DESCRIPTION

Phenylpropanolamine (PPA) is a common over-the-counter decongestant.

FORMS AND USES

PPA is used as a decongestant and appetite suppressant. Pharmaceutical preparations that contain PPA include:

• Numerous decongestants including St. Joseph Cold Tablets for Children, Allerest Maximum Strength 12-hour Caplets, Contac Maximum Strength 12-hour Caplets, Ornade Spansules, Contac 12-hour Capsules, Teldrin 12-hour Allergy Relief Capsules, Vicks DayQuil Allergy Relief 12-hour Tablets, Tavist-D Tablets, Vicks DayQuil Allergy Relief 4-hour Tablets, Demazin Syrup, Temazine Cold Syrup, Dimetapp Elixir, Triaminic Syrup, Dimetapp Cold & Allergy, Triaminic Oral Infant Drops, Naldelate Pediatric Syrup, Naldecon Pediatric Syrup, Nalgest Pediatric Syrup, Naldecon Pediatric Drops, Alka Seltzer Plus Cold Tablets, Coricidin Maximum Strength Sinus Headache Tablets, Congestant D Tablets, Drixoral Cough & Sore Throat Liquid Caps, Alka-Seltzer Plus Cold & Cough Tablets, Alka-Seltzer Plus Night Time Cold Tablets, Maximum Strength Comtrex Liqui-Gels (Capsules), Comtrex Max Strength Multi-Symptom Cold & Flu Relief Liqui-Gels, Triaminic-DM Syrup, and numerous generic forms.
• Appetite suppressants including Dexatrim, Control, and Acutrim.
• Therapeutic dosages for nasal decongestion: adult, 20 to 25 mg every 4 hours up to 150 mg/day; pediatric (6-12 years), 10 to 12.5 mg every 4 hours up to 75 mg/day
• Therapeutic dosages for appetite suppression: adult, 25 mg three times a day up to 75 mg/day; pediatric (2-6 years), 6.25 mg every 4 hours up to 37.5 mg/day

TOXIC DOSE

• Twice the maximum daily dose is tolerated well by children or adults.
• Death in adults has been reported at ingestions exceeding 500 mg.

PATHOPHYSIOLOGY

• PPA is a sympathomimetic agent that is an indirect alpha-receptor agonist, but may also have some direct stimulatory properties.
• The CNS, cardiovascular, and gastrointestinal systems are the target organs.

EPIDEMIOLOGY

• Poisoning is common.
• Toxic effects following exposure are typically mild to moderate.
• Death is associated with massive overdose or concurrent abuse of other drugs.

CAUSES

• Toxic ingestion is usually accidental, and by a child.
• Adolescents may purchase PPA to achieve an amphetamine-like "high."
• Child abuse or neglect must be considered if the patient is less than 1 year of age; suicide attempt if the patient is over 6 years of age.

DRUG AND DISEASE INTERACTIONS

• Persons with hypertension, atherosclerotic peripheral vascular disease, or diabetes mellitus should avoid this drug unless prescribed by their physician.
• Concurrent use with an monoamine oxidase (MAO) inhibitor may cause severe hypertension.
• Concurrent use of caffeine may enhance absorption or inhibit elimination, thereby increasing adverse effects.
• Concurrent use of bromocriptine may cause possible exacerbation of side effects.
• Indomethacin may enhance the vasoconstrictive effects of PPA.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
• Women who are pregnant should use this drug with caution.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

• Toxic causes of tachycardia, hypertension, agitation, and seizures include other sympathomimetic agents (cocaine, amphetamines, MAO inhibitors, phenylephrine, fenfluramine, others), caffeine, theophylline, and others.
• Nontoxic causes include diseases with adrenergic excess: hyperthyroidism, manic behavior, alcohol or sedative-hypnotic withdrawal, and many others.

SIGNS AND SYMPTOMS

• Patients are typically anxious and nauseated, and have headache.
• Dry mouth, psychosis, and seizures are possible.
• Patient presentation with hypertension and reflex bradycardia is possible.

Vital Signs

Tachycardia and hypertension are common. Reflex bradycardia may occur instead of tachycardia.

HEENT

Blurred vision and mydriasis may occur.

Cardiovascular

• Tachycardia, bradycardia, and hypertension may occur.
• Myocardial ischemia is possible due to hypertensive crisis.

Pulmonary

Tachypnea and dry mouth may occur.

Gastrointestinal

Anorexia, vomiting, and nausea may occur.

Renal

Acute renal failure and rhabdomyolysis may occur in severe cases.

Musculoskeletal

Rhabdomyolysis can occur with seizures or severe agitation.

Neurologic

• Anxiety, restlessness, irritability, psychosis, seizures, and altered mental status may occur.
• Intracranial hemorrhage has occurred with hypertensive crisis.

PROCEDURES AND LABORATORY TESTS

Essential Tests

No tests may be needed in minimally symptomatic patients.

Recommended Tests

• ECG and cardiac enzymes in patients with possible myocardial ischemia
• Serum creatine kinase to assess muscle injury
• Serum electrolytes, BUN, and creatinine to assess acid-base balance and renal function
• Urinalysis to assess renal injury
• ECG, serum acetaminophen and aspirin levels in overdose setting to detect occult ingestion
• Head CT, lumbar puncture, bacterial cultures, other tests as needed to assess altered mental status or fever of unknown etiology

Not Recommended Tests

Serum levels of PPA are not clinically useful.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Renal
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Not Recommended Tests

• Treatment should focus on control of airway, agitation, seizures, and support of hemodynamic function.
• Dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care provider should call the poison control center when:

• Seizure, dysrhythmia, or other severe effects are present.
• Toxic effects are not consistent with PPA.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Toxic effects develop.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted if the patient exhibits severe or persistent cardiac or CNS toxicity.

DECONTAMINATION

Out of Hospital

Emesis should be induced with ipecac within 1 hour of ingestion in asymptomatic children who have ingested 6 to 10 mg/kg if health-care evaluation will be delayed.

In Hospital

• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of a large ingestion or if serious effects are present.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.

ANTIDOTES

There is no specific antidote for PPA poisoning.

ADJUNCTIVE TREATMENT

Agitation or Seizure

• Airway must be secured.
• A benzodiazepine familiar to the provider should be administered.
  • Diazepam. Adult dose 5 to 10 mg intravenously; pediatric dose 0.2 to 0.5 mg/kg intravenously; doses repeated at 10-minute intervals, titrating to effect
  • Lorazepam. Adult dose 2 to 4 mg intravenously; pediatric dose 0.05 to 0.1 mg/kg; doses repeated every 10 minutes, titrating to effect.
• Airway must be monitored closely.

Hypertension

If hypertension is not responsive to benzodiazepines, or end-organ damage develops (aortic dissection, CNS bleed, myocardial infarction), a short-acting titratable agent (e.g., nitroprusside) should be administered until desired response is seen.

Hypotension

• Hypotension should be treated with isotonic fluid infusion, Trendelenburg positioning, and vasopressor if needed; dopamine is preferred.
• Norepinephrine can be used for refractory hypotension.

Ventricular Dysrhythmia

• The standard Advanced Cardiac Life Support algorithms should be followed.
• Lidocaine (1 mg/kg intravenous bolus; repeat 0.5 mg/kg bolus if necessary and follow with 20 to 40 µg/kg/min infusion) may be used for ventricular tachycardia or frequent premature ventricular contractions.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT
  • Agitation or Seizure
  • Hypertension
  • Hypotension
  • Ventricular Dysrhythmia

PATIENT MONITORING

Cardiac and respiratory function should be monitored continuously until toxic effects resolve.

EXPECTED COURSE AND PROGNOSIS

Following acute ingestion, toxicity develops soon, peaks within hours, and patient recovers within 24 hours unless complications of hypertension, seizures, or intracranial bleeding develop.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department
  • Asymptomatic patients with normal blood pressure may be discharged following gastrointestinal decontamination, a 4- to 6-hour observation period, and psychiatric evaluation, if needed.
  • A longer observation period should be considered for ingestions involving sustained-release products.
• From the hospital. Patients may be discharged following gastrointestinal decontamination, resolution of complications, and psychiatric evaluation, if needed.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS

• Combinations with other oral decongestants or antihistamines are common in overdoses.
• Due to the popularity of diet aids, there is great potential for abuse and these should be suspected.

Poisoning by drugs primarily affecting the autonomic nervous system: Sympathomimetics (adrenergics).

See Also: SECTION II, Hypertension, Hypotension, Seizures, and Ventricular Dysrhythmias chapters; and SECTION III, Nitroprusside chapter.

RECOMMENDED READING

Dietz A. Amphetamine-like reactions to phenylpropanolamine. JAMA 1981;245:601-602.

Goldfrank LR, Lewin NA, Weisman RS. Dieting agents and regimens. In: Goldfrank LR, et al., eds. Goldfrank's toxicologic emergencies, 6^th ed. Norwalk, CT: Appleton & Lange, 1998.

Author: Kathleen M. Wruk

Reviewer: Richard C. Dart