DESCRIPTION

• Excess autonomic stimulation by adrenergic substances produces the clinical syndrome described as “sympathomimetic.”
• The sequelae of sympathomimetic overdose are generally neurologic, cardiovascular, and psychiatric.
• Severe problems may include agitation-induced hyperthermia, cardiac dysrhythmia, hypertension, myocardial ischemia, infarction, cerebrovascular accident (CVA), seizure, and cardiovascular collapse.

EPIDEMIOLOGY

• Cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA; also called “Molly” or “ecstasy”) are the three most common illicit stimulants causing emergency visits in the United States.
• Prescription stimulants such as methylphenidate and albuterol are often frequent causes of intentional as well as unintentional poisoning.
• Bath salts (mephedrone and methylenedioxypyrovalerone [MDPV] among others) are associated with a much higher incidence of psychotic events than other sympathomimetics.
• Potent amphetamine analogs, such as paramethoxymethamphetamine (PMA), which have a high incidence of morbidity and mortality, are increasingly common components of tablets sold as MDMA.

ETIOLOGY

Causative agents:

• Agents with combined α- and β-adrenergic activity: all amphetamines, cocaine, ephedrine, norepinephrine, pseudoephedrine, and dopamine
• α1-Adrenergic agonists: phenylephrine, phenylpropanolamine
• β-Adrenergic agonists: nonselective β-agonist isoproterenol
• Selective β1 agonists: dobutamine
• Selective β2 agonists: albuterol, salmeterol, terbutaline
• Overdose from sympathomimetic agents occurs secondary to the use of prescription drugs, nonprescription drugs such as over-the-counter (OTC) cold medicine (e.g., pseudoephedrine), dietary supplements (e.g., ephedra, synephrine), and illicit drugs such as cocaine, amphetamine, and methamphetamine.
• Illicit drugs: cocaine, amphetamine, methamphetamine, MDMA (ecstasy), MDPV (bath salts)
• Theophylline and caffeine may cause a clinical syndrome of sympathomimetic poisoning.

PATHOPHYSIOLOGY

• Pathophysiology is based on the adrenergic receptor type stimulated by the drug in question. The adrenergic receptors of relevance include α1, β1, and β2 receptors.
• Common adverse toxic effects of stimulants include the following:
  • Tachycardia, palpitations, chest pain, and tremor
  • Hypertension
  • Nausea, vomiting
  • Anxiety, headache
  • End-organ injury may result in stroke intracranial hemorrhage, or myocardial infarction.
• Sympathomimetic toxicity is highly variable depending on the half-life.
  • For most amphetamines and cocaine, this typically peaks in 1 to 2 hours and lasts 4 to 8 hours.
  • Sustained-release medications may alter this time course and cause much longer toxicity.
• Ephedrine and pseudoephedrine stimulate both α and β receptors:
  • Excessive cardiovascular stimulation results in effects similar to catecholamines.
  • Ephedrine and pseudoephedrine have weaker penetration of the CNS relative to other stimulants.
  • As a result, users may suffer from systemic complications of the relatively larger doses necessary to achieve the CNS “high” of other stimulants.
• Selective β2-adrenergic agonists are commonly used, and these include albuterol, levalbuterol, salmeterol, terbutaline, and others. Besides stimulant toxicity, other effects of β2 agonists include the following:
  • Hypotension, often with widened pulse pressure
  • Hyperglycemia and hypokalemia
  • Elevation of creatine phosphokinase (CPK) as well as troponin, although myocardial infarction is never expected to occur in otherwise healthy children with selective β2 agonist exposure

COMMONLY ASSOCIATED CONDITIONS

• Many sympathomimetic agents are capable of producing psychiatric symptoms, particularly psychosis similar to or indistinguishable from schizophrenia.
• Two rare results of MDMA use include serotonin syndrome and syndrome of inappropriate antidiuretic hormone (SIADH) with symptomatic hyponatremia.