole for ethylene glycol and methanol).
TOXICOLOGY LABORATORY SCREENING
An antidote is a drug that neutralizes or reverses the toxicity of another
substance. Some antidotes displace drugs from receptor sites (e.g.,
naloxone for opioids, flumazenil for benzodiazepines), and some can
inhibit the formation of toxic metabolites (e.g., N-acetylcysteine [NAC]
for acetaminophen, fomepizole for ethylene glycol and methanol).
TOXICOLOGY LABORATORY SCREENING
Urine drug screens can be useful in a patient with coma of unknown
etiology, when the presented history is inconsistent with clinical findings,
or when more than one drug might have been ingested. Qualitative
screening is intended to identify unknown substances involved in the
toxic exposure. A benzodiazepine screen can detect oxazepam, a
common benzodiazepine metabolite, but it will not detect alprazolam and
lorazepam as they are not metabolized to oxazepam. Opioid screens
may not detect synthetic opioids such as fentanyl and methadone.
Quantitative testing determines how much of a known drug is present
and can help determine the severity of toxicity and the need for
aggressive interventions (e.g., hemodialysis in ethylene glycol, methanol,
A toxidrome is a consistent constellation of signs and symptoms
associated with some specific classes of drugs. The most common
toxidromes are those associated with anticholinergic activity, increased
sympathetic activity, and central nervous system (CNS) stimulation or
depression. Anticholinergic drugs increase heart rate and body
temperature, decrease GI motility, dilate pupils, and produce drowsiness
or delirium. Sympathomimetic drugs increase CNS activity, heart rate,
body temperature, and blood pressure. Opioids, sedatives, hypnotics, and
antidepressants depress the CNS, but the specific class of CNS
depressant often cannot be easily identified.
Acute ingestion of 150 to 300 mg/kg aspirin causes mild-to-moderate
intoxication, greater than 300 mg/kg indicates severe poisoning, and
greater than 500 mg/kg is potentially lethal. Symptoms of intoxication
include vomiting, tinnitus, delirium, tachypnea, metabolic acidosis,
respiratory alkalosis, hypokalemia, irritability, hallucinations, stupor,
coma, hyperthermia, coagulopathy, and seizures. Salicylate intoxication
mimics other medical conditions and can be easily missed. Patients with
a chronic salicylate exposure, acidosis, or CNS symptoms and those
who are elderly are at high risk and should be considered for early
Acute elemental iron ingestions of less than 20 mg/kg are usually
nontoxic; doses of 20 to 60 mg/kg result in mild-to-moderate toxicity,
and doses of greater than 60 mg/kg are potentially fatal. Symptoms of
toxicity include nausea, vomiting, diarrhea, abdominal pain, hematemesis,
bloody stools, CNS depression, hypotension, and shock. Patients with
severe iron poisoning do not exhibit the second stage of so-called
recovery but continue to deteriorate.
Severe toxicity has been associated with doses of 15 to 25 mg/kg.
Symptoms include tachycardia with prolongation of the PR, QTc, and
QRS intervals, ST and T-wave changes, acidosis, seizures, coma,
hypotension, and adult respiratory distress syndrome. A QRS segment
greater than 100 milliseconds is commonly seen in severe tricyclic
Toxicity is associated with acute ingestions greater than 150 mg/kg or
more than 7.5 g total in adults. Symptoms in patients with toxicity
include vomiting, anorexia, abdominal pain, malaise, and progression to
characteristic centrilobular hepatic necrosis. Acetaminophen-induced
hepatotoxicity is universal by 36 hours after ingestion, but patients who
receive NAC within 8 to 10 hours after ingestion rarely exhibit
hepatotoxicity. There is no consensus as to the best route of NAC
administration, the optimal dosage regimen, or the optimal duration of
This chapter reviews common strategies for the evaluation and management of drug
overdoses and poisonings. Information for the management of specific drug
overdoses is best obtained from a poison control center (reached by calling 1-800-
222-1222 anywhere in the United States).
AMERICAN ASSOCIATION OF POISON CONTROL CENTERS AND
Toxicity secondary to drug and chemical exposure commonly occurs in children. The
incidence of exposure to specific agents and the severity of outcomes varies based on
the population studied (Table 5-1).
1–3 The number of reported toxic exposures in the
United States in 2013 was approximately 2.2 million, according to the American
Association of Poison Control Centers (AAPCC).
reported cases were treated at home, saving millions of dollars in medical costs.
According to the Drug Abuse Warning Network, almost 5.1 million US emergency
department (ED) visits involved drug misuse or abuse in the year 2011. Illicit drugs
include cocaine, heroin, marijuana, ecstasy, gamma-hydroxyutyric acid,
flunitrazepam (Rohypnol), ketamine, lysergic acid, phencyclidine, and hallucinogens.
Of those cases, illicit drug use was mentioned more than 2.7 million times because
many of the visits involved multiple drugs of abuse.
Stratifying patients by age can be useful in assessing the likelihood of severe toxicity
from an exposure. Most unintentional ingestions by children 1 to 6 years of age occur
because children are curious, becoming more mobile, and beginning to explore their
surroundings, and they often put objects or substances into their mouths.
toxicity in young children is relatively uncommon as exposures usually involve the
ingestion of relatively small amounts of a single substance.
data also report medication errors, which in the pediatric population commonly
result from confusing units of measurement (e.g., teaspoons vs. milliliters or
tablespoons vs. teaspoons), incorrect formulation or concentration administered,
dispensing cup errors, and incorrect formulation or concentration dispensed from the
In children older than 6 years of age, the reasons for toxic exposure to medications
7 Adolescent children generally have poor knowledge of the toxicity of
medications and can overdose themselves unintentionally.
attempts or intentional substance abuse should not be ignored in older children.
These intentional overdoses commonly involve mixed exposures to illicit drugs,
prescribed medications, or ethanol and are associated with more severe toxicity and
death than unintentional toxic exposures.
In geriatric patients, overdoses tend to have a greater potential for severe adverse
effects compared with overdoses in other age groups.
9 Although the elderly constitute
13% of the population, they account for 33% of the drug use and 16% of the
10 Patients aged 65 or older take an average of 5.7 prescription medications
along with 2 to 4 nonprescription drugs daily.
9,10 The elderly are more likely to have
underlying illnesses and often have access to a variety of potentially dangerous
medications. This results in higher rates of completed suicides than in other age
A vast number of substances can be involved in a poisoning or overdose. Reliable
data about the contents of products, toxicities of substances, and treatment
approaches need to be readily accessible. POISINDEX, a computerized database,
provides information on thousands of drugs by brand name, generic name, and street
name, as well as foreign drugs, chemicals, pesticides, household products, personal
care items, cleaning products, poisonous insects, poisonous snakes, and poisonous
plants. Annual subscriptions to POISINDEX, updated quarterly, are expensive and
are generally available only in large medical centers.
Substances Most Commonly Involved in Poisonings
Children Adults Fatal Exposures (All Ages)
Personal care products Analgesics Sedatives/hypnotics/antipsychotics
Cleaning substances Sedatives/hypnotics/antipsychotics Cardiovascular agents
Analgesics Antidepressants Opioids
Topical products Cardiovascular agents Stimulants
Vitamins Cleaning substances Alcohols, acetaminophen-containing
Antihistamines Alcohols Acetaminophen
Pesticides Pesticides Fumes/gases/vapors
Cough and cold products Bites, envenomations Antidepressants
Plants Antiepileptic agents Antihistamines
GI products Personal care products Tricyclic antidepressants, aspirin
Antimicrobials Antihistamines Muscle relaxants
Cardiovascular Hormones and hormone antagonists Antiepileptic agents
Arts and office supplies Hydrocarbons Nonsteroidal anti-inflammatory drugs
Hormones and hormone antagonists Antimicrobials
aPoisoning exposures are listed in order of frequency encountered.
Data System (NPDS): 31st Annual Report. Clin Toxicol (Phila). 2014;S2:1032.
Textbooks and manuals also provide useful clinical information about the
presentation, assessment, and treatment of toxicities. Goldfrank’s Toxicologic
13 and the pocket-size Poisoning & Drug Overdose
useful than computerized databases because information must be condensed and
cannot be updated as frequently. Some drug package inserts also refer to treatment of
acute toxicities; however, the information can be inadequate or inappropriate.
Poison control centers provide the most cost-effective and accurate information to
health care providers and to the general public.
17,18 Poison centers are staffed by
trained poison information specialists who have a pharmacy, nursing, or medical
background. Physician backup is provided 24 hours a day by board-certified medical
toxicologists. The nonphysician clinical toxicologists, pharmacists, and nurses who
staff poison control centers are certified as specialists in poison information by the
AAPCC or as clinical toxicologists by the American Board of Applied Toxicology.
The specialist must communicate this assessment along with treatment information
quickly, accurately, and professionally in a reassuring manner. Subsequent to
telephone consultations, poison control center staff should initiate follow-up calls to
determine the effectiveness of the recommended treatment and the need for additional
Effective communication is essential to the assessment of potential poisonings. In
most situations, the person seeking guidance on the management of a potentially toxic
exposure is the parent of a small child who may have ingested a substance. The caller
is usually anxious about the child and may feel guilty about the exposure. To calm the
caller, the health care provider should quickly reassure the individual that
telephoning for help was appropriate and that the best assistance possible will be
If English is not the first language of the caller, or if there are other
communication barriers (e.g., panic), solutions must be found to enhance outcomes.
Most poison centers subscribe to translation services or have bilingual staff to
communicate with non–English-speaking callers. Poison centers also have special
equipment to serve the hearing- and speech-impaired populations.
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