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Drug Of Abuse Screen, Urine

Urine drug screens are frequently ordered on patients who exhibit symptoms of intoxication, experience trauma or have a history of drug ingestion. Most hospital laboratories use immunoassays to detect drugs because they are relatively simple to perform, have high sensitivity for drugs of abuse and provide rapid turnaround time. One example is the Triage® TOX Drug Screen, which is a fluorescence immunoassay for the qualitative detection of 10 distinct drug classes in urine, including acetaminophen/paracetamol, amphetamines, methamphetamines, barbiturates, benzodiazepines, cocaine, methadone, opiates, phencyclidine, tetrahydrocannibinol (THC) and tricyclic antidepressants (TCA).

Screening assays for drug of abuse are designed to detect urine drug levels above a predetermined cutoff concentration. The threshold concentration, above which each drug class will be detected by the Triage TOX Drug Screen, is summarized in the following table. The acetaminophen/paracetamol assay will yield positive results when acetaminophen/paracetamol is ingested at or above therapeutic doses.

The laboratory often receives phone calls asking how long a particular drug of abuse can be detected in urine. The detection window for the most common drugs of abuse is summarized below.

1 – 3 days occasional use

7– 10 days chronic use

1 – 3 days occasional use

7 -1 0 days chronic use

2 – 3 days occasional use

4 days chronic use

3 – 5 days occasional use

8 weeks chronic use

Reference value is a negative result for all drugs tested. A positive result on a drug screen is not evidence that the person providing the specimen was under the influence of that drug at the time the specimen was submitted. A positive result only indicates previous use of the particular drug that was detected in the urine.

Confirmation of Positive Drug Screens

Most hospital laboratories use a rapid immunoassay to screen for drugs of abuse in urine. The major problem with all rapid immunoassays is their less than perfect specificity for each drug class. Positive drug screen results are confirmed by liquid chromatography/ tandem mass spectroscopy. Recently, all positive drug screen results reported in one month were reviewed to determine the false positive rate.

No false positives (FP) occurred for amphetamine, PCP or cocaine. Marijuana (THC), benzodiazepines and barbiturates had the highest number of false positive results. Interestingly, most of the false positive screening results occurred when 2 to 4 drugs were positive in the same specimen, suggesting some nonspecific interference in the screening assay.

Prescription drugs, over the counter medications and herbal supplements may also cause false positive screening results. False positive THC reactions are most commonly associated with Clozaril, Propulsid, Protonix, Paxil, Tegretol and Zocor. Chlorpromazine and dextromethorphan can produce false positive results in the phencyclidine assay. Oxaprozin and sertraline have been reported to cause false positive results for benzodiazepines. Herbal supplements containing ephedra may produce a positive amphetamine reaction. Other drugs that can give a positive result for amphetamine or methamphetamine include phentermine, pseudoephedrine, adderall, selegiline, benzphetamine and Vicks inhaler. Ingestion of poppy seeds may produce a positive opiate reaction.

Physicians need to be aware of the limitations of urine drug screens. If a falsely positive drug screen is suspected, a confirmatory drug screen should be ordered. There are at least five instances in which confirmatory testing might be warranted:

• Urine drug screen is positive for a drug that should be absent (e.g. cocaine metabolite) and patient denies use
• Urine drug screen is negative for a prescribed drug that should be present (e.g. morphine) and the patient states they have been compliant
• Urine drug screen is positive and physician suspects abuse of an opiate drug other than the one prescribed
• A quantitative result is needed for a patient who claims to have given up an illicit drug (e.g. cannabis)
• Benzodiazepine use is suspected but urine drug screen is negative

As a reminder, many laboratories attach a comment to urine drug screen results such as, “This drug screen provides presumptive results for medical purposes only. False positive results may occur. Physicians should order confirmatory testing on this sample if the results are considered clinically significant”.

Freshly voided urine specimens should be collected in a clean, previously unused glass or plastic container. If the specimen will not be tested immediately, it should be refrigerated at 2 °C to 8 °C for a maximum of two days. Stat drug screens are available 24 hours a day. Turnaround time is approximately 30 minutes.

Urine specimens are stored for at least one week, so that confirmatory testing can be done at a later time. Specific plasma drug levels are also available if overdose of a particular medication is suspected.

Amphetamines are a class of phenethylamine compounds with varying degrees of sympathomimetic activity, which means that they mimic the actions of endogenous neurotransmitters and strongly stimulate the sympathetic nervous system. The amphetamine class of drugs includes:

• Amphetamine
• Methamphetamine
• 3,4-methylenedioxyamphetamine (MDA)
• Methylenedioxymethamphetamine (MDMA or Ectasy)
• Methylphenidate
• Pemoline
• Ephedrine

The therapeutic indications for amphetamines are obesity, narcolepsy and attention deficit hyperactivity disorder. Derivatives of amphetamines such as ephedrine, phentermine and phenylpropanolamine are consitituents of over the counter diet pills. The l-forms of amphetamine and methamphetamine cause vasoconstriction but lack potent sympathetic stimulating activity. For this reason, drugs such as pseudoephedrine, phenylpropanolamine and phenylephrine are present in over the counter cold medications.

Because of their stimulant properties, methamphetamine and Ectasy have become some of the most frequently abused drugs. Their desirable properties include increased wakefulness, alertness and energy, decreased appetite and an overall sensed of euphoria. Undesirable side effects include headache, palpitations, dizziness, agitation, confusion, dysphoria, delirium, aggressiveness and hallucinations.

Most amphetamine immunoassays are designed to detect amphetamine and methamphetamine, while some are designed to detect MDMA and MDA. Drugs commonly considered to be illicit amphetamines include the D-isomers of amphetamine, methamphetamine, MDA, MDMA and methylphenidate. Many over the counter sympathomimetic amines may produce false positive screening results. Herbal supplements containing ephedra may produce a positive amphetamine reaction.

Amphetamines are highly lipid soluble and well absorbed orally. Their circulating half is approximately 10 hours. Amphetamines can be detected in urine within 3 hours of any type of administration and remain detectable for 1 to 3 days after single use and 7 to 10 days after chronic use. Administering ammonium chloride to acidify the urine can accelerate amphetamine elimination.

These drugs are powerful central nervous system depressants. Low doses induce relaxation, moderate doses induce sleep and high doses induce anesthesia. Tolerance of some of the barbiturates’ desired effects develops rapidly. Physical dependence develops when a user’s daily intake exceeds a threshold value; once a user is physically dependent, abrupt withdrawal can precipitate symptoms severe enough to cause death. Short acting barbiturates can be detected up to two days after use. Phenobarbital can be detected one to three weeks after use.

Cocaine is a potent, naturally occurring central nervous system stimulant derived from the plant Erythroxylon coca that results in a state of increased alertness and euphoria. These effects are attributed by the blocking of dopamine reuptake by nerve synapses. Sympathomimetic effects include increased blood pressure, heart rate and body temperature. The route of administration has a marked impact on its addictive potential. The more rapid the rate of increase in drug levels in blood and brain, the greater the risk of addiction. Intravenous and smoked cocaine are much more addictive than intranasal snorting. Cocaine is rapidly metabolized in the blood and liver after inhalation and only small quantities of parent drug are excreted in urine. Benzoylecgonine and ecgonine methyl ester are the two main cocaine metabolites; neither is pharmacologically active. The half life of cocaine ranges from 0.5 to 1.5 hours, ecgonine methyester from 3 to 4 hours and benzoylecgonine from 4 to 7 hours. Because of its longer half life, most screening immunoassays have been designed to detect benzoylecgonine.

Opiates are natural or synthetic analgesic and sedative drugs that have a morphine-like pharmacologic action and affect the cardiovascular and gastrointestinal systems. Opiates include morphine, codeine, hydrocodone, hydromorphone and oxycodone. Heroin is a synthetic opiate that is made from morphine. Both codeine and heroin are metabolized to morphine. Opiates have a high abuse potential because they produce euphoria, relaxation and feelings of well being. Long term use can lead to tolerance and both physical and psychological dependence.

Most immunoassays detect morphine with varying levels of crossreactivity to codeine, hydrocodone, and hydromorphone. Most of the opiates can be detected in urine for two to three days after single use and four to five days after chronic use. Oxycodone, oxymorphone, and meperidine cannot be reliably detected by the majority of screening assays.

Poppy seeds contain a number of substances including morphine and codeine. After the ingestion of large quantities of poppy seeds, a urine drug screen may be positive for opiates. Most urine drug screens have an opiate threshold of 300 ng/mL.

The cut-off used for confirmation of both codeine and morphine is 2000 ng/mL. Poppy seed ingestion is usually associated with concentrations well below this cut-off. However, some ethnic communities that cook with poppy seed paste may have very high urine morphine concentrations. Morphine levels usually peak within 3 to 8 hours and remain positive for as long as 48 to 60 hours after ingestion of poppy seeds.

These drugs are widely prescribed as anxiolytics, sedative-hynotics, anticonvulsants and for treatment of obsessive compulsive disorder. Clonazepam, lorazepam and alprazolam are among the most commonly prescribed drugs in the United States and the second most commonly abused class of prescribed drugs after opiates. They may cause cognitive impairment. Chronic benzodiazepine use increases the risk of developing dependence and abuse.

Most urine drug screens were designed to detect classic benzodiazepine drugs such as diazepam (Valium), nordiazepam, temazepam and oxazepam. Newer benzodiazepines include lorazepam, midazolam, chlordiazepoxide and flunitrazepam. Urine drug screens are much less sensitive in detecting the newer benzodiazepine drugs that are more potent, have different chemical groups attached to the benzodiazepine nucleus and are given at a lower dosage.

Two major factors are responsible for the majority of false negative results with benzodiazepine screening assays. Most benzodiazepine immunoassays are designed to detect unconjugated forms of oxazepam or nordiazepam, but some of the newer benzodiazepines such as lorazepam and alprazolam are excreted in urine as glucuronide conjugates. Clonazepam is metabolized to 7-aminoclonazepam is also not detected.

Most urine drug screens use a threshold of 300 ng/mL for detection of benzodiazepines. This cutoff point was based on the standard dosage of older benzodiazepines. New benzodiazepines are more potent and given at lower dosage. A threshold of less than 200 ng/mL may be needed to detect these new drugs.

Screening assays cannot distinguish between individual benzodiazepines. Benzodiazepines are undetectable in the urine after single use, but some can be detected for one to five weeks after chronic use. Over the counter remedies, such as oxaprozin, may produce false positive results in some benzodiazepine screening assays.

Phencyclidine (PCP) is a dangerous drug of abuse that produces visual and auditory hallucinations, feelings of dissociation, intense euphoria, and distortions in perception of time, space and body image. It is taken orally, inhaled or injected. PCP can be detected one week after single use and two weeks after chronic use. Dextromethorphan and Doxylamine (Unisom) have been reported to cause false positive results with PCP screening immunoassays. Over the counter remedies can produce false positive results in some phencyclidine screening assays.

Marijuana is a mixture of dried leaves and the flowering tops of the plant Cannabis sativa and is the most widely used illicit drug. Delta-9-tetrahydrocannabinol (9-THC) is the principal psychoactive ingredient in marijuana. Street preparations of marijuana commonly contain 0-5% 9-THC. Hashish, the resinous coating from Cannabis sativa L. leaves and flowers, contains 5-15% 9-THC. The compound is quickly and effectively absorbed by inhalation or from the gastrointestinal tract and is almost completely metabolized. Fatty tissue absorbs 9-THC and then slowly releases it into the plasma. After exposure, 9-THC is rapidly incorporated and distributes to the adipose tissue, liver, lungs, and spleen. It is then released back into the blood slowly and eventually is metabolized and changed into THC-COOH, which is excreted in the urine. THC-COOH is the most important compound for clinical testing. Multiple factors can influence the duration of detectability of THC-COOH in the urine, including frequency of marijuana use, timing of specimen collection, body fat content, and degree of urine dilution. The window of detection for THC-COOH ranges from a few days in infrequent marijuana users to weeks or months in frequent users.

Marinol (dronabinol) is a prescription drug that contains THC. Patients taking this drug may test positive for THC-COOH. Cesamet (nabilone) is a synthetic cannabinoid that is primarily prescribed for treatment of nausea and vomiting associated with chemotherapy. It is not detected by urine drug screens.

False positive reactions for THC occur most commonly because several prescription medications including Clozaril, Propulsid, Protonix, Paxil, Tegretol and Zocor cross-react with the anti-THC monoclonal antibody used in some screening assays.

K2 is an unregulated mixture of dried herbs that are sprayed with a synthetic cannabinoid-like substance, which is currently legally sold as incense. This product is also known as K2 Spice, Spice, K2 Summit, Genie and Zohai. The Missouri Regional Poison Center has recently reported several adverse reactions in patients between the ages of 14 and 27 years after smoking K2. Signs and symptoms include:

• Tachycardia
• Hypertension
• Anxiety
• Agitation
• Hallucinations
• Pallor
• Numbness and tingling
• Tremors and seizures

This constellation of signs and symptoms may suggest that K2 is contaminated with other unknown chemicals in addition to synthetic cannabinoid. K2 has also been used in combination with other legal and illegal substances. It is important to realize that K2 does not cross-react with tetrahydrocannibinol (THC) and is not detected by most drug screens performed in hospital laboratories.