- Email: [email protected]
Drugs Used in Acquaintance Rape
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Drugs Used in Acquaintance Rape Kelly M. Smith
Objective: To describe gamma-hydroxybutyrate (GHB), flunitrazepam, and ketamine and their purported uses to facilitate acquaintancerape. Patient presentation characteristics, treatment regimens, processes to detect the presence of the medications by toxicology screening, and methods to avoid exposure are discussed. Data Sources: MEDLINE search from 1985 to 1998; additional references found within the articles; information obtained from the Internet. Study Selection: Clinical trials, reviews, and press releases concerning the use of GHB, flunitrazepam, and ketamine to facilitate acquaintance rape. Trials and reviews describing clinical effects, adverse effects, pharmacokinetics/pharmacodynamics, and usage trends were evaluated. Literature judged to be pertinent by the author was included in the discussion. Data Extraction/Data Synthesis: Reports of the use of GHB, flunitrazepam, and ketamine in acquaintance rape appear in the medical literature and lay press. Many health care professionals may not be familiar with these medications, and information about caring for patients under their influence is limited. Victims lose their ability to ward off attackers, developamnesia, and are unreliable witnesses. Because symptoms caused by these agents mimic those of alcohol, not all victims are screened for their presence. Legislative efforts to further limit the use of or access to GHB, flunitrazepam, and ketamine have been initiated at the state and federal levels. Pharmacists should know the symptoms of exposure to the three agents; they should understand treatment regimens, methods to detect the presence of these and other drugs that may have been used in a sexual assault, and techniques individuals can use to avoid becoming victims of drug-assisted acquaintance rape. Conclusion: Because of their extensive drug knowledge and frequent access to patients, pharmacists are uniquely positioned to educate patients and other health care professionals about the dangers of acquaintance rape drugs and methods to reduce their risk of becoming victims. JAm Pharm Assoc. 1999;39:519-25.
It is estimated that 25% of women in the United States will be raped during their lifetimes. I Of these victims, 75% are thought to know their assailants.2 Such assaults are termed acquaintance rapes. Rapists may surreptitiously administer drugs in a victim's beverage to induce sedation or amnesia. The use of chemical substances to facilitate criminal assault has not been well documented in the medical literature.3 However, anecdotal reports ' of "knockout drops" date back to the early 20th century. Perhaps the most familiar example is the "Mickey Finn," which Received November 24, 1998, and in revised form March 8, 1999. ~Pted for publication March 19, 1999. Kelly M. Smith, PharmD, is drug information specialist and clinical assistant professor, University of Kentucky Medical Center, Lexington. Correspondence: Kelly M. Smith, PharmD, Drug Information Center, University of Kentucky Hospital, 800 Rose Street, Room Cl13, Lexington, KY 40536-0293. Fax: (606) 323-2049. E-mail: [email protected]. Continuing education credits: See page 581 for learning objectives and test questions for this article, which is number202-000-99-126-HOl in APhA's educational programs.
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involves the addition of chloral hydrate to an ethanol-based beverage. 4 The extent to which drugs are used today in acquaintance rape is unknown, but references to three particular substances as "date rape drugs" appear in the medical literature as well as the lay press. 5- 13 Flunitrazepam, a benzodiazepine marketed outside of the United States, gamma-hydroxybutyric acid (GHB), an investigational sleep aid, and the anesthetic agent ketamine have all been associated with acquaintance rape. This article describes the signs and symptoms of the ingestion of these substances, patient management techniques, and processes to detect the presence of the drugs by toxicology screening.
GHB Gamma-hydroxybutyric acid (GHB) is also known as gammahydroxybutyrate and sodium oxybate. GHB is sold on the street under a variety of names, including Liquid Ecstasy, Gib, Natural Sleep-500, Somatomax, Georgia Home Boy, Grievous Bodily
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Hann, Liquid X, Liquid E, GBH, Soap, Scoop, Easy Lay, Salty Water, G-Riffick, Cherry Menth, and Organic Quaalude. 5.6
Availability The product is currently available in the United States only for investigational use as a treatment for narcolepsy. Thus, possession of GHB is not illegal, but under the provisions of the Food, Drug, and Cosmetic Act, its sale is prohibited. 6 The Drug Enforcement Administration (DEA) reports that clandestine manufacture is widespread, and the agency is considering a recommendation that GHB be classified federally as a controlled substance. Twenty states have already controlled GHB, and New Jersey and Texas have determined it to be illegal for use, with penalties similar to those associated with marijuana. 14
Pharmacology/Therapeutic Use Synthesized in 1960, GHB was demonstrated to cross the blood-brain barrier and in 1963 was found to be a naturally occurring substance in the brain. Although a mechanism of action has not been elucidated, some researchers have suggested that GHB acts as a neurotransmitter. 15 The agent appears to increase dopamine levels and affect the endogenous opioid system. The central nervous system (CNS) depressant has an affinity for a GHB-specific receptor and the GABA B receptor.16 In the 1970s GHB was first used in the United States in the treatment of sleep disorders, and its use in this area continues to be studied. Investigators believe the depressant induces rapid eye movement (REM) sleep, thus decreasing symptoms of narcolepsy. It has also been used as an anesthetic in Europe, but its use decreased when seizure-like activity and poor analgesia were associated with the agent. 5 A 1977 study reported steroid-enhancing effects of GHB. The investigators hypothesized that the agent simulated the effects of growth hormone, but this hypothesis has never been proven. However, bodybuilders continue to use the product to increase muscle mass. 5 GHB has also been investigated as adjunctive therapy in alcohol and opiate withdrawal. 17- 19
Epidemiology GHB was introduced commercially in the United States in health food stores in 1990. It was promoted as a sedative alternative to L-tryptophan, which was removed from the market in 1989. After reports of adverse effects surfaced, including gastrointestinal distress, CNS depression, and seizures and comas, the Food and Drug Administration (FDA) removed GHB from the market in November 1990.20 Nevertheless, the drug is often used for its euphoric effects, and clandestine manufacture has continued. Since 1997 DEA has been aware of at least 100 cases involving illicit GHB laboratories. The death of actor River Phoenix outside a Los Angeles club in 1993 was rumored to have been associated with GHB. Although this linkage was never sub-
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stantiated, this tragedy sparked a renewed interest among illicit drug users in GHB as a recreational agent. 5 The agent continues to be used in social settings, particularly at "rave" dance parties. along with methedrine or methamphetamine (speed) and Ecstasy (methylenedioxymethamphetamine [MDMAD. 5•7 Recipes for the manufacture of GHB are available on the Internet, as well as dos· ing, combination drug use, and mail order information. 5 As of March 1999 DEA had received 22 reports of sexual assault in victims under the influence of GHB since 1996. 14 A 1997 report from poison control centers in Texas and New York listed 69 poisonings and 1 death caused by GHB in a 13-month period beginning in August 1995. Poison control centers through· out the country reported an increase in use of the product in 1997. 5 Misuse is prevalent in California, Florida, Georgia, and Texas. 6 The United Kingdom and Australia have reported misuse of the agent. 5 I In January 1999 FDA requested a voluntary recall of products containing gamma-butyrolactone (GBL), a GHB precursor, and advised consumers not to purchase or use these products. Although GBL was found in products labeled as dietary supplements and promoted to build muscle mass, improve physical performance, diminish insomnia, enhance sex, and reduce stress, FDA considers the agent an unapproved new drug because it is converted to GHB. The warning was issued based on 55 reports of adverse effects, including 1 death. In 19 cases, patients lost consciousness and many required intubation.2 1
Clinical Effects GHB is a white powder that precipitates when sodium hydrox- . ide solution is added to GBL. It is generally available as a colorless, odorless liquid with a mild, salty, or soapy taste that is easily masked. 5 Clinical effects are increased when the agent is given in combination with alcohol, marijuana, and other drugs, as is the risk of aspiration pneumonia. 5•s Some experts report a pronounced coma and respiratory depression within 15 to 30 minutes after ingestion of 5 to 30 mL of GHB and alcohol. Intubation may be necessary, although patients may recover spontaneously in a matter of hours. Some patients have recovered during intubation. , typically displaying signs and symptoms of amnesia.5 •22 GHB is used as an acquaintance rape drug because it has a ~ rapid onset of effect, is relatively easy to obtain on the black market and manufacture at home, and is easy to administer. Also, it has been purported to have aphrodisiac properties. 23 Because the product is often a colorless, odorless liquid, and because relatively small quantities produce the desired effect, it can be given in a beverage to an unwitting victim. Victims often experience amnesia or hallucinations and are thus unable to serve as reliable witnesses to a crime. Within 15 to 30 minutes of ingestion, the victim begins experi- . encing the effects of GHB, which are often confused with the effects of alcohol (see Table 1). Initial symptoms may incIudl drowsiness, confusion, and dizziness. Rapid coma, vomiting·
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;ie 1.
Features of Exposure to Acquaintance Rape Drugs GHB
Flunitrazepam
15 to 30 minutes
20 to 30 minutes
15 to 20 minutes
Drowsiness Disorientation Dizziness
Drowsiness Disorientation Dizziness Slurred speech Hot or cold flashes Nausea
Analgesia Disorientation Amnesia Hypersalivation
Subsequent symptoms
Vom iting Rapid onset coma Amnesia
Difficulty speaking and moving Rapid onset coma Amnesia
Dizziness Hallucinations Delirium Nystagmus Respiratory depression
High-dose symptoms
Respiratory depression Bradycardia Clonic muscle contractions Anesthesia Diminished cardiac output
Prolonged psychomotor impairment Respiratory depression
Dissociative anesthesia Seizures Arrhythmias Cardiac arrest
Management techniques
Blood pressure, heart rate, and respiratory rate monitoring Airway protection Recovery position with bedside suction Supplemental oxygen Atropine as needed for bradycardia Co-ingestion: Gastric lavage or activated charcoal Rapid-sequence intubation w ith succinylcholine Specific antagonists for co-ingested agents (e.g., naloxone)
Blood pressure, heart rate, and Blood pressure, heart rate, respiratory rate monitoring and and respiratory rate support as needed monitoring and support as Severe overdose: needed Gastric lavage or activated charcoal Quiet recovery area with Airway protection minimal environmental Flumazenil (primarily for respiratory stimulation depression) if no contraindications
;;;-10 symptom onset ,IORial symptoms
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Ketamine
' GHB = gamma-hydrox ybutyric acid .
respiratory depression, and Cheyne-Stokes respiration, bradycardia, clonic muscle contractions, and induction and emergence delirium may follow. Alert patients may present with tachycardia, hypertension, and psychotic symptoms, including paranoia and hallucinations. 5 Manifestations of ingestion appear to be dose-related. Amnesia and hypotonia have been reported with doses of 10 mg/kg body weight. Cycles of REM and non-REM sleep are associated with 20 10 30 mg/kg doses, whereas anesthesia may result from 50 mg/kg doses. Doses exceeding 50 mg/kg may produce coma, severe respiratory depression, seizure-like activity, and diminished cardiac oUlput. 6,20 A series of case reports describes loss of consciousness with profound respiratory depression in seven patients. Several of the patients were too combative to intubate, and all required physical reslraints.23 Other reports of GHB use list a characteristic rapid return to consciousness, often followed by nausea and vomiting. 5,) Clinical course and recovery may be related to presenting level of consciousness. In one study, patients with an initial Glasgow Coma Score (GCS) of 8 or less experienced bradycardia or emesis. The same investigators also hypothesized that the initial Gcs may also predict time to recovery.24
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Early reports of seizure activity with GHB exposure have not been confirmed. However, epileptiform activity resembling petit mal epilepsy has been reported in animal and human models, but not in normal human volunteers. 25 - 27 GHB has been linked to clonic muscle contractions and combativeness. Random clonic movements of the extremities and face associated with GHB may be confused with epileptic activity.8,24,28
Diagnosis and Management Diagnosis of GHB intoxication can be challenging. Short of a reliable hi~tory, the hallmark feature of GHB ingestion is marked agitation upon stimulation, despite prolonged apnea and hypoxia. U waves may also be present on ECG. In one case series, five of seven patients, three of whom experienced significant cardiac abnormalities, had U waves present without significant hypokalemia. 23 Patients may also experience hypothermia. 24,29,3o Hypotension may
be present and is generally associated with co-ingestion of other agents. Because vomiting is common, victims are susceptible to aspiration, requiring airway protection. This is of particular concern because GHB preparations are generally made in clandestine
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laboratories. Purity is uncertain, and an improperly prepared product may have excessive amounts of caustic sodium hydroxide. Benzodiazepines and opiates have no role in patient management. Because GHB is often administered in relatively small volumes (e.g., 1 to 60 mL) and is rapidly absorbed, gastric lavage or activated charcoal are of little use,5 although these methods are recommended for drugs concomitantly ingested. Naloxone has been reported to be of no use.3.4 Li and colleagues suggest the following management principles for patients with spontaneous breathing: recovery position with bedside suction, supplemental oxygen, intravenous access, and atropine for persistent symptomatic bradycardia. 3! In patients with GHB ingestion complicated by other substances, advanced airway protection via rapid-sequence intubation is indicated. 29.3!.32 Because GHB victims are already sedated, only succinylcholine paralysis is required. After 6 hours of observation, patients should be admitted to the hospital if they are deemed clinically intoxicated, or discharged if clinically well. 3!
Detection The presence of GHB is difficult to detect, because the drug is eliminated rapidly. Its half-life ranges from 20 minutes to 1 hour, and the product is virtually undetectable in urine after 12 hours. Victims often recover spontaneously within I to 2 hours. This allows the assailant an opportunity to escape before the victim awakens. 5 Only laboratories equipped to perform urine assays using quantitative gas chromatography-mass spectrometry (GC-MS) can routinely detect GHB. One report indicates that, in the Los Angeles area, only two hospitals have adequate facilities for such an assay. The test, which also detects GHB metabolites, requires 1 day to process and costs between $230 and $310.7.33 In areas that do not have access to GC-MS, health care professionals can call upon the services of a national forensic laboratory (National Medical Services, Willow Grove, Pennsylvania; 800-522-6671) for approximately $100 a specimen.
Flunitrazepam Availability/Epidemiology Flunitrazepam (Rohypnol-Roche) is a fast-acting benzodiazepine that is approximately 10 times more potent than diazepam.34 Flunitrazepam is available in oral tablets and as an injection. 35 It is used in Mexico, South America, Asia, and Australia for sedation and treatment of insomnia. Loss of memory about events that occur while under the influence of the drug make it particularly useful as a preoperative sedative. Flunitrazepam is sold on the street under such names as Roofies, Rophies, Roopies, Roches, Roaches, Ropanol, Robinol, Rohibinol, Reynol, Roofenol, Ruffiew, Rubies, R2s, Ropes, Rib, Pappas, Peanuts, Pastas, Forget Pill, Whiteys, Ro-shays, Circles, Mexican Valium, and La Roche. "Roached out" is a slang term
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for being under the influence of flunitrazepam.9.36.37 One tablet: costs up to $5.00. 37 .38 In 1989 flunitrazepam was first seized in the United States by law enforcement officials. 9 Abuse of the drug was first docu· mented 4 years later. 36 Flunitrazepam is often used to enhance the effects of heroin, alcohol, or marijuana. It can also be used to ease the symptoms of withdrawal from heroin and diminish some of the stimulant effects of cocaine. The agent may be chewed, dissolved under the tongue, snorted, injected, or smoked, in addition to its more frequent oral route of administra· tion. 9 More than 1,000 law enforcement investigations involving flunitrazepam were undertaken between 1990 and 1995. Approx. imately 1.5 million tablets were brought across the Mexican bor· der into Laredo, Texas, alone in 1995. 39 Importation of flunitrazepam from Mexico into the United States was banned in 1996. This regulation made the prescription, sale, or importation of flunitrazepam illegal. 40 From 1994 to 1998, at least 26 sexual assault cases have involved or have potentially involved flunitrazepam. According to an international treaty, flunitrazepam is considered a Schedule IV controlled substance. However, eight states have classified the agent as a Schedule I controlled substance, making penalties for its possession equivalent to those for other drugs of abuse, such as heroin. Some other states have stiffened the penalties for distribution.!4 Use of flunitrazepam is more common in the southern border states. Mexico and South America are the most common sources of the illegally imported medication. However, clandestine laboratories produce some of the street supply.37
Pharmacokinetics/Pharmacodynamics Approximately 80% to 90% of an oral flunitrazepam dose is absorbed. The drug is rapidly distributed, as best described by a three-compartment concentration-time curve. An extensive metabolism, primarily by the kidneys, follows, with an elimination half-life of 20 hours. Because the drug is rapidly distributed into tissues, the duration of its clinical effects is much shorter than would be expected from such a prolonged half-life. 34 Sedation generally occurs 20 to 30 minutes after ingestion. with maximal effects at 1 to 2 hours. Doses of up to 2 mg may induce psychomotor impairment for nearly 12 hours following ingestion. The anterograde amnesia associated with the benzodiazepine may begin within 30 minutes. 34 In one trial, a 1 mg dose I resulted in amnesia in 65% of patients; only 30% of patients experienced this effect with a 0.5 mg dose. 4 !
Clinical Effects Flunitrazepam is a tasteless, odorless medication that easil) dissolves in alcohol. Typically administered in a beverage to an unknowing victim, the sedative is a particularly effective "date rape" drug because of its amnestic, hypnotic, and disinhibito0 effects. Alcohol multiplies the effects of the medication.
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Victims may first notice dizziness, disorientation, lack of 'UXlrdination, slurred speech, hot and cold flashes in rapid alter'nation, or nausea. Speech and motor difficulties usually pre:(fdethe loss of consciousness. All of these effects can be con!(used with those of alcohol. Administration with a carbonated [tverage, coffee, or fruit juice may enhance the psychological effects of the medication.9 As with other benzodiazepines, resIfiralOry depression is a primary concern.42 Effects may last 2 to ! hours, so victims often wake after their attacker is gone. Iymptoms may be prolonged in the presence of hepatic or renal dysfunction .43 Roche Pharmaceuticals has attempted to minimize the use of flunitrazepam in acquaintance rapes by reducing the number of iMexican distributors, ceasing direct sales to pharmacies, and dis'continuing production of the strongest tablet (2 mg). Also, the 'manufacturer has reformulated the product to dissolve more slowI~ inliquid. The new formulation also turns clear beverages bright blue and causes dark beverages to appear murky.44
Management Gastrointestinal decontamination and airway protection may be required in severe overdoses. The true role of decontamination is currently under dispute; however, activated charcoal may have a role in management. 45 Supportive care alone is generally sufficient for most patients, with improvement apparent within 6 oours. The benzodiazepine antagonist flumazenil , at an initial dose of 0.2 mg IV, may reverse the effects of the benzodiazepine, but repeated doses may be necessary to sustain a reversal. If the patient does not respond, a 0.3 mg dose should follow in Iminute, increasing to 0 .5 mg per minute up to a total of 3 mg orpatient response. 43 Flumazenil may be particularly useful in patients with respiratory depression or when the substance ingested is unknown. A rapid response to flumazenil would assist in the diagnosis and subsequent management. However, routine use of the benzodiazepine antagonist is unwarranted ;because of the need for frequent readministration, cost of the agent, and because supportive care is usually sufficient. MoreOver, flumazenil has been associated with the unmasking of seiZure disorders, particularly those controlled by benzodiazepines. The potential for co-ingestion with tricyclic antidepressants or cocaine also contraindicates the use of flumazenil.46
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sponsored by Hoffmann-La Roche. The service, which is free of charge to law enforcement agencies, rape crisis centers, and emergency departments, can be accessed by calling 800-608-6540. The test is a series of three assays, including GC-MS. Urine samples should be refrigerated or frozen to minimize degradation before testing. 47
Ketamine Availability Ketamine is a general anesthetic used primarily in emergency medicine and critical care settings and veterinary medicine. A chemical cousin of phencyclidine (PCP), ketamine is available in the United States as an injectable prescription drug, but may be administered orally. The product is manufactured under the trade names Ketalar (Parke-Davis) and Ketaject (Bristol-Myers Squibb), and is also available from several generic manufacturers. Slang terms for ketarnine include K, Special K, Kay, Keets, Green, Jet, Mauve, Purple, Special LA Coke, Super Acid, and Super c. 42 Ketamine has several illicit uses, and many users deem the effects superior to those of PCP or lysergic acid diethylamide (LSD). It may be snorted, swallowed, smoked, or injected. 48 DEA is aware of at least one case in which ketamine was demonstrated to facilitate rape. In 1993 use of the medication in acquaintance rape was first reported in Florida. Use of the drug for this purpose spread across the South, and soon reached the East Coast. In 1998 Governor George Pataki signed legislation making ketamine a Schedule III controlled substance in New York, reducing legal access to the drug and requiring accountability in cases of theft or loss. Possession and sale of ketamine was declared a criminal offense. 1o Ketamine is also a controlled substance in 17 other states, and the Department of Health and Human Services has recommended that the anesthetic be placed in Schedule III. 14
Pharmacokinetics/Pharmacodynamics In low doses, ketamine produces analgesia. A low bioavailability (16%) requires higher oral doses to achieve adequate analgesia, often within 30 minutes. Ketamine has a distribution pattern similar to thiopental. It reaches highly perfused tissues first, such as the heart, brain, and lungs, followed by muscle and peripheral tissues, and is then redistributed into fat. The anesthetic undergoes extensive liver metabolism. 49,50
iDetection
Clinical Effects
Most commercially available toxicology screens are unable to detect flunitrazepam, which is typically administered in small quantities. Definitive tests to confirm its presence include GCMS. A 2 mg dose can be detected in urine up to 72 hours after Ingestion.43 ,44 If the presence of flunitrazepam is suspected, a urine specimen may be submitted to a screening program
The analgesic effects of ketamine generally last from 20 to 45 minutes. Increasing doses result in a dissociative anesthesia, which patients often describe as feeling detached from their surroundings or floating above their own body. Other effects include hypertension, vomiting, hypersalivation, and rapid movements. Dizziness, disorientation, vivid dreams, hallucinations, delirium,
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Table 2. Methods to Reduce Risk of Exposure to Acquaintance Repe Drugs Do Discard any beverages that have been left unattended. Bring your own beverages to social gatherings, when possible. Be alert to a friend's behavior that is symptomatic of a drug ingestion, and have them reciprocate the favor. Look for the signs listed in Table 1. Do not Leave beverages unattended in a social setting. Accept open beverage containers from someone other than a bartender or server. Share or exchange beverages with anyone. Drink beverages from a common container (e.g., punch bowl). Drink anything that has an unusual appearance (e.g., excessive foam, cloudiness) or taste (e.g., salty). Source: Reference 55.
and nystagmus are eNS effects that may ensue. There have been reports of flashbacks weeks after recovery, but such reactions are disputed.51 ,52 Patients typically experience a rapid return to consciousness, but full recovery from the anesthetic effects may take several hours. 41 ,51,53 Ketamine may be used as a "date rape" drug because amnesia about events that occurred during exposure to the drug begins as soon as 15 to 20 minutes after ingestion, and victims frequently lose consciousness abruptly. Hallucinations or dreams so intense that they cannot be easily discerned from reality make victims of sexual assault unreliable witnesses. 51 The drug can be easily administered in beverages to unknowing subjects.
was detected in only five samples, four of which contained other substances. Ketamine was not identified. The testing service. which continues today, is funded by Hoffmann-La Roche as a public service.44,54 Polysubstance abuse in combination with GHB irtgestion Was found in all seven patients described in a recent case repon.2] Alcohol was found in all patients, five had cocaine detected in urine screening, and two had evidence of other sympathomimetic agents. In the emergency department of an urban public hospital, nearly 40% of patients exposed to GHB used alcohol concomi· tantly, and other drugs were present in more than 25% of the patients. 24 Health care professionals should be aware of the possibility that victims may have been exposed to other or additional substances. Treatment should follow based on signs and symptoms of exposure, as well as the results of laboratory monitoring and toxicology screening. Consumers should be advised about the potential risks of these amnestic drugs and methods to reduce their risk of exposure (see Table 2). Most of the methods require the use of caution in social settings.
Conclusion
Pharmacists and other health care professionals should be aware of drugs that may be used to facilitate sexual assault. Most reports detail the use of flunitrazepam, GHB, and ketamine Despite the reputation these three agents have garnered as hann· ful drugs, the latter two agents have legitimate or expanding uses in the United States, and flunitrazepam is used clinically in sever· al other countries. Trials of the use of GHB, primarily in nar· Management colepsy and resuscitation, are ongoing or on the horizon. 23 In Supportive care is the cornerstone of patient management. actuality, other substances (e.g., alcohol, cocaine) are more com· Blood pressure, heart rate, and respiratory rate should be closely monly used in acquairttance rapes. monitored. The risks of blood pressure changes and respiratory Victims that present with amnesia, appear irttoxicated, or awak· depression increase when ketamine is combined with alcohol. en partially clothed or nude in a strange place should be screened ~ Because victims may experience hallucinations, it is important to for the presence of illicit substances. Urine samples should be minimize environmental stimuli.42 ,5l,53 A quiet recovery area is obtained, and toxicology screens that detect flunitrazepam, GAB. recommended to minimize any symptoms of emergence. ketamine, and other amnestic agents should be performed, I Patients should be treated symptomatically and observed for sev' l eral hours 'after their symptoms resolve. Other Substances Used in Pharmacists may be irt the most advantageous position to eduAcquaintance Rape cate the public about the potential risks of drug-irtduced acquain· tance rape. Because of their extensive drug knowledge and fre· I Although GHB, flunitrazepam, and ketamine appear most fre- quent access to patients, pharmacists are the ones to whom quently in the literature, they are not the only substances associat- consumers often direct their questions and from whom they seek ed with sexual assault. A study reported at the American Acade- advice. The pharmacist's professional knowledge may also be of my of Forensic Sciences 1998 Annual Meeting detailed the value to law enforcement officials, rape counselors, or other presence of some 20 different substances potentially associated health care professionals who deal with potential acquaintance with acquaintance rape in specimens obtained from victims. 54 Of rape victims. 578 samples, 208 contained alcohol, 93 marijuana, and 40 The author declares no conflicts of interest or financial interests in anY cocaine. GHB was found in 32 specimens, 11 of which contained product or service mentioned in the manuscript, including grants, alcohol and 14 of which contained other drugs. Flunitrazepam emptoyment, gifts, and honoraria.
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l4. Hernandez M, McDaniel CH, Costanza CD, et al. GHB-induced delirium:
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acase report and review of the literature on gamma hydroxybutyric acid. Am J Drug Alcohol Abuse. 1998;24: 17~. Banerjee PK, Snead ~C. Presynaptic gamma-hydroxybutyric .acid IGHB) and gamma-aminobutyric acid B (GABA.,) receptor-mediated release of GABA and glutamate (GlU) in rat tlialamic ventrobasal nucleus (VG): a possible mechanism for the generation of absence-like seiZures induced by GHB. J Pharmacol Exp Ther. 1995;273:1534-43.
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26. Tunnicliff G. Significance of gamma-hydroxybutyric acid in the brain. Gen Pharmaco/. 1992;23:1027-34. 27. Entholzner E, Mielke l, Pichlmeier R, et al. EEG changes during sedation with gamma-hydroxybutyric. Anesthetist. 1994;44:321-4. 28. Dyer JE. Gamma hydroxybutyrate: a health food product producing coma and seizure activity. Am J Emerg Med. 1991;9:321-4. 29. Ross TM. Gamma hydroxybutyrate overdose: two cases illustrate the unique aspects of this dangerous drug. J Emerg Nurs. 1995;21 :274-5. 30. Suner S, Szlatenyi C, Wang R. Pediatric gamma hydroxybutyrate intoxication. Acad Emerg Med. 1997;4:1041-5. 31. Li J, Stokes SA, Woeckener A. A tale of novel intoxication: a review of the effects of gamma-hydroxybutyric acid with recommendations for management. Ann Emerg Med. 1998;31:729-36. 32. Morris IR. Pharmacologic aids to intubation and the rapid sequence induction. Emerg Med Clin North Am. 1988;6:7~. 33. Chin Rl, Sporer KA, Cullison B, et al. Clinical course of gamma-hydroxybutyrate overdose. Ann Emerg Med. 1998;31 :716-22. 34. Mattila MAK, Larni HM. Flunitrazepam: a review of its pharmacological properties and therapeutic use. Drugs. 1980;20:353-74. 35. Rohypnol international standard product information. Nutley, NJ: Hoffmann-La Roche, Inc; 1994. 36. Maxwell J, Hall J. Memorandum to members. NIDA Community Epidemiology Work Group. May 2, 1995. 37. Drug Enforcement Administration. Flunitrazepam fact sheet. Washington, DC: U.S. Department of Justice; 1995. 38. National Institute on Drug Abuse . Epidemiologic trends in drug abuse-advance report. Community Epidemiology Work Group; June 1995. 39. Drug implicated in date rape faces import ban. Drug Topics. 1996; April 8:110. 40. Facts on Rohypnol (flunitrazepam). Toronto, Ontario: Metro Toronto Research Group on Drug Use;1996:1(3). 41. McKay AC, Dundee JW. Effect of oral benzodiazepines on memory. Br J Anaesth. 1980;52:1247-57. 42. Rumack BH, Toll lL, Gelman CR, eds. POISINDEX System. Englewood, Colo: MICROMEDEX, Inc; (Vol. 98, expires 11130198). 43. Anglin D, Spears KL, Hutson HR. Flunitrazepam and its involvement in date or acquaintance rape. Acad Emerg Med. 1997;4:323-6. 44. Flunitrazepam (Rohypnol) testing: basic facts. Nutley, NJ: Hoffmann-La Roche, Inc; 1996. 45. Henry JA, Hoffman JR. Continuing controversy on gut decontamination. Lancet. 1998;352:41CH . 46. Flumazenil (Romazicon) [package insertl. Nutley, NJ: Roche Pharmaceuticals; 1998. 47. Testing for drugs in sexual assault. Oxford, Miss: EISohly Laboratories, Inc; 1997. 48. Ketamine abuse increasing [press releasel. Drug Enforcement Administration. U.S. Department of Justice; February 4, 1997. 49. Grant IS, Nimmo WS, Clements JA. Pharmacokinetic and analgesic effects of 1M and oral ketamine. BrJ Anaesth. 1981 ;53:805-10. 50. Reich Dl, Silvay G. Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth. 1989;36:186-S7. 51. USP Drug Information for the Health Care Professional. 18th ed. Rockville, Md: United States Pharmacopeial Convention, Inc; 1998. 52. Hersack RA. Ketamine's psychological effects do not contraindicate its use based on a patient' s occupation. Aviat Space Environ Med. 1994;65:1041-6. 53. Van Hemelrijck J, Gonzales JM, White PF. Pharmacology of intravenous anesthetic agents. In: Rogers MC, Tinker JH, Covino BG, et ai, eds. Principles and Practice of Anesthesiology. SI. louis, Mo: Mosby Year Book; 1993:1131-54. 54. Study sheds light on drug-related rape [press releasel. Oxford, Miss: EISohly Laboratories, Inc; February 13, 1998. 55. DC Rape Crisis Center expresses concern over narrow focus on date rape drugs [press releasel. Washington, DC: DC Rape Crisis Center; November 3, 1997.
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Drugs Used in Acquaintance Rape Kelly M. Smith
Objective: To describe gamma-hydroxybutyrate (GHB), flunitrazepam, and ketamine and their purported uses to facilitate acquaintancerape. Patient presentation characteristics, treatment regimens, processes to detect the presence of the medications by toxicology screening, and methods to avoid exposure are discussed. Data Sources: MEDLINE search from 1985 to 1998; additional references found within the articles; information obtained from the Internet. Study Selection: Clinical trials, reviews, and press releases concerning the use of GHB, flunitrazepam, and ketamine to facilitate acquaintance rape. Trials and reviews describing clinical effects, adverse effects, pharmacokinetics/pharmacodynamics, and usage trends were evaluated. Literature judged to be pertinent by the author was included in the discussion. Data Extraction/Data Synthesis: Reports of the use of GHB, flunitrazepam, and ketamine in acquaintance rape appear in the medical literature and lay press. Many health care professionals may not be familiar with these medications, and information about caring for patients under their influence is limited. Victims lose their ability to ward off attackers, developamnesia, and are unreliable witnesses. Because symptoms caused by these agents mimic those of alcohol, not all victims are screened for their presence. Legislative efforts to further limit the use of or access to GHB, flunitrazepam, and ketamine have been initiated at the state and federal levels. Pharmacists should know the symptoms of exposure to the three agents; they should understand treatment regimens, methods to detect the presence of these and other drugs that may have been used in a sexual assault, and techniques individuals can use to avoid becoming victims of drug-assisted acquaintance rape. Conclusion: Because of their extensive drug knowledge and frequent access to patients, pharmacists are uniquely positioned to educate patients and other health care professionals about the dangers of acquaintance rape drugs and methods to reduce their risk of becoming victims. JAm Pharm Assoc. 1999;39:519-25.
It is estimated that 25% of women in the United States will be raped during their lifetimes. I Of these victims, 75% are thought to know their assailants.2 Such assaults are termed acquaintance rapes. Rapists may surreptitiously administer drugs in a victim's beverage to induce sedation or amnesia. The use of chemical substances to facilitate criminal assault has not been well documented in the medical literature.3 However, anecdotal reports ' of "knockout drops" date back to the early 20th century. Perhaps the most familiar example is the "Mickey Finn," which Received November 24, 1998, and in revised form March 8, 1999. ~Pted for publication March 19, 1999. Kelly M. Smith, PharmD, is drug information specialist and clinical assistant professor, University of Kentucky Medical Center, Lexington. Correspondence: Kelly M. Smith, PharmD, Drug Information Center, University of Kentucky Hospital, 800 Rose Street, Room Cl13, Lexington, KY 40536-0293. Fax: (606) 323-2049. E-mail: [email protected]. Continuing education credits: See page 581 for learning objectives and test questions for this article, which is number202-000-99-126-HOl in APhA's educational programs.
! VG/. 39, No.3
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involves the addition of chloral hydrate to an ethanol-based beverage. 4 The extent to which drugs are used today in acquaintance rape is unknown, but references to three particular substances as "date rape drugs" appear in the medical literature as well as the lay press. 5- 13 Flunitrazepam, a benzodiazepine marketed outside of the United States, gamma-hydroxybutyric acid (GHB), an investigational sleep aid, and the anesthetic agent ketamine have all been associated with acquaintance rape. This article describes the signs and symptoms of the ingestion of these substances, patient management techniques, and processes to detect the presence of the drugs by toxicology screening.
GHB Gamma-hydroxybutyric acid (GHB) is also known as gammahydroxybutyrate and sodium oxybate. GHB is sold on the street under a variety of names, including Liquid Ecstasy, Gib, Natural Sleep-500, Somatomax, Georgia Home Boy, Grievous Bodily
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Hann, Liquid X, Liquid E, GBH, Soap, Scoop, Easy Lay, Salty Water, G-Riffick, Cherry Menth, and Organic Quaalude. 5.6
Availability The product is currently available in the United States only for investigational use as a treatment for narcolepsy. Thus, possession of GHB is not illegal, but under the provisions of the Food, Drug, and Cosmetic Act, its sale is prohibited. 6 The Drug Enforcement Administration (DEA) reports that clandestine manufacture is widespread, and the agency is considering a recommendation that GHB be classified federally as a controlled substance. Twenty states have already controlled GHB, and New Jersey and Texas have determined it to be illegal for use, with penalties similar to those associated with marijuana. 14
Pharmacology/Therapeutic Use Synthesized in 1960, GHB was demonstrated to cross the blood-brain barrier and in 1963 was found to be a naturally occurring substance in the brain. Although a mechanism of action has not been elucidated, some researchers have suggested that GHB acts as a neurotransmitter. 15 The agent appears to increase dopamine levels and affect the endogenous opioid system. The central nervous system (CNS) depressant has an affinity for a GHB-specific receptor and the GABA B receptor.16 In the 1970s GHB was first used in the United States in the treatment of sleep disorders, and its use in this area continues to be studied. Investigators believe the depressant induces rapid eye movement (REM) sleep, thus decreasing symptoms of narcolepsy. It has also been used as an anesthetic in Europe, but its use decreased when seizure-like activity and poor analgesia were associated with the agent. 5 A 1977 study reported steroid-enhancing effects of GHB. The investigators hypothesized that the agent simulated the effects of growth hormone, but this hypothesis has never been proven. However, bodybuilders continue to use the product to increase muscle mass. 5 GHB has also been investigated as adjunctive therapy in alcohol and opiate withdrawal. 17- 19
Epidemiology GHB was introduced commercially in the United States in health food stores in 1990. It was promoted as a sedative alternative to L-tryptophan, which was removed from the market in 1989. After reports of adverse effects surfaced, including gastrointestinal distress, CNS depression, and seizures and comas, the Food and Drug Administration (FDA) removed GHB from the market in November 1990.20 Nevertheless, the drug is often used for its euphoric effects, and clandestine manufacture has continued. Since 1997 DEA has been aware of at least 100 cases involving illicit GHB laboratories. The death of actor River Phoenix outside a Los Angeles club in 1993 was rumored to have been associated with GHB. Although this linkage was never sub-
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stantiated, this tragedy sparked a renewed interest among illicit drug users in GHB as a recreational agent. 5 The agent continues to be used in social settings, particularly at "rave" dance parties. along with methedrine or methamphetamine (speed) and Ecstasy (methylenedioxymethamphetamine [MDMAD. 5•7 Recipes for the manufacture of GHB are available on the Internet, as well as dos· ing, combination drug use, and mail order information. 5 As of March 1999 DEA had received 22 reports of sexual assault in victims under the influence of GHB since 1996. 14 A 1997 report from poison control centers in Texas and New York listed 69 poisonings and 1 death caused by GHB in a 13-month period beginning in August 1995. Poison control centers through· out the country reported an increase in use of the product in 1997. 5 Misuse is prevalent in California, Florida, Georgia, and Texas. 6 The United Kingdom and Australia have reported misuse of the agent. 5 I In January 1999 FDA requested a voluntary recall of products containing gamma-butyrolactone (GBL), a GHB precursor, and advised consumers not to purchase or use these products. Although GBL was found in products labeled as dietary supplements and promoted to build muscle mass, improve physical performance, diminish insomnia, enhance sex, and reduce stress, FDA considers the agent an unapproved new drug because it is converted to GHB. The warning was issued based on 55 reports of adverse effects, including 1 death. In 19 cases, patients lost consciousness and many required intubation.2 1
Clinical Effects GHB is a white powder that precipitates when sodium hydrox- . ide solution is added to GBL. It is generally available as a colorless, odorless liquid with a mild, salty, or soapy taste that is easily masked. 5 Clinical effects are increased when the agent is given in combination with alcohol, marijuana, and other drugs, as is the risk of aspiration pneumonia. 5•s Some experts report a pronounced coma and respiratory depression within 15 to 30 minutes after ingestion of 5 to 30 mL of GHB and alcohol. Intubation may be necessary, although patients may recover spontaneously in a matter of hours. Some patients have recovered during intubation. , typically displaying signs and symptoms of amnesia.5 •22 GHB is used as an acquaintance rape drug because it has a ~ rapid onset of effect, is relatively easy to obtain on the black market and manufacture at home, and is easy to administer. Also, it has been purported to have aphrodisiac properties. 23 Because the product is often a colorless, odorless liquid, and because relatively small quantities produce the desired effect, it can be given in a beverage to an unwitting victim. Victims often experience amnesia or hallucinations and are thus unable to serve as reliable witnesses to a crime. Within 15 to 30 minutes of ingestion, the victim begins experi- . encing the effects of GHB, which are often confused with the effects of alcohol (see Table 1). Initial symptoms may incIudl drowsiness, confusion, and dizziness. Rapid coma, vomiting·
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;ie 1.
Features of Exposure to Acquaintance Rape Drugs GHB
Flunitrazepam
15 to 30 minutes
20 to 30 minutes
15 to 20 minutes
Drowsiness Disorientation Dizziness
Drowsiness Disorientation Dizziness Slurred speech Hot or cold flashes Nausea
Analgesia Disorientation Amnesia Hypersalivation
Subsequent symptoms
Vom iting Rapid onset coma Amnesia
Difficulty speaking and moving Rapid onset coma Amnesia
Dizziness Hallucinations Delirium Nystagmus Respiratory depression
High-dose symptoms
Respiratory depression Bradycardia Clonic muscle contractions Anesthesia Diminished cardiac output
Prolonged psychomotor impairment Respiratory depression
Dissociative anesthesia Seizures Arrhythmias Cardiac arrest
Management techniques
Blood pressure, heart rate, and respiratory rate monitoring Airway protection Recovery position with bedside suction Supplemental oxygen Atropine as needed for bradycardia Co-ingestion: Gastric lavage or activated charcoal Rapid-sequence intubation w ith succinylcholine Specific antagonists for co-ingested agents (e.g., naloxone)
Blood pressure, heart rate, and Blood pressure, heart rate, respiratory rate monitoring and and respiratory rate support as needed monitoring and support as Severe overdose: needed Gastric lavage or activated charcoal Quiet recovery area with Airway protection minimal environmental Flumazenil (primarily for respiratory stimulation depression) if no contraindications
;;;-10 symptom onset ,IORial symptoms
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Ketamine
' GHB = gamma-hydrox ybutyric acid .
respiratory depression, and Cheyne-Stokes respiration, bradycardia, clonic muscle contractions, and induction and emergence delirium may follow. Alert patients may present with tachycardia, hypertension, and psychotic symptoms, including paranoia and hallucinations. 5 Manifestations of ingestion appear to be dose-related. Amnesia and hypotonia have been reported with doses of 10 mg/kg body weight. Cycles of REM and non-REM sleep are associated with 20 10 30 mg/kg doses, whereas anesthesia may result from 50 mg/kg doses. Doses exceeding 50 mg/kg may produce coma, severe respiratory depression, seizure-like activity, and diminished cardiac oUlput. 6,20 A series of case reports describes loss of consciousness with profound respiratory depression in seven patients. Several of the patients were too combative to intubate, and all required physical reslraints.23 Other reports of GHB use list a characteristic rapid return to consciousness, often followed by nausea and vomiting. 5,) Clinical course and recovery may be related to presenting level of consciousness. In one study, patients with an initial Glasgow Coma Score (GCS) of 8 or less experienced bradycardia or emesis. The same investigators also hypothesized that the initial Gcs may also predict time to recovery.24
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Early reports of seizure activity with GHB exposure have not been confirmed. However, epileptiform activity resembling petit mal epilepsy has been reported in animal and human models, but not in normal human volunteers. 25 - 27 GHB has been linked to clonic muscle contractions and combativeness. Random clonic movements of the extremities and face associated with GHB may be confused with epileptic activity.8,24,28
Diagnosis and Management Diagnosis of GHB intoxication can be challenging. Short of a reliable hi~tory, the hallmark feature of GHB ingestion is marked agitation upon stimulation, despite prolonged apnea and hypoxia. U waves may also be present on ECG. In one case series, five of seven patients, three of whom experienced significant cardiac abnormalities, had U waves present without significant hypokalemia. 23 Patients may also experience hypothermia. 24,29,3o Hypotension may
be present and is generally associated with co-ingestion of other agents. Because vomiting is common, victims are susceptible to aspiration, requiring airway protection. This is of particular concern because GHB preparations are generally made in clandestine
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laboratories. Purity is uncertain, and an improperly prepared product may have excessive amounts of caustic sodium hydroxide. Benzodiazepines and opiates have no role in patient management. Because GHB is often administered in relatively small volumes (e.g., 1 to 60 mL) and is rapidly absorbed, gastric lavage or activated charcoal are of little use,5 although these methods are recommended for drugs concomitantly ingested. Naloxone has been reported to be of no use.3.4 Li and colleagues suggest the following management principles for patients with spontaneous breathing: recovery position with bedside suction, supplemental oxygen, intravenous access, and atropine for persistent symptomatic bradycardia. 3! In patients with GHB ingestion complicated by other substances, advanced airway protection via rapid-sequence intubation is indicated. 29.3!.32 Because GHB victims are already sedated, only succinylcholine paralysis is required. After 6 hours of observation, patients should be admitted to the hospital if they are deemed clinically intoxicated, or discharged if clinically well. 3!
Detection The presence of GHB is difficult to detect, because the drug is eliminated rapidly. Its half-life ranges from 20 minutes to 1 hour, and the product is virtually undetectable in urine after 12 hours. Victims often recover spontaneously within I to 2 hours. This allows the assailant an opportunity to escape before the victim awakens. 5 Only laboratories equipped to perform urine assays using quantitative gas chromatography-mass spectrometry (GC-MS) can routinely detect GHB. One report indicates that, in the Los Angeles area, only two hospitals have adequate facilities for such an assay. The test, which also detects GHB metabolites, requires 1 day to process and costs between $230 and $310.7.33 In areas that do not have access to GC-MS, health care professionals can call upon the services of a national forensic laboratory (National Medical Services, Willow Grove, Pennsylvania; 800-522-6671) for approximately $100 a specimen.
Flunitrazepam Availability/Epidemiology Flunitrazepam (Rohypnol-Roche) is a fast-acting benzodiazepine that is approximately 10 times more potent than diazepam.34 Flunitrazepam is available in oral tablets and as an injection. 35 It is used in Mexico, South America, Asia, and Australia for sedation and treatment of insomnia. Loss of memory about events that occur while under the influence of the drug make it particularly useful as a preoperative sedative. Flunitrazepam is sold on the street under such names as Roofies, Rophies, Roopies, Roches, Roaches, Ropanol, Robinol, Rohibinol, Reynol, Roofenol, Ruffiew, Rubies, R2s, Ropes, Rib, Pappas, Peanuts, Pastas, Forget Pill, Whiteys, Ro-shays, Circles, Mexican Valium, and La Roche. "Roached out" is a slang term
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for being under the influence of flunitrazepam.9.36.37 One tablet: costs up to $5.00. 37 .38 In 1989 flunitrazepam was first seized in the United States by law enforcement officials. 9 Abuse of the drug was first docu· mented 4 years later. 36 Flunitrazepam is often used to enhance the effects of heroin, alcohol, or marijuana. It can also be used to ease the symptoms of withdrawal from heroin and diminish some of the stimulant effects of cocaine. The agent may be chewed, dissolved under the tongue, snorted, injected, or smoked, in addition to its more frequent oral route of administra· tion. 9 More than 1,000 law enforcement investigations involving flunitrazepam were undertaken between 1990 and 1995. Approx. imately 1.5 million tablets were brought across the Mexican bor· der into Laredo, Texas, alone in 1995. 39 Importation of flunitrazepam from Mexico into the United States was banned in 1996. This regulation made the prescription, sale, or importation of flunitrazepam illegal. 40 From 1994 to 1998, at least 26 sexual assault cases have involved or have potentially involved flunitrazepam. According to an international treaty, flunitrazepam is considered a Schedule IV controlled substance. However, eight states have classified the agent as a Schedule I controlled substance, making penalties for its possession equivalent to those for other drugs of abuse, such as heroin. Some other states have stiffened the penalties for distribution.!4 Use of flunitrazepam is more common in the southern border states. Mexico and South America are the most common sources of the illegally imported medication. However, clandestine laboratories produce some of the street supply.37
Pharmacokinetics/Pharmacodynamics Approximately 80% to 90% of an oral flunitrazepam dose is absorbed. The drug is rapidly distributed, as best described by a three-compartment concentration-time curve. An extensive metabolism, primarily by the kidneys, follows, with an elimination half-life of 20 hours. Because the drug is rapidly distributed into tissues, the duration of its clinical effects is much shorter than would be expected from such a prolonged half-life. 34 Sedation generally occurs 20 to 30 minutes after ingestion. with maximal effects at 1 to 2 hours. Doses of up to 2 mg may induce psychomotor impairment for nearly 12 hours following ingestion. The anterograde amnesia associated with the benzodiazepine may begin within 30 minutes. 34 In one trial, a 1 mg dose I resulted in amnesia in 65% of patients; only 30% of patients experienced this effect with a 0.5 mg dose. 4 !
Clinical Effects Flunitrazepam is a tasteless, odorless medication that easil) dissolves in alcohol. Typically administered in a beverage to an unknowing victim, the sedative is a particularly effective "date rape" drug because of its amnestic, hypnotic, and disinhibito0 effects. Alcohol multiplies the effects of the medication.
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Victims may first notice dizziness, disorientation, lack of 'UXlrdination, slurred speech, hot and cold flashes in rapid alter'nation, or nausea. Speech and motor difficulties usually pre:(fdethe loss of consciousness. All of these effects can be con!(used with those of alcohol. Administration with a carbonated [tverage, coffee, or fruit juice may enhance the psychological effects of the medication.9 As with other benzodiazepines, resIfiralOry depression is a primary concern.42 Effects may last 2 to ! hours, so victims often wake after their attacker is gone. Iymptoms may be prolonged in the presence of hepatic or renal dysfunction .43 Roche Pharmaceuticals has attempted to minimize the use of flunitrazepam in acquaintance rapes by reducing the number of iMexican distributors, ceasing direct sales to pharmacies, and dis'continuing production of the strongest tablet (2 mg). Also, the 'manufacturer has reformulated the product to dissolve more slowI~ inliquid. The new formulation also turns clear beverages bright blue and causes dark beverages to appear murky.44
Management Gastrointestinal decontamination and airway protection may be required in severe overdoses. The true role of decontamination is currently under dispute; however, activated charcoal may have a role in management. 45 Supportive care alone is generally sufficient for most patients, with improvement apparent within 6 oours. The benzodiazepine antagonist flumazenil , at an initial dose of 0.2 mg IV, may reverse the effects of the benzodiazepine, but repeated doses may be necessary to sustain a reversal. If the patient does not respond, a 0.3 mg dose should follow in Iminute, increasing to 0 .5 mg per minute up to a total of 3 mg orpatient response. 43 Flumazenil may be particularly useful in patients with respiratory depression or when the substance ingested is unknown. A rapid response to flumazenil would assist in the diagnosis and subsequent management. However, routine use of the benzodiazepine antagonist is unwarranted ;because of the need for frequent readministration, cost of the agent, and because supportive care is usually sufficient. MoreOver, flumazenil has been associated with the unmasking of seiZure disorders, particularly those controlled by benzodiazepines. The potential for co-ingestion with tricyclic antidepressants or cocaine also contraindicates the use of flumazenil.46
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sponsored by Hoffmann-La Roche. The service, which is free of charge to law enforcement agencies, rape crisis centers, and emergency departments, can be accessed by calling 800-608-6540. The test is a series of three assays, including GC-MS. Urine samples should be refrigerated or frozen to minimize degradation before testing. 47
Ketamine Availability Ketamine is a general anesthetic used primarily in emergency medicine and critical care settings and veterinary medicine. A chemical cousin of phencyclidine (PCP), ketamine is available in the United States as an injectable prescription drug, but may be administered orally. The product is manufactured under the trade names Ketalar (Parke-Davis) and Ketaject (Bristol-Myers Squibb), and is also available from several generic manufacturers. Slang terms for ketarnine include K, Special K, Kay, Keets, Green, Jet, Mauve, Purple, Special LA Coke, Super Acid, and Super c. 42 Ketamine has several illicit uses, and many users deem the effects superior to those of PCP or lysergic acid diethylamide (LSD). It may be snorted, swallowed, smoked, or injected. 48 DEA is aware of at least one case in which ketamine was demonstrated to facilitate rape. In 1993 use of the medication in acquaintance rape was first reported in Florida. Use of the drug for this purpose spread across the South, and soon reached the East Coast. In 1998 Governor George Pataki signed legislation making ketamine a Schedule III controlled substance in New York, reducing legal access to the drug and requiring accountability in cases of theft or loss. Possession and sale of ketamine was declared a criminal offense. 1o Ketamine is also a controlled substance in 17 other states, and the Department of Health and Human Services has recommended that the anesthetic be placed in Schedule III. 14
Pharmacokinetics/Pharmacodynamics In low doses, ketamine produces analgesia. A low bioavailability (16%) requires higher oral doses to achieve adequate analgesia, often within 30 minutes. Ketamine has a distribution pattern similar to thiopental. It reaches highly perfused tissues first, such as the heart, brain, and lungs, followed by muscle and peripheral tissues, and is then redistributed into fat. The anesthetic undergoes extensive liver metabolism. 49,50
iDetection
Clinical Effects
Most commercially available toxicology screens are unable to detect flunitrazepam, which is typically administered in small quantities. Definitive tests to confirm its presence include GCMS. A 2 mg dose can be detected in urine up to 72 hours after Ingestion.43 ,44 If the presence of flunitrazepam is suspected, a urine specimen may be submitted to a screening program
The analgesic effects of ketamine generally last from 20 to 45 minutes. Increasing doses result in a dissociative anesthesia, which patients often describe as feeling detached from their surroundings or floating above their own body. Other effects include hypertension, vomiting, hypersalivation, and rapid movements. Dizziness, disorientation, vivid dreams, hallucinations, delirium,
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Table 2. Methods to Reduce Risk of Exposure to Acquaintance Repe Drugs Do Discard any beverages that have been left unattended. Bring your own beverages to social gatherings, when possible. Be alert to a friend's behavior that is symptomatic of a drug ingestion, and have them reciprocate the favor. Look for the signs listed in Table 1. Do not Leave beverages unattended in a social setting. Accept open beverage containers from someone other than a bartender or server. Share or exchange beverages with anyone. Drink beverages from a common container (e.g., punch bowl). Drink anything that has an unusual appearance (e.g., excessive foam, cloudiness) or taste (e.g., salty). Source: Reference 55.
and nystagmus are eNS effects that may ensue. There have been reports of flashbacks weeks after recovery, but such reactions are disputed.51 ,52 Patients typically experience a rapid return to consciousness, but full recovery from the anesthetic effects may take several hours. 41 ,51,53 Ketamine may be used as a "date rape" drug because amnesia about events that occurred during exposure to the drug begins as soon as 15 to 20 minutes after ingestion, and victims frequently lose consciousness abruptly. Hallucinations or dreams so intense that they cannot be easily discerned from reality make victims of sexual assault unreliable witnesses. 51 The drug can be easily administered in beverages to unknowing subjects.
was detected in only five samples, four of which contained other substances. Ketamine was not identified. The testing service. which continues today, is funded by Hoffmann-La Roche as a public service.44,54 Polysubstance abuse in combination with GHB irtgestion Was found in all seven patients described in a recent case repon.2] Alcohol was found in all patients, five had cocaine detected in urine screening, and two had evidence of other sympathomimetic agents. In the emergency department of an urban public hospital, nearly 40% of patients exposed to GHB used alcohol concomi· tantly, and other drugs were present in more than 25% of the patients. 24 Health care professionals should be aware of the possibility that victims may have been exposed to other or additional substances. Treatment should follow based on signs and symptoms of exposure, as well as the results of laboratory monitoring and toxicology screening. Consumers should be advised about the potential risks of these amnestic drugs and methods to reduce their risk of exposure (see Table 2). Most of the methods require the use of caution in social settings.
Conclusion
Pharmacists and other health care professionals should be aware of drugs that may be used to facilitate sexual assault. Most reports detail the use of flunitrazepam, GHB, and ketamine Despite the reputation these three agents have garnered as hann· ful drugs, the latter two agents have legitimate or expanding uses in the United States, and flunitrazepam is used clinically in sever· al other countries. Trials of the use of GHB, primarily in nar· Management colepsy and resuscitation, are ongoing or on the horizon. 23 In Supportive care is the cornerstone of patient management. actuality, other substances (e.g., alcohol, cocaine) are more com· Blood pressure, heart rate, and respiratory rate should be closely monly used in acquairttance rapes. monitored. The risks of blood pressure changes and respiratory Victims that present with amnesia, appear irttoxicated, or awak· depression increase when ketamine is combined with alcohol. en partially clothed or nude in a strange place should be screened ~ Because victims may experience hallucinations, it is important to for the presence of illicit substances. Urine samples should be minimize environmental stimuli.42 ,5l,53 A quiet recovery area is obtained, and toxicology screens that detect flunitrazepam, GAB. recommended to minimize any symptoms of emergence. ketamine, and other amnestic agents should be performed, I Patients should be treated symptomatically and observed for sev' l eral hours 'after their symptoms resolve. Other Substances Used in Pharmacists may be irt the most advantageous position to eduAcquaintance Rape cate the public about the potential risks of drug-irtduced acquain· tance rape. Because of their extensive drug knowledge and fre· I Although GHB, flunitrazepam, and ketamine appear most fre- quent access to patients, pharmacists are the ones to whom quently in the literature, they are not the only substances associat- consumers often direct their questions and from whom they seek ed with sexual assault. A study reported at the American Acade- advice. The pharmacist's professional knowledge may also be of my of Forensic Sciences 1998 Annual Meeting detailed the value to law enforcement officials, rape counselors, or other presence of some 20 different substances potentially associated health care professionals who deal with potential acquaintance with acquaintance rape in specimens obtained from victims. 54 Of rape victims. 578 samples, 208 contained alcohol, 93 marijuana, and 40 The author declares no conflicts of interest or financial interests in anY cocaine. GHB was found in 32 specimens, 11 of which contained product or service mentioned in the manuscript, including grants, alcohol and 14 of which contained other drugs. Flunitrazepam emptoyment, gifts, and honoraria.
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References
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1. Schwartz IL. S~xual violence against women: prevalence, consequences, sOCietal factors, and preventi on . Am J Prev Med. 1991 ;7:363-73.
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