fatal reactions during desensitization are rare.139

Uneventful β-lactam desensitization, however, does not guarantee patients will be without reaction during full-dose therapy.

Approximately 25% to 30% of patients experience a mild reaction during therapy, and 5% experience more severe reactions,

including drug-induced serum sickness, hemolytic anemia, or

urticaria.30 Reaction rates are no different in severely ill or pregnant patients compared with stable or nonpregnant patients,

although those with cystic fibrosis may be more difficult to desensitize because of their high frequency of allergic reactions.140,141

Despite the occurrence of reactions, full-dose therapy is possible

for most tolerance-induction procedures, but suppression of the

reaction (e.g., by diphenhydramine) may be required.139 Tolerance induction is also dose-dependent as allergic symptoms can

appear after a substantial increase in the dose after tolerance has

been achieved.30

CASE 3-9, QUESTION 4: If K.A. requires penicillin at a later

date, will she need to undergo desensitization again? What

is chronic desensitization?

The desensitized state, once achieved, will persist for approximately 48 hours after the last full dose of antibiotic; after this time,

drug sensitivity will return.30,139 Thus, if K.A. requires future

courses of penicillin, she will need to undergo desensitization

once again. In some cases, those requiring long-term antibiotic

therapy (e.g., for endocarditis), those who may require β-lactams

at a future date (e.g., those with cystic fibrosis), or those who have

occupational exposure to β-lactams, maintenance of the desensitized state can be considered. Chronic twice daily dosing of oral

penicillin has safely resulted in “chronic desensitization.” Similar

to acute desensitization, once therapy is interrupted, the allergic

state returns.13,30

OTHER DRUGS

CASE 3-9, QUESTION 5: Have patients allergic to drugs

besides β-lactams been desensitized successfully?

Although most experience with desensitization is with penicillin and other β-lactams, desensitization also has been accomplished with numerous other drugs, including allopurinol,

vancomycin, antineoplastic agents, aspirin, and monoclonal

antibodies.80,138,139 Interestingly, not all of these cases represent

IgE-mediated hypersensitivity reactions. For example, reactions

to trimethoprim-sulfamethoxazole commonly occur in patients

infected with HIV and may not be IgE mediated. Yet, given its

role in treating and preventing Pneumocystis jiroveci pneumonia,

successful desensitization to trimethoprim-sulfamethoxazole is

commonly used.139

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at http://

thepoint.lww.com/AT10e. Below are the key references for this

chapter, with the corresponding reference number in this chapter

found in parentheses after the reference.

Key References

Antonov D, et al. Drug-induced lupus erythematosus. Clin Dermatol. 2004;22:157. (96)

Dedeoglu F. Drug-induced autoimmunity. Curr Opin Rheumatol.

2009;21:547. (89)

64 Section 1 General Care

Frumin J, Gallagher JC. Allergic cross-sensitivity between penicillin, carbapenem, and monobactam antibiotics: what are the

chances? Ann Pharmacother. 2009;43:304. (56)

Hoover T et al. Angiotensin converting enzyme inhibitor induced

angio-oedema: a review of the pathophysiology and risk factors.

Clin Exp Allergy. 2010;40:50. (120)

Kemp SF et al. Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization. Allergy.

2008;63:1061. (70)

Khan DA, Solensky R. Drug allergy. J Allergy Clin Immunol. 2010;

125(2 Suppl 2):S126. (7)

Lieberman P et al. The diagnosis and management of anaphylaxis

practice parameter: 2010 update [published correction appears

in J Allergy Clin Immunol. 2010;126:1104]. J Allergy Clin Immunol.

2010;126:477. (59)

Patel RA, Gallagher JC. Drug fever. Pharmacotherapy. 2010;30:57.

(82)

Pichler WJ et al. Drug hypersensitivity reactions: pathomechanism and clinical symptoms. Med Clin North Am. 2010;94:645.

(79)

Sanchez-Borges M. NSAID hypersensitivity (respiratory, cutaneous, and generalized anaphylactic symptoms). Med Clin North

Am. 2010;94:853. (114)

Scherer K, Bircher AJ. Danger signs in drug hypersensitivity. Med

Clin North Am. 2010;94:681. (8)

Schnyder B. Approach to the patient with drug allergy. Immunol

Allergy Clin North Am. 2009;29:405. (80)

Solensky R. Drug desensitization. Immunol Allergy Clin North Am.

2004;24:425. (139)

ten Holder SM et al. Cutaneous and systemic manifestations of

drug-induced vasculitis. Ann Pharmacother. 2002;36:130. (94)

Wedner HJ. Drug allergy prevention and treatment. Immunol

Allergy Clin North Am. 1991;11:679. (137)

Managing Drug Overdoses 4

and Poisonings

Judith A. Alsop

CORE PRINCIPLES

CHAPTER CASES

EPIDEMIOLOGY

1 In 2009, 2.48 million poisonings were reported to the American Association of

Poison Control Centers. Half of these exposures occur in children younger than

6 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 elderly have access to

numerous and dangerous medications and have a higher rate of completed suicide

attempts than other age groups.

Case 4-1 (Questions 2, 3)

GENERAL MANAGEMENT

1 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.

Case 4-4 (Questions 1, 5, 6)

GASTROINTESTINAL DECONTAMINATION

1 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 several

hours.

Case 4-3 (Questions 6, 7),

Case 4-4 (Questions 11, 12,

16), Case 4-5 (Question 3)

ANTIDOTES

1 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

methanol).

Case 4-4 (Questions 2, 4)

continued

65

66 Section 1 General Care

CHAPTER CASES

TOXICOLOGY LABORATORY SCREENING

1 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 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).

Case 4-4 (Questions 1, 7)

TOXIDROMES

1 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.

Case 4-4 (Questions 1, 2, 5)

SALICYLATES

1 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 high-risk and should be considered for early dialysis.

Case 4-1 (Question 3),

Case 4-2 (Questions 1–6)

IRON

1 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.

Case 4-3 (Questions 2–14)

TRICYCLIC ANTIDEPRESSANTS

1 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 antidepressant overdoses.

Case 4-4 (Questions 9–17)

ACETAMINOPHEN

1 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 therapy.

Case 4-5 (Questions 1–15)

67Managing Drug Overdoses and Poisonings Chapter 4

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).

Epidemiologic Data

AMERICAN ASSOCIATION OF POISON CONTROL

CENTERS AND DRUG ABUSE WARNING NETWORK

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 4-1).1–3 The number of reported toxic exposures

in the United States in 2009 was approximately 2.48 million,

according to the American Association of Poison Control Centers

(AAPCC).3 In most cases, little or no toxicity was associated with

the exposure. Although 24.1% of patients received treatment at

a health care facility, only 6.1% reported moderate or severe

symptoms and 0.06% resulted in fatalities.

According to the Drug Abuse Warning Network (DAWN),

almost 2 million US emergency department (ED) visits involved

drug misuse or abuse in the year 2008. Of those cases, illicit drug

use was mentioned more than 2.7 million times because many

of the visits involved multiple drugs of abuse.4 These disparate

statistics from two national sources underscore the difficulty in

determining the true incidence of poisoning and overdoses.5

AGE-SPECIFIC DATA

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.6 Of all reported poisonings, 38.9% occur in children younger than 3 years and 51.9% occur in children younger

than 6 years of age.3 According to AAPCC statistics, 11.26% of

pediatric (younger than 6 years of age) poisoning cases were

treated in a health care facility, and the remaining cases were

TABLE 4-1

Substances Most Commonly Involved in Poisoningsa

Children Adults Fatal Exposures (All Ages)

Personal care products Analgesics Sedatives/hypnotics/antipsychotics

Analgesics Sedatives/hypnotics/antipsychotics Cardiovascular agents

Cleaning substances Antidepressants Opioids

Topical products Cleaning substances Acetaminophen-containing products

Vitamins Cardiovascular agents Antidepressants

Antihistamines Alcohols Acetaminophen

Cough and cold products Bites, envenomations Alcohols