Harmful Effects of Opioids PDF

## 11.8: Extent of Opioid Use Globally, approximately 0.7% of adults use opioids, though in North America the prevalence is substantially higher at approximately 3.8% (United Nations Office on Drugs and Crime, 2015). In the United States, there are indications of a recent upward trend in heroin...

## 11.8: Extent of Opioid Use Globally, approximately 0.7% of adults use opioids, though in North America the prevalence is substantially higher at approximately 3.8% (United Nations Office on Drugs and Crime, 2015). In the United States, there are indications of a recent upward trend in heroin use, which had been stable since the early 2000s. The United Nations attributes this increase, in part, to the reformulation of OxyContin, which now has abuse-deterrent properties, and a greater availability and decreased price of heroin in some parts of the country. Results of the 2014 Monitoring the Future Survey reported that 0.9-1% of 8th, 10th, and 12th graders had used heroin during their lifetime with only 0.2% choosing to administer the drug by means other than injection. The rate of lifetime heroin use was lower (0.3%) in college students and higher (1.4%) in young adults aged 19-28 years who did not attend college (Miech, Johnston, O'Malley, Bachman, & Schulenberg, 2015). A substantially higher percentage of young people reported having ever used opioids other than heroin, such as Vicodin, OxyContin, and Percocet, outside of medical supervision. Roughly 10% of both 12th graders and college students had illicitly used prescription opioids whereas more than 16% of non-college-attending young adults had done so (this question was not posed to 8th and 10th graders; Miech et al., 2015). Forty-two percent of grade-12 students said that prescription opioids would be "fairly easy" or "very easy" to get. Most are illicitly obtained for free or purchased from a friend, whereas others were previously prescribed to the student or given by, bought, or stolen from a relative (Miech et al., 2015). The most popular of these prescription drugs were Vicodin (hydrocodone and acetaminophen) and OxyContin (oxycodone), both of which were used more by males. Annual prevalence rates of illicit non-heroin opioid use are presented in Figure 11-3. This figure is based on data from the 2014 Monitoring the Future survey and shows the percentage of adults in different age categories who reported having used opioids other than heroin within the past year, outside of medical supervision. You can see a large increase in illicit opioid use starting in the mid-1990s which, about a decade later, had begun to or had already leveled off. The increase was greatest in the younger age categories (those under 30), with rates of use reaching as high as 10% for 23-26 year olds in 2008 and 2010 (Johnston et al., 2015). Since then, the prevalence of illicit non-heroin opioid use has been falling, quite dramatically in some cases. For instance, only 6.8% of 23-26 year olds reported illicit use in 2014 (Johnston et al., 2015). Young people's use of Vicodin, in particular, has been in steady decline from a high of 9.3% in 2005 to a low of 4.8% in 2014. Still, according to the 2014 National Survey on Drug Use and Health, pain relievers are the second-most illicitly used drug class (next to cannabis) with young people reporting the greatest use (Center for Behavioral Health Statistics and Quality, 2015). Of the estimated 4.3 million nonmedical users of prescription pain relievers in the United States in 2014, 978,000 were between the ages of 18 and 25 years. An estimated 1.9 million prescription opioid abusers develop pain reliever use disorder (i.e., abuse or addiction) with the highest rates found amongst 18-25 year olds (Center for Behavioral Health Statistics and Quality, 2015). ## Figure 11-3 The percentage of people surveyed in the United States who reported having used an opioid analgesic within the past year, outside the care of a physician Data are broken down by age groups. (Adapted from Johnston et al., 2015 used with permission.) * 18-22 Year olds * 23-26 Year olds * 27-30 Year olds * 35 Year olds * 40 Year olds * 45 Year olds ## Figure 11-3 Full Alternative Text Since 1999, there has been a shift in the licit (medically supervised) use of different-strength opioid analgesics, with physicians increasingly prescribing drugs that are "stronger than morphine." Whereas only 17% of the opioids prescribed in 1999 were more potent than morphine (and 42.4% were less potent), 37% of prescriptions obtained in 2012 were for opioids stronger than morphine (20% were for less potent opioids; Frenk, Porter, & Paulozzi, 2015). The increased distribution of highly potent medications is a relevant factor in abuse liability, both in terms of the potential for diversion or theft as well as the risk of increasing the already high number (up to 50%) of chronic pain sufferers who develop opioid addiction (Højsted & Sjøgren, 2007). Research conducted in the 1950s and 1960s suggested that, as heroin users get older, there is a maturing out-addicts spontaneously discontinue their use of the drug (Winick, 1962). Usually, they reach this point in their 30s or 40s after some 5 to 10 years of heroin use. It is difficult to determine the percentage of addicts who eventually mature out; estimates range from more than two-thirds (Winick, 1962) to less than a quarter (Ball & Snarr, 1969). In general, the longer a person has used heroin, the less likely the chance of maturing out. A great many heroin addicts never do manage to leave the habit behind, and they survive into old age still using heroin. Addiction workers are reporting an increasing number of heroin-addicted seniors (Jones, 2005) In fact, in the United States, the proportion of those over 50 enrolled in heroin treatment programs tripled between 1994 and 2004, and the number is expected to double again by 2020. These figures have led some to suspect that maturing out may have been restricted to studies done in the 1950s and 1960s (Darke, 2011). However, more recent long-term research on cohorts of Vietnam War veterans revealed that addiction to many drugs, including opioids, shows high levels of spontaneous remission-that is, recovery without medical intervention. Over a 25-year period, 59 out of 136 heroin users attempted to stop on their own and, of these, 52 were successful (Price, Risk, & Spitznagel, 2001). ## 11.9: Harmful Effects ### 11.9.1: Acute Lethal Effects Opium has historically been used as a poison, so it is not surprising that people sometimes die from an accidental opioid overdose. At high doses, opioids produce a comatose state with severe depression of breathing, which can eventually cause death. Unlike barbiturates, opioids lower the seizure threshold and may, at high doses, cause convulsions . Describes how an analog of fentanyl was used by the Russian security forces on Chechen rebels who seized a Moscow theater in 2002. The drug killed the hostage takers along with many hostages. ### BOX 11-1 The Mysterious, Deadly Opioid Gas On October 23, 2002, at about 9:00 p.m., 41 Chechen terrorists invaded a popular Moscow theater. They took over 800 people hostage and demanded that the Russians withdraw their troops from Chechnya. The terrorists threatened to start shooting the hostages and detonate the explosives they had strapped to their bodies. The Russian government refused to negotiate and the standoff lasted 57 hours. Early on the morning of October 27, the Russian Federal Security Service pumped a gas into the theater which they then stormed and took it by force. The gas was effective-the terrorists were rendered unconscious so quickly that they were not able to blow up the theater. Unfortunately, the gas proved lethal to many; 127 of the hostages and all but two of the terrorists were killed by the gas. An additional 650 hostages required hospitalization. At the time, the Russians would not divulge what kind of gas they had used. Several days later, in response to international pressure, they revealed that it had been a fentanyl derivative. But questions still remained. There are several derivatives of fentanyl that could have been used, the most likely of which would have been carfentanil. Potency would have been an important consideration, and carfentanil is greater than 100 times more potent than fentanyl and 10,000 times more potent than morphine. It is usually used as a tranquilizer for very large animals, such as African elephants. Like morphine or any of the other opioids, fentanyl and its derivatives are not normally a gas at room temperature. This means that carfentanil must have been nebulized and made into an aerosol-that is, turned into very fine particles and dispersed into the air. This is a complicated process and, the more potent the drug, the less nebulization would have been needed. Compared to morphine, carfentanil and other fentanyl derivatives have a fairly high therapeutic index (TI). The TI of morphine is about 70, while the TI of carfentanil is 10,600. Since a high therapeutic index indicates a wide separation between effective and lethal drug doses (i.e., a safe drug), this raises the question: why did so many people die? There are two possible answers. The first is that the dose received by each individual would have varied greatly, depending on where each person was. The aerosol was introduced into the theater by the ventilation system, and those close to the air vents would have received a much higher dose. The inability to control the dose is an inherent problem with using gases and aerosols in this manner. But there is another possibility: another agent may have been mixed with the fentanyl derivative. One advantage of using an opioid drug to induce sedation is that there is a very effective and fast-acting antidote available: naloxone. After the raid, many victims were treated in nearby hospitals that had been warned to stock up on their supplies of naloxone. Unfortunately, the emergency room doctors were not told that the gas the hostages had inhaled was an opioid. They spent hours trying various ineffective antidotes, such as atropine (a logical choice, had the gas been sarin), before they hit on naloxone. In many cases, however, when naloxone was used, it did not seem to be effective. This led to speculation that another agent had been mixed with the fentanyl derivative, perhaps the gaseous anesthetic halothane. Many survivors recalled a sweet smell as the gas took effect. This is a property of halothane. In addition, a toxicological analysis from one survivor showed traces of halothane. If halothane were mixed with carfentanil, that might explain the number of deaths. Halothane has a very low therapeutic index and, additionally, it does not have an antidote. In these days of terrorism and hostage taking, there is little doubt that many militaries around the world are developing "calmative" or rapidly acting agents capable of quickly incapacitating people without killing them. Normally, such research is never made public, so this incident provides us with a speculative glimpse of military practice . The United Nations Office on Drugs and Crime ( estimates that, throughout the globe in 2013, there were 187,000 drug-related deaths amongst 15 to 64 year olds, a mortality rate of 40.8 per million people. The primary cause of drug-related death was overdose, and the drugs most often responsible were heroin and prescription opioids. With 23% of all deaths worldwide, North America leads the other continents in drug-related mortality . In particular, the United States experiences a rate of drug-related mortality that is 4.6-times higher than the global average. An estimated 1 out of every 5 drug-related deaths worldwide occurs in the United States, though this high figure may, in part, be influenced by better monitoring and reporting of drug-related deaths compared to in other world regions. The prevalence of drug-overdose deaths more than doubled between 1999 and 2013 (from 6.1 to 13.8 deaths per 100,000 population). Approximately 55.7% of drug-overdose deaths in 2013 were caused by heroin or prescription opioids. In 2013, heroin overdose caused more than 8,500 deaths in the United States, which equates to 2.7 deaths per 100,000 population. Compared to 2010, this is a near tripling in mortality rate. Four times as many deaths occurred in men as in women, and most individuals were between 25 and 44 years old . Amongst heroin users, overdose is the leading cause of death. In fact, in some communities, it is the leading cause of death in males between the ages of 25 and 54. In Australia, an estimated 2% of heroin users die every year, the majority due to overdose . Most heroin overdose deaths occur in people with 5 to 10 years of experience using the drug; only about 17% are new users. These deaths do not seem to be related to changes in the purity of street heroin . One mystery related to heroin overdose is that, many times, the victim has not self-administered more heroin than usual or more heroin than other people are also using. One factor that increases the risk of overdose is the mixing of heroin with other drugs that potentiate its effects so that an otherwise-normal dose of heroin is rendered lethal. An estimated 85% of users who die from heroin overdose had combined the drug with another central nervous system depressant, such as alcohol or benzodiazepines . Many famous celebrities and musicians-Jim Morrison of The Doors, Hillel Slovak of The Red Hot Chili Peppers, vocalist Janis Joplin, actors River Phoenix and Philip Seymour Hoffman, among others-succumbed to the effects of heroin or a mixture of heroin with alcohol or other drugs. Another possible cause of an unexplained overdose is a loss of tolerance to the drug. Often, this loss is due to a period of abstinence. Addicts are at a seven-times increased risk of overdose during the first 2 weeks following release from residential treatment . Loss of tolerance may be due in part to conditioned effects; as described in of Chapter 3 tolerance may depend on the specific environment in which the drug is normally given. If the drug is used in a new environment, tolerance is diminished, and what is a normal dose for an addict may suddenly be lethal. In comparison to the 8,500 deaths caused by heroin, there were more than 16,200 overdose deaths in the United States in 2013 that resulted from misuse of prescription analgesics . Compared to 1999, this is a near quadrupling of mortality rate (from 1.4 to 5.1 deaths per 100,000 population; ). About 70% of these deaths involved natural and semisynthetic opioids, including morphine, hydrocodone, and oxycodone. Methadone alone is responsible for about 26% of all prescription opioid overdose deaths. The remainder involved fully synthetic opioids, such as fentanyl, meperidine, and dextropropoxyphene . In 31% of opioid-overdose deaths, the co-administration of benzodiazepines played a role. Figure 11-4 illustrates the trend in heroin and prescription opioid mortality rates from 2000 through 2013. ## Figure 11-4 Heroin- and opioid-analgesic-related mortality rates in the United States from 2000 to 2013. Note the higher number of drug-poisoning deaths related to prescription opioids and the increase in heroin-related deaths since 2010. (Adapted from ). ## Figure 11-4 Full Alternative Text Between 30 and 80% of drug abusers overdose at some point and nearly half experience multiple overdoses within a short period of only a few months . For every fatal drug overdose, there are an additional 20 or more non-fatal drug poisonings. Every year, an estimated 1.1 million people visit a U.S. emergency department due to drug overdose. Most are between the ages of 20 and 34 years, with males and females represented in roughly equal proportions . Males are more likely to experience unintentional drug poisoning, whereas roughly equal proportions of females require emergency care due to unintentional or self-inflicted drug overdose . Opioids are directly implicated in roughly 14% of drug poisonings that require an emergency room visit; 5.7% are caused by heroin and methadone . Risk of overdose is increased by numerous factors, including high frequency of drug use (e.g., daily or binge use), higher drug purity, injecting drugs, as opposed to administering them orally or by inhalation, and polydrug use, especially the combining of opioids with amphetamines, cocaine, alcohol, or benzodiazepines . ### 11.9.2: Chronic Effects In addition to the effects of opioids on the body described earlier, there are additional concerns that arise from long-term opioid use. ### Lifestyle Effects Although opioids exert direct negative consequences to health, there is also indirect harm that arises from the lifestyle of most addicts. Heroin is expensive and illegal to possess, and supporting a habit requires a lot of money and risk. Because acquiring and using the drug take such priority, housing and nutrition suffer, and so does health. Added to these difficulties is the greatly increased exposure to disease caused by the practice of shooting up. Drug injections are seldom done with clean needles and syringes ; many people often use the same paraphernalia, providing direct access into the body for diseases such as hepatitis and HIV/AIDS. An unprecedented 33-year longitudinal study followed 581 heroin-addicted, male criminal offenders admitted to the California Civil Addict Program between 1962 and 1964. The average age of the group at admission was 25.4 years. At last follow-up interview, in 1997, nearly half the group (282 men) had died. This represents a death rate of 50 to 100 times that of the general population of men the same age. Drug overdose and accidental poisoning were the most common cause of death (21.6%); 19.5% of deaths were homicides, suicides, and accidents. Liver disease, cancer, and cardiovascular disease accounted for the majority of remaining deaths . Nearly 40% of those alive at follow-up in 1997 had used heroin within the past year, and nearly 10% were in methadone treatment. ### Years of Potential Life Lost When a heroin addict dies at a young age, it is a tragedy not only for the individual who has lost the opportunity to lead a full, productive life, but also for the person's family and community. A method of reporting fatality that emphasizes the tragedy of deaths in younger people is called years of potential life lost (YPLL; sometimes referred to as PYLL for potential years of life lost). Rather than merely report the number of deaths as a fraction of the total population, the YPLL method calculates the number of years of potential life that are lost within a specific segment of the population. The Centers for Disease Control and Prevention (CDC) customarily uses 65 years of age as a reference point against which to assess premature mortality. For every death due to a certain cause, researchers calculate how many years of potential life were lost by subtracting the age at death from 65; this is the YPLL. The YPLL are summed across individuals within a category to produce a single indicator that can be used to gauge differences in health status between populations. In a 2007 study published in Preventive Medicine, Breda Smyth and her colleagues analyzed the data from the 33-year longitudinal study of heroin addicts enrolled in the California Civil Addict Program between 1962 and 1964 (described earlier), and reported findings in terms of YPLL. presents the eight causes of death that contributed most significantly to premature mortality among the group of heroin addicts. Included are details about the number (N) of deaths, according to each particular cause, as well as the summed YPLL (blue bars) and the percentage (%) of total YPLL (orange line) accounted for by each cause-of-death category. As you can see, heroin overdose was the primary cause of premature death among addicts, accounting for more than 1,150 YPLL across 49 individuals. More than half of these overdose deaths occurred within 15 years of being admitted to the program. The second leading cause of premature death in this study was chronic liver disease, likely due to high rates of hepatitis B and C caused by needle sharing and heavy drinking. Other predominant causes of early mortality among heroin addicts were accidents or injuries, overdose from other drugs, homicide, and cancer, most likely resulting from the high (98%) rate of tobacco smoking within the study participants. On average, the heroin addicts in the study lost 18.3 years of potential life before the age of 65 years .