DESCRIPTION

• Amphetamines are commonly abused drugs.
• Slang terms include crank, crystal, ice, jeff, and speed.

FORMS AND USES

• Numerous illicit preparations are available.
• Amphetamine substances available by prescription include Adderall, benzphetamine (Dridex), biphetamine, chlorphentermine, dextroamphetamine (Bontril, Dexedrine, Dextrostat), diethylpropion, ephedrone, mazindol, mephentermine, pemoline, phendimetrazine tartrate (Prelu-2 Timed Release), phenmetrazine, phen-termine (Fastin, Ionanimin, Obenix, Oby-Cap, Zantryl), Oby-Trim, and Xtrozine.
• Methamphetamine and methylphenidate are covered in other chapters.
• Therapeutic uses include treatment of attention deficit disorder, narcolepsy, and obesity.
• Typical doses are:
  • Adderall 50 to 60 mg/day
  • Benzphetamine 25 to 50 mg one to three times daily
  • Dextroamphetamine 5 to 60 mg/day in divided doses
  • Phendimetrazine 105 mg/day
  • Phenterimine 15 to 37.5 mg/day

TOXIC DOSE

• The toxic dose is variable; therefore, serial observation of the patient is used to assess severity.
• Repeated users develop tolerance; therefore, higher doses are needed to produce toxicity.

PATHOPHYSIOLOGY

Amphetamines are indirectly acting sympathomimetic drugs that stimulate norepinephrine release and have direct agonist effects on alpha- and beta-adrenergic receptors.

EPIDEMIOLOGY

• Poisoning is common, with large regional variations in the incidence of abuse.
• Toxic effects following exposure are typically mild to moderate.
• Death occurs in patients abusing amphetamines at escalating doses.

CAUSES

• Poisoning usually results from recreational abuse.
• Child neglect or abuse should 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

• There is a synergistic effect with other sympathomimetic agents and tricyclic antidepressants.
• Use with monoamine oxidase inhibitors may produce severe toxicity.

PREGNANCY AND LACTATION

• Most amphetamine drugs. 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.
• Diethylpropion. US FDA Pregnancy Category B. Animal studies indicate no fetal risk, and there are no controlled human studies, or animal studies show an adverse fetal effect but well-controlled studies in women do not.
• Abruptio placentae may occur.
• Withdrawal syndrome has been reported in neonates.
• The fetus is at risk for premature delivery and low birth weight.

Section Outline:

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

DIFFERENTIAL DIAGNOSIS

• Toxicologic causes of agitation, seizures and hyperthermia include ingestion or abuse of other sympathomimetic agents (cocaine, ephedrine, and many others).
• Nontoxicologic causes include diseases with adrenergic excess: hyperthyroidism, manic behavior, alcohol withdrawal, and many others.

SIGNS AND SYMPTOMS

• Tachycardia, hypertension, diaphoresis, agitation, and seizures are common.
• Hyperthermia, dysrhythmia, shock, rhabdomyolysis, hepatic necrosis, and acute renal failure may develop in severe overdose.

Vital Signs

• Hypertension, tachycardia, and mild hyperthermia are common.
• Severe hyperthermia and hypotension may develop with life-threatening overdose.

HEENT

Mydriasis may develop.

Cardiovascular

• Dysrhythmia, hypotension, aortic dissection, myocardial infarction, or cardiomyopathy may occur.
• Arterial spasm and localized tissue ischemia may develop after arterial injection.

Pulmonary

Pulmonary edema and adult respiratory distress syndrome may develop with severe overdose.

Hepatic

Hepatic necrosis may develop in patients with severe hyperthermia.

Renal

Acute renal failure may complicate hypotension, seizures, and rhabdomyolysis.

Hematologic

Coagulopathy may develop in severe cases.

Fluids and Electrolytes

• Dehydration and hypokalemia are common.
• Lactic acidosis is common and may become severe if hypotension or hyperthermia develops.

Musculoskeletal

Rhabdomyolysis may develop due to hyperthermia or seizures.

Neurologic

• Headache, agitation, and seizures are common.
• Intracranial hemorrhage, ischemic infarcts, and cerebral vasculitis may occur.

Psychiatric

Paranoid delusions and psychosis may persist beyond the acute phase.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Laboratory testing may not be needed in asymptomatic patients.
• Serum electrolytes, BUN, and creatinine should be determined; metabolic acidosis and renal injury suggest severe intoxication.
• ECG and cardiac monitoring should be performed.
  • Sinus tachycardia is common; other dysrhythmia suggests severe intoxication.
  • Ischemia may occur.

Recommended Tests

• Liver function, coagulation studies, and serum creatine kinase may be abnormal in patients with hyperthermia or agitation.
• Serum acetaminophen and aspirin levels should be performed in overdose setting to detect occult ingestion.
• Head CT, lumbar puncture, and cultures should be performed in patients with altered mental status, headache, seizures, or fever.
• Chest radiograph should be taken in patients with hypoxia or pulmonary symptoms.
• Abdominal radiographs should be taken in patients suspected of ingesting packets.

Not Recommended Test

Serum levels of amphetamine are not available nor useful.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Cardiovascular
  • Pulmonary
  • Hepatic
  • Renal
  • Hematologic
  • Fluids and Electrolytes
  • Musculoskeletal
  • Neurologic
  • Psychiatric
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Not Recommended Test

• Treatment should be focused on controlling agitation, reversing hyperthermia, and supporting hemodynamic function.
• The dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

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

• Severe effects such as shock, hyperthermia, renal or hepatic injury, or coagulopathy are present.
• Toxic effects are not consistent with amphetamine.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Patients should be referred to a health-care facility when:

• There has been inadvertent ingestion of more than a daily dose.
• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Toxic effects are present.
• Coingestant, drug interaction, or underlying disease presents unusual problem.

Admission Considerations

Inpatient treatment is warranted for patients with refractory agitation, recurrent seizures, hyperthermia, persistent tachycardia, or other end-organ injury.

DECONTAMINATION

Out of Hospital

Induction of emesis is not recommended.

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 to 2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.
• Whole-bowel irrigation should be considered in patients ingesting packets, 1 to 2 L/h until rectal effluent is clear.

ANTIDOTES

There is no specific antidote for amphetamine poisoning.

ADJUNCTIVE TREATMENT

Control of Agitation

A benzodiazepine with which the provider has experience should be administered.

• Diazepam
  • Adult dose is 5 to 10 mg intravenously.
  • Pediatric dose is 0.2 to 0.5 mg/kg intravenously.
  • Doses are repeated at 10-minute intervals, titrating to effect.
• Lorazepam
  • Adult dose is 2 to 4 mg intravenously.
  • Pediatric dose is 0.1 mg/kg intravenously.
  • Doses are repeated at 10-minute intervals, titrating to effect.
• The airway should be monitored closely.

Seizure

• An adequate airway and oxygenation should be ensured.
• A benzodiazepine should be administered for initial control.
  • Diazepam
    • Adult dose is 5 to 10 mg by intravenous push, repeated every 10 minutes as needed.
    • Pediatric dose is 0.2 to 0.5 mg/kg, repeated every 10 minutes as needed.
  • Lorazepam
    • Adult dose is 2 to 4 mg by intravenous push over 2 to 5 minutes, repeated every 10 minutes as needed.
    • Pediatric dose is 0.1 mg/kg by intravenous push over 2 to 5 minutes, not to exceed 2 mg/dose.
    • Doses are repeated at 10-minute intervals as needed.
• The airway should be monitored closely.
• If seizures persist or recur, another anticonvulsant such as phenobarbital or phenytoin should be added.
• The use of neuromuscular blockade and artificial ventilation should be considered in refractory patients, especially if hyperthermia is present.

Hypertension

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

Hypotension

• The patient should be given 10 to 20 ml/kg 0.9% saline and placed in the Trendelenburg position.
• Further fluid therapy should be guided by central pressure monitoring to avoid volume overload.
• If hypotension does not respond to treatment, a vasopressor is administered.
  • Dopamine
    • Initial dosage for both children and adults is 2 to 5 µg/kg/min intravenously, titrated upward to effect.
    • Rates greater than 20 µg/kg/min are unlikely to provide further benefit.
  • Norepinephrine
    • Initial dosage for both children and adults is 0.1 to 0.2 µg/kg/min, titrated upward to effect.
    • High rates of infusion may cause tissue ischemia.

Ventricular dysrhythmia

Treatment methods are discussed in SECTION II, Ventricular Dysthythmias chapter.

Rhabdomyolysis

• Adequate hydration and urine output (1 to 2 ml/kg/h) should be ensured.
• Urinary alkalinization has not been shown to be beneficial.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT
  • Control of Agitation
  • Seizure
  • Hypertension
  • Hypotension
  • Ventricular dysrhythmia
  • Rhabdomyolysis

PATIENT MONITORING

Symptomatic patients require continuous monitoring of respiratory and hemodynamic function and core temperature.

EXPECTED COURSE AND PROGNOSIS

• Patients generally recover quickly after oral amphetamine overdose.
• Complications are more common in patients with massive or chronic intravenous abuse.
• Possible complications include:
  • End-organ injury from hypertension or seizures.
  • Hepatic necrosis from severe hyperthermia.
  • Acute renal failure from severe rhabdomyolysis or hypotension.
  • Vasculitis and other sequelae of chronic intravenous abuse (endocarditis, abscess, HIV, sepsis, hepatitis, and tetanus).

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department
  • Asymptomatic patients may be discharged after decontamination, observation for 4 to 6 hours, and psychiatric evaluation, if needed.
  • Patients should be referred for substance abuse treatment.
• From the hospital
  • Patients may be discharged after effects have resolved, mental status has returned to baseline, and laboratory values have normalized.
  • Patients should be referred for substance abuse treatment.

Section Outline:

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

• Mental status changes, hypertension, and hyperthermia should prompt evaluation for CNS bleed, infection, or infarct as well as infectious complications.
• The laboratory should be asked about substances that may cause a false-positive screen for amphetamines.

Poisoning by psychotropic agents: psychostimulants.

See Also: SECTION II, Hypotension, Seizures (Unexplained), and Ventricular Dysrhythmias chapters; SECTION III, Nitroprusside and Whole-Bowel Irrigation chapters; and SECTION IV, Methamphetamine and Methylphenidate chapters.

RECOMMENDED READING

Derlet RW, Rice P, Horowitz BZ, et al. Amphetamine toxicity: experience with 127 cases. J Emerg Med 1989;7:157-161.

Morgan JP. Amphetamine and methamphetamine during the 1990s. Pediatr Rev 1992;13:330-333.

Author: Katherine M. Hurlbut

Reviewer: Luke Yip