Drug abuse IV: major drugs of abuse other than alcohol and nicotine

CHAPTER 40


Drug abuse IV: major drugs of abuse other than alcohol and nicotine


In this chapter, we discuss all of the major drugs of abuse except alcohol (Chapter 38) and nicotine and tobacco (Chapter 39). As indicated in Table 40–1, abused drugs fall into seven major categories: (1) opioids, (2) psychostimulants, (3) depressants, (4) psychedelics, (5) dissociative drugs, (6) anabolic steroids, and (7) miscellaneous drugs of abuse. The basic pharmacology of many of these drugs is presented in previous chapters, and hence their discussion here is brief. Agents that have not been addressed previously (eg, marijuana, d-lysergic acid diethylamide [LSD]) are discussed in depth. Structural formulas of representative controlled substances are shown in Figure 40–1. Street names for abused drugs are given in Table 40–2.




TABLE 40–2 


Some Street Names for Abused Drugs






















































































































Drug Street Names
Opioids
Heroin H, Harry, horse, junk, smack, skag
Hydrocodone Hydro, vikes, vico
Hydromorphone Juice
Methadone Dolly
Oxycodone Hillbilly heroin, OC, oxy, oxycottons
Psychedelics
d-Lysergic acid diethylamide LSD, LSD-25, acid, blotter, microdot
Dimethyltryptamine DMT, businessman’s trip
Mescaline Peyote, cactus buttons
2,5-Dimethoxy-4-methylamphetamine DOM, STP
Psilocybin Magic mushrooms
Psilocin Magic mushrooms
Salvia Magic mint, sage of seers, Sally D
Psychostimulants
Amphetamine Bennies, hearts, whites, cartwheels
Dextroamphetamine Dexies, oranges, footballs
Methamphetamine Speed, bombita, crank, crystal meth, ice, glass
Methylphenidate Kiddie dope, R-ball, vitamin R
Biphetamine Black beauties
Cocaine Coke, crack, snow, blow, flake, nose candy, toot
General CNS Depressants
Amobarbital Blue devils
Flunitrazepam [Rohypnol]* Forget-me pill, Roche, R2, roofies, rope, rophies
Gamma-hydroxybutyrate (GHB)* Grievous bodily harm, Georgia homeboy, liquid ecstasy
Pentobarbital Yellow jackets
Secobarbital Red devils
Methaqualone Ludes, spoors
Dissociative Drugs
Phencyclidine PCP, angel dust, dummy dust, hog, ozone, peace pill, rocket fuel, sheets, wack
Ketamine Special K, vitamin K, cat Valium
Miscellaneous Agents
3,4-Methylenedioxymethamphetamine MDMA, ectasy, hug, XTC, the love drug
Marijuana Pot, grass, reefer, weed, Panama red, Acapulco gold, Mary Jane, many others
Combinations
Heroin + cocaine Speedball
Heroin + crack cocaine Moon rock
Heroin + marijuana Atom bomb
Marijuana + phencyclidine Killer joints, crystal supergrass


image


*Associated with sexual assault.


image
Figure 40–1  Structural formulas of representative drugs of abuse.
(LSD = d-lysergic acid diethylamide; THC = tetrahydrocannabinol.)



Heroin, oxycodone, and other opioids


The opioids (eg, heroin, oxycodone, meperidine) are major drugs of abuse. As a result, most opioids are classified as Schedule II substances. The basic pharmacology of the opioids is discussed in Chapter 28.




Patterns of use

Opioid abuse is encountered in all segments of society. Formerly, opioid abuse was limited almost exclusively to lower socioeconomic groups residing in cities. Today, however, opioid abuse is more widespread, occurring in small towns as well as big cities, and among the rich and middle class as well as the poor.


For most abusers, initial exposure to opioids occurs either socially (ie, illicitly) or in the context of pain management in a medical setting. The overwhelming majority of individuals who go on to abuse opioids begin their drug use illicitly. Only an exceedingly small percentage of those exposed to opioids therapeutically develop a pattern of compulsive drug use.


Opioid abuse by healthcare providers deserves special consideration. It is well established that physicians, nurses, and pharmacists, as a group, abuse opioids to a greater extent than all other groups with similar educational backgrounds. The vulnerability of healthcare professionals to opioid abuse is due primarily to drug access.




Preferred drugs and routes of administration

Which opioids do people abuse? Practically all of them. In the past, heroin was the most commonly abused opioid drug. But no longer. Prescription opioid analgesics are now abused much more commonly than heroin: In 2009, more than 5.3 million Americans reported past-month abuse of these drugs.



Heroin.

Among street users, heroin is the traditional opioid of choice. Why? Because of its high lipid solubility, heroin crosses the blood-brain barrier with ease, causing effects that are both immediate and intense. This combination of speed and intensity sets heroin apart from other opioids. According to the 2008 National Survey on Drug Use and Health, 213,000 Americans age 12 and older reported past-month abuse of heroin.


Heroin can be administered in several ways. The order of preference is IV injection, smoking, and nasal inhalation (known as sniffing or snorting). Intravenous injection produces effects with the greatest intensity and fastest onset (7 to 8 seconds). When heroin is smoked or snorted, effects develop more slowly, peaking in 10 to 15 minutes. Among users who seek addiction treatment, injection is the predominant method of administration. However, because sniffing and smoking are safer and easier than injection, these routes have become increasingly popular.


It should be noted that, when heroin is administered orally or subcutaneously, as opposed to intravenously, its effects cannot be distinguished from those of morphine and other opioids. This observation is not surprising given that, once in the brain, heroin is rapidly converted into morphine, its active form.



Oxycodone.

In some parts of the United States, people are abusing the controlled-release formulation of oxycodone [OxyContin], an opioid similar to morphine. The controlled-release tablets were designed to provide steady levels of oxycodone over an extended time, and are safe and effective when swallowed intact. However, abusers do not ingest the tablets whole. Rather, they crush the tablets, and then either snort the powder, or dissolve it in water and then inject it IV. As a result, the entire dose is absorbed immediately, producing blood levels that are dangerously high. Hundreds of deaths have been reported. The risk of respiratory depression and death is greatest in people who have not developed tolerance to opioids.


In an effort to reduce OxyContin abuse, the controlled-release tablets were reformulated in 2010. The new formulation bears the imprint OP, rather than OC, which appeared on the old formulation. Compared with the old tablets, OxyContin OP tablets are much harder to crush into a powder. And if exposed to water or alcohol, the tablets just form a gummy blob, rather than a solution that can be drawn into a syringe and injected. However, there is no evidence that OxyContin OP tablets are less subject to abuse, diversion, overdose, or addiction than the old tablets. As noted in Chapter 28, oxycodone is also available in a tamper resistant immediate-release formulation, sold as Oxecta.




Tolerance and physical dependence




Treatment of acute toxicity

Treatment of acute opioid toxicity is discussed at length in Chapter 28 and summarized here. Overdose produces a classic triad of symptoms: respiratory depression, coma, and pinpoint pupils. Naloxone [Narcan], an opioid antagonist, is the treatment of choice. This agent rapidly reverses all signs of opioid poisoning. However, dosage must be titrated carefully. Why? Because if too much is given, the addict will swing from a state of intoxication to one of withdrawal. Owing to its short half-life, naloxone must be re-administered every few hours until opioid concentrations have dropped to nontoxic levels, which may take days. Failure to repeat naloxone dosing may result in the death of patients who had earlier been rendered symptom free.


Nalmefene [Revex], a long-acting opioid antagonist, is an alternative to naloxone. Because of its long half-life, nalmefene does not require repeated dosing—an obvious advantage. However, if the dose is excessive, nalmefene will put opioid-dependent patients into prolonged withdrawal—an obvious disadvantage.



Detoxification

Persons who are physically dependent on opioids experience unpleasant symptoms if drug use is abruptly discontinued. Techniques for minimizing discomfort are presented below.



Methadone substitution.

Methadone, a long-acting oral opioid, is the agent most commonly employed for easing withdrawal. The first step in methadone-aided withdrawal is to substitute methadone for the opioid upon which the addict is dependent. Because opioids display cross-dependence with one another, methadone will prevent an abstinence syndrome. Once the subject has been stabilized on methadone, withdrawal is accomplished by administering methadone in gradually smaller doses. The resultant abstinence syndrome is mild, with symptoms resembling those of moderate influenza. The entire process of methadone substitution and withdrawal takes about 10 days.


When substituting methadone for another opioid, suppression of the abstinence syndrome requires that methadone dosage be closely matched to the existing degree of physical dependence. Hence, to ensure that methadone dosing is adequate, the extent of physical dependence must be assessed. This can be accomplished by taking a history on the extent of drug use and by observing the patient for symptoms of withdrawal. Of the two approaches, observation is the more reliable. Estimates of drug use based on patient histories may be unreliable because (1) street users don’t know the purity of the drugs they have taken, (2) claims of drug use may be inflated in hopes of receiving larger doses of methadone, and (3) addicts from the ranks of the healthcare professions may report minimal consumption to downplay the extent of abuse. Because information from addicts is not likely to permit accurate assessment of dependence, it is essential to observe the patient to make certain methadone dosage is sufficient to suppress withdrawal.


Use of methadone for maintenance therapy and suppressive therapy is discussed separately below.








Buprenorphine.


As discussed in Chapter 28, buprenorphine is an agonist-antagonist opioid. Like methadone, buprenorphine can be substituted for the opioid upon which an addict is physically dependent, and can thereby prevent symptoms of withdrawal. After the addict is stabilized on buprenorphine, the dosage is gradually reduced, thereby keeping symptoms of withdrawal to a minimum. Use of buprenorphine for maintenance therapy is discussed below.






Drugs for long-term management of opioid addiction

Three kinds of drugs are employed for long-term management: opioid agonists, opioid agonist-antagonists, and opioid antagonists. Opioid agonists (methadone) and agonist-antagonists (buprenorphine) substitute for the abused opioid and are given to patients who are not yet ready for detoxification. In contrast, opioid antagonists (naltrexone) are used to discourage renewed opioid use after detoxification has been accomplished. Drugs used for long-term management of opioid addiction are summarized in Table 40–3.



TABLE 40–3 


Drugs for Long-Term Management of Opioid Addiction





































































Drug Trade Name Formulation Dosing Schedule CSA Schedule Comments
Opioid Agonist
Methadone Methadose, Diskets Dispersible tablets used to make an oral suspension Once a day II Methadone maintenance may be provided only by Opioid Treatment Programs certified by the federal Substance Abuse and Mental Health Services Administration and approved by the designated state authority.
  Methadose Concentrated oral liquid Once a day  
Opioid Agonist-Antagonist
Buprenorphine Subutex Sublingual tablet Once a day III Subutex and Suboxone may be prescribed in a primary care setting by any physician or nurse practitioner who has received authorized training and has registered with the Substance Abuse and Mental Health Services Administration.
  Suboxone* Sublingual tablet Once a day  
  Suboxone* Sublingual film Once a day  
  Probuphine† Sustained-release subdermal implant Lasts at least 6 months  
Opioid Antagonist
Naltrexone ReVia Oral tablet Once a day NR Naltrexone is not a controlled substance and hence prescribers do not require special training or certification. IM naltrexone [Vivitrol] is the only drug approved for opioid addictions that is given monthly, rather than daily. Before receiving naltrexone, patients must undergo opioid detoxification.
  Vivitrol Extended-release suspension for IM injection Once a month  


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CSA = Controlled Substances Act, NR = not regulated under the CSA.


*In addition to buprenorphine, Suboxone contains naloxone, an opioid antagonist, to discourage IV dosing.


†Probuphine is not approved in the United States or Canada.



Methadone.

In addition to its role in facilitating opioid withdrawal, methadone [Methadose, Diskets] can be used for maintenance therapy and suppressive therapy. These strategies are employed to modify drug-using behavior in addicts who are not ready to try withdrawal.


Methadone maintenance consists of transferring the addict from the abused opioid to oral methadone. By taking methadone, the addict avoids both withdrawal and the need to procure illegal drugs. Maintenance dosing is done once a day. Maintenance is most effective when done in conjunction with nondrug measures directed at altering patterns of drug use.


Suppressive therapy is done to prevent the reinforcing effects of opioid-induced euphoria. Suppression is achieved by giving the addict progressively larger doses of methadone until a very high dose (120 mg/day) is reached. Building up to this dose creates a high degree of tolerance, and hence no subjective effects are experienced from the methadone itself. Because cross-tolerance exists among opioids, once the patient is tolerant to methadone, taking street drugs, even in high doses, cannot produce significant desirable effects. As a result, individuals made tolerant with methadone will be less likely to seek out illicit opioids.


Use of methadone to treat opioid addicts is restricted to Opioid Treatment Programs approved by the designated state authority and certified by the federal Substance Abuse and Mental Health Services Administration. These restrictions on the nonanalgesic use of methadone are needed to control abuse of methadone, a Schedule II drug with the same abuse liability as morphine and other strong opioids. Because the number of certified clinics is limited, gaining access to one is hard in many parts of the country.


The basic pharmacology of methadone is presented in Chapter 28.



Buprenorphine.

Buprenorphine [Subutex, Suboxone], an agonist-antagonist opioid, was approved for treating addiction in 2002. As discussed in Chapter 28, the drug is a partial agonist at mu receptors and a full antagonist at kappa receptors. Buprenorphine can be used for maintenance therapy and to facilitate detoxification (see above). When used for maintenance, buprenorphine alleviates craving, reduces use of illicit opioids, and increases retention in therapeutic programs.


Unlike methadone, which is available only through certified Opioid Treatment Programs, buprenorphine can be prescribed and dispensed in general medical settings, such as primary care offices. Prescribers must receive at least 8 hours of authorized training, and must register with the Substance Abuse and Mental Health Services Administration.


Buprenorphine has several properties that make it attractive for treating addiction. Because it is a partial agonist at mu receptors, it has a low potential for abuse—but can still suppress craving for opioids. If the dosage is sufficiently high, buprenorphine can completely block access of strong opioids to mu receptors, and can thereby prevent opioid-induced euphoria. With buprenorphine, there is a ceiling to respiratory depression, which makes it safer than methadone. Development of physical dependence is low, and hence withdrawal is relatively mild.


Buprenorphine is currently available in three formulations that are dosed once a day. One formulation—sublingual tablets marketed as Subutex—contains buprenorphine alone. The other two formulations—sublingual tablets and sublingual films, both maketed as Suboxone—contain buprenorphine combined with naloxone. Subutex is used for the first few days of treatment, and then Suboxone is used for long-term maintenance. What’s the purpose of the naloxone in Suboxone? It’s there to discourage IV abuse. If taken IV, the naloxone in Suboxone will precipitate withdrawal. However, with sublingual administration, very little naloxone is absorbed, and hence, when the drug is administered as intended, the risk of withdrawal is low. Nonetheless, because there is a small risk with sublingual Suboxone, treatment is initiated with Subutex, thereby allowing substitution of buprenorphine for the abused opioid. Thereafter, Suboxone is taken for maintenance.


An investigational buprenorphine formulation—sustained-release subdermal implants [Probuphine]—has effects that persist for at least 6 months, an obvious advantage over the once-daily formulations when adherence is hard to achieve.


The basic pharmacology of buprenorphine is presented in Chapter 28.



Naltrexone.

After a patient has undergone opioid detoxification, naltrexone [ReVia, Vivitrol], a pure opioid antagonist, can be used to discourage renewed opioid abuse. Benefits derive from blocking euphoria and all other opioid-induced effects. By preventing pleasurable effects, naltrexone eliminates the reinforcing properties of opioid use. When the former addict learns that taking an opioid cannot produce the desired response, drug-using behavior will cease. Naltrexone is not a controlled substance, and hence prescribers require no special training or certification.


Naltrexone is available in oral and IM formulations. The oral formulation, sold as ReVia, is dosed once a day. The IM formulation, sold as Vivitrol, is dosed once a month. At this time, Vivitrol is the only long-acting drug for managing opioid addiction. All other drugs must be taken every day.


The basic pharmacology of naltrexone is presented in Chapter 28.



Sequelae of compulsive opioid use

Surprisingly, chronic opioid use has very few direct detrimental effects. Addicts in treatment programs have been maintained on high doses of methadone for a decade with no significant impairment of health. Furthermore, individuals on methadone maintenance can be successful socially and at work. It appears, then, that opioid use is not necessarily associated with poor health, lack of productivity, or inadequate social interaction.


Although opioids have few direct ill effects, there are many indirect hazards. These risks stem largely from the lifestyle of the opioid user and from impurities common to street drugs. Infections secondary to sharing nonsterile needles occur frequently. The infections that opioid abusers acquire include septicemia, subcutaneous ulcers, tuberculosis, hepatitis C, and HIV. Foreign-body emboli have resulted from impurities in opioid preparations. Opioid users suffer an unusually high death rate. Some deaths reflect the violent nature of the subculture in which opioid use often takes place. Many others result from accidental overdose.



General CNS depressants


The family of CNS depressants consists of barbiturates, benzodiazepines, alcohol, and other agents. With the exception of the benzodiazepines, all of these drugs are more alike than different. The benzodiazepines have properties that set them apart. The basic pharmacology of the benzodiazepines, barbiturates, and most other CNS depressants is presented in Chapter 34; the pharmacology of alcohol is presented in Chapter 38. Discussion here is limited to abuse of these drugs. Two CNS depressants notorious for their roles in date rape are discussed in Box 40–1.



imageBOX 40–1    SPECIAL INTEREST TOPIC


DATE-RAPE DRUGS: ROHYPNOL AND GHB


Two powerful sedative-hypnotics—Rohypnol and gamma-hydroxybutyrate (GHB)—are notorious for facilitating rape. Use of either drug to commit sexual assault is a federal crime, punishable under the Drug-Induced Rape Prevention and Punishment Act. Street names for Rohypnol include roofies, Roche, rope, rophies, R2, forget-me pill, and Mexican Valium. Street names for GHB include Georgia homeboy, grievous bodily harm, and liquid ecstasy.


Rohypnol


Rohypnol is the trade name for flunitrazepam, a potent benzodiazepine. Like diazepam [Valium] and other benzodiazepines, Rohypnol causes sedation, psychomotor slowing, muscle relaxation, and retrograde amnesia. When used to facilitate sexual assault, the drug is slipped into the victim’s drink. The combination of alcohol and flunitrazepam produces a vulnerable state characterized by suggestibility, impaired judgment, loss of inhibition, extreme sleepiness, weakness, and inability to remember what happened after the drugs took effect; most victims eventually lose consciousness. Because an intoxicated person is considered legally incapable of consent, performing sex with such a person is considered an aggressive criminal act, and can be prosecuted as felony sexual assault. Unfortunately, owing to Rohypnol-induced amnesia, the victim is often unsure that rape actually took place, and certainly can’t attest to details. As a result, prosecution is difficult. Two precautions can reduce the risk of being secretly drugged: In public settings (parties, nightclubs, etc.), never leave a drink unattended, and never accept a drink from a person you don’t know and trust.


Facilitation of rape is neither the only nor the principal reason for Rohypnol abuse. Most people take it just to get high. As a rule, the drug is combined with another abused substance, typically alcohol or heroin. Because Rohypnol is relatively cheap (about $5 a dose), the drug is especially popular among high school and college students. In the United States, abuse of Rohypnol is most common in the East and Southwest.


Rohypnol, manufactured by Hoffmann LaRoche, is available for medical use in several countries, but not the United States or Canada. In Europe, Rohypnol is widely prescribed for relieving insomnia. Effects begin within 30 minutes, peak in 2 hours, and persist for 8 hours. The principal difference between Rohypnol and other benzodiazepines is that Rohypnol is very potent—about 10 times more potent than diazepam. Hence, a small dose has a big effect. One source claims that taking 2 mg of Rohypnol is like drinking an entire six-pack of beer.


To make secretive use of Rohypnol more difficult, Hoffmann LaRoche reformulated the pill. The new formulation dissolves more slowly than the old one and contains a dye that turns pale drinks bright blue and makes dark drinks murky. In addition, the pill contains insoluble particles that float on top of all drinks. However, since flunitrazepam is also made in clandestine laboratories, not all formulations produce these conspicuous effects.


Because of its abuse potential, the legal status of flunitrazepam has changed. Initially, this drug, like all other benzodiazepines, was classified under Schedule IV. In 1995, the World Health Organization reclassified it under Schedule III. In the United States, importation of flunitrazepam has been banned, and the Drug Enforcement Agency is considering placing it in Schedule I.


In 1996, Congress passed the Drug-Induced Rape Prevention and Punishment Act. The law imposes a maximum prison term of 20 years for importing and distributing 1 gm or more of flunitrazepam. The act also stiffens the penalty for administering a controlled substance without consent and with the intent of committing rape or any other violent crime.



GHB


Gamma-hydroxybutyrate, or GHB, has two notable actions: It depresses CNS function and, by causing release of growth hormone, it promotes muscle growth. During the 1990s, GHB gained popularity as a drug of abuse, primarily among adolescents and young adults. The drug is taken in social settings (parties, raves, clubs, etc.) to produce relaxation, euphoria, and disinhibition. Athletes take it to increase strength. And predators give it clandestinely to facilitate sexual assault. When used for assault, GHB is much like Rohypnol. The perpetrator simply slips a few drops of the colorless, odorless, tasteless liquid into the intended victim’s drink and then, within 20 minutes, the GHB produces incoordination, confusion, and deep sedation, along with amnesia about what has taken place.


The pharmacology of GHB is similar to that of other CNS depressants. This is no surprise given that GHB is a metabolite of gamma-aminobutyric acid, the major inhibitory transmitter in the brain. When taken in moderate doses, GHB produces sedation, relaxation, and mild euphoria. Overdose produces significant respiratory depression, which is made worse by concurrent use of alcohol. Seizures may occur, especially with combined use of methamphetamine. Overdose can also cause nausea, vomiting, bradycardia, hypothermia, agitation, delirium, unconsciousness, and coma. GHB has been linked to more than 200 deaths and thousands of emergency department admissions.


Repeated use of GHB appears to cause tolerance and physical dependence. Tolerance is indicated by the need for bigger and bigger doses to produce relaxation and euphoria. Physical dependence is indicated by signs of withdrawal—agitation, delirium, tachycardia, insomnia, anxiety, tremors, sweating—when regular use stops.


GHB has only one approved use: reduction of cataplexy in patients with narcolepsy (see Chapter 107). The drug is regulated as a Schedule III substance.


A precursor of GHB, known as 1,4-butanediol, undergoes conversion to GHB in the body, and hence has effects identical to those of GHB itself. Butanediol is used as an industrial solvent, and is also available as a “dietary supplement.” The supplements are claimed to enhance muscle growth, fight aging, increase sexual desire, promote relaxation, and elevate mood. Trade names for the supplements include Thunder Nectar, Inner G, and Zen.

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Jul 24, 2016 | Posted by in NURSING | Comments Off on Drug abuse IV: major drugs of abuse other than alcohol and nicotine

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