Opioids

OPIOIDS

For centuries opium was used for both medicinal and recreational purposes. Derived from the poppy Papaver somniferum, it contains numerous opiates, the primary one of which is morphine. The term opiate has largely been replaced by opioid, which represents all com-pounds with morphinelike activity and includes mor-phine, morphine derivatives, and peptides. Opiate is used to refer to morphinelike drugs derived from the plant and structurally similar analogues. These drugs are frequently referred to as narcotics, a Greek term for stu-por, which is scientifically obsolete. Even in its early his-tory, opium presented a problem when it was smoked or taken orally. The introduction of the hypodermic needle and syringe, however, drastically enhanced the euphoric properties of opioids and thereby altered their abuse li-ability. In addition, the synthesis of heroin resulted in an opioid that was more potent than morphine and ideally suited for intravenous administration.

Extent and Pattern of Abuse

The abuse of opioids falls into two distinct categories of users, those who initiate use solely for recreational pur-poses and those who become physically dependent as a result of being treated medically with opioids. As dis-cussed, the primary use of opioids is for the control of moderate to severe pain. However, few patients receiving opioids for pain management become dependent. Furthermore, dependence is less likely if opioids are used judiciously. Acute pain can be con-trolled with opioids such as hydromorphone or oxy-codone, which have a rapid onset and short duration of action. In contrast, chronic pain is better treated with opioids such as methadone or morphine (e.g., Dura-morph, MS Contin), which are less likely to produce euphoria because of their slow onset of action. De-pendence in patients is most likely to occur in those with pain of unexplained or poorly defined etiology. Avoiding long-term use of opioids in this population re-duces the risk of developing dependence. Development of dependence should not be a consideration in the man-agement of terminal cancer pain.

The primary illicit opioid is heroin (diacetylmor-phine), which was once used almost exclusively by the intravenous route. In recent years, the purity of street heroin has risen to levels that allow it to be smoked or snorted.

Pharmacological Aspects

First-time users frequently experience unpleasant, or dysphoric, effects that may include nausea and vomiting. The frequent user experiences a rush, or warm flushing feeling, in the skin and lower extremities that is often equated with sexual orgasm. This intense euphoria lasts for one to several minutes and is followed by sedation, relaxation, and tranquility lasting up to an hour. This lat-ter period is sometimes called being on the nod. All ef-fects have largely dissipated within 3 to 5 hours, which requires the user to inject at frequent intervals.

Pharmacokinetics plays a very important role in the manner in which opioids are abused. Morphine and many of its derivatives are slowly and erratically ab-sorbed after oral administration, which makes this route suitable for long-term management of pain but not for producing euphoria. In addition, opioids undergo con-siderable first-pass metabolism, which accounts for their low potency after oral administration. Heroin is more potent than morphine, although its effects arise prima-rily from metabolism to morphine. The potency differ-ence is attributed to heroin’s greater membrane perme-ability and resultant increased absorption into the brain.

Tolerance and Dependence

Tolerance to the unpleasant effects experienced by some individuals at the initiation of opioid use develops readily. Significant tolerance also occurs to the anal-gesic, respiratory depressant, emetic, and euphoric ef-fects, although it develops somewhat more slowly to respiratory depression. Little tolerance to the GI effects and miosis develops. Cross-tolerance occurs with all known opioid analgesics. Opioid tolerance develops more quickly and to a greater extent than it does for most other drugs of abuse. The lethal opioid dose can be 20-fold higher in a tolerant individual than in a neo-phyte. Tolerance develops within a few days if potent opioids are given at frequent intervals, such as every 4 to 6 hours. Development of tolerance requires several weeks if the opioid is given only twice a day.

The continued use of opioids results in the develop-ment of physical dependence, as demonstrated by the appearance of a characteristic abstinence syndrome upon interruption or cessation of use. The symptoms of withdrawal include hyperactivity, anxiety, restlessness, yawning, diarrhea, vomiting, chills, fever, lacrimation, and runny nose. Piloerection (gooseflesh or cold turkey), mydriasis, increased blood pressure and heart rate, and hyperpyrexia may be observed. Tremors, ab-dominal cramps, and muscle and joint pain may be pres-ent. Drug craving is an important feature of opioid with-drawal. In contrast to some other drugs of abuse, withdrawal is not life threatening.

Treatment of Opioid Dependence

Although the ultimate goal of treatment programs is to achieve drug-free status as quickly as possible, it is rarely achieved without pharmacotherapy. The most commonly used strategy is to switch the patient from a short-acting opioid, such as heroin, to a long-acting ag-onist, such as methadone. It is easier to withdraw pa-tients from methadone because it produces a protracted withdrawal syndrome that is less intense than that pro-duced by heroin.

Opioid antagonists, such as naltrexone, provide an-other treatment option in that addicts who are com-pletely withdrawn from an opioid can be maintained on antagonists that will block the pleasurable effects of subsequent injections of heroin. Mixed opioid agonist– antagonists show promise in that they have sufficient agonist effects to reduce craving while at the same time exhibiting antagonist properties.