Chapter 124

• Amphetamine toxicity results from generalized sympathetic stimulation
• Manifestations of toxicity include tachycardia, diaphoresis, hypertension, tachypnea, tremor, and possibly seizures
• Seratonin syndrome and hyponatremia are associated with MDMA use
• Moderate amphetamine toxicity is treated with benzodiazepines
• Benzodiazepines are the first line treatment for amphetamine associated seratonin syndrome and seizures.

Amphetamines have been used for medicinal and recreational purposes over the past century. Initially developed as a treatment for respiratory conditions, they were also noted to have stimulant properties. These stimulant properties were exploited to enhance alertness and decrease sleepiness in soldiers during World War II. The “high” that is often experienced with amphetamines made these drugs popular for recreational use. Modifications to amphetamines have led to the development of compounds with hallucinogenic effects enhancing their appeal to the recreational users.

Strictly, the term “amphetamine” is an acronym used to describe the phenylethylamine stimulant alpha-methylphenylethylamine. Over time, a number of different modifications to the phenylethylamine molecule have spawned many other amphetamine-related compounds with a variety of stimulant and hallucinogenic effects, including methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Collectively, these compounds are often referred to as “amphetamines” as well (Fig. 124–1).

###### Figure 124-1.

Chemical structures of common amphetamines.

Over the past 30 years, amphetamines have been gaining increasing popularity. Methamphetamine has taken over as the leading drug of abuse in the western United States,1 and MDMA has become a leading drug of abuse among adolescents and young adults. MDMA is especially popular at dance parties (e.g., “raves”) and other social gatherings.2 This increased popularity of amphetamines in illicit drug activities has led to the creation of laws that limit access to some over-the-counter decongestants. These medications are structurally related to the amphetamine compounds and were used as part of the production of certain amphetamines—particularly methamphetamine.

In 2006, there were 12 021 amphetamine, 1932 hallucinogenic amphetamine, and 1186 methamphetamine exposures reported to the American Association of Poison Control Centers National Poison Database System (NPDS)—over half of these exposures occurred in patients younger than 19 years.3 Despite the reported numbers to the NPDS, the true prevalence of amphetamine toxicity is likely much higher.

In general, amphetamines are relatively lipophilic and cross the blood–brain barrier readily. The serum half-life of amphetamine varies from 8 to 30 hours, that of methamphetamine from 12 to 34 hours, and that of MDMA from 5 to 10 hours. Frequent use may lead to an accumulation of drug in the body prolonging the half-life and duration of effect.

Amphetamines act to increase the amount of monoamines released for neurosynaptic transmission leading to the indirect general activation of monoamine receptors—notably adrenergic and dopaminergic receptors. The mechanisms by which these amphetamines elicit this response are very complex and are not completely elucidated.4 Some ...

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