Sympathomimetic Poisoning

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Basics

Description

  • Excess autonomic stimulation by adrenergic agents produces the clinical syndrome typically 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; commonly called “Molly” or “ecstasy”) are the three most common illicit stimulant drugs 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) appear to be associated with a much higher incidence of psychotic events than other sympathomimetics.
  • A number of 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.

Pathophysiology

  • Relevant 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 effects of stimulant toxicity include the following:
    • Tachycardia, palpitations, chest pain, and tremor
    • Hypertension
    • Nausea, vomiting
    • Anxiety, fear, and headache also may occur.
    • More severe symptoms may be associated, if associated with end-organ injury such as stroke or intracranial hemorrhage, myocardial infarction, or other cardiovascular injury.
  • 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 symptoms qualitatively similar to those that occur with catecholamines.
    • Ephedrine and pseudoephedrine have weaker penetration of the CNS relative to drugs of abuse.
    • As a result, users may suffer from systemic complications of the relatively larger doses necessary to achieve the CNS “high” of other stimulants.
  • Isoproterenol, rarely used, is the prototypical nonselective β-agonist causing the following:
    • Tachycardia, hypotension, tachydysrhythmia, myocardial ischemia, and flushing due to its cardiostimulatory and vasodilatory properties
    • Commonly, CNS effects of anxiety, fear, and headache occur.
  • 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:
    • 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
  • Selective α1 agonists include phenylephrine and phenylpropanolamine, although the latter is no longer commercially produced in any meaningful quantity in the United States.
    • Hypertension due to direct vasoconstrictive effects is the most common effect.
    • Reflex bradycardia may occur, particularly with phenylpropanolamine.
    • Headache due to elevated BP and even CVA may occur.

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)
  • Recently, many newer amphetamine congeners have come into use. These are available for purchase over the internet, and until specific legislation can be passed against a certain new drug, it can be legal.
    • Examples of new but illegal stimulants are mephedrone and MDPV (“bath salts”).
    • 1,3-dimethylamylamine (DMAA) is an example of a stimulant widely sold over the internet. DMAA was briefly banned in the United States but is currently legal again.
  • Theophylline and caffeine may cause a clinical syndrome of sympathomimetic poisoning.

Commonly Associated Conditions

  • Many sympathomimetic agents are capable of producing psychiatric symptoms, particularly psychosis.
  • This psychosis is 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.

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