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The Tox Cave

The Tox Cave will dissect interesting ED cases from the perspective of a toxicologist, focusing on applying up-to-date management of the poisoned patient. The name Tox Cave was coined by a former toxicology fellow to describe our small office space, likening it to the Bat Cave. The Tox Cave is where Drexel toxicology fellows and attendings have gathered to discuss the nuances of toxicology over the years.

Monday, June 1, 2015

The Good, the Bad, and the Ugly

The urine drug screen commonly utilized in the emergency department is an immunoassay that uses antibodies to detect specific drugs or their metabolites. This allows for rapid screening for drugs of abuse, but it has many limitations.

 

Gas chromatography-mass spectrometry (GC-MS) is the confirmatory test, but it is more costly, time-consuming, and generally can only be performed by outside laboratories. This confirmatory test is generally not useful in the emergency department, but has a role in cases of pediatric exposures, research, or occupational drug testing.

 

 

One of the limitations of a urine drug screen are the false-positive results from the interference of other drugs with the immunoassay, many of which are from structural similarities. Diphenhydramine and quetiapine commonly cause a false-positive for tricyclic antidepressants (TCA).

 

                            

TCA, left; diphenhydramine, center; quetiapine, right.

 

The specificity for phencyclidine (PCP) immunoassays is generally poor and false-positives may result from dextromethorphan, venlafaxine, tramadol, ketamine, and diphenhydramine.

 

                               

PCP, left; dextromethorphan, center; venlafaxine, right.

 

The amphetamine/methamphetamine screen has many false-positives, including bupropion (Wellbutrin), dextroamphetamine (Adderall), methylphenidate (Ritalin), promethazine (Phenergan), pseudoephedrine, trazodone, and ranitidine.

 

Case reports have also documented false-positives for opiates (levofloxacin, poppy seeds), THC (pantoprazole, hemp-containing foods, efavirenz), cocaine (coca leaf tea), and amphetamine (ma huang and ephedrine).

 

False-negatives may result from drug concentrations below the cutoff limit as well as adulterating, substituting, and diluting urine samples. Specific drugs in a drug class also may not be detected depending on the immunoassay used.

 

The assay most commonly used in hospitals tests for opiates. The term opioids is a broad term that includes the naturally occurring opiates, semi-synthetic opioids, and synthetic opioids. Specific testing for fentanyl, methadone, buprenorphine, oxycodone, or hydrocodone may be requested depending on your laboratory’s resources.

 

Opioids

Opiates

Semi-Synthetic

Synthetic

Opium*

Morphine*

Codeine*

Heroin*

Hydrocodone

Hydromorphone

Oxycodone

Oxymorphone

Buprenorphine

Fentanyl

Methadone

Tramadol

* Generally detected by the urine drug immunoassay.

 

Most benzodiazepine immunoassays detect oxazepam and nordiazepam, the metabolites of chlordiazepoxide (Librium), diazepam (Valium), and temazepam (Restoril). A false-negative benzodiazepine test result may occur despite the presence of other benzodiazepines, such as alprazolam (Xanax), lorazepam (Ativan), and versed (Midazolam).

 

The manufacturer’s package insert of the assay should be referenced if there are any questions about the immunoassay’s detection abilities to avoid incorrect interpretations. The detection time of a drug in urine may vary depending on pharmacokinetics of a drug, cutoff limits, metabolites, and chronicity of use. It is important to emphasize that the detection of a drug in the urine does not necessarily equate to intoxication.

 

Table 1. Duration of Detection Time of Drugs in Urine

Drug

Time

Amphetamine

48 hours

Diazepam

30 days

Cocaine metabolite (benzoylecgonine)

2-4 days

Cocaine metabolite: chronic user

Several weeks

Marijuana: single use

3 days

Marijuana: 4 times/week

5-7 days

Marijuana: daily use

10-15 days

Marijuana: long-term, heavy smoker

>30 days

Heroin

48 hours

Morphine

48-72 hours

Oxycodone

2-4 days

Phencyclidine (PCP)

8 days

Adapted from Mayo Clinic Proceedings 2008;83[1]:66.

Urine drug screens can be thought of as the good, the bad, and the ugly. Screens that are positive for cocaine, THC, or barbiturates are usually true-positives. Screens that are negative for benzodiazepines or opiates could be false-negatives. Depending on the clinical scenario, urine drug screens positive for TCAs, amphetamines, or PCP are more likely to be a false-positive than a true-positive.

 

References:

Moeller KE, Kelly CL, Kissack JC. "Urine drug screening: Practical guide for clinicians." Mayo Clinic Proceedings 2008;83[1]:66.

 

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