Background
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 2008, approximately 46,400 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 reported in the Seattle area and the number of deaths nationally secondary to sympathomimetics. Cocaine, methamphetamine, and ecstasy are 3 of the most common drug-related causes of emergency department visits in the United States. 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 DEA moved to makemethylenedioxypyrovalerone, 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.
Pathophysiology
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.
Epidemiology
Frequency
United States
Sympathomimetic poisoning continues to be a very common toxicologic emergency. The 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System reported approximately 46,000 sympathomimetic and street drug exposures and approximately 180 fatalities.[1] This category includes exposures to amphetamines, cocaine, and methamphetamine.
Mortality/Morbidity
In 2008, the AAPCC reported approximately 184 deaths from stimulants and street drugs.[1]
Race
No scientific data have demonstrated that outcomes of sympathomimetic exposure are dependent on race.
Sex
No scientific data have demonstrated that outcomes of sympathomimetic exposure are dependent on sex.
Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). Dec 2008;46(10):927-1057. [Medline].
Swanson SM, Sise CB, Sise MJ, Sack DI, Holbrook TL, Paci GM. The scourge of methamphetamine: impact on a level I trauma center. J Trauma. Sep 2007;63(3):531-7. [Medline].
Wood DM, Davies S, Greene SL, Button J, Holt DW, Ramsey J, et al. Case series of individuals with analytically confirmed acute mephedrone toxicity. Clin Toxicol (Phila). Nov 2010;48(9):924-7. [Medline].
Centers for Disease Control and Prevention. Emergency department visits after use of a drug sold as "bath salts" --- michigan, november 13, 2010--march 31, 2011. MMWR Morb Mortal Wkly Rep. May 20 2011;60(19):624-7. [Medline].
Schwartz BG, Rezkalla S, Kloner RA. Cardiovascular effects of cocaine. Circulation. Dec 14 2010;122(24):2558-69. [Medline].
Bronstein AC, Spyker DA, Cantilena LR Jr, Green J, Rumack BH, Heard SE. 2006 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS). Clin Toxicol (Phila). Dec 2007;45(8):815-917. [Medline].
Budisavljevic MN, Stewart L, Sahn SA. Hyponatremia associated with 3,4-methylenedioxymethylamphetamine ("Ecstasy") abuse. Am J Med Sci. Aug 2003;326(2):89-93. [Medline].
Chiang WK. Amphetamines. In: Goldfrank LR, ed. Goldfrank's Toxicologic Emergencies. 2002. 7th ed. New York: McGraw-Hill; 2002:1020-1033.
Curry SC, Mills KC, Graeme KA. Neurotransmitters. In: Goldfrank LR, ed. Goldfrank's Toxicologic Emergencies. 7th ed. New York, NY: McGraw-Hill; 2002:133-165.
Duffy MR, Ferguson C. Role of dantrolene in treatment of heat stroke associated with Ecstasy ingestion. Br J Anaesth. Jan 2007;98(1):148-9. [Medline].
Hollander JE, Henry TD. Evaluation and management of the patient who has cocaine-associated chest pain. Cardiol Clin. Feb 2006;24(1):103-14. [Medline].
Hollander JE, Hoffman RS. Cocaine. In: Goldfrank LR, ed. Goldfrank's Toxicologic Emergencies. 7th ed. New York, NY: McGraw-Hill; 2002:1004-1019.
Kolecki P. Inadvertent methamphetamine poisoning in pediatric patients. Pediatr Emerg Care. Dec 1998;14(6):385-7. [Medline].
Lineberry TW, Bostwick JM. Methamphetamine abuse: a perfect storm of complications. Mayo Clin Proc. Jan 2006;81(1):77-84. [Medline].
Paredes VL, Rea TD, Eisenberg MS. Out-of-hospital care of critical drug overdoses involving cardiac arrest. Acad Emerg Med. Jan 2004;11(1):71-4. [Medline].
Sue YM, Lee YL, Huang JJ. Acute hyponatremia, seizure, and rhabdomyolysis after ecstasy use. J Toxicol Clin Toxicol. 2002;40(7):931-2. [Medline].
Print
