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Dextroamphetamine (Dexedrine) and methylphenidate (Ritalin) are used for the treatment of narcolepsy and for attention-deficit disorders in children. Methamphetamine (“crank,” “speed”), 3,4-methylenedioxymethamphetamine (MDMA; “ecstasy”), paramethoxyamphetamine (PMA), and several other amphetamine derivatives (see also “Lysergic Acid Diethylamide [LSD] and Other Hallucinogens”), as well as a number of prescription drugs, are used as illicit stimulants and hallucinogens. “Ice” is a smokable form of methamphetamine. Methamphetamine precursors such as phenylpropanolamine, ephedrine, and other over-the-counter decongestants are discussed in Paraquat and Diquat. Several amphetamine-related drugs (benzphetamine, diethylpropion, phendimetrazine, phenmetrazine, and phentermine) are marketed as prescription anorectic medications for use in weight reduction (Table II–1). Fenfluramine and dexfenfluramine were marketed as anorectic medications but were withdrawn from the market in 1997 because of concerns about cardiopulmonary toxicity with long-term use.

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Table II-1 Amphetamine-Like Prescription Drugsa
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Cathinone (found in the shrub Catha edulis, or khat), methcathinone, and mephedrone (4-methylmethcathinone) are chemically related drugs with amphetamine-like effects. Newer synthetic analogs, such as 3,4-methylenedioxypyrovalerone and various derivatives of methcathinone, are becoming popular drugs of abuse, often sold on the Internet as “bath salts” with names such as “Ivory Wave,” “Bounce,” “Bubbles,” “Mad Cow,” and “Meow Meow.” Atomoxetine is a specific norepinephrine reuptake inhibitor approved as a nonstimulant alternative for the treatment of attention-deficit/hyperactivity disorder (ADHD). Modafinil is a nonamphetamine stimulant used in the treatment of narcolepsy, sleep disorders associated with shift work, and sleep apnea.

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  1. Mechanism of toxicity

    1. Amphetamine and related drugs activate the sympathetic nervous system via CNS stimulation, peripheral release of catecholamines, inhibition of neuronal reuptake of catecholamines, and inhibition of monoamine oxidase. Amphetamines, particularly MDMA, PMA, fenfluramine, and dexfenfluramine, also cause serotonin release and block neuronal serotonin uptake. The various drugs in this group have different profiles of catecholamine and serotonin action, resulting in different levels of CNS and peripheral stimulation.

    2. Modafinil is a nonamphetamine stimulant. Its mechanism of action is unclear, but CNS levels of dopamine, norepinephrine, serotonin, histamine, and glutamate are increased while gamma-aminobutyric acid (GABA) is decreased. Atomoxetine is a specific norepinephrine reuptake inhibitor.

    3. Pharmacokinetics. All these drugs are well absorbed orally and ...

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