J Am Board Fam Med: first published as 10.3122/jabfm.2008.01.070071 on 4 January 2008. Downloaded from

CLINICAL REVIEW Abuse of Prescription and Over-the-Counter Medications

James E. Lessenger, MD, and Steven D. Feinberg, MD, MPH

The nonmedical use of prescription or over-the-counter (OTC) medications implies that the user is us- ing them for reasons other than those indicated in the prescribing literature or on the box label. The abuse of these medications is a national issue. Intentional drug abuse of prescribed and OTC medicines has climbed steadily. Data from the 2005 National Survey on Drug Use and Health demonstrated that 6.4 million (2.6%) people aged 12 or older had used prescription drugs for nonmedical reasons during the past month. Of these, 4.7 million used pain relievers, 1.8 million used tranquilizers, and 1.1 million used stimulants. The nonmedical use of prescription drugs in the past month among young adults aged 18 to 25 increased from 5.4% in 2002 to 6.3% in 2005, primarily because of an increase in the abusive use of pain relievers. Physicians need to watch for prescription and OTC medication abuse. Treatment strategies include (1) inquiring about prescription, OTC, and herbal drug use at the initial examination (even though many individuals are drug-abuse savvy, some are naı¨veand do not realize that OTC medications can be problematic); (2) inquiring about drug use during office visits; (3) providing disposal containers that patients can use to dispose of their unused or unneeded prescription or OTC medications; (4) treating pain aggressively and appropriately; (5) practicing careful record keeping of prescription refills and controls over prescription blanks; (6) referring patients who are addicted to medications to 12-step

programs such as Alcoholic Anonymous, Narcotics Anonymous, and Pills Anonymous; and (7) consider- copyright. ing detoxification. (J Am Board Fam Med 2008;21:45–54.)

The nonmedical use of a prescription or over-the- Scope of the Problem counter (OTC) medication implies that the user is Intentional drug abuse of prescribed and OTC using it for reasons other than those indicated in medicines has climbed steadily over the years. Data 1 the prescribing literature or on the box label. The from the 2005 National Survey on Drug Use and abuse of these medications is a national issue. Pre- Health demonstrated that 6.4 million (2.6%) peo- http://www.jabfm.org/ scription medications are those pharmaceuticals ple aged 12 or older used prescription psychother- dispensed by a pharmacist on the presentation of a apeutic drugs for nonmedical reasons during the prescription written by a physician, dentist, or previous month. Of these, 4.7 million used pain other health care provider who is legally authorized relievers, 1.8 million used tranquilizers, and 1.1 to write prescriptions. OTC medications are phar- million used stimulants (including 512,000 using maceuticals that do not require a prescription and methamphetamines). Nonmedical use of prescrip- are sold on the shelves of markets, stores, and tion drugs in the previous month among young on 24 September 2021 by guest. Protected pharmacies.2 adults aged 18 to 25 increased from 5.4% in 2002 to 6.3% in 2005. This was primarily because of an increase in the use of pain relievers, which was This article was externally peer reviewed. 3 Submitted 11 March 2007; revised 28 July 2007; accepted 4.1% in 2002 and 4.7% in 2003, 2004, and 2005. 7 August 2007. In 2005, among people aged 12 or older who From private practice, Benicia, California (JEL), and the Department of Orthopaedic Surgery-Physical and Rehabil- used pain relievers for nonmedical reasons in the itative Medicine, Stanford University School of Medicine, previous 12 months, 59.8% reported that it was California (SDF). Funding: none. obtained free from a friend or relative. Another Conflict of interest: none declared. 16.8% reported they obtained the drug from one or Corresponding author: James E. Lessenger, MD, FAAFP, FACOEM, 750 West K Street, Benicia, CA 94510 (E-mail: more doctors. Only 4.3% purchased the pain re- [email protected]). lievers from a drug dealer or other stranger, and doi: 10.3122/jabfm.2008.01.070071 Abuse of Prescription and OTC Medications 45 J Am Board Fam Med: first published as 10.3122/jabfm.2008.01.070071 on 4 January 2008. Downloaded from

Table 1. 2002 Emergency Department Admissions from Use of Prescription and Over-the-Counter Medications

Substance % Age at First Use Source of Feferral

Opioids 55 26 Self Stimulants 28 20 Criminal justice system Tranquilizers, muscle relaxers 10 24 Self Sedatives 6 23 Self OTC medications 1 20 Self

Data from the National Survey on Drug Use and Health.5 OTC, over the counter.

0.8% reported buying the drug on the Internet. In son with 1992 data demonstrated an increase in 2005 the specific illicit drugs that had the highest opiate and OTC use, with a relative decrease of levels of dependence or abuse in the previous year sedative and tranquilizer use. The use of stimulants were marijuana (4.1 million), cocaine (1.5 million), remained the same7,8 (Table 15). and pain relievers (1.5 million). Nonmedical use of pain relievers (2.2 million) and marijuana (2.1 mil- Trends in Use lion) accounted for the largest number of first-time 3 People use potentially addicting prescription or abuse among people aged 12 or older. OTC medications in the following manners: In a recent New Mexico study of deaths from unintentional drug poisoning, 0.9% were from ● For legitimate, prescribed medical treatment; for OTC medications.4 A 2004 national survey dem- example, methamphetamines for narcolepsy and onstrated that suicide-prone patients with a diag- opiates for severe trauma. nosis of substance abuse who possess prescription ● As an additional drug to use when the DOC is copyright. medications are more likely to overdose on OTC unavailable on the streets. medications.5 ● As a booster for a more intense high. A study of Tulare County, California, Drug ● As an alternative addictive drug when their DOC Court clients found that 8.5% admitted to abusing has been eliminated from use by drug testing. prescription drugs and 16.2% admitted to abusing ● As an alternative addictive drug prescribed by OTC medications, mostly ephedrine and other physicians; for example, amphetamines in diet stimulants. None of the clients admitted to pre- clinics. These prescriptions may be issued either scription drugs or OTC medications as their drug- 9,10

naively by the physician or for profit. http://www.jabfm.org/ of-choice (DOC), although some admitted addic- tion to Vicodin after the study was completed.6 This study suggests that some drug addicts may Data from the Drug Abuse Warning Network only resort to prescriptive or OTC medications demonstrate the following about people who abuse when their illegal drugs are not available. prescription or OTC medications: In emergency departments in the United States, prescription and OTC drugs were the primary sub- ● They tend to be white. on 24 September 2021 by guest. Protected stances of abuse for 4% of the 1.9 million patients ● They tend to be younger (when stimulants are admitted for drug treatment in 2002. Prescription the DOC). medications were primarily opioids, stimulants, ● They tend to use opiates. tranquilizers, and sedatives. OTC drugs included ● They tend to be women; women tend to use aspirin, cough syrup, diphenhydramine and other tranquilizers and sedatives. antihistamines, sleep aids, and other legally ob- ● They tend to mix their medications with alcohol. tained medications.7 In 2002, 55% of the total ● They tend to use prescription and OTC medica- drug-related emergency department admissions tions in conjunction with alcohol as a vehicle for were for prescription narcotics. Most of the people suicide. seen in the emergency departments were white and ● They obtain the prescription medications by pre- female and had never had a previous emergency scription from their physicians or dentists, as department visit because of illicit drugs. Compari- gifts from friends, or purchase them on the black

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market. OTC medications are, of course, pur- Dependence on Medication and Pseudo-addiction chased at stores.7,8,11,12 There are clear differences between the physical dependence on medication, active addiction, addic- tion in remission, and pseudo-addiction. The de- Many of the medications in this paper have le- pendence on medication may be therapeutic re- gitimate medical uses for people with a variety of gardless of the class to which it belongs. Physical illnesses and injuries. They may even be used in dependence of a therapeutic drug may occur, re- high doses for selected medical problems. The sulting in withdrawal symptoms if the medication is question arises as to whether the medication is suddenly stopped. This is a physiologic response to being prescribed by the physician and used by the the chronic use of a medication, just as stopping a client appropriately or if it is being inappropriately blood pressure medicine suddenly can cause hyper- prescribed or used. This problem is most common tension, heart attack, or stroke. Drug-seeking be- in the use of opioids and stimulants.13 havior, actions to obtain drugs either by a prescrip- When a legal medication is the addict’s primary tion or otherwise, may in some people reflect not DOC, it was either prescribed by a physician or addiction but rather difficulty in obtaining appro- purchased on the streets. There are 3 people in- priate medications because they are labeled as ad- volved in the abuse: (1) the physician, who either dicts. Some people with a history of addiction to knowingly or naively prescribes pharmaceuticals to illicit drugs may also have a chronic pain syndrome a person who is faking pain; (2) the person who that would benefit from appropriate opiate pain fakes or exaggerates an illness to obtain a prescrip- medication. A person recovering from drug addic- tion, which is then filled in a pharmacy and may be tion may need a stimulant for narcolepsy or a tran- sold at locations where he or she can obtain high quilizer for anxiety. If these problems are under- prices; and (3) the addict who purchases the med- treated because of physician fear, a syndrome of ications for his own use.10,13 pseudo-addiction may occur, in which the person Physicians who prescribe or dispense medica- engages in drug-seeking behavior simply to obtain copyright. tions that can be abused are at risk for becoming a therapeutic and effective dosage level of a medi- part of the problem. Some physicians are part of cation.14 the illegal network of drug sales, but others fall into Patients in drug-addiction recovery may be even the trap of trying to help people as best they can. more vigilant than the physician. They are acutely Recent campaigns to treat pain as a vital sign along aware of the consequences of relapse and do not with blood pressure, pulse, respiratory rate, and want to experience the problems of addiction again. temperature make it necessary for professionals to For that reason, some people in recovery may forgo treat pain aggressively and appropriately. The Fed- opioid medications even in the face of severe trauma.14 http://www.jabfm.org/ eral and state governments’ campaign against the illicit use of prescription opiates, on the other hand, Disposal of Prescription and OTC Medications has made it difficult at times for patients to obtain A recurring problem facing patients in drug addic- relief for the pain of cancer or a debilitating disease. tion recovery is the disposal of prescription and Under-treatment of pain has also become a prob- OTC medications they have on hand. Especially lem among prescribing physicians, resulting from early in their program, patients may have hundreds on 24 September 2021 by guest. Protected fears of investigation by regulatory agencies. Phy- of prescription and OTC tablets as well as herbal sicians have found themselves fearful of govern- preparations and supplements. They may be using ment sanctions if they prescribe these medications. these as part of their abuse pattern or keeping them Paradoxically, some patients refuse to take opiates in case their addictive cravings overwhelm them.15 and other medications for pain control at the end of Disposal of these remedies becomes problematic their lives for fear of becoming addicted.13,14 because the patients cannot throw them in the Professionals who prescribe or work around trash, which could be searched by law enforcement controlled drugs also are at risk of abusing readily authorities. A similar situation exists if they try to available medications and becoming addicted. Part give it to friends. In many states, pharmacies cannot of the problem is that not only do the professionals legally take back the medications and other phar- divert medications for their own use, but, in some macies may refuse because of liability concerns. In cases, they rob patients of necessary medications.9 addition, there are many environmental concerns doi: 10.3122/jabfm.2008.01.070071 Abuse of Prescription and OTC Medications 47 J Am Board Fam Med: first published as 10.3122/jabfm.2008.01.070071 on 4 January 2008. Downloaded from

Table 2. Commonly Used Prescription Drugs with fax the same prescription to several Internet phar- Potential for Abuse macies. There has also been a trend toward online

Category Drugs Examples consultation in lieu of a prescription. In 2006, 99 Web sites offered such a service.18 Sedatives Barbiturates Amytal, Nebutal Flunitrazepam Rohypnol Dissociative anesthetics Ketamine Ketalar SV Sedatives Opioids and morphine Codeine Tylenol with codeine Barbiturates are typically used as a sedative and derivates Fentanyl Duragesic Morphine Duramorph anticonvulsant, but they have an equal role as the Opium Laudanum means to decrease the likelihood of seizures and Others Oxycontin other symptoms in alcohol, heroin, and other types Stimulants Amphetamines Dexedrine of drug withdrawal. This class of medications is Cocaine Cocaine hydrochloride easily abused as a hypnotic and overdose is com- Methamphetamine Desoxyn mon, resulting in death through respiratory depres- Methylphenidate Ritalin sion. They are addictive but tolerance can occur; a Anabolic steroids Anadrol withdrawal syndrome exists, consisting of agitation, Tranquilizers and Benzodiazepines Ativan, Halcion headaches, psychomotor retardation, confusion, muscle relaxers Carisoprodol Soma and possible seizures. Addicts may seek out barbi- Data from the National Institute on Drug Abuse.17 turates as a sleep aid and as a method of self- detoxification if they know that a Department of Transportation drug test is nearing.19 about the disposal of medications and contami- nated syringes. A possible solution might be to provide locked, hazardous waste collection contain-

Opioids and Morphine Derivatives copyright. ers at the physician’s offices where a patient can 6 Considerable controversy exists about the use of dispose of used syringes and medications. Although this article focuses on abuse, there are opioids for the treatment of chronic pain not orig- other nonmedical uses of prescription medications. inating from cancer and the resulting increase in These include bartering, especially in jails and pris- medications available for diversion to illicit use. ons; use as a mechanism of suicide; use as a mech- Under-treatment of pain has also become a prob- anism of homicide; and accidental ingestion.16 lem among physicians because of fears of investi- gation by regulatory agencies. One response to

Abused Prescription Drugs under-treatment has been the appearance of drug- http://www.jabfm.org/ Commonly abused prescription drugs are summa- seeking behavior among people with legitimate 20 rized in Table 2. Detection of these pharmaceuti- non-cancer pain. Myriad state and Federal laws cals is difficult because the Federal Department of and polices provide physicians with a confusing Transportation drug test panel, or a standard fo- picture of when and to whom these medications rensic drug test panel, may not pick up some of can be prescribed. these substances, including oxycodone. Detoxifica- A recent survey of physicians regarding drug on 24 September 2021 by guest. Protected tion and withdrawal from any of the medications abuse showed that doctors perceive the 4 mecha- may be problematic and may require inpatient nisms of diversion to be (1) doctor shopping to find treatment and appropriate pharmacological sup- a cooperative professional; (2) obtaining controlled port (Table 2).17 substances from multiple doctors; (3) patient de- The Internet is a major source of prescription ception or manipulation of doctors; and (4) forged 16 drugs that are used for nonmedical uses. A 2006 or altered prescriptions. A fifth source, not well survey documented that 89% of sites selling con- studied, consists of doctors and dentists who pre- trolled prescription drugs have no prescription re- scribe controlled drugs for money or who divert quirements, a figure that is down from 94% in them for their own use. Reports from England 2004. Of the 11% of sites that required a prescrip- document that most opioids that are used by ad- tion, 70% only required a prescription be faxed, dicts for nonmedical indications are prescribed by a allowing a customer to easily forge prescriptions or small number of physicians.21

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Stimulants Pharmaceuticals for Erectile Dysfunction Of particular concern are stimulant medications Sildenafil (Viagra; Pfizer, Inc., New York, NY) has used to treat attention deficit hyperactivity disor- become the sentinel erectile dysfunction medica- der. In 2004, there were 7873 emergency depart- tion in the drug-using culture; an underground ment visits by people who were found to be suffer- network of faked prescriptions, foreign imports, ing from poisoning because of the nonmedical use and Internet purchases exists. Both homosexual and of amphetamine-dextroamphetamine or methyl- heterosexual men and women are documented to phenidate. Of visits to the emergency department have demonstrated drug-seeking behavior with this for attention deficit hyperactivity disorder medica- substance.24 In a survey of sexually active males tion problems, 48% were for nonmedical use of the aged 18 to 25 years, 13% reported erectile dysfunc- medications, 34% were adverse reactions associated tion and 6% used medications, but rarely under with medical use, 10% were accidental ingestion, medical supervision and often mixed with recre- and 8% were suicide attempts. The rates were ational drugs.25 Among British illicit drug users, higher for the 12- to 17-year-old age group than Sildenafil use among night clubbers, a sentinel pop- for patients aged 18 or older. Over two thirds ulation of illicit drug users, was first reported in (68%) of the visits involved nonmedical use of these 1999. Use by both men and women was reported, 2 drugs and another substance, such as alcohol, an with elevated prevalence levels among both gay illicit drug, or a pharmaceutical.8 men and women.26 Among gay men and women, Sildenafil along Tranquilizers and Muscle Relaxers with cocaine, crystal methamphetamines, amyl ni- Benzodiazepines are commonly diverted for non- trate poppers, Ecstasy, gamma-hydroxybuterate, medical uses. They are typically prescribed as sleep and ketamine has become a “club drug.”27 Meth- aids or as anti-anxiety medications. They are also amphetamine and Sildenafil use are linked to un- useful in detoxification from alcohol or other sub- protected receptive and insertive anal sex, respec- stances and are useful in the treatment of convul- tively, in a sample of gay men.28 Sildenafil use copyright. sive disorders. Overdose can cause respiratory de- appears to have become a stable fixture of the sexual pression, especially when used with other sedative culture of gay men and is associated with a general medications or alcohol.22 behavioral risk patter for transmission of HIV and There is a syndrome of paradoxical disinhibition other sexually transmitted diseases.29 The concom- that results in increased excitement, irritability, ag- itant use of Viagra, testosterone, and antidepres- gression, hostility, and impulsivity. In rare cases, sants among HIV-seropositive gay and bisexual these conditions can lead to attacks of rage or men has been associated with unintended negative violence or other antisocial behaviors. Tolerance effects because of the additive risk of side effects.30 http://www.jabfm.org/ can develop with the use of these medications.22 Recent anecdotal evidence suggest that Sildena- High benzodiazepine doses are used by addicts to fil abuse is becoming increasingly popular among enhance the euphoria effects of opioids; boost Ecstasy users to attempt to negate the erectile dys- methadone or heroin fixes; temper cocaine highs; function side-effects of the drug or to enhance the augment the effects of alcohol; or ease the effects of drug experience through the concomitant use of withdrawal from heroin, methadone, and other erectile dysfunction drugs.31 on 24 September 2021 by guest. Protected drugs.22 Muscle relaxants can also be addicting. Cariso- prodol, a centrally acting muscle relaxant sold un- Abused OTC Drugs der the name of Soma, is an example. Its active OTC drugs are easily purchased, are difficult to metabolite is meprobamate, a class IV substance detect on routine drug testing, and can be used as and a highly addictive and potent sedative-hyp- an alternative DOC when the addicted person’s notic. Ingestion can cause addiction and a mild primary drug had been removed.32 The literature is sense of euphoria. Higher doses cause euphoria and sparse about OTC medications and herbal reme- impaired hand-eye coordination and balance. Tol- dies. Herbal remedies are especially problematic erance exists and there is a withdrawal syndrome of because they can be sold at swap meets and other anxiety, tremor, muscle twitching, insomnia, auditory unregulated venues; they are not subject to the and visual hallucinations, and bizarre behavior.23 scrutiny of the Food and Drug Administration; doi: 10.3122/jabfm.2008.01.070071 Abuse of Prescription and OTC Medications 49 J Am Board Fam Med: first published as 10.3122/jabfm.2008.01.070071 on 4 January 2008. Downloaded from

Table 3. Abused Over-the-Counter Medications (Representative List)

Physical Findings of Class Medication Medical (Legal) Use Nonmedical Use Nonmedical Use

Dietary supplements Supplement with Anorexia Hallucinations Acute psychosis piperazine Dissociative substances Dextromethorphan Cough suppressant Dissociative effect Psychiatric effects Coricidin Decongestant Euphoria Euphoria psychosis Chlorpheniramine Decongestant Euphoria Euphoria psychosis Dimenhydrinate Antiemetic Euphoria, hallucinations Extreme euphoria, hallucinations Diphenhydramine Sedation Euphoria ЉhighЉ Tachycardia, euphoria, hallucinations, psychosis Stomach preparations Calcium-bromide Antacid stomach Euphoria, hallucinations Neuropsychiatric symptoms combinations medication Stimulants Nicotine gum Smoking cessation ЉHighЉ Agitation Phenylpropanolamine Decongestant ЉHighЉ physical Agitation, rapid heartbeat performance enhancement Ephedrine Anti-asthma Prolonged erection and Priapism sexual performance Pseudoephedrine Decongestant Prolonged erection and Priapism sexual performance Methylephedrine Decongestant Prolonged erection and Priapism sexual performance Caffeine Awareness Performance enhancement Agitation, rapid heartbeat Ephedra Stimulant ЉHighЉ Agitation, tachycardia, flushing Cyclizine Antihistamine Euphoria Euphoria copyright. Epinephrine Bronchodilator Euphoria Headache, nausea, chest pains Laxatives Oral and rectal Anticonstipation Psychological dependence GI disturbances laxatives Sedatives Diphenhydramine Sedation Sedation Somnolence, coma Steroids Androstenedione Hormone Exercise enhancement Acne, glandular failure, (herbal sources) replacement hyperaggressive behavior Herbal Antidepressant Antidepressant Adverse psychiatric Psychosis reactions

Detox cocktail Detox from drugs Serotonin syndrome Psychosis http://www.jabfm.org/

they may be imported from other countries, espe- roid use within the last 3 years. Among women the cially Mexico and China, that do not have strict rates were 3%, 13%, and 0%, respectively.33 controls on their contents; they may include heavy metals such as lead; the there are few systematic Dextromethorphan on 24 September 2021 by guest. Protected studies of efficacy or safety.32 A representative list Dextromethorphan hydrobromide (DXM, or of abused OTC drugs is found in Table 3. Partic- “robo”), a constituent of more than 125 OTC ularly dangerous drugs or combinations of drugs cough and cold remedies, is the most popular are discussed individually below (Table 3). cough medication in the United States and is widely used in other parts of the world. The most common source of DXM is “extra-strength” cough OTC Steroids in Exercise Gymnasiums syrup, which contains 3 mg of the drug per 1 ml of In a study of 511 men entering 5 exercise gymna- syrup. The recommended dose for treating coughs siums it was found that 18% reported use of an- is 1/6 to 1/3 ounce of medication containing 15 mg drostededione or other anabolic steroids to increase to 30 mg of DXM. At higher doses it produces a muscle mass; 25% used ephedrine as a stimulant. dissociative effect similar to phencyclidine and ket- Among the same group, 5% reported anabolic ste- amine.34

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Cough syrups or capsules also contain additional hydrobromide, chlorpheniramine maleate, phenyl- ingredients such as acetaminophen, chlorpheni- propanolamine hydrochloride, and acetaminophen. ramine maleate, guaifenesin, and pseudoephedrine. The Texas Poison Network reported 78 cases of Toxicity with overdose is additive to that of DXM Coricidin intoxication from 1998 to 1999. Of these alone. An unknown number of adolescents in the 78 cases, 63% of the patients were men and 38% United States and Europe intoxicate themselves were women. The mean age was 14.67 years, with with acute megadoses of dextromethorphan, de- 77% being between 13 and 17 years old. Eighteen fined as 5 to 10 times the dose recommended for different symptoms were reported: tachycardia control of annoying nonproductive coughs. Al- (50%); somnolence (24.4%); mydriasis and hyper- though a moderate overdose of pure DXM hydro- tension (16.7%); agitation (12.8%); disorientation bromide is free of serious adverse effects, approxi- (10.3%); slurred speech (9%); ataxia (6.4%); vom- mately 5% of people of European ethnicity lack the iting (5.1%); dry mouth and hallucinations (3.9%); ability to metabolize the drug normally, leading to tremor (2.6%); and headache, dizziness, syncope, rapid, acute toxic levels. Variable quantities of pure seizure, chest pain, and nystagmus (1.3% each).38 DXM powder in multiples of 1 g are available from the Internet. Recipe-like extraction procedures are available online, allowing for simple and inexpen- Rapture sive home manufacture of concentrated DXM A 20-year-old man developed a brief psychotic ep- powder from Coricidin HBP Cough & Cold Tab- isode associated with per secutory delusional beliefs lets (Schering-Plough HealthCare Products, Inc., and auditory and visual hallucinations, leading him Kenilworth, NJ) (street name “triple C”). Acute to commit arson. The episodes occurred 12 hours megadoses of the drug have profound psychologi- after he took large doses of an OTC dietary sup- cal and physiologic effects similar to those of phen- plement containing piperazine, a stimulant known cyclidine. Megadoses of DXM used to self-intoxi-

on the streets as “rapture.” The patient also used copyright. cate can produce a false-positive screening test for small doses of cannabis and nitrous oxide and had phencyclidine in a urine specimen.35 no prior psychiatric history. He reportedly com- DXM can cause psychosis, dependence, and pletely recovered.39 physical withdrawal. It has specific serotonergic and sigma-1 opioidergic properties. Dextrorphan, the active metabolite of DXM, has similar proper- Dimenhydrinate ties; however, it is a weaker sigma opioid receptor The OTC anti-emetic dimenhydrinate (Gravol or agonist and a stronger N-methyl-D-aspartic acid

Dramamine) is a compound of diphenhydramine http://www.jabfm.org/ receptor antagonist. DXM and its metabolite, dex- trorphan, display specific biological features of ad- and 8-chlorotheophylline. Drug users abuse it for diction, including tolerance, and are capable of in- the acute effects of euphoric sensations and hallu- ducing specific psychiatric sequelae. There are cinations, whereas psychiatric patients abuse it be- 40 more profound and potentially life-threatening ef- cause of its anti-anxiety effects. Patients suffering fects at even higher doses. Dextrorphan has phar- from schizophrenia may be at risk because of its macodynamic properties and its intoxication effects anticholinergic effects. One report suggests that 40 on 24 September 2021 by guest. Protected produce dissociation, a state that abusers seek. clozapine reduces cravings for dimenhydrinate. Withdrawal is manifested by a profound depres- Dimenhydrinate is an H1 histamine receptor sion.36 Chronic addiction has been described in the antagonist but it interacts either directly or indi- literature.37 rectly with other neurotransmitter systems, includ- ing acetylcholine, serotonin, norepinephrine, dopa- Coricidin Intoxication mine, opioids, or adenosine. Animal behavioral Coricidin HBP is a popular OTC antihistamine studies looking at self-administration, conditioned and decongestant that is safe and effective when for place preference, drug discrimination, and used as directed on the product label. It is also sold modulation of operant responding, show that anti- as Coricidin D, Coricidin D (long acting), and histamines have abuse potential. Further support Coricidin D (cold, flu, and sinus). These medica- comes from reports of acute and chronic abuse of tions contain a combination of dextromethorphan dimenhydrinate by humans.40 doi: 10.3122/jabfm.2008.01.070071 Abuse of Prescription and OTC Medications 51 J Am Board Fam Med: first published as 10.3122/jabfm.2008.01.070071 on 4 January 2008. Downloaded from

Diphenhydramine Cyclizine The antihistaminic drug diphenhydramine is Abuse of cyclizine hydrochloride, a nonprescrip- mainly used as a sedative, hypnotic, and antiemetic. tion medication, was noted to occur frequently in In many countries it is available OTC under the Utah. Cyclizine is an OTC antihistamine. A retro- name Benadryl. It is very common and generally spective review of the Utah Poison Control Center regarded as a harmless drug. The recreational goal records of patients younger than 18 years of age and the intoxication syndrome affect 2 separate who intentionally ingested cyclizine and demon- populations differently. People with a nonaddictive strated abuse accounted for 89% of cyclizine toxic genetic constitution use it as a long-term hypnotic ingestions. Hallucinations (70%) and confusion to aid with sleeping. Those with a genetic predis- and disorientation (40%) were the most notable position to addiction use it for the subjective high symptoms. Tachycardia (52%) and systolic hyper- of a stimulant.41 tension (69%) were frequently present in patients The intoxication symptoms are also inconsis- who presented to a hospital. No serious complica- tent. Some people present with somnolence, se- tions occurred. The researchers concluded that dation, and retardation. In people with a genetic abuse of OTC medications by adolescents may be predisposition to addiction, there are tachycar- more appealing than illicit drug use for numerous dia, anticholinergic syndrome, agitation, halluci- reasons, and may be more common than appreci- 46 nations, confusion, tremor, convulsions, delir- ated. ium, and coma. A toxic psychosis is possible. Diphenhydramine can be used orally or intrave- OTC Analgesics nously. Medical personnel are at risk for addic- Using high levels of OTC analgesics, including tion because diphenhydramine is commonly on aspirin and acetaminophen, over long periods of stock in hospitals and clinics to treat allergic time have been associated with dysphoric mood states. Phenacetin, which was taken off the market reactions. Tolerance does exist with this OTC copyright. medication, and withdrawal results in sedation in the 1970s, had intoxicating effects and produced 34 and memory impairment.42,43 a dissociative state.

Intravenous Epinephrine Hydroxycut A case that demonstrates the lengths that people Because herbal products are not subject to the same will take to convert OTC medications to drugs of rigorous Food and Drug Administration regula- abuse concerns a 19-year-old man who intrave- nously injected 1.1 mg of epinephrine (adrenalin) tions that are required for prescription and OTC http://www.jabfm.org/ products, consumers unknowingly risk adverse ef- that was removed from an OTC bronchodilator fects when taking these products. A 22-year-old inhaler usually used for asthma. The man had a man was hospitalized after unexplained seizure-like history of intravenous cocaine and amphetamine activity and unresponsiveness. A urine toxicology abuse. Within seconds, he developed headache, screen was negative for salicylates, acetaminophen, nausea, numbness of the hands and feet, chest pain, alcohol, and drugs-of-abuse. Medical history was and palpitations. The electrocardiograph demon- 46 insignificant with the exception of recent (within 2 strated ischemic changes. on 24 September 2021 by guest. Protected weeks) ingestion of Hydroxycut, a dietary supple- ment purported to enhance energy, build muscle, OTC Hypnotics (Sleep Aids) and burn fat. The agent contains ephedra alkaloids Used in excess amounts, OTC sleep aids (Sominex, and caffeine, both of which are central nervous Nytol, and Sleep Eze) can cause hallucinations, system stimulants. The seizure was attributed to delirium, and confusion. When use is stopped, re- their consumption. Because of a significant number covery is rapid and there is no withdrawal syn- 41 of reported adverse events, the Food and Drug drome. Administration proposed regulations for dietary supplements containing ephedra alkaloids and re- Strategies for Physicians quested an independent review of case reports Physicians must be on the alert for prescription and linked to these products.44 OTC medication abuse. Strategies that can be em-

52 JABFM January–February 2008 Vol. 21 No. 1 http://www.jabfm.org J Am Board Fam Med: first published as 10.3122/jabfm.2008.01.070071 on 4 January 2008. Downloaded from ployed include (1) inquiring about prescription, aberrant outpatient prescriptions for extended-re- OTC, and herbal drug use at the initial examina- lease oxycodone. Am J Health Syst Pharm 2005;62: tion (although many individuals are drug-abuse 2604–8. 11. National Household Survey on Drug Abuse. Non- savvy, some are naı¨ve and don’t realize that OTC medical use of prescription-type drugs among youths medications can be problematic); (2) inquiring and young adults. Washington, DC: Office of Ap- about illegal drug use during office visits; (3) pro- plied Studies, Substance Abuse and Mental Health viding disposal containers that patients can use to Services Administration; 2003. dispose of their unused or unneeded prescription or 12. Drug Abuse Warning Network. Emergency depart- OTC medications; (4) treating pain aggressively ment visits involving ADHD stimulant medications. and appropriately; (5) practicing careful record Washington, DC: Office of Applied Studies, Sub- stance Abuse and Mental Health Services Adminis- keeping of prescription refills and controls over tration; 2006. prescription blanks; (6) referring patients who are 13. Miller NS. Physicians and the controlled substance addicted to medications to 12-step programs such laws for opiate prescription medications. Psychiatr as Alcoholic Anonymous, Narcotics Anonymous, Ann 2006;36:422–9. and Pills Anonymous; and (7) considering detoxifi- 14. Weaver M, Schnoll S. Abuse liability in opioid ther- cation, either inpatient or outpatient. apy for pain treatment in patients with an addiction history. Clin J Pain 2002;18:S61–9. 15. London M. Prevention of substance abuse. Curr References Opin Psychiatry 2001;14:207–11. 1. DuPont RL. Prescription stimulant abuse. Psychiatr 16. Gilson AM, Ryan KM, Joranson DE, Dahl JL. A Ann 2005;35:93–7. reassessment of trends in the medical use and abuse 2. Collins GB, McAllister MS. Combating abuse and of opioid analgesics and implications for diversion diversion of prescription opiate medications. Psychi- control: 1997–2002. J Pain Symptom Manage 2004; atr Ann 2006;36:410–6. 28:176–88. 3. Substance Abuse and Mental Health Services Ad- 17. National Institute on Drug Abuse. Prescription drug

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