DESCRIPTION

• Methamphetamine is a class II controlled substance and a common drug of abuse.
• Slang terms include meth, speed, crank, ice, crystal, and crystal meth.

FORMS AND USES

Methamphetamine is available by prescription as 5-mg tablets (Desoxyn), 10-mg tablets (Methampex), and 5-, 10-, or 15-mg long-acting tablets (Desoxyn Gradumet).

• FDA-approved indications are attention deficit disorder with hyperactivity and exogenous obesity.
• The typical dosage for adults is 2.5 to 5.0 mg/day.
• Illicit methamphetamine is smoked, ingested, or injected. Ice is a clear crystalline form of illicit methamphetamine that may be smoked. Compounds sold illicitly often contain other minor sympathomimetics instead of methamphetamine.

TOXIC DOSE

For the naive user, 1 mg/kg may cause serious toxicity. Much higher doses may be tolerated by chronic users.

PATHOPHYSIOLOGY

• Methamphetamine is a potent, synthetic sympathomimetic structurally related to norepinephrine.
• Peripherally, methamphetamine stimulates the release of norepinephrine from adrenergic neurons and the adrenal cortex, as well as directly stimulating alpha- and beta-adrenergic receptors.
• Centrally, methamphetamine is a potent stimulator of the cerebral cortex, medullary respiratory center, and reticular activating system.
• Methamphetamine is more potent than amphetamine in its central effects and less potent in its peripheral effects.

EPIDEMIOLOGY

• Poisoning is common, with large regional variation in the incidence of abuse.
• Toxic effects following exposure are typically mild.
• Death occurs in patients who take escalating doses.

CAUSES

• Overdose is usually the result of recreational abuse.
• The possibility of child abuse should be considered in patients under 1 year of age; suicide attempt in patients over 6 years of age.

RISK FACTORS

• In geriatric patients, preexisting liver or kidney dysfunction increases toxic potential.
• A history of cardiovascular disease, cerebrovascular disease, seizure disorder, or psychosis predisposes to toxicity.

DRUG AND DISEASE INTERACTIONS

• All stimulants have an additive effects when used together.
• Use with monoamine oxidase inhibitors may cause hypertensive crisis.

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.
• Birth defects reportedly associated with methamphetamine use during pregnancy include cardiac malformations, cleft palate, exencephaly, microcephaly, and mental retardation.
• Neonatal withdrawal symptoms have been reported.
• Infants exposed to methamphetamine have been reported to have low birth weight and to be prone to prematurity.

Section Outline:

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

DIFFERENTIAL DIAGNOSIS

• Toxic causes of agitation and seizure include amphetamine, theophylline, cocaine, isoniazid, tricyclic antidepressants, and monoamine oxidase inhibitors, among others.
• Nontoxic causes include alcohol withdrawal, meningitis, intracranial hemorrhage, hyperthyroidism, manic behavior, psychotic episode, seizure disorder, and cardiovascular crisis.
• Metabolic disorders and infectious processes also must be excluded.

SIGNS AND SYMPTOMS

• Toxicity is manifested by initial hypertension, hyperpyrexia, agitation, and hyperactivity.
• Fasciculation, seizures, and coma may develop.
• Toxic effects are persistent because of the drug's long half-life.
• Methamphetamine may cause serotonin syndrome (see SECTION II, Neuromalignant Syndrome and Serotonin Syndrome chapter).

Vital Signs

Hypertension, hyperthermia, and tachycardia are common.

Dermatologic

Skin is usually pale and diaphoretic.

Cardiovascular

A variety of dysrhythmias, myocardial ischemia or infarction, and aortic dissection have been reported.

Pulmonary

• Use of "Ice" has been associated with acute onset of pulmonary edema.
• Pulmonary hypertension may develop.

Genitourinary

• Increased sphincter tone may cause dysuria or acute urinary retention.
• Renal failure can occur secondary to dehydration or rhabdomyolysis.

Gastrointestinal

Anorexia, vomiting, diarrhea, and gastrointestinal hemorrhage have been reported.

Musculoskeletal

Rhabdomyolysis may occur.

Neurologic

• Symptoms range from restlessness, hyperactivity, talkativeness, insomnia, and headache to seizures and coma.
• Stroke and cerebral vasculitis have been reported.

Psychiatric

• Delusions, paranoia, and aggressive behavior are most common.
• Paranoid psychosis is the classic manifestation of chronic abuse.
• Visual, tactile, or auditory hallucinations may occur.
• Patients may also present with dyskinesia (bruxism, tics) and compulsive, repetitive, or stereotypical behavior.

PROCEDURES AND LABORATORY TESTS

Essential Tests

Laboratory testing may not be needed in asymptomatic patients.

Recommended Tests

• Serum electrolytes, glucose, BUN, and creatinine should be measured to assess the presence of metabolic acidosis or renal injury.
• ECG may reveal sinus tachycardia; other dysrhythmia suggests severe intoxication; ischemia may occur.
• Liver function, coagulation studies, and serum creatine kinase may be abnormal in patients with hyperthermia or agitation.
• Serum acetaminophen and aspirin levels and urine toxicology screen 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 obtained in patients with hypoxia or pulmonary symptoms.

Not Recommended Tests

Serum levels are not available or useful.

Section Outline:

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

• After decontamination, treatment is supportive and symptomatic, focusing on airway control and prompt treatment of hyperthermia, seizures, and dysrhythmias.
• 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:

• Altered mental status, seizure, cardiac dysrhythmia, or other severe effects are present.
• Toxic effects are not consistent with the reported poisoning.
• Coingestant, drug interaction, or underlying disease presents unusual problems.

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

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Signs of toxicity develop.
• Coingestant, drug interaction, or underlying disease presents unusual problems.

Admission Considerations

Inpatient treatment in an intensive care setting is warranted when a patient develops persistent acidosis or CNS or cardiac toxicity.

DECONTAMINATION

Out of Hospital

Emesis with ipecac should not be induced due to the potential for seizures.

In Hospital

• Gastric lavage should be administered in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of a substantial 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 available for methamphetamine poisoning.

ADJUNCTIVE TREATMENT

Agitation

A benzodiazepine familiar to the provider should be administered to control agitation.

• Diazepam
  • The adult dose is 5 to 10 mg administered intravenously.
  • The pediatric dose is 0.2 to 0.5 mg/kg administered intravenously.
  • Doses are repeated at 10-minute intervals, titrated to effect.
• Lorazepam
  • The adult dose is 1 to 2 mg administered intravenously.
  • The pediatric dose is 0.05 mg/kg administered intravenously.
  • Doses are repeated at 10-minute intervals, titrating to effect.
• The airway should be monitored closely.

Seizure

• Patent airway should be ensured.
• A benzodiazepine should be administered for initial control.
• If seizures persist or recur, another anticonvulsant, such as phenobarbital, should be added.

Hypertension

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

Hypotension

• Hypotension should be treated with isotonic fluid infusion, Trendelenburg positioning, and a vasopressor if needed.
• Dopamine is preferred; norepinephrine is added for refractory hypotension.

Ventricular Dysrhythmia

Standard treatment should be initiated (see SECTION II, Ventricular Dysrhythmia chapter).

Rhabdomyolysis

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

Section Outline:

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

PATIENT MONITORING

Respiratory and cardiac function should be monitored continuously for at least 24 hours, or as long as dysrhythmia is present.

EXPECTED COURSE AND PROGNOSIS

• Many cases of methamphetamine toxicity can be managed conservatively.
• Admitted patients can be usually be discharged within 48 hours.
• Complete recovery usually occurs over 1 to 2 days unless complications of rhabdomyolysis, seizures, or hyperthermia develop.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Asymptomatic or minimally symptomatic patients may be discharged after 6 hours of observation, following gastrointestinal decontamination and psychiatric evaluation, if needed.
• From the hospital
  • Patients may be discharged after monitoring for at least 24 hours, when a normal mental status and ECG have been achieved.
  • Patients should be referred for substance abuse treatment.

Section Outline:

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

DIAGNOSIS

• Methamphetamine abuse should be considered in any patient presenting with psychosis, violence, seizures, or cardiovascular abnormalities.
• Intravenous drug abusers should always be examined for infectious complications of abuse.

TREATMENT

Many methamphetamine users are polydrug abusers.

FOLLOW-UP

After abrupt cessation of methamphetamine use, withdrawal symptoms peak in 2 to 3 days (headaches, lethargy, dyspnea, and severe depression).

Section Outline:

• DIAGNOSIS
• TREATMENT
• FOLLOW-UP

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

See Also: SECTION II, Hypertension, Hypotension, Seizure (Unexplained), Neuroleptic Malignant Syndrome and Serotonin Syndrome, and Ventricular Dysrhythmias chapters; and SECTION III, Nitroprusside chapter.

RECOMMENDED READING

Beebe DK, Walley E. Smokable methamphetamine ("ice"): an old drug in a different form. Am Fam Phys 1995;51:449-453.

Derlet RW, Heischober B. Methamphetamine: stimulant of the 90's? West J Med 1990;153:625-628.

Author: David Nyman

Reviewer: Richard C. Dart