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INTRODUCTION

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Opioids are among the oldest therapies in our armamentarium, and clinicians recognize their universal utility to limit human distress from pain. Opioids enjoy widespread use as potent analgesics, even though they are abused because of their psychoactive properties. Although the therapeutic and toxic doses are difficult to predict because of the development of tolerance with chronic use, the primary adverse event from excessive dosing is respiratory depression.

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HISTORY AND EPIDEMIOLOGY

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The medicinal value of opium, the dried extract of the poppy plant Papaver somniferum, was first recorded around 1500 b.c. in the Ebers papyrus. Raw opium is typically composed of at least 10% morphine, but extensive variability exists depending on the environment in which the poppy is grown.89 Although reformulated as laudanum (deodorized tincture of opium; 10 mg morphine/mL) by Paracelsus, paregoric (camphorated tincture of opium; 0.4 mg morphine/mL), Dover’s powder (pulvis Doveri), and Godfrey’s cordial in later centuries, the contents remained largely the same: phenanthrene poppy derivatives, such as morphine and codeine. Over the centuries since the Ebers papyrus, opium and its components have been exploited in two distinct manners: medically to produce profound analgesia and nonmedically to produce psychoactive effects.

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Currently, the widest clinical application of opioids is for acute or chronic pain relief. Opioids are available in various formulations that allow administration by virtually any route: epidural, inhalational, intranasal, intrathecal, oral, parenteral (ie, subcutaneous {SC}, intravenous {IV}, intramuscular {IM}), rectal, transdermal, and transmucosal. Patients also may benefit from several of the nonanalgesic effects engendered by certain ­opioids. For example, codeine and hydrocodone are widely used as antitussives, and diphenoxylate is used as an antidiarrheal.

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Unfortunately, the history of opium and its derivatives is marred by humankind’s endless quest for xenobiotics that produce pleasurable effects. Opium smoking was so problematic in China by the 1830s that the Chinese government attempted to prohibit the importation of opium by the British East India Company. This act led to the Opium Wars between China and Britain. China eventually accepted the importation and sale of the drug and was forced to turn over Hong Kong to British rule. The euphoric and addictive potential of the opioids is immortalized in the works of several famous writers, such as Thomas de Quincey (Confessions of an English Opium Eater, 1821), Samuel Coleridge (The Rime of the Ancient Mariner, 1798), and Elizabeth Barrett Browning (Aurora Leigh, 1856).

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Because of mounting concerns of addiction and toxicity in the United States, the Harrison Narcotic Act, enacted in 1914, made nonmedicinal use of opioids illegal. Since that time, recreational and habitual use of heroin and other opioids have remained epidemic in the United States and worldwide despite extensive and diverse attempts to curb their availability.

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Morphine was ...

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