It is difficult to imagine modern medical practice without the use of opioid analgesics. These drugs have been part of health care since 300 B.C. Opium and codeine were isolated in the early nineteenth century, opioid-like substances produced by the body were recognized in the 1970s, and the first endogenous opioid was isolated in 1995. As important as these substances are to modern medicine, opioid drugs have many disadvantages, including overdosage and dependency; close to 1 million individuals in the United States are opioid-dependent. All opioid drugs are capable of producing a heroin-like intoxication, as well as tolerance and withdrawal.

Pharmacology
The prototypic opiates, morphine and codeine (3-methoxymorphine), are derived from the milky juice of the poppy Papaver somniferum . The semisynthetic drugs produced from the morphine or thebane molecules include hydromorphone, diacetylmorphine (heroin), and oxycodone. The purely synthetic opioids and their cousins include meperidine, propoxyphene, diphenoxylate, fentanyl, buprenorphine, tramadol, methadone, and pentazocine.

Endogenous opioid peptides (i.e., enkephalins, endorphins, dynorphins, and others) have distinct distributions in the central nervous system (CNS) and appear to be natural ligands for opioid receptors.

As summarized in (Table 373-1), the receptors with which opioid peptides interact differentially produce analgesia, respiratory depression, constipation, euphoria, and other actions. Substances capable of antagonizing one or more of these actions include nalorphine, levallorphan, cyclazocine, butorphanol, buprenorphine, and pentazocine, each of which has mixed agonist and antagonist properties, as well as naloxone, nalmefene, and naltrexone, which are pure opiate antagonists. The availability of relatively specific antagonists has helped identify at least three different receptor subtypes, including receptors, which influence some of the more classic opioid actions such as pain control, reinforcement, constipation, hormone levels, and respiration; K receptors, with possible similar functions along with sedation and effects on hormones; and beta receptors, thought to relate mostly to analgesia, mood, reinforcement, and breathing. A fourth possible receptor subtype, sensitive to another endogenous peptide, is sometimes called nociceptin or orphanin and may influence pain. The major features of tolerance, dependence, and withdrawal are thought to be mediated primarily by receptors, and these are affected by all prescription opioids.

The most rapid and pronounced effects of opioids occur following intravenous administration, with only slightly less efficient absorption after smoking or inhaling the vapor (“chasing the dragon”). The least intense effects occur after oral consumption. Most of the metabolism of opioids occurs in the liver, primarily through conjugation with glucuronic acid, and only small amounts are excreted directly in the urine or feces. The plasma half-lives of these drugs range from 2.5 to 3 h for morphine to more than 22 h for methadone and even longer for levomethadyl acetate (LAAM).

Street heroin is typically only 5 to 10% pure, mixed with sugars, quinine, powdered milk, phenacetin, caffeine, antipyrine, and strychnine. Unexpected increases in the purity of street drugs can cause unintentional lethal overdoses.

Opioid Drug Abuse and Dependence

• Acute and Chronic Effects of Opioids
• Opioid Abuse and Dependence
• Opioid Drug Abuse and Dependence: Introduction