Sympathomimetic Toxicity

Updated: Apr 28, 2015
  • Author: Paul Kolecki, MD, FACEP; Chief Editor: Asim Tarabar, MD  more...
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Poisoning from sympathomimetic agents occurs secondary to the use of prescription and nonprescription agents. The public commonly uses prescription sympathomimetic agents, especially for treating diseases such as asthma and narcolepsy. Examples of nonprescription sympathomimetic agents include the over-the-counter cold agents (containing ephedrine), illegal street drugs (eg, cocaine, amphetamines, methamphetamine, mephedrone), dietary supplements (eg, ephedra alkaloids), and the very popular illicit designer drugs (eg, 3,4-methylenedioxy methamphetamine [MDMA, "ecstasy"]).

Cocaine is one of the most commonly abused drugs in the United States, especially in urban areas. Methamphetamine is frequently made and abused throughout the United States. Recent reports state that methamphetamine use has been linked to a rise in HIV transmission. In 2011, approximately 66,540 cases of sympathomimetic and street drug exposures were reported to the American Association of Poison Control Centers. [1] Even more alarming are the number of out-of-hospital cardiac arrests secondary to sympathomimetic toxicity and the number of deaths nationally secondary to sympathomimetics. Methamphetamine use in trauma patients has increased significantly and has been associated with a financial burden on trauma centers. [2]

Mephedrone, a synthetic stimulant, comes in tablet or powder forms and users typically swallow, snort, or inject this drug. The clinical effects reported after mephedrone use are very similar to those caused by cocaine and MDMA. [3] Bath salts are designer drugs that often contain mephedrone and are widely available on the Internet and in stores. The "street names" for mephedrone bath salts are numerous and include ivory snow, vanilla sky, arctic blast, white rush, and white knight. In 2011, the Centers for Disease Control and Prevention (CDC) conducted the first public health investigation of emergency department cases resulting from the use of bath salts. During a 4-month period (November to March), 35 patients who had inhaled, injected, or ingested bath salts presented to emergency departments in Michigan. Of these 35 patients, 17 were hospitalized and one was dead upon arrival. [4] Due to the increase in emergency department visits by people overdosing on bath salts, the DEAmovedtomakemethylenedioxypyrovalerone, mephedrone, and methylone illegal. As of September 7, 2011 possessing and selling these chemicals or the products that contain them is illegal in the US.

The many different sympathomimetic agents produce their physiologic and toxicologic properties through several different mechanisms. Toxicity secondary to these agents typically presents with classic sympathomimetic signs and symptoms that include tachycardia, hypertension, diaphoresis, hyperthermia, agitation, and combativeness.

The general treatment for preventing the potentially significant end-organ damage that is possible after overdose is similar for the sympathomimetic agents because their clinical presentation of toxicity is similar. Most sympathomimetic agents produce central stimulation following overdose. When central stimulation occurs in patients, the most important treatment involves physical and, more importantly, pharmacological control of their agitation.



Sympathomimetic agents produce their physiologic and toxic effects by 5 different mechanisms, as follows:

  • The first mechanism involves direct stimulation of the alpha- and beta-adrenergic receptors. Albuterol is a very commonly used direct-acting beta2-agonist.
  • The second mechanism involves the indirect release of norepinephrine from the presynaptic cytoplasm through a process that bypasses exocytosis. Amphetamine and its derivatives work through this mechanism.
  • The third mechanism involves direct stimulation of adrenergic receptors and an indirect release of presynaptic norepinephrine. Dopamine is the classic example of a mixed-acting agent.
  • The fourth mechanism involves the prevention of presynaptic uptake of norepinephrine. By preventing uptake, norepinephrine concentration rises in the synapse, leading to excessive stimulation of adrenergic receptors. Cocaine and the tricyclic antidepressants produce their sympathomimetic effects mainly by inhibiting presynaptic norepinephrine uptake.
  • The final mechanism involves the prevention of norepinephrine metabolism. As norepinephrine is mainly metabolized by the enzyme monoamine oxidase, the monoamine oxidase inhibitors (MAOIs) are the class of drugs that produce their sympathomimetic effects through this final mechanism.

The pathophysiology of sympathomimetic toxicity is much more involved than what was just listed. To explore these mechanisms in more detail, references for further reading are provided in the reference section. An important clinical point is that the signs and symptoms produced by these 5 different mechanisms are very similar. In most cases, clinical poisoning by one sympathomimetic agent is indistinguishable from that of a second sympathomimetic agent with a different mechanism of action.




United States

Sympathomimetic poisoning continues to be a very common toxicologic emergency. The 2011 Annual Report of the American Association of Poison Control Centers' National Poison Data System reported approximately 66,540 sympathomimetic and street drug exposures and approximately 169 fatalities. [1] This category includes exposures to amphetamines, cocaine, and methamphetamine.


In 2011, the AAPCC reported approximately 169 deaths from stimulants and street drugs. [1]


No scientific data have demonstrated that outcomes of sympathomimetic exposure are dependent on race.


No scientific data have demonstrated that outcomes of sympathomimetic exposure are dependent on sex.