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Use
of opioids for medical purposes but without the supervision of health
care practitioners and all use for nonmedical purposes can lead
to consequences such as delirium and injury. Chronic use can lead
to dependence. Dependence is marked by an overpowering compulsion
to continue taking opioids, the development of tolerance so that
the dosage must be increased to obtain the initial effect, and physical
dependence that increases in intensity with increased dosage and
duration of use.
Dependence on opioids is increasing. Heroin is the most commonly used recreational opioid, whereas opium use is uncommon. Dependence on prescription analgesic opioids, such as morphine and oxycodone , is increasing, with some of the increase accounted for by people who are taking them for legitimate medical purposes. Additionally, many people find that opioid use allows them to bear what they once considered the unbearable stresses of life.
Physical dependence necessitates continued use of the same opioid or a related one to prevent withdrawal. Withdrawal of the drug or administration of an antagonist precipitates a characteristic, self-limited withdrawal syndrome.
Therapeutic doses taken regularly over 2 to 3 days can lead to some tolerance and dependence, and when the drug is stopped, the user may have mild withdrawal symptoms which are scarcely noticed or are flu-like.
Patients with chronic pain requiring long-term use should not be labeled addicts, although they may have some problems with tolerance and physical dependence. Opioids induce cross-tolerance so that abusers can substitute one for another. People who have developed tolerance may show few signs of drug use and may function normally in their usual activities, but obtaining the drug is an ever-present problem. Tolerance to the various effects of these drugs frequently develops unevenly. Heroin users, for example, may become largely tolerant to the drug's euphoric and lethal effects but continue to have constricted pupils and constipation.
Symptoms and Signs
Acute intoxication (overdose) is characterized by euphoria, flushing, itching (particularly with morphine ), miosis, drowsiness, decreased respiratory rate and depth, hypotension, bradycardia, and decreased body temperature.
Physical dependence is suggested by a history of ≥ 3 opioid injections/day, fresh needle marks, withdrawal symptoms and signs, or morphine glucuronide in a urine specimen (heroin is biotransformed to morphine , conjugated with glucuronide, and excreted). Because heroin is often snorted, the nasal septum may be perforated.
The withdrawal syndrome generally includes symptoms and signs of CNS hyperactivity. Severity of the syndrome increases with the size of the opioid dose and the duration of dependence. Symptoms appear as early as 4 h after withdrawal and, for heroin, peak within 72 h. Anxiety and a craving for the drug are followed by increased resting respiratory rate (> 16 breaths/min), usually with yawning, perspiration, lacrimation, and rhinorrhea. Other symptoms include mydriasis, piloerection (gooseflesh), tremors, muscle twitching, hot and cold flashes, aching muscles, and anorexia. The withdrawal syndrome in people who were taking methadone (which has a long half-life) develops more slowly and is overtly less severe than heroin withdrawal, although users may describe it as worse.
Complications:
Complications of heroin addiction may be related to the unsanitary administration of the drug or to the drug's inherent properties, overdose, or intoxicated behavior accompanying drug use. Common complications are pulmonary, bone, and neurologic disorders; hepatitis; and immunologic changes.
Aspiration pneumonitis, pneumonia, lung abscess, septic pulmonary emboli, and atelectasis may occur. Pulmonary fibrosis from talc granulomatosis may develop when opioid analgesic tablets are injected. Chronic heroin addiction results in a decreased vital capacity and a mild to moderate decrease in diffusion capacity. These effects are distinct from the pulmonary edema that may occur acutely with heroin injection. Many opioid addicts smoke ≥ 1 pack of cigarettes/day, making them particularly susceptible to a variety of pulmonary infections.
Viral hepatitis types A, B, and C may develop. The combination of viral hepatitis and the frequently high alcohol intake may account for the high incidence of liver dysfunction.
Osteomyelitis (particularly lumbar vertebral) is the most common musculoskeletal complication, probably due to hematogenous spread of organisms from unsterile injections. Infectious spondylitis and sacroiliitis may occur. In myositis ossificans (drug abuser's elbow), the brachialis muscle is damaged by inept needle manipulation, followed by replacement of the muscle bundle with a calcific mass (extraosseous metaplasia).
Hypergammaglobulinemia of both IgG and IgM occurs in ≤ 90% of addicts. The reason is unknown but may reflect repeated antigenic stimulation from infections or from daily parenteral injection of foreign substances. Hypergammaglobulinemia diminishes with methadone maintenance. Heroin addicts and other IV drug users are at extremely high risk of HIV infection and AIDS. In communities in which sharing of needles and syringes is common, the spread of AIDS is devastating.
Neurologic disorders in heroin addicts are usually noninfectious complications of coma and cerebral anoxia. Toxic amblyopia (apparently due to adulteration of heroin by quinine ), transverse myelitis, various mononeuropathies and polyneuropathies, and Guillain-Barré syndrome may occur. Cerebral complications include those secondary to bacterial endocarditis (bacterial meningitis, mycotic aneurysm, brain abscess, and subdural and epidural abscesses), those due to viral hepatitis or tetanus, and acute cerebral falciparum malaria. Some neurologic complications may be due to allergic responses to the heroin-adulterant mixture.
Superficial cutaneous abscesses, cellulitis, lymphangitis, lymphadenitis, and phlebitis from contaminated needles may occur. Many heroin addicts begin with subcutaneous injections (skin popping) and may return to this mode when extensive scarring makes their veins inaccessible. As addicts become more desperate, cutaneous ulcers in unlikely sites may be found. Contaminated needles and inoculum may lead to bacterial endocarditis, hepatitis, and HIV infection. These complications follow frequent injection. Because heroin potency has recently increased, more users are snorting and smoking, which may diminish problems with infectious contamination.
Some problems of the heroin-addicted mother are transferred to the fetus. Because heroin and methadone freely cross the placental barrier, the fetus readily becomes physically dependent. A mother infected with HIV or hepatitis B virus may transmit the virus to her newborn. Pregnant addicts seen early enough should be encouraged to enter a methadone maintenance program. Abstinence is better for the fetus, but abstinent mothers often revert to heroin use and withdraw from prenatal care. Withdrawal of heroin or methadone from pregnant women late in the 3rd trimester may precipitate early labor; thus, pregnant women seen at or near term may best be stabilized with methadone rather than disturbed by attempts to withdraw opioids. The methadone -maintained mother may nurse her newborn without causing any apparent clinical problems in the child, because concentration of the drug in breast milk is minimal.
Infants of opioid-dependent mothers may present with tremors, a high-pitched cry, jitters, seizures (rarely), and tachypnea. Problems of the newborn, including drug withdrawal and fetal alcohol syndrome, are discussed in Metabolic, Electrolyte, and Toxic Disorders in Neonates: Prenatal Drug Exposure.
Treatment
Acute use:
Overdose is usually managed with the opioid antagonist naloxone (0.4 to 2 mg IV) because it has no respiratory depressant properties (see Table 8: Poisoning: Symptoms and Treatment of Specific Poisons  ). It rapidly reverses unconsciousness due to an opioid. Because some patients become agitated, delirious, and combative as they recover from a comatose state, physical restraints may be required and should be applied before the antagonist is given. All patients treated for overdose should be hospitalized and observed for at least 24 h because the action of naloxone is relatively short. Also, respiratory depression may recur within several hours, especially with methadone , at which time methadone should be re-administered at an appropriate dose. Severe pulmonary edema, which may cause death from hypoxia, is usually not responsive to naloxone and has an unclear relationship to overdose.
Chronic use:
The clinical management of opioid addicts is extremely difficult. The AIDS epidemic has provoked a harm-reduction movement, seeking to offer services that reduce the harm of drug use without requiring cessation. For example, providing clean needles and syringes for injection users reduces the spread of HIV. Despite this evidence of harm reduction, US federal funding cannot be used to establish needle or syringe provision to IV users. Other harm-reduction approaches, including easy access to methadone or buprenorphine maintenance, alternative maintenance strategies, and eased restrictions on the prescribing of psychoactive drugs, are more prevalent in some European countries than in the US, where programs viewed as abetting drug consumption behavior are resisted.
Physicians must be fully aware of federal, state, and local regulations. Treatment is complicated by the need to deal with the societal attitudes toward the treatment of addicts (including the attitudes of law enforcement officers and other physicians and health care practitioners). In most cases, the physician should refer addicts to specialized treatment centers rather than attempt to care for them alone.
To legally use an opioid drug in treating an addict, a physician must establish the existence of physical opioid dependence. However, many addicts who seek treatment use low-grade heroin, which may not cause physical dependence. Low-grade opioid dependence (as may occur in people who have used opioid analgesics for a long time) can be treated by reducing the opioid dose slowly, by substituting a weak opioid (eg, propoxyphene ), or by using benzodiazepines (which are not cross-tolerant to opioids) in decreasing doses.
The withdrawal syndrome is self-limited and, although severely uncomfortable, is not life threatening. Minor metabolic and physical withdrawal effects may persist up to 6 mo. Whether this protracted withdrawal syndrome contributes to relapse is unclear. The patient's drug-seeking behavior usually begins with the first symptoms of withdrawal, and hospital personnel must be aware that he will try to obtain drugs. Visitors may have to be restricted. Many patients with withdrawal symptoms have other medical problems that must be diagnosed and treated.
Methadone substitution is the preferred method of opioid withdrawal for more seriously addicted patients because of its long half-life and less profound sedation and euphoria. Methadone is given orally in the smallest amount (generally, 15 to 40 mg once/day) that will prevent severe but not necessarily all symptoms of withdrawal. Higher doses should be given when evidence of withdrawal is observed. Doses of ≥ 25 mg can produce unconsciousness if the person has not developed tolerance. After the appropriate dose has been established, it should be reduced progressively by not more than 20%/day. Patients commonly become angry and request additional medication. The withdrawal syndrome induced by methadone resembles that of heroin, but onset is more gradual and delayed, beginning 36 to 72 h after stopping the drug. Acute manifestations of withdrawal usually subside within 10 days, but patients often report deep muscle aches. Weakness, insomnia, and severe pervasive anxiety are common for several months. Methadone withdrawal for addicts coming from a methadone maintenance program may be particularly difficult because their dose of methadone may be as high as 100 mg once/day. In general, detoxification should be started by reducing the dose to 60 mg once/day over several weeks before attempting complete detoxification.
The central adrenergic drug clonidine can halt almost all signs of opioid withdrawal. It probably decreases central adrenergic outflow secondary to stimulation of central receptors (the same mechanism by which clonidine lowers BP). However, clonidine can cause hypotension and drowsiness, and its withdrawal may precipitate restlessness, insomnia, irritability, tachycardia, and headache. Clonidine may help people withdraw from heroin or methadone before they begin oral naltrexone treatment. The mixed opioid agonist-antagonist buprenorphine also has been successfully used in withdrawal.
Maintenance:
No consensus exists regarding long-term treatment of opioid-dependent users. In the US, thousands of opioid addicts are in methadone maintenance programs, which are intended to meet the supply problems of addicts by providing large doses of oral methadone , thus enabling addicts to be socially productive. Methadone blocks the effects of injected heroin and alleviates the user's drug hunger. For many, the program has worked. However, the widespread use of methadone has provoked societal and political anger, and many people distrust its usefulness as treatment.
Buprenorphine , an agonist-antagonist, is available as maintenance treatment for opioid addicts and is becoming preferred over methadone . It blocks receptors, thereby interfering with illicit use of heroin or of other opioid analgesics. Buprenorphine can be prescribed by specially trained physicians certified by the federal government. Typical dose is an 8- or 16-mg tablet once/day. For many opioid addicts, this option is preferable to methadone maintenance because it eliminates the need for attending a methadone maintenance clinic.
Levomethadyl acetate (LAAM) is a longer-acting opioid related to methadone . QT interval abnormalities have been found in some patients taking LAAM. Its use is therefore discouraged, and patients receiving it are best transferred to methadone therapy. LAAM is used 3 times/wk, thereby diminishing the expense and the problems of daily client visits or take-home drugs. A dose of 100 mg 3 times/wk is comparable to methadone 80 mg once/day.
Naltrexone , an orally bioavailable opioid antagonist, blocks the effects of heroin. It has little agonist effect, and many opioid addicts will not voluntarily consume it. The usual dose is 50 mg once/day or 350 mg/wk in 2 or 3 divided doses.
The therapeutic community concept, pioneered by Daytop Village and Phoenix House, involves nondrug treatment in communal residential centers, where drug users receive training, education, and redirection to help them build new lives. Residency is usually 15 mo. These communities have helped, even transformed, some users. However, initial dropout rates are extremely high. How well these communities work, how many will be opened, and how much funding society will give remain unanswered.
Last full review/revision November 2005
Content last modified November 2005
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