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INTRODUCTION

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Image not available. Opiate analgesics have been abused since at least 300 B.C. Nepenthe (Greek “free from sorrow”) helped the hero of The Odyssey, but widespread opium smoking in China and the Near East has caused harm for centuries. Since the first chemical isolation of opium and codeine 200 years ago, a wide range of synthetic opioids have been developed, and opioid receptors were cloned in the 1990s. Two of the most important adverse effects of all these agents are the development of opioid use disorder and overdose. The 0.1% annual prevalence of heroin dependence in the United States is only about one-third the rate of prescription opiate use and is substantially lower than the 2% rate of morphine users in Southeast and Southwest Asia. Prescription opiates are primarily used for pain management, but due to ease of availability, adolescents procure and use these drugs with dire consequences. In 2011, for example, 11 million individuals in the United States used nonmedically prescribed pain killers that were linked to over 420,000 emergency department visits and nearly 17,000 overdose deaths. Although these rates are low relative to other abused substances, their disease burden is substantial, with high rates of morbidity and mortality; disease transmission; increased health care, crime, and law enforcement costs; and less tangible costs of family distress and lost productivity.

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The terms “dependence” and “addiction” are no longer used to describe substance use disorders. Opioid-related disorders encompass opioid use disorder, opioid intoxication, and opioid withdrawal. The diagnosis of opioid use disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) requires the repeated use of the opiate while producing problems in two or more areas in a 12-month period. The areas include tolerance, withdrawal, use of greater amounts of opiates than intended, craving, and use despite adverse consequences. This new definition of opiate use disorder, reducing the criteria for diagnosis from three problem areas to two, is not expected to change the rates of these disorders because most individuals using these substances meet more than three criteria.

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A striking recent aspect of illicit opiate use has been its marked increase as the gateway to illicit drugs in the United States. Since 2007, prescription opiates have surpassed marijuana as the most common illicit drug that adolescents initially use, although overall rates of opiate dependence are far lower than marijuana. The most commonly used opiates are diverted prescriptions for oxycodone and hydrocodone, followed by heroin and morphine, and—among health professionals—meperidine and fentanyl. Heroin is derived from morphine and acts as a prodrug that more readily penetrates the brain and is converted rapidly to morphine in the body. Two opiate maintenance treatment agents—methadone and buprenorphine—are also misused, but at substantially lower rates, and the partial opiate agonists such as butorphanol, tramadol, and pentazocine are misused even less frequently. Because the chemistry and general pharmacology of these agents are covered in major pharmacology texts, this chapter focuses ...

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