AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Cough and cold suppressant medicines are widely used and favored by medical professionals and parents alike. However, minimal data exist to support their effectiveness. Because these medications are available over-the-counter (OTC) and are found in most households, they frequently are implicated in pediatric toxic ingestions, both accidental and intentional. The most common reported calls that involve OTC medications to poison control centers are for the ingestion of acetaminophen and cough and cold preparations.

The 3 main components of most cough and cold medicines are antihistamines, decongestants, and antitussives. First-generation antihistamines can be divided into 5 different categories. The most commonly used antihistamines in OTC preparations come from the alkylamine (eg, chlorpheniramine, brompheniramine) and ethanolamine (eg, diphenhydramine, clemastine) groups. Toxicity caused by these agents usually is not due to antihistamine properties, but to anticholinergic properties. The 3 most commonly used oral decongestants are pseudoephedrine, phenylephrine, and phenylpropanolamine (withdrawn from US market). These agents stimulate alpha-adrenergic receptors and cause a sympathomimetic response at toxic doses. The most common antitussive in OTC preparations is dextromethorphan.

Most poisonings are asymptomatic or mildly symptomatic and do not require specific therapy. However, the clinician may encounter severe intoxications that require prompt recognition and appropriate disposition. Involvement of the regional poison control center, as well as a medical toxicology consultant, if available, may aid in the treatment and follow-up care of these patients, and they should be contacted for all significant ingestions.

Pathophysiology

Antihistamines

Antihistamines compete with histamine at H1 receptor sites on effector cells. Histamine is not a major mediator of the common cold, and the benefits of antihistamine in relieving congestion appear to be secondary to its anticholinergic properties. Toxicity is caused by anticholinergic properties. Atropine, the prototype of anticholinergics, and other substances with anticholinergic properties competitively inhibit the muscarinic effect of acetylcholine by blocking its action in the autonomic ganglia and at the neuromuscular junctions of the voluntary muscle system. They affect the peripheral and central autonomic nervous systems. Clinical toxicity is demonstrated by central nervous system depression or agitation, hyperactivity or psychosis, blurred vision, or abdominal discomfort.

Antihistamines generally are well absorbed after ingestion. Therapeutic effects begin within 15-30 minutes and are fully developed within 1 hour. They have varied peak plasma concentrations with a range of 1-5 hours. Diphenhydramine is toxic in acute doses of more than 5 mg/kg and potentially lethal in doses more than 10 mg/kg. In children, seizures have been observed with 150 mg of diphenhydramine, and fatalities have occurred with doses of less than 500 mg.

Decongestants

Pseudoephedrine, phenylephrine, and phenylpropanolamine cause direct presynaptic catecholamine release and also may block catecholamine reuptake and influence enzymes slowing catecholamine breakdown. Blood pressure elevation often is accompanied by a reflex bradycardia caused by the baroreceptors and results in postural hypotension. Clinical manifestations result from a direct effect on adrenergic receptors in muscles and glands and stimulation of the respiratory center and CNS. This causes bronchodilation, hyperexcitability, hallucinations, seizures, psychosis, intracranial bleeding or restlessness.

One case report described a cardiomyopathy and left ventricular dysfunction as a result of persistant tachycardia from pseudoephedrine use with resolution upon its termination. Decongestants are absorbed readily from the GI tract (except for phenylephrine because of irregular absorption and first pass metabolism by the liver) and attain a high concentration in the CNS. Peak plasma concentrations are achieved within 1-2 hours after oral administration. Toxic levels of pseudoephedrine have not been identified.

Phenylpropanolamine often has been implicated in pediatric ingestion, with toxicity starting at 6-10 mg/kg. In November 2000, in an article in the New England Journal of Medicine, phenylpropanolamine was noted to increase the risk of stroke. Other effects of phenylpropanolamine are seizure, cerebral vasculitis and kidney failure. Although this study did not include children, phenylpropanolamine was removed from the OTC market in the United States. However, preparations containing this substance still may be in homes and in medications from foreign countries. It is recommended that all household medications be checked for phenylpropanolamine and be discarded if containing any.

Antitussives

Dextromethorphan is the methylated dextro-isomer of levorphanol, a codeine analog. It is a synthetic opioid and acts at s opiate receptors in the CNS but does not have any of the other effects of typical opiates; it has no analgesic and minimal addictive properties. Dextromethorphan has shown agonist activity at the serotonergic transmission, inhibiting the reuptake of serotonin at synapses and causing potential serotonin syndrome, especially when used concomitantly with monoamine oxidase inhibitors (MAOIs).

In addition, dextromethorphan and its primary active metabolite, dextrorphan, which shows similar effects to other N-methyl-D-aspartate (NMDA) antagonists such as phencyclidine (PCP), demonstrate anticonvulsant activity in animals by antagonizing the action of glutamate and are classified as a dissociative medication. The usefulness of quantitative determination for dextromethorphan is unclear because no correlation exists between blood levels and clinical effects. However, qualitative determination in blood or urine can demonstrate the presence or absence of dextromethorphan. The pharmacokinetics of dextromethorphan are such that a peak serum concentration of 0.1-0.2 mg/mL was reached after a single 20-mg oral dose in healthy volunteers. Five percent of persons of European ethnicity lack the ability to metabolize the drug normally, leading to toxic levels with smaller doses.

Note that adolescents have become increasingly interested in dextromethorphan for intentional intoxications at social gatherings. The effects of megadosing are similar to that of PCP by causing ataxia, abnormal muscle movements, and respiratory depression. Dextromethorphan can cause false positive test-results for PCP in urine toxicologic screening tests. The half-life of dextromethorphan is short, with the mainstay of treatment being supportive care. Narcan has been used with intermittent success to reverse ataxia and respiratory depression.

Chlorpheniramine is an OTC antihistamine that is usually used in adults. However, the abuse potential of this medication by adolescents has been recently reported. Its effects in deliberate megadosing for intoxication are similar to that of dextromethorphan.

Codeine is also thought to have antitussive effects and may be prescribed in combination with promethazine (Phenergan) for cough in the pediatric population. This medication is not recommended for use in the pediatric population. Codeine is an opioid analgesic and is the most commonly ingested opioid, in toxic doses, by children less than 6 years, as reported by the American Association of Poison Control Centers (AAPCC). Doses greater than 5 mg/kg are. reported to produce respiratory and CNS depression.

Frequency

United States

The AAPCC reports that cough and cold preparations account for 68,943 annual exposures for children younger than 6 years and 24,703 annual exposure in children aged 6-17 years, based on cumulative data reported in 2003. Although cough and cold preparations represent a large majority of exposures in the pediatric population, they are not responsible for a significant proportion of pediatric morbidity and mortality.

Mortality/Morbidity

• Morbidity and mortality differ based on the 2 categories of pediatric toxic ingestion, accidental (children <6 y) and intentional (adolescents aged 13-19 y).
• The AAPCC reported an incidence of 27 deaths per year and 27.5 deaths per million exposures in children younger than 6 years and 61 deaths per year and 523.7 deaths per million exposures in adolescents aged 13-19 years.

Sex

• According to the AAPCC, females represent 57% of reported pediatric toxic exposures in young children and 66% of the reported exposures in adolescents.

Age

• Accidental exposures tend to occur in children younger than 6 years because they are eager to explore their environment and place objects into their mouths. Unfortunately, as many as 30% of children who experience one ingestion experience a repeat ingestion.
• The peak age for childhood poisoning ranges from 1-3 years. Based on cumulative data from 1991-95, the AAPCC reported that 43% of toxic ingestions are in children younger than 6 years. Only 50% of reported adolescent ingestions are accidental, whereas 46% are motivated by suicide. Hence, suicidal ingestion occurs with increased frequency in the teenage population, and it may involve multiple substances at higher doses. Studies have shown that when adolescents are surveyed their knowledge of the lethal potential of OTC medications is poor. In fact, 50% believed some, like acetaminophen, were benign.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Accidental ingestion
• • Accidental exposures tend to occur in children younger than 6 years because they are eager to explore their environment and place objects into their mouths.
  • Accidental ingestion typically represents a smaller dose of the toxic substance, and the child presents to the ED soon after ingestion.
  • Unfortunately, as many as 30% of children who experience one ingestion experience a repeat ingestion. In this age group, it is imperative to explore the possibility of child abuse or neglect.
• Intentional ingestion
• • Only 50% of reported adolescent ingestions are accidental, whereas 46% are motivated by suicide. Hence, suicidal ingestion occurs with increased frequency in the teenage population, and it may involve multiple substances at higher doses.
  • Dextromethorphan has been used as a recreational drug by adolescents

Physical

• General findings
• • Physical findings vary greatly, depending on the agent or combination of agents ingested.
  • If a single antihistamine agent has been ingested, a predominance of anticholinergic effects are demonstrated. The anticholinergic toxidrome consists of agitation; fever; urinary retention; dry, hot, flushed skin; and dilated pupils.
  • Although most cough and cold preparations are a combination of medications, a single toxidrome may not be present. The history is helpful to guide the expected physical examination findings; however, the history often is inaccurate.
• The following physical examination findings are examples of what is possible, in addition to the common findings; however, the presentation of a patient with a toxic ingestion is not always straightforward. In general, the combined effects of the various classes of drugs in OTC preparations have been broken down into the following systems based on the approach in POISINDEX.
• • Vital signs
  • • Findings include hyperthermia, tachypnea, tachycardia, and hypertension.
    • Hyperthermia has been reported with ingestion of both diphenhydramine and OTC antihistamine/decongestant combinations. Case reports secondary to combination products are ascribed to the sympathomimetic component.
• • Head, ears, eyes, nose, and throat (HEENT)
  • • Anticholinergic effects include mydriasis, nasal dryness and stuffiness, eye dryness, and mouth and throat dryness secondary to antihistamines.
    • Dilated and minimally reactive pupils have been seen with antihistamine toxicity related to anticholinergic effects.
    • Mydriasis and nystagmus may be observed with dextromethorphan ingestion.
• Cardiovascular
• • Abnormalities include arrhythmia (eg, AV block) and cardiac arrest.
  • ECG changes occur secondary to the antihistamine and the sympathomimetic components. Antihistamines commonly cause tachycardia.
• Respiratory: Findings include respiratory depression and adult respiratory distress syndrome.
• Neurologic: Abnormal findings include dizziness, ataxia, hyperexcitability, somnolence, seizures, dystonia, dyskinesia, toxic psychosis (anxiety, agitation, hallucination), intracranial hemorrhage, and coma.
• Gastrointestinal: Gastroenteritis (diarrhea, nausea, vomiting) can occur with the ethanolamine class of antihistamines.
• Genitourinary
• • Urinary retention is a common anticholinergic adverse effect of the antihistamines.
  • Rhabdomyolysis (ie, decreased urinary output and increased creatinine phosphokinase) has been associated with doxylamine overdose and may require treatment with IV hydration, furosemide, and urine alkalization.
• Hematologic
• • Most hematologic effects are secondary to long-term use.
  • Findings include hemolytic anemia, thrombocytopenia, and agranulocytosis
• Psychiatric: Children may experience visual hallucinations following therapeutic doses of triprolidine (antihistamine/pseudoephedrine) combinations.
• Dermatologic: Urticaria, hot dry skin
• Effects during breastfeeding: Potential changes in behavior of the infant include irritability, disturbed sleep patterns, and excessive crying.
• Other: Drug interactions between MAOIs or serotonin reuptake inhibitors with dextromethorphan may result in a serotonin syndrome. Serotonin syndrome consists of mental status changes, such as agitation, myoclonus, hyperreflexia, diaphoresis, shivering, tremor, diarrhea, headache, fever, or incoordination.

Causes

• Drug abuse
• • Drug abuse has been reported with dextromethorphan.
  • Deliberate ingestion can lead to intoxication with symptoms of euphoria, bizarre behavior, hyperactivity, auditory hallucinations, visual hallucinations, and association of sounds with colors.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Altered mental status: Trauma, tumor, intussusception, shock, alcohol or drug abuse, epilepsy, encephalopathy, inborn errors, opiates, uremia

Neurologic conditions: Subdural or arachnoid hemorrhage

Psychosis: Psychiatric (schizophrenia, mania), drug-induced (amphetamines, hallucinogens), withdrawal states (alcohol, barbiturates), cerebrovascular, endocrine (hyperthyroid, steroid), hypoxia (carbon monoxide, anemia), metabolic (encephalopathy, uremia), neoplastic (glioblastoma), pyogenic infections (CNS abscess, sepsis), seizure disorder (postictal psychosis, temporal lobe seizures), trauma, viral infections (encephalitis)

Seizures: Febrile, new-onset, drug-induced

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Emergency drug screens
• • Emergency drug screens rarely aid clinical decisions because turn-around time often is very long; furthermore, screens are not sensitive or specific for many drugs, leading to either a missed diagnosis or a false diagnosis of systemic drug presence.
  • In addition, it is difficult to use a positive screen result as the explanation for a patient's presentation because cause and effect can be ascertained only from patient history.
  • In the setting of an intentional overdose, the patient's history may be unreliable and unverifiable.
  • In general, drug screens are ordered when poisoning is suspected as the cause of an altered level of consciousness, unexplained seizures, or new onset of unusual behavior.
  • Drugs can be screened in blood or urine. Serum concentrations of OTC cough and cold preparations are not helpful.
  • Which drug screens to order should be decided in coordination with a regional toxicology center because most of these tests are costly and add little to a complete history with a known ingestion.
• Blood and urine analysis
• • An electrolyte panel and a CBC count are recommended for all cases of possible toxicity.
  • A plasma creatinine kinase level test may be helpful if rhabdomyolysis is suspected secondary to a antihistamine/decongestant combination that contains phenylpropanolamine, pseudoephedrine, or phenylephrine. The test result for myoglobin should be positive if rhabdomyolysis is present.
  • Several antihistamine/decongestant combinations also are combined with salicylates or acetaminophen. Blood levels should be measured for potential concurrent acetaminophen or salicylate ingestion.

Imaging Studies

• Imaging studies are not useful in identifying ingestion of cold and cough preparations.
• A chest x-ray is useful if the patient has severe respiratory or CNS depression. This rules out pulmonary edema and adult respiratory distress syndrome.

Other Tests

• Electrocardiogram
• • An ECG is indicated especially if tachycardia or bradycardia is present.
  • Antihistamines may cause a prolonged QTc or QRS complex and ST-T segment abnormalities. Several cases of prolonged QTc and QRS intervals, with nonspecific ST and T wave changes, have been reported secondary to antihistamine ingestions.

Procedures

• A lumbar puncture is helpful in excluding other causes (eg, infectious, autoimmune) of altered mental status or new-onset seizures in the setting of an unknown toxic exposure.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• General guidelines
  • Make sure is the patient has adequate airway, breathing, and circulation. Place the child on a cardiorespiratory monitor and/or obtain IV access if the child appears ill or is symptomatic. Administer oxygen, naloxone, and glucose to the patient if an unexplained decreased level of consciousness is observed.
  • Obtain the patient's history through a relative or Emergency Medical Technician (EMT). Examine the patient, looking for an anticholinergic toxidrome.
  • Obtain appropriate lab tests and an ECG.
  • Consider decontamination with activated charcoal.
  • Provide other supportive measures. Consider admission to a hospital if ingestion is significant or if the patient continues to be symptomatic.
  • Contact the regional poison control center.
• GI decontamination
  • Activated charcoal is the first-line defense in GI decontamination and should be given to the patient if a significant ingestion has occurred within recent hours before presentation.
  • Optimal dose of charcoal is not well established. The usual dose is 25-100 g in adults and adolescents, 25-50 g in children aged 1-12 years, and 1 g/kg in infants younger than 1 year. It is most effective if administered within 1 hour of ingestion.
  • Complications include emesis and aspiration.
• Other methods of decontamination
  • Controversial methods of decontamination include gastric lavage and ipecac syrup. Use of these agents should be on the advice of a poison center or toxicologist.
  • Ipecac and gastric lavage have fallen into disfavor, and cathartic therapy is not recommended, especially in children. Emesis usually is not recommended and is contraindicated specifically if there is a depressed gag reflex, CNS depression, ingestion of a corrosive substance, or situation with high aspiration potential.
• Treatment of dystonic reactions
  • Dystonic reactions are treated with diphenhydramine in doses of 1 mg/kg IV every 2 minutes, with a maximum of 5 mg/kg per day, unless the dystonic reaction is thought to be caused by or involve antihistamine intoxication.
  • Acute dystonic reactions to antihistamines may be treated with PO or IV diazepam in children. The dose is 0.1-0.3 mg/kg (slowly if IV) and up to 10 mg in adults.
• Treatment of seizures
  • Seizures can be treated with lorazepam. The pediatric dose is 0.05-0.1 mg/kg every 5 minutes as needed.
  • Monitor for hypotension, respiratory depression, and the need for endotracheal intubation.
• Treatment of serotonin syndrome
  • Serotonin syndrome must be managed by addressing each symptom individually.
  • Hyperthermia should be managed by undressing the patient and enhancing evaporative heat loss by keeping the skin damp and using cooling fans.
  • Muscle activity and agitation may be diminished with the use of diazepam.
  • Cyproheptadine is a nonspecific 5-hydroxytryptamine (5HT, serotonin) antagonist that has been shown to block development of serotonin syndrome in animals and is suggested as an antidote for serotonin syndrome in humans. It is available only as an oral preparation.
  • Propranolol also has been used to some benefit as a 5HT1A receptor antagonist.
• Treatment of other conditions
  • Cardiac arrhythmia can be managed with the appropriate cardiac medicine per pediatric advanced life support (PALS) guidelines. In diphenhydramine overdoses, bicarbonate may be helpful in treating QRS complex abnormalities and cardiac dysrhythmias. Treatment with bicarbonate in this overdose should be used in concert with poison center or medical toxicology consultation.
  • Rhabdomyolysis needs to be managed by ensuring adequate hydration and renal function, followed by a solution of sodium bicarbonate and potassium chloride to produce adequate urine flow and a urine pH of at least 7.5. Monitor sodium pH to avoid inducing severe alkalemia. Furosemide or mannitol may be needed to maintain diuresis. Chart strict intake and outputs.
  • Muscle rigidity and hyperactivity are secondary to sympathomimetic toxicity and can be controlled with neuromuscular paralysis.
  • Hyperthermia associated with sympathomimetics can be controlled with external evaporative cooling, removing the patient's clothes, and spraying with tepid water and fanning.
• Use of physostigmine
  • Use of physostigmine in antihistamine poisoning is extremely controversial, and it should not be given unless directed by a regional poison control center or in direct consultation with a medical toxicologist. Physostigmine, an anticholinesterase, may be indicated in the suspected anticholinergic poisoning for its therapeutic value.
  • It is a tertiary amine that crosses the blood brain barrier and reverses both the central and the peripheral effects of anticholinergics. Long-lasting reversal of anticholinergic signs and symptoms is not achieved because of the relatively short duration of action from physostigmine (20-60 min). Indications are severe life-threatening complications, such as coma, hypotension with dysrhythmias unresponsive to other attempts at treatment, and intractable seizures.
  • Adolescent and adult trial dosages are 2 mg IV slowly every 5 minutes. To administer, dilute the dose of physostigmine in 10 mL of dextrose 5% in water (D5W) or in 10 mL of isotonic sodium chloride solution.

Consultations

• Contact a regional poison control center.
• Consult a toxicologist or pediatric toxicologist.
• Psychiatric and neurologic complications require consultation.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Drug Category: Antidotes

Used in the management of poisoning and overdose, prevention of toxic effects, and metabolic disorders in which toxic substances accrue. Mechanisms of action are variable (eg, antagonists, toxin transformation, altered metabolism, chelation, directed antibodies).

Drug Category: Decontamination agents

Consider activated charcoal decontamination in any patient who presents within 4 hours of ingestion.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients with persistent or significant hypertension, dysrhythmia, or CNS stimulation require admission for monitoring.
• The decision to admit the patient to the ICU should be based on the initial presentation, any comorbid diseases, nature and number of the involved agents, and the potential for delayed toxicity.
• For all intentional overdoses, a psychiatric evaluation is necessary.

Further Outpatient Care

• Most regional poison control centers have their own protocols on who may be observed at home; it is important to contact them if ingestion has occurred.
• As a general rule, patients who ingest less than 3 times the maximum daily dose can be observed at home.
• If symptoms are present (other than mild somnolence) or ingestion is more than 4 times the maximum daily dose, the patient should be referred to a health care facility. The patient should be observed for 4-6 hours following ingestion of liquid and immediate-release solid preparations. Ingestion of sustained-release products may result in delayed onset of symptoms and may require longer periods of observation.
• If the patient has ingested less than 10 mg/kg of dextromethorphan, the patient can be treated at home. If the patient has ingested a long-acting dextromethorphan, refer the patient to a health care facility for evaluation.
• If the ingestion was intentional, prompt psychiatric evaluation and admission is warranted.
• Further outpatient treatment should include teaching the patient's caretaker about medication storage and safety.

Deterrence/Prevention

• Medications should be labeled and stored safety.
• Child-resistant closures should be applied to all medications and substances that can cause significant toxicity, such as cough and cold medications.

Patient Education

• Patient education is an important part of pediatric toxicology. Half of children who ingested a poison do it again within a year. Review poison prevention techniques with parents. Encourage poison proofing of the home and posting local poison control center telephone numbers by telephones throughout the home.
• One study showed that only 30% of caregivers who administered acetaminophen were able to demonstrate both accurate measuring and correct dosage for their child.
• Parents should be taught the following 4 guidelines to prevent future ingestions:
  1. Keep household cleaning products in high locked cabinets rather than under the sink. Safety latches should be place on all kitchen and bathroom cabinets and drawers that contain potentially hazardous substances.
  2. Parents should lock all reachable medicine cabinets, always keep medications in their original (childproof) containers and dispose of unused prescriptions by flushing them down the toilet.
  3. Medication should be considered "medicine," not a toy or candy. Medicine should never be referred to as candy and, if possible, not administered in front of other children. Parents, relatives, and friends also should childproof their homes.
  4. Although ipecac syrup has fallen into disfavor within some medical circles, it is still recommended that parents have it readily available in the home for use with medical direction from a physician or poison control center.
• For excellent patient education resources, visit eMedicine's Drug Overdose Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Some states have laws mandating the reporting of child abuse, suspicion of child abuse, and neglect. If the history of ingestion is suspicious, reporting may be necessary.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• American Academy of Pediatrics. Use of codeine- and dextromethorphan-containing cough remedies in children. American Academy of Pediatrics. Committee on Drugs. Pediatrics. Jun 1997;99(6):918-20. [Medline].
• Cardoni AA, Mofenson HC, George DJ. Toxicological management: dextromethorphan. In: Poisindex. 1998.
• Chien C, Marriott JL, Ashby K, Ozanne-Smith J. Unintentional ingestion of over the counter medications in children less than 5 years old. J Paediatr Child Health. May-Jun 2003;39(4):264-9. [Medline].
• Delorio NM. Cerebral infarcts in a pediatric patient secondary to phenylpropanolamine, a recalled medication. J Emerg Med. Apr 2004;26(3):305-7. [Medline].
• Fine JS. Pediatric Principles. Goldfrank's Toxicologic Emergencies. 6th ed. 1995:1687-1697.
• Gadomski A, Horton L. The need for rational therapeutics in the use of cough and cold medicine in infants. Pediatrics. Apr 1992;89(4 Pt 2):774-6. [Medline].
• Goetz CM, Lopez G, Dean BS, Krenzelok EP. Accidental childhood death from diphenhydramine overdosage. Am J Emerg Med. Jul 1990;8(4):321-2. [Medline].
• Gunn VL, Taha SH, Liebelt EL, Serwint JR. Toxicity of over-the-counter cough and cold medications. Pediatrics. Sep 2001;108(3):E52. [Medline].
• Hestand HE, Teske DW. Diphenhydramine hydrochloride intoxication. J Pediatr. Jun 1977;90(6):1017-8. [Medline].
• Hubel PI, Barlas D, Caraccio TR. Pediatric poisonings. In: Emergency Toxicology. 2nd ed. 1998:209-219.
• Huott MA, Storrow AB. A survey of adolescents'' knowledge regarding toxicity of over-the-counter medications. Acad Emerg Med. Mar 1997;4(3):214-8. [Medline].
• Jones J, Dougherty J, Cannon L. Diphenhydramine-induced toxic psychosis. Am J Emerg Med. Jul 1986;4(4):369-71. [Medline].
• Katcher ML. Cold, cough, and allergy medications: uses and abuses. Pediatr Rev. Jan 1996;17(1):12-7. [Medline].
• Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med. Dec 21 2000;343(25):1826-32. [Medline].
• Koppel C, Ibe K, Tenczer J. Clinical symptomatology of diphenhydramine overdose: an evaluation of 136 cases in 1982 to 1985. J Toxicol Clin Toxicol. 1987;25(1-2):53-70. [Medline].
• Lindsay CA, Williams GD, Levin DL. Fatal adult respiratory distress syndrome after diphenhydramine toxicity in a child: a case report. Crit Care Med. Apr 1995;23(4):777-81. [Medline].
• Miller SC. Coricidin HBP cough and cold addiction. J Am Acad Child Adolesc Psychiatry. 2005;44:509-10.
• Pruitt AW. Rational use of cold and cough preparations. Pediatr Ann. Apr 1985;14(4):289-91. [Medline].
• Roberge RJ, Hirani KH, Rowland PL 3rd. Dextromethorphan- and pseudoephedrine- induced agitated psychosis and ataxia: a case report. J Emerg Med. 1999;17:285-8.
• Rumack BH, Normann SA. Toxicologic management: antihistamine/decongestant. In: Poisindex. 1997.
• Schwartz RH. Adolescent abuse of dextromethorphan. Clin Pediatr (Phila). Sep 2005;44(7):565-8. [Medline].
• Simon HK, Weinkle DA. Over-the-counter medications. Do parents give what they intend to give?. Arch Pediatr Adolesc Med. Jul 1997;151(7):654-6. [Medline].
• Tenenbein M. General management principles for poisoning. In: Pediatric Emergency Medicine: Concepts and Clinical Practice. 2nd ed. 1997:527-534.
• Wasserman GS, Mydler TT, Sharma V. Specific toxins. In: Pediatric Emergency Medicine: Concepts and Clinical Practice. 2nd ed. 1997:535-567.
• Wyngaarden JB. The toxic effects of anti-histaminic drugs. JAMA. 1951;145:277-82.
• von Muhlendahl KE, Scherf-Rahne B, Krienke EG, Baukloh G. Codeine intoxication in childhood. Lancet. Aug 7 1976;2(7980):303-5. [Medline].

Article Last Updated: Jul 14, 2006