TOXICOLOGY

DEXTROMETHORPHAN

General Overview

Dextromethorphan is a synthetic compound related structurally to codeine. Although it has some opioid-like characteristics at excessive doses, its main clinical purpose is suppression of coughing rather than pain relief.

Common Preparations and Uses

Dextromethorphan is widely found in nonprescription cough and cold remedies. When taken within the recommended dosage range, it generally does not produce clinically important analgesia, sedation, or suppression of breathing.

Toxicity Threshold

Toxic effects are more likely when a person consumes an amount exceeding approximately ten times the usual therapeutic dose.

Mechanism of Toxicity

When taken in excessive amounts, dextromethorphan may produce mild opioid-like effects on the central nervous system. It also affects serotonin activity by reducing serotonin reuptake, which can contribute to serotonin toxicity under certain circumstances.

Frequency of Poisoning

Clinically significant poisoning from dextromethorphan is relatively uncommon. Severe toxicity occurs less frequently than mild or moderate intoxication.

Circumstances of Exposure

Many clinically important overdoses are intentional. In very young children, particularly those younger than 1 year, inappropriate administration, neglect, or abuse should be considered. In older children and adolescents, deliberate ingestion or self-harm may need to be evaluated.

Important Drug Interactions

Dextromethorphan may interact with medications that increase serotonin activity. Use with monoamine oxidase inhibitors or selective serotonin reuptake inhibitors can, although rarely, contribute to serotonin syndrome.

Pregnancy Considerations

Available reports have not clearly linked dextromethorphan exposure with congenital malformations when used during pregnancy.

DIAGNOSIS

Conditions That May Resemble Toxicity

Respiratory slowing and central nervous system depression can result from many other substances. Possible alternatives include sedative medications, opioids, alcohol, antidepressants, and other toxic agents.

Eye and Head Findings

Visual disturbance may occur during intoxication. The pupils may become either enlarged or constricted, and involuntary rhythmic eye movements may also be present.

Cardiovascular Findings

An overdose may cause an increased heart rate and elevated blood pressure.

Gastrointestinal Findings

Digestive symptoms may include nausea, vomiting, diarrhea, or constipation.

Respiratory Findings

A very large ingestion can interfere with normal breathing and may lead to respiratory depression.

Neurologic and Behavioral Findings

Neurologic toxicity may present with unusual behavior, agitation, excessive activity, exaggerated reflexes, increased muscle tone, hallucinations, psychotic behavior, drowsiness, poor coordination, slurred speech, or seizures.

Features of Severe Poisoning

Marked intoxication may progress from profound drowsiness to stupor or coma.

INVESTIGATIONS

Testing in Asymptomatic Patients

Routine laboratory testing is often unnecessary when the patient has no symptoms and there is no concern for another substance or medical condition.

Basic Laboratory Assessment

Electrolytes, blood urea nitrogen, and creatinine may be measured when altered mental status is present or another medical explanation needs to be excluded.

Evaluation for Combination Products

Because dextromethorphan is often included in products containing other medications, ethanol and acetaminophen levels may be useful when a mixed preparation is suspected.

Assessment of Breathing

Patients with reduced respiratory function should have oxygen saturation monitored. Arterial blood gas testing may be considered when clinically indicated.

Evaluation of Altered Mental Status

Additional investigations should be selected according to the patient’s clinical condition and other possible causes of altered consciousness.

Intentional Ingestion

When an overdose is deliberate, assessment may include an electrocardiogram together with serum acetaminophen and salicylate measurements to identify potentially hidden coingestants.

TREATMENT

Main Treatment Approach

Management is mainly supportive. Airway, breathing, and circulation should be stabilized, and advanced resuscitative measures should be provided when required.

When Poison-Control Advice Is Appropriate

Specialist toxicology or poison-control advice is appropriate when hallucinations, abnormal mental status, serious symptoms, unexpected clinical findings, medication interactions, coingestants, or significant underlying disease complicate the case.

When Medical Evaluation Is Needed

Assessment at a health-care facility is appropriate when intentional self-harm or harm by another person is suspected, symptoms of toxicity are present, supervision at home is unreliable, or another drug or illness creates additional risk.

Admission Considerations

Patients whose symptoms persist should remain under medical evaluation until the abnormalities improve and serious complications have been excluded.

Gastrointestinal Decontamination Outside Hospital

The historical source describes the use of ipecac within 1 hour of ingestion in selected alert patients when medical evaluation would be delayed.

Gastrointestinal Decontamination in Hospital

The historical source also describes gastric emptying measures in selected patients presenting soon after a large ingestion or when major toxicity is present.

Activated Charcoal

A single dose of activated charcoal was described for substantial recent ingestion when airway protection and other clinical circumstances permit its use.

Naloxone

Naloxone has occasionally improved respiratory or central nervous system depression following dextromethorphan poisoning. Its response, however, is unpredictable and it may not produce improvement in every patient.

FOLLOW-UP

Airway Observation

Patients with severe intoxication require careful respiratory monitoring because deterioration in airway protection or breathing may occur.

Monitoring for Serotonin Toxicity

Extra observation is required when dextromethorphan has been taken together with serotonergic drugs such as an MAO inhibitor or SSRI.

Temperature Monitoring

Body temperature should be followed in patients with significant intoxication because serotonin-related toxicity may cause abnormal temperature elevation.

Expected Recovery

Most patients experience relatively mild effects and recover without major complications. Symptoms commonly improve within approximately 24 hours.

Discharge Considerations

Patients who remain free of symptoms may be considered for discharge following an appropriate observation period, commonly around 4 to 6 hours, provided no other medical or toxicologic concerns are identified.

Mental Health Assessment

Psychiatric assessment may be required when the ingestion was deliberate or when self-harm is suspected.

CLINICAL PITFALLS

Avoiding Diagnostic Anchoring

Altered consciousness should not automatically be attributed to dextromethorphan. Other toxic, metabolic, neurologic, and medical causes should remain part of the assessment.

Classification

ICD-9-CM 965.09 refers to poisoning involving expectorants and cough preparations containing codeine-related compounds.

DIETHYLSTILBESTROL (DES)

General Overview

Diethylstilbestrol, commonly abbreviated as DES, is a synthetic nonsteroidal compound that produces effects similar to naturally occurring estrogen.

Available Preparations

DES has historically been supplied as oral tablets in several strengths, as well as in rectal and intravenous preparations.

Historical Therapeutic Uses

Previous clinical applications included palliative treatment of advanced prostate cancer and certain breast cancers. DES was also used for emergency postcoital contraception, menopausal symptoms, postpartum breast discomfort, suppression of lactation, and hormonal feminization.

Acute Toxicity

A single large ingestion usually causes gastrointestinal symptoms rather than severe systemic poisoning. Nausea, vomiting, and diarrhea are among the more typical acute effects.

Effects of Long-Term Exposure

Repeated therapeutic exposure is more concerning than a single overdose because prolonged estrogenic effects may result in significant adverse events.

Fetal Risk

Exposure during pregnancy can affect fetal development and has historically been associated with abnormalities in individuals exposed before birth.

Mechanism of Action

During chronic administration, DES behaves similarly to endogenous estrogen and can affect multiple estrogen-sensitive tissues and organ systems.

Effects in Females Exposed Before Birth

Females exposed to DES during early fetal development have been reported to experience increased rates of menstrual abnormalities, infertility, miscarriage, and premature delivery.

Effects in Males Exposed Before Birth

Male fetal exposure has been associated with epididymal cysts, undescended testes, reduced gonadal function, and impaired sperm production.

Cancer Association

Prenatal DES exposure in females has been associated with an increased occurrence of vaginal clear-cell adenocarcinoma. Cervical abnormalities and other reproductive tract complications have also been described.

Major Risk Factor

Administration of DES during pregnancy represents the most important historical risk factor for fetal exposure.

Cancer-Related Interaction

Because DES has estrogen-like activity, it may stimulate the growth of certain hormone-sensitive malignancies, particularly in susceptible patients.

Pregnancy Classification

DES was formerly classified as FDA Pregnancy Category X because fetal harm had been demonstrated and the risks of use during pregnancy outweighed any potential therapeutic benefit.

DIAGNOSIS

Skin Manifestations

Some patients receiving DES have developed skin eruptions or rashes.

Cardiac Effects

Long-term exposure has been associated with an increased risk of myocardial ischemia.

Thrombotic Complications

Chronic DES use has also been linked with blood clot formation, including stroke, deep-vein thrombosis, pulmonary embolism, mesenteric thrombosis, and retinal vascular thrombosis.

Gastrointestinal Effects

Following an acute overdose, patients may experience nausea, vomiting, abdominal discomfort, or abdominal distension.

Liver Effects

Prolonged DES therapy may occasionally cause liver injury, including hepatitis accompanied by cholestatic jaundice.

Renal and Metabolic Effects

Urethral narrowing and porphyria have been reported during long-term exposure.

Fluid Balance

Chronic estrogenic activity may promote fluid retention and peripheral edema.

Reproductive Effects

Women receiving DES may develop abnormal vaginal bleeding, painful menstruation, or absence of menstrual periods.

Calcium Disturbance

Hypercalcemia may occur, particularly in immobilized patients or those with osteoporosis, impaired kidney function, or metastatic disease involving bone.

Hormonal Effects in Males

Long-term exposure in males may lead to breast enlargement, breast tenderness, changes in body hair, excessive hair growth in certain areas, or hair loss.

INVESTIGATIONS

Acute Asymptomatic Exposure

Patients who remain well after an isolated acute ingestion may not require extensive laboratory testing.

Blood Count

For patients undergoing chronic treatment, a complete blood count may be useful to identify possible bone-marrow abnormalities.

Calcium Measurement

Serum calcium can be assessed when there is concern for abnormal calcium regulation, including hypercalcemia.

Cardiovascular Investigation

An electrocardiogram, chest imaging, and additional cardiovascular tests may be required when cardiac ischemia or thromboembolic disease is suspected.

Liver Assessment

Liver enzymes may be measured to evaluate possible drug-related hepatic injury.

Screening for Other Ingestions

In an overdose situation, acetaminophen and salicylate levels may be obtained when an unrecognized coingestion is possible.

TREATMENT

General Management

Treatment depends mainly on the patient’s symptoms and any complications that develop, as isolated acute DES poisoning is usually associated with relatively low immediate toxicity.

Poison-Control Consultation

Specialist toxicology advice should be considered when symptoms are severe, prolonged, unusual, or complicated by another medication, coingestant, or underlying illness.

Referral for Medical Assessment

Patients who develop clinically significant symptoms should be evaluated in a health-care facility, particularly when another substance or medical condition could increase risk.

Hospital Admission

Inpatient management may be required when intentional self-harm is involved or when major cardiovascular or hematologic complications develop.

Accidental Single Exposure

An otherwise well child or adult with an isolated accidental ingestion may often be observed without hospital admission when appropriate medical advice and supervision are available.

Out-of-Hospital Decontamination

The historical source advises against using ipecac after an isolated DES ingestion because acute toxicity is generally low.

Hospital Decontamination

Gastric lavage is rarely necessary following DES ingestion because major acute toxicity is uncommon. It was historically considered mainly when a dangerous coingestant was involved or another strong indication existed.

Activated Charcoal

The source describes a single dose of activated charcoal for substantial recent ingestion when clinically appropriate.

Specific Antidote

There is no specific antidote available for DES poisoning.

FOLLOW-UP

Long-Term Gynecologic Surveillance

Women who received DES and women exposed to DES before birth require appropriate gynecologic follow-up because of the possibility of delayed reproductive tract complications.

Screening

Periodic pelvic examination and cytologic screening have historically been recommended for individuals at increased risk from DES exposure.

Monitoring for Complications

Follow-up investigations should be guided by the complication being considered. For example, patients with symptoms suggestive of pulmonary embolism require appropriate cardiopulmonary assessment.

Expected Course After Acute Overdose

A single acute overdose usually produces gastrointestinal symptoms lasting several hours before spontaneous improvement occurs.

Long-Term Prognosis

For patients with prolonged exposure, the clinical outcome depends mainly on whether serious complications such as thromboembolic disease, cardiac ischemia, or malignancy develop.

Discharge Criteria

Hospital or emergency department discharge may be considered after acute toxic effects have resolved or become medically stable.

Psychiatric Assessment

Mental health evaluation may be appropriate when ingestion occurred intentionally or self-harm is suspected.

CLINICAL PITFALLS

Importance of Long-Term Monitoring

Failure to recognize and monitor the delayed hematologic, cardiovascular, reproductive, and gynecologic effects associated with chronic DES exposure may allow complications to progress without early detection.

Classification

ICD-9-CM 962 refers to poisoning involving hormones and synthetic hormonal substitutes.

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