DRUGS OF ABUSE And Their Detection in Urine Ed Uthman, MD [GEnie: E.UTHMAN] Diplomate, American Board of Pathology April, 1993 HOW DRUG SCREENS ARE PERFORMED The aims of the drug screen are to detect the presence of frequently abused drugs in the urine of human subjects. Drug screens are used for one of three purposes: 1) medical purposes (e.g., to monitor a patient's progress in a medical treatment program for a drug abuse problem the patient has acknowledged), 2) legal purposes (e.g., to determine if a suspect had taken controlled substances prior to some accident or crime), and 3) medicolegal purposes (e.g., in an employer's drug abuse program aimed at both preventing drug-related accidents and crimes and identifying and treating employees with drug abuse problems). For medical purposes, laboratories often use simple, less-expensive methods aimed at identifying specific drugs with which the patient has had problems in the past. It is not expected that the results of such drug tests will be used as evidence against the patient in court. If these results are used as evidence, it is likely that defense testimony will successfully impugn the evidence. For legal and medicolegal purposes, more stringent testing is necessary to obtain information that will successfully withstand technical criticism in court. Therefore, drug screens done for these purposes often take a two-tiered approach. First, there is a screening test done on the subject's urine. This is usually a sensitive test that may have some discrepancies in specificity (for instance, some popular over-the-counter cold medicines may yield a positive amphetamine screen). Only if this test is positive for one or more drugs is the second, more expensive test performed. Generally courts will uphold testimony based on a drug test if positive results were obtained on two separate tests based on different chemical methods. AMPHETAMINES Examples: amphetamine sulfate, dextroamphetamine (Dexedrine), methamphetamine (Desoxyn, Methedrine). Medical uses: Attention deficit disorder (hyperactivity) of childhood, narcolepsy, obesity (occasionally and for limited period) Effects attractive to abuser: Euphoria, increased ability to concentrate, increased alertness, heightened ability to perform intellectual and physical tasks, appetite suppression (for weight loss). Adverse effects: Insomnia, restlessness, irritability, palpitations, rapid heartbeat, sweating, dilation of pupils, confusion, psychosis, convulsions, death. How abused: Pills taken orally; solution injected intravenously; occasionally snorted into the nose in granular form. Typical urine detection cutoff level: 300 ng/mL Period detectable after last dose: Up to 30 hours on low dose, 120 hours on high dose. Substances causing false positive results (on initial drug screen only): decongestants (ephedrine [Vatronol, Efedron], phenylpropanolamine [Propagest, Sucrets Decongestant Formula, Rhindecon]); "diet pills" (phenmetrazine [Preludin], phentermine [Phentrol, Tora, Fastin, Obe-Nix, Obephen, Obermine, Obestin, Parmine, Phentamine, Phentrol 2, Unifast, Wilpowr, Adipex-P, Dapex-37.5, Ionamin, Phentrol], phenylpropanolamine [Diadax, Prolamine, Control, Dex-A-Diet, Dexatrim-15, Unitrol, Maximum Strength Acutrim, Appedrine]; blood vessel dilators (isoxuprine [Vasodilan], nylidrin [Adrin, Arlidin]). Only confirmatory testing of the urine will determine if these interfering drugs are present. It should be noted that some of these drugs, such as phenmetrazine and phentermine, while not technically amphetamines, have similar abuse potential and similar adverse effects. Phenylethylamine (a product of decomposing, unpreserved urine) may produce false-positive screens in unrefrigerated, old specimens which have not been treated with fluoride preservative. BARBITURATES Examples: Long acting- phenobarbital; intermediate-acting- amobarbital (Amytal), butabarbital, talbutal; short-acting- secobarbital (Seconal), pentobarbital (Nembutal). Medical uses: Treatment of insomnia (short term only, and avoided altogether by most physicians), long-term treatment of epilepsy (phenobarbital), surgical anesthesia. Effects attractive to abuser: Sedation, loss of inhibitions, induction of sleep. Generally, the short-acting barbiturates have more abuse potential than long-acting types. Adverse effects: Agitation, confusion, nightmares, hallucinations, lethargy, hangover, suppression of breathing reflexes, coma, death. Physical dependence is well known, and withdrawal effects can be severe and dangerous, even fatal. How abused: Pills taken orally; solution injected intravenously. Typical urine detection cutoff level: 300 ng/mL Period detectable after last dose: long-acting 7 days, intermediate-acting 2-3 days; short-acting 1-2 days. Substances causing false positive results: None reported. METHADONE Examples: Roxane, Dolophine Medical uses: Treatment of opiate addicts in approved program Effects attractive to abuser: Same as opiates (below) Adverse effects: Same as opiates (below) but with lesser degree of physical dependency (addiction) How abused: Pills taken orally; solution injected intravenously. Period detectable after last dose: 7.5-56 hours Substances causing false positive results: doxylamine [Unisom Nighttime Sleep Aid]. Presence of this substance would be ruled out by confirmatory testing. OPIATES Examples: Morphine, heroin, codeine (as found in many prescription cough medicines, such as Robitussin-AC, and pain medications, such as Tylenol #3, Phenaphen #3 & #4, Empirin #3 & #4), oxycodone (Percodan), hydromorphone (Dilaudid), hydrocodone (as in many prescription cough medicines). Medical uses: Relief of moderate to severe pain, treatment of persistent cough (codeine), treatment of diarrhea. >>> Continued to next message * OLX 2.1 TD * ..What we got here is an ability to communicate.. ___ Olms 1.60 [PSTB94B4] Ä Area: alt.drugs ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ Msg#: 463 Date: 02-07-95 20:29 From: Dr_.dan@helix.eskimo.com Read: Yes Replied: No To: All Mark: Subj: drug tests 2/4 ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ Path: nic.tip.net!sunic!trane.uninett.no!nntp.uio.no!ifi.uio.no!sics.se!eua.ericsson. se!erinews.ericsson.se!cnn.exu.ericsson.se!convex!cs.utexas.edu!swrinde!pipex!uu net!eskimo!helix!Dr_.Dan From: Dr_.Dan@helix.eskimo.com (Dr. Dan) Date: 07 Feb 95 20:29:49 -0800 Newsgroups: alt.drugs Subject: drug tests 2/4 Message-ID: <03e_9502072146@helix.eskinews.eskimo.com> X-Mail-Agent: GIGO+ sn 5 at helix vsn 0.99w32 Organization: helix.uucp =FidoNet/DharmaNet= 206.783.6368 Lines: 150 >>> Continued from previous message Effects attractive to abuser: Euphoria, sedation. Adverse effects: Drowsiness, apathy, confusion, nausea, vomiting, suppression of breathing reflexes, constricted pupils, physical addiction, coma, death. How abused: Pills taken orally; solution injected intravenously or subcutaneously; occasionally snorted into the nose in granular form. Typical urine detection cutoff level: 300 ng/mL Period detectable after last dose: heroin, 1-4 days; meperidine, 4-24 hours; morphine, 84 hour minimum Notes: This family of drugs undergoes extensive chemical changes due to the normal detoxification processes of the body. Therefore, the drug detected in the urine screen may not be the same as that originally taken by the subject. For instance, both heroin and codeine are converted to morphine before excretion in the urine. Substances causing false positive results: none reported; however, foods containing poppy seeds (the natural source of traditional opiate drugs) will produce true positive results when screening the urine of an otherwise innocent subject. BENZODIAZEPINES Examples: Diazepam (Valium), chlordiazepoxide (Librium), flurazepam (Dalmane), oxazepam (Serax), lorazepam (Ativan), clonazepam (Clonopin). Medical uses: Treatment of anxiety disorders, convulsions, and muscle spasms. Effects attractive to abuser: Euphoria, sedation, relief of anxiety, induction of sleep. Adverse effects: Drowsiness, apathy, fatigue, decreased activity level, dizziness, fainting, impaired ability to concentrate on tasks, disturbance of vision and hearing, physical addiction. How abused: Pills taken orally. Typical urine detection cutoff level: 300 ng/mL Period detectable after last dose: around 2-4 days, but depending greatly on dose. For instance, a single 10 mg PO dose of diazepam may not ever be detected, but a 5 times daily dose of 10 mg will be detectable for 3-7 days. Substances causing false positive results: none reported. CANNABINOIDS Examples: Marijuana, hashish, hash oil Medical uses: Treatment of nausea and vomiting due to cancer chemotherapy. Effects attractive to abuser: Euphoria, intensified sensual and aesthetic perceptions. Adverse effects: Paranoia, panic, impairment of memory and ability to perform tasks, distorted perception of time, physical and psychological dependence. How abused: Smoked in cigarettes or pipe; occasionally eaten as ingredient baked into confections. Typical urine detection cutoff level: 100 ng/mL or 20 ng/mL (optional) Period detectable after last dose: This is highly variable. A one joint per week user has detectable levels of cannabinoids form 7 to 34 days, while a heavy daily user may be detected from 6 to 81 days after last use. Substances causing false positive results: none reported. A screen detection cutoff level of 20 ng/mL, requested by some laboratory clients, may produce false positives due to passive inhalation of marijuana smoke, but this is controversial. At the cutoff level of 100 ng/mL, persons exposed passively to the smoke of others by virtue of being in the same room with abusers should be negative on urine drug screen, although more sensitive chemical techniques (such as gas chromatography/mass spectrometry, which has a sensitivity of 10 ng/mL) may demonstrate the drug in such an individual's urine. COCAINE Examples: Cocaine hydrochloride is the typical form used by abusers who ingest the drug by snorting the granular form into the nose; it can also be dissolved in water and injected intravenously. Cocaine base is available in a waxy cake form ("rock" or "crack") which is vaporized with a torch and the vapors inhaled through a tube. Medical uses: Used almost exclusively by ear, nose and throat doctors to produce local anesthesia and control blood loss during minor nasal surgery. Effects attractive to abuser: Euphoria, increased ability to concentrate, increased alertness, heightened ability to perform intellectual and physical tasks, sexual stimulation, heightened sociability, enhanced self-confidence. Adverse effects: Restlessness, nervousness, tremor, convulsions, disturbances in heart rhythm, psychological dependence, myocardial infarction, sudden death. How abused: Snorted, injected, or smoked (see above). Typical urine detection cutoff level: 300 ng/mL Period detectable after last dose: 8-48 hours Note: The laboratory detection of cocaine is performed by analyzing the urine for the presence of benzoylecgonine, a substance produced by the body's chemical detoxification of cocaine. Continuous conversion of cocaine to the metabolite occurs in voided, standing urine specimens (even with fluoridation and refrigeration) unless the specimen is kept at acid pH (<5). This may give the appearance of a negative specimen "turning positive" during storage, if the initial level of the metabolite was too low to trigger the screen in the fresh specimen. In truth, the specimen was positive all along, of course. Substances causing false positive results: none reported; however, some legal South American herbal teas may contain small amounts of coca leaf extract, which may trigger a positive test in an "innocent" subject. Please note that cocoa, cacao, and Coca Cola are all completely unrelated to coca, which is the source of cocaine. METHAQUALONE Examples: Quaalude, Sopor Medical uses: Once used as a sleeping pill/sedative, now methaqualone is virtually never used for medical purposes. Effects attractive to abuser: Same as that for barbiturates (see above) Adverse effects: Same as that for barbiturates (see above) How abused: Pills taken orally. Typical urine detection cutoff level: 300 ng/mL Period detectable after last dose: up to 90 hours, depending on dose >>> Continued to next message * OLX 2.1 TD * ..What we got here is an ability to communicate.. ___ Olms 1.60 [PSTB94B4] Ä Area: alt.drugs ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ Msg#: 464 Date: 02-07-95 20:29 From: Dr_.dan@helix.eskimo.com Read: Yes Replied: No To: All Mark: Subj: drug tests 3/4 ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ Path: nic.tip.net!sunic!trane.uninett.no!nntp.uio.no!ifi.uio.no!sics.se!eua.ericsson. se!erinews.ericsson.se!cnn.exu.ericsson.se!convex!cs.utexas.edu!swrinde!pipex!uu net!eskimo!helix!Dr_.Dan From: Dr_.Dan@helix.eskimo.com (Dr. Dan) Date: 07 Feb 95 20:29:50 -0800 Newsgroups: alt.drugs Subject: drug tests 3/4 Message-ID: <03f_9502072146@helix.eskinews.eskimo.com> X-Mail-Agent: GIGO+ sn 5 at helix vsn 0.99w32 Organization: helix.uucp =FidoNet/DharmaNet= 206.783.6368 Lines: 148 >>> Continued from previous message Substances causing false positive results: none reported. PHENCYCLIDINE Examples: PCP, "angel dust" Medical uses: Veterinary tranquilizer; not used in human medicine. Effects attractive to abuser: Hallucinogenic effects Adverse effects: Lethargy, loss of co/rdination; unpredictable psychosis, sometimes with criminally violent behavior; death. How abused: Taken orally, smoked in cigarette (often mixed with marijuana), injected intravenously as a solution, snorted into the nose in granular form. Typical urine detection cutoff level: 75 ng/mL Period detectable after last dose: 5-10 days Substances causing false positive results: Thioridazine (Mellaril), an antipsychotic drug, has been reported to cause false positive results, as has the insecticide parathion. PROPOXYPHENE Examples: Darvon, Dolene, Doxaphene, Profene 65 Medical uses: Relief of mild to moderate pain. Effects attractive to abuser: Same as that for opiates (see above) Adverse effects: Same as that for opiates (see above). How abused: Pills taken orally; occasionally injected as solution made by dissolving pills in water. Period detectable after last dose: 1-3 days Note: Propoxyphene is technically an opiate and is chemically closely related to methadone. As a pain-relieving drug, it is two-thirds as potent as codeine. Although considered something of a minor leaguer in the opiate world, it is nevertheless a cause of many drug-related deaths (including that of former football star John Matuszak) especially if used in combination with alcohol and other drugs. Substances causing false positive results: Methadone (see above) at high, toxic concentrations may cause false positive results. Confirmation testing will eliminate interference by this drug. ALCOHOL (ETHANOL) Examples: Beer, wine, distilled spirits Medical uses: Rarely, if ever, used for medical purposes. Effects attractive to abuser: Release of social inhibitions, euphoria, sedation Adverse effects: Same as that for barbiturates (see above). Also, use by pregnant women, even in small ("social") amounts may have adverse effect on the fetus. How abused: Drunk in beverage Period detectable after last dose: 8-10 hours Note: Alcohol is the only drug of abuse (other than tobacco) that is legal for all adults to use. Illegal use (as in driving while intoxicated) is defined by the presence of a blood alcohol level of greater than 100 mg/dL (0.10% by volume) in Texas (lower in some other states). It is impossible to determine if a subject is legally intoxicated by measurement of the urine alcohol level. A blood specimen must be collected for this determination to be made by a clinical laboratory. LIMITATIONS OF DRUG SCREENS From a practical viewpoint it is impossible to determine in every case that a given individual is impaired in the workplace due to drug abuse. Just as in the case of alcohol, the use of drugs spans a wide spectrum of behavior, from the occasional recreational user who assiduously avoids coming to work under the influence, to the hard-core addict whose only motivation is the acquisition of his or her next dose. Generally the clinical laboratory is not able to distinguish these two types of individuals. Such a distinction comes about only by careful evaluation by professionals specially trained in the psychology and physiology of drug abuse. The laboratory should be used only as a helpful tool for such professionals. Urine drug screens panels are set up to analyze urine for a variety of drugs that are known to have high abuse potential and affect task performance. To rule out the presence of all drugs that may impair a worker's performance is not generally allowable within the bounds of cost containment. Certain drugs which are not usually picked up on routine drug screens are noted below. If intoxication by any of the drugs listed below is suspected, it is recommended that the client contact the B&A pathologist, who will be glad to help determine a strategy as to how the case should be most efficiently handled. Methylphenidate (Ritalin), phentermine (Fastin, Parmine), phenmetrazine (Preludin), phendimetrazine (Plegine), diethylpropion (Tenuate), mazindol (Mazanor, Sanorex), benzphetamine (Didrex) and fenfluramine (Pondimin) all have amphetamine-like effects and abuse potential. Some of them, such as phentermine, benzphetamine, fenfluramine and diethylpropion, may not be picked up on routine screens. Methylenedioxyamphetamine (MDA, "Ecstasy") is has been popular in Houston high schools. Although it is technically an amphetamine, it requires a special analysis to be identified. Lysergic acid diethylamide (LSD) is also chemically related to the amphetamines, but it is much better known for its profound hallucinogenic effects. Special analysis is available. Meperidine (Demerol) and pentazocine (Talwin) have physiological effects and abuse potential essentially identical to those of opiates. However, since they are chemically dissimilar to morphine, they may not show up as "opiates" on a routine screen. Special analysis is available. Barbiturates which are not easily detected on drug screens include amobarbital (Amytal), pentobarbital (Nembutal), and butethal. The detection systems used to pick up barbiturates are optimized for secobarbital (Seconal), which is probably the most important barbiturate in abusing populations. Flurazepam (Dalmane), a benzodiazepine used as a sleeping pill, is not ordinarily picked up on benzodiazepine screens. Glutethimide (Doriden), ethchlorvynol (Placidyl), meprobamate (Miltown, Equanil), methyprylon (Noludar), and ethinamate (Valmid) are sedative drugs that can produce dependence and impaired function. Although they may have some effects similar to those of the barbiturates, they are chemically unrelated and must be detected with special procedures. Hydrocarbon solvents. These are inhaled by glue sniffers to produce a euphoric effect. Although this seems to be less of a problem socially now than in previous years, special analysis of hydrocarbons and chlorinated hydrocarbons is available. >>> Continued to next message * OLX 2.1 TD * ..What we got here is an ability to communicate.. ___ Olms 1.60 [PSTB94B4] Ä Area: alt.drugs ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ Msg#: 465 Date: 02-07-95 20:29 From: Dr_.dan@helix.eskimo.com Read: Yes Replied: No To: All Mark: Subj: drug tests 4/4 ÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄÄ Path: nic.tip.net!sunic!trane.uninett.no!nac.no!ifi.uio.no!sics.se!eua.ericsson.se!er inews.ericsson.se!cnn.exu.ericsson.se!convex!cs.utexas.edu!swrinde!pipex!uunet!e skimo!helix!Dr_.Dan From: Dr_.Dan@helix.eskimo.com (Dr. Dan) Date: 07 Feb 95 20:29:51 -0800 Newsgroups: alt.drugs Subject: drug tests 4/4 Message-ID: <040_9502072146@helix.eskinews.eskimo.com> X-Mail-Agent: GIGO+ sn 5 at helix vsn 0.99w32 Organization: helix.uucp =FidoNet/DharmaNet= 206.783.6368 Lines: 97 >>> Continued from previous message Ketamine (Ketalar), chemically related to phencyclidine (PCP), is used as a general anesthetic but has been abused, often by health care workers. It must be injected for effect. Analysis is available only through specialized laboratories, and turnaround time is typically long. Designer opiates. These, like meperidine, are synthetic analogues of natural opiates. Accordingly, their chemical structure may be so alien to that of natural opiates that they go completely undetected. These are medically very significant drugs. For instance, 3-methylfentanyl ("China white") is 3000 times as potent as morphine and has been responsible for over 100 overdose deaths in California. Another, 1-methyl-4- phenylpropionoxypiperidine (MPPP), may be contaminated with an unintended byproduct (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, or MPTP) which destroys the substantia nigra of the brain and produces permanent parkinsonism. Adulteration of urine samples with such substances as lemon juice, vinegar, chlorine bleach, and NaCl has been used to successfully interfere with detection of cannabinoids. Also, marked overhydration of the subject (by quaffing large volumes of water) may so dilute the urine that the concentration of the telltale metabolite falls below the detection threshold of the screen. A WORD ON TEST RELIABILITY Published data indicate that a system of drug screening similar to that used by most laboratories has a sensitivity of 76% and a specificity of 99%. This excellent specificity parameter means that of 100 persons who do not use drugs, 99 would be expected to test negative by confirmation. This is certainly an excellent specificity for any medical determination. However, one should also be aware of another parameter, the predictive value of a positive test. As applied to drug testing, this figure expresses the probability that a subject that has tested positively has in fact used the drug. Although a high specificity, such as 99%, optimizes the predictive value, a more significant factor is the prevalence of drug use in the population being tested. The more prevalent the usage of drugs in a subject population, the greater the reliability of drug testing procedure. Given the sensitivity and specificity values quoted above, the following table indicates the predictive value for several levels of drug abuse prevalence. Percentage of tested population | Probability that a given using drugs (the prevalence of | subject that tests positive drug abuse) | has really taken the drug | (the predictive value of a | positive test) ______________________________________________________________________ 0.1% | 7.1% 1.0% | 43.4% 10.0% | 89.4% 20.0% | 95.0% 50.0% | 98.7% Therefore, in a population with a high incidence of drug use (200 per thousand), the false positive rate on drug screens is only 5%, while in a low-incidence population (1 per thousand) the false positive rate on randomly screened individuals (i.e., those of whom there is no particular suspicion of drug use) is expected to be a whopping 93%! For this reason, it is my recommendation that drug screens not be applied on a random, not-for-cause basis, except in situations where the prevalence of drug use is known to be high (such as in substance abuse treatment programs). DISTRIBUTION RESTRICTIONS: This monograph may be freely duplicated and reformatted, as long as the informational content is not altered. It may be freely distributed, if 1) the author is given credit, and 2) it is not used as an aid for marketing or maintaining commercial laboratory accounts without prior express written permission of the author Copyright (C) 1989, 1993, Edward O. Uthman CH OH | 3 | |____ |____ / \ /----\ / \___/ \__ C H \\ // \\ // 5 11 \\ // \\ // ----\ /---- \___O /\ :%%%%%%%%%%%%%%%%%%%%%%%%%%%%%: / \ : CYBERSOOFIES OF PUGET SOUND : CH CH :%%%%%%%%%%%%%%%%%%%%%%%%%%%%%: 3 3 * OLX 2.1 TD * ..What we got here is an ability to communicate.. ___ Olms 1.60 [PSTB94B4]