Drug Testing (Encyclopedia of Nursing & Allied Health)
Drug testing is the assessing of drug use (or non-use) by a person. The drugs for which one tests fall into three main types: illegal drugs, alcohol, and performance-enhancing drugs. Illegal drugs include marijuana, cocaine, amphetamines, and phencyclidine (PCP, the hallucinogen known as "angel dust"). Alcohol is, of course, a legal drug for adults, but since such activities as driving under its influence are illegal, it is sometimes very important to test for the level of alcohol in the bloodstream. Performance-enhancing drugs may be legal, but their use by athletes may be forbidden by the rules of an athletic association sponsoring a competition, rules designed to be fair to all the players.
One line of attack in the "war against drugs" in the United States involves compulsory drug testing. Specific drug-test laws vary from state to state, but drug tests are commonly administered in schools, athletic competitions, and the workplace. When results of some tests are being evaluated, it is important to keep in mind the fact that sometimes legitimate prescription drugs for such conditions as arthritis and asthma can produce test results that falsely suggest illegal drug use.
Some schools test students in general for drug use; others focus on student athletes because drug use increases the risk of sports-related injury, and also because the use of performance-enhancing drugs would give the athletes who use them an unfair advantage over the other athletes. The United States Supreme Court ruled in 1995 that schools may test entire teams of student athletes, even if individual team members are not suspected of using drugs. On the state level, courts are divided on the circumstances under which such testing can legally
occur. Some states provide more protection than others for the rights of students to privacy and due process.
In the 1970s, the issue of performance-enhancing drug use among athletes came into the forefront. Many athletes use performance-enhancing drugs (ergogenic drugs) such as anabolic steroids, growth hormone, and erythropoietin. Some athletes also use stimulants because of their ability to mask fatigue. Athletes are tested for use of forbidden drugs at many major meets.
The federal government laid the groundwork for drug testing in the workplace when, in the late 1980s, it initiated mandatory drug testing of federal employees, and began to require that government contractors establish drug-testing programs for their workers. Today, many large companies in the United States administer drug tests to their employees, but testing in smaller organizations is significantly less common.
Some workplace drug-testing policies are considerably stricter than others. Federal employees can be subject to compulsory random drug tests, as can private-sector employees with responsibility for the lives and safety of others. It is obviously not as dangerous to the public for the person raking leaves in a park to take illegal drugs as for an airplane pilot, a truck driver, or a person producing atomic weapons. Much workplace testing is conducted under such circumstances as the following:
- Pre-employment. Employers offer employment on condition of a negative drug test.
- Reasonable suspicion. Employers test an employee after direct observation of drug use or possession, patterns of erratic behavior, or drug-related arrests.
- Post-accident. Employees involved in accidents are sometimes asked to take a drug test immediately after an incident to determine whether alcohol or drug use was a factor.
- Treatment follow-up. Employees returning to work after treatment for substance abuse are often subject to follow-up testing.
Urine is the most common sample used in drug testing. Urine tests for federal employees are first analyzed by laboratories certified by the Substance Abuse and Mental Health Services Administration (SAMHSA), and any samples that come up positive are double-checked by gas chromatograph mass spectrometry, the "gold standard" test that identifies the exact molecular structure of a substance. Some private employers also follow SAMHSA procedures and use federal laboratories for testing, but others use commercial drug-testing kits. These commercial kits have often been criticized for generating a high rate of false positives. The problems associated with urine testing have sparked interest in alternative techniques, such as the testing of hair, sweat, or saliva.
SAMHSA advocates drug testing in order to help businesses achieve a drug-free workplace. A survey from the United States National Institute on Drug Abuse (NIDA) estimated that employee drug misuse cost the country billions of dollars in lost productivity, as well as in medical expenses and in worker-compensation claims. Mandatory drug testing in the workplace deters those who abuse drugs and alcohol from engaging in this unhealthy behavior at least while they are on the job, and it may deter non-users from ever starting to abuse drugs and alcohol. Also, it can sometimes help those with abuse problems to admit them and so to start getting help, but some abusers are in such deep denial that they cannot be helped in this way.
Opponents of these views point out problems with drug testing. Workplace testing may actually dampen company productivity because it is time-consuming, has the potential to violate the confidentiality that medical personnel are obliged to practice, and undermines staff morale and loyalty. More importantly, it may needlessly
Amphetamine chemical mixture that can strongly stimulate the central nervous system. Over time, users tend to need stronger doses, and eventually they may develop a physical dependence on it and thus become addicted.
Anabolic steroid synthetic or semisynthetic substance that promotes the production within the body of the proteins that build up tissues, especially muscle tissues.
Cocainen alkaloid chemical obtained from the leaves of the coca plant (or from some related species). It is addictive, it can cause mental and physical problems, and an overdose can lead to coma and death.
Ergogeniciving rise to, or enhancing, work, activity, functioning, and the like.
Erythropoietin protein produced mostly in the kidneys, and now available synthetically, that stimulates the production of red blood cells in the bone marrow.
False negative test result that erroneously gives a negative finding when the actual condition should have given a positive finding.
False positive test result that erroneously gives a positive finding when the actual condition should have given a negative finding.
Gas chromatograph mass spectrometry technique by which complex organic compounds are identified by the use of two sophisticated instruments. First, a gas chromatograph heats the compounds until they vaporize into gases which ascend a column and emerge one at a time. Then, each separate fraction of these gases is sent to a mass spectrograph which identifies the fragments of the molecules according to their mass. One thus gets a kind of chemical fingerprint of the substance being tested, and checks in a data base of thousands of such fingerprints of known substances to see which substance one has just tested.
Growth hormone substance produced naturally in the body, and now available synthetically, that promotes the development of flesh and bone, and influences the metabolism of proteins, carbohydrates, and fats.
Hallucinogen drug that can cause false sensations, such as hearing voices when there are no voices and no other sounds that could reasonably be confused with voices, or seeing persons or things that are not present.
Marijuanahe dried leaves, stems, and flowers of plants of the cannabis family. It is often smoked, sometimes eaten. It can produce distorted perceptions (which the users consider to be a form of elevated consciousness) and sometimes causes out-right hallucinations.
Phencyclidine chemical used legally as a veterinary anesthetic and illegally as a drug that alters consciousness (a psychedelic drug).
harm the careers of employees whose legitimate use of prescription medicines causes confusing or ambiguous test results. Also, it may identify substances at insignificant doses because of recreational drug use outside working hours, use that has no bearing on employee performance, according to civil-rights groups such as the American Civil Liberties Union (ACLU). The ACLU advises that employees in safety-sensitive positions such as airline pilots should indeed be tested for impairment, and that any individuals found to be impaired should then be referred to special programs called Employee Assistance Programs (EAPs). EAPs can in turn direct these persons to the appropriate substance-abuse programs. The ACLU also recommends more rigorous reference-checking to avoid hiring someone with a history of drug-abuse problems in the first place. However, if the person no longer has a drug problem, such an approach could illegally and unfairly violate this person's rights.
Many health-care organizations that provide qualified support for drug testing oppose its more radical uses, such as random testing or testing without suspicion. The American Nurses Association (ANA) opposes random drug testing of health-care workers, viewing it in violation of the basic principle of "innocent until proven guilty," but provides qualified support for testing under reasonable suspicion, and with evidence that job performance has been impaired by alcohol or drug usage. Employees who initially test positive for drugs should be offered a reassessment of the test results and should be given the chance to explain what legitimate medications they are taking which might have produced false-positive results. Even when the drug use is confirmed, counseling and treatment are recommended before any disciplinary action is taken, according to the ANA. The American Hospital Association (AHA) advocates pre-employment testing, suspicion-based testing, testing after certain incidents or injuries, and testing following drug rehabilitation, but not random testing without cause.
Some health-care organizations have also issued position statements on drug-testing policies in the community. The American Academy of Pediatrics has stated opposition to drug testing without cause as a prerequisite to student participation in school activities. And the American Medical Association (AMA) is opposed to the practice of reporting positive drug results for pregnant women to law-enforcement officials. Proponents say such practices protect unborn children, but the AMA states they are an invasion of medical confidentiality and a violation of the provider/patient relationship. Such practices may also discourage some women from seeking prenatal care.
Nurses may draw blood samples, for example, when testing for alcohol level. They must be certain that they have the informed consent of the person from whom they are drawing blood, or else that they have clear-cut legal authorization, such as a court order, to do so. In the case of testing of urine, hair, saliva, and sweat, nurses should instruct the person being tested and then properly store and label the specimen provided. Medical technologists or clinical-laboratory scientists are responsible for running the tests, for reporting the results accurately, and in some cases for estimating the margin of error or assessing the likelihood that the result is a false positive or a false negative. All health personnel must see that the results of such tests are disclosed only to those authorized to have them, and must otherwise maintain strict professional confidentiality.
Annas, G. J. "Testing Poor Pregnant Women for CocainePhysicians as Police Investigators." New England Journal of Medicine 344, no. 22 (31 May 2001): 1729732.
Kennedy, M. M. and R. B. Pickett. "An Uncomfortable Issue: Dealing with Substance Abuse." Clinical Laboratory Management Review: Official Publication of the Clinical Laboratory Management Association/CLMA 15, no. 3 (Mayune 2001): 18384.
Kraus, J. F. "The Effects of Certain Drug-Testing Programs on Injury Reduction in the Workplace: An Evidence-Based Review." International Journal of Occupational and Environmental Health: Official Journal of the International Commission on Occupational Health 7, no. 2 (Aprilune 2001): 10308.
Kunsman, K. "Oral Fluid Testing Arrives." Occupational Health and Safety (Waco, TX) 69, no. 4 (April 2000): 280, 34.
Laws, J. "Rewriting the Testing Rulebook." Occupational Health and Safety (Waco, TX) 69, no. 4 (April 2000): 368.
American Civil Liberties Union. 125 Broad Street, New York, NY 10004-2400. (212) 549-2500. email@example.com. <<a href="http://aclu.org">http://aclu.org>.
American Medical Association. The Council on Ethical and Judicial Affairs. 515 North State Street, Chicago, IL 60610-4320. (312) 464-4823. <<a href="http://www.amaassn.org/ama/pub/category/2498.html">http://www.amaassn.org/ama/pub/category/2498.html>.
American Nurses Association, ANA, 600 Maryland Avenue, SW, Suite 100 West, Washington, DC 20024-2571. (800) 274-4ANA. <<a href="http://www.nursingworld.org">http://www.nursingworld.org>.
American Society of Addiction Medicine. 4601 North Park Avenue, Arcade Suite 101, Chevy Chase, MD 20815-4520. (301) 656-3920. <<a href="http://www.asam.org">http://www.asam.org>.
Division of Workplace Programs, Center for Substance Abuse Prevention, Substance Abuse and Mental Health Services Administration. 5600 Fishers Lane, Rockwall II Building, Room 815, Rockville, MD 20857. (301) 443-6780. <<a href="http://workplace.samhsa.gov">http://workplace.samhsa.gov>.
National Clearinghouse for Alcohol and Drug Abuse Information (NCADI) Center for Substance Abuse Prevention. 5600 Fishers Lane, Rockville, MD 20857.(301) 443-0365. <<a href="http://www.health.org">http://www.health.org>.
National Institute on Drug Abuse. 6001 Executive Boulevard, Bethesda, MD 20892. (301) 443-1124. www.nida.nih.gov.
NSNA, National Student Nurses Association, 555 West 57th Street, New York, NY 10019. (212) 581-2211. <<a href="http://www.nsna.org">http://www.nsna.org>.
Drug Tests (Encyclopedia of Nursing & Allied Health)
Drug tests are analytical procedures that may be performed on blood, urine, or gastric fluid for the purpose of identifying an unknown drug or measuring the concentration of a specific drug.
Drug tests are usually performed for three reasons. 1) To identify an abuse drug. The majority of drug abuse involves one or more of the following substances and these comprise a typical drug of abuse panel: amphetamines, cannabinoids, cocaine, ethanol, opiates (morphine and codeine compounds), and phencyclidine (PCP). Over 85% of drug abuse cases involve those drugs or one of the following: barbiturates, benzodiazepines, methadone, propoxyhene, LSD, methaqualone, and anti-depressants. 2) To identify a drug which may have been ingested or administered in a toxic or lethal dose either accidentally or on purpose. In addition to poisons such as pesticides and heavy metals such as arsenic, drugs are often implicated in accidental overdose and suicide situations. The three most commonly encountered drugs seen in overdose situations are ethanol, salicylate (aspirin), and acetaminophen. 3) To determine whether the amount of a drug in the blood is within therapeutic limits. This process, called therapeutic drug monitoring (TDM), is used to insure that the dose and dose interval of the drug are sufficient to maintain a therapeutic blood concentration throughout drug therapy without risk of toxicity. TDM is also performed to verify that a patient is complying with the physician's orders.
Drug abuse testing
Drug screening may be performed on urine, blood serum or plasma, or gastric fluid, but urine is the sample of choice for symptomatic cases because drugs and their metabolites concentrate in the urine. Clinical or emergency department settings require the use of a screening method because the identity of the drug is not usually known. Drug screening methods may be designed to detect a class of related drugs. For example, a drug test for amphetamines may detect methamphetamine, dexamphetamine, methylenedeoxymethamphetamine (Ectasy), and phenylpropanolamine. The latter drug is a decongestant that sometimes cross reacts with the antibodies used in the amphetamine assay (analysis). Although drug screening may be sufficient to treat the patient, medicolegal implications are usually involved and this necessitates the need for positive sample identification and confirmatory drug testing. The confirmatory test need not be more specific than the screening test, but must utilize a different method of detection. This obviates the chance of a false positive test result caused by an interfering substance unless the interferent affects both methods. Drug screening programs are also used in occupational settings as a condition of employment, and extensively by the criminal justice system for criminal investigations and monitoring persons who have been convicted of drug related offenses. These situations require stringent adherence to procedures for documenting chain-of-custody of the specimen and confirmatory testing. Federal drug testing worksites must follow the Department of Transportation (DOT) chain-of-custody procedures for collection and transport of urine samples for drug testing. Labor-atories certified by the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) must use the gas chromatography with mass spectroscopy (GC-MS) method to confirm a positive drug screening test. This method is the gold standard for drug identification because it determines the mass spectrum of the drug which is a fingerprint of its chemical composition.
Specimen collection and transport
Urine specimens should be collected in a room with separate areas for workspace and toilet. The sink should be located in the workspace area. The patient or client must be positively identified via two forms of photoidentification or a passport. A form such as a DOT Custody Control Form should be used for chain-of-custody documentation. This form should include labels for the collection bottle and bag, and signature lines for all persons who will receive the specimen. At minimum the client must be observed entering and leaving the toilet area and should be instructed to remove outer garments and empty his or her pockets. The toilet should contain a bluing agent and the client should be instructed not to flush the toilet. The collection container should be unwrapped in the client's presence and affixed with a temperature measuring strip. The sample should be examined by the collector for adulteration and rejected if not within perscribed limits for volume (at least 30 mL) and temperature (90-100°F). An acceptable sample is labeled across the lid and side so the seal will be broken if the lid is removed. The laboratory should perform a test for urinary creatinine, pH, or specific gravity to check specimen integrity.
Blood samples are collected by venipuncture using standard precautions for reducing exposure to blood-borne pathogens. It is not necessary to restrict fluids or food prior to collection. Blood should be collected in tubes containing no additive. Risks of venipuncture include bruising of the skin or bleeding into the skin.
The EMIT principle
The most commonly used drug screening method is immunoassay. There are several immunoassay methods available including the enzyme multiplied immunoassay technique (EMIT), solid phase immunoassay fluorescence polarization immunoassay (FPIA), and cloned enzyme donor immunoassay (CEDIA). In addition, thin layer chromatography is sometimes used as a screening test. This method is more time consuming than immunoassay but is more comprehensive. The EMIT method is the most commonly used platform for drug of abuse screening. All EMIT assays follow the same scheme regardless of the drug being tested. EMIT assays measure enzyme activity. In a typical EMIT assay, urine is mixed with an antibody specific for the drug (e.g., methadone) and an enzyme-conjugated form of the drug. The enzyme used in EMIT testing is glucose-6-phosphate dehydrogenase. If not bound by the antibody, the enzyme will catalyze the oxidation of glucose-6-phosphate in the reagent forming 6-phosphogluconate and NADH. The production of NADH causes an increase in the absorption of 340 nm light. If no drug is present in the urine sample, all of the antibody will bind to the enzyme-conjugated drug. The antibody will block the catalytic site of the enzyme preventing the formation of NADH. If the drug is present in the urine sample, it will bind to some of the antibody, reducing the amount of antibody available to bind to the enzyme-conjugated drug. Therefore, the activity of the enzyme will be proportional to the concentration of drug in the urine sample.
In order to give maximum sensitivity the concentration of antibody is less than the concentration of the enzyme-conjugated drug. The labeled drug competes with any drug in the urine for binding sites on the antibody. If no drug is present in the sample, there will still be some unbound enzyme-conjugated drug that will produce NADH. However, the rate of enzyme activity will be less than that of the cutoff calibrator solution.
The enzyme activity of the sample is compared to that of a cutoff calibrator. The concentration of drug in the calibrator is set to a level recommended by SAMHSA for a positive test result. If the patient's sample result is greater than that of the cutoff calibrator, the drug test is presumed to be positive. Results below the cutoff calibrator are interpreted as negative. Activity less than the cutoff can result from endogenous drug present at very low levels in the absence of substance abuse. For example, poppy seeds used in baking contain minute amounts of opiates that cause some reactivity with enzyme immunoassays for opiates. Generally, the level of opiate detected will be below the cutoff value. Typically, the low calibrator and positive and negative urine control samples are assayed at least once per day along with the urine specimens.
EMIT is approved by the FDA only for urine specimens. Samples should be collected in clean plastic containers and refrigerated if not run within one hour. They can be refrigerated for up to three days or frozen, if longer storage is required. The pH of the sample must be between five and eight.
Confirmatory drug testing
Confirmation of a positive drug test by immunoassay is performed by a chromatographic method. Confirmatory methods include gas chromatography (GC), gas chromatography with mass spectroscopy detection (GC-MS), thin layer chromatography (TLC), and high performance liquid chromatography (HPLC). The methods most commonly employed in clinical practice are GC and TLC. In forensic laboratories and SAMHSA approved toxicology laboratories confirmation is done using GC-MS. All chromatography techniques require extraction of the drug from the biological fluid. This is accomplished by adjusting the pH of the sample to minimize ionization of the drug and addition of an organic solvent. The nonionized drug molecules will be more soluble in the organic phase and can be separated from water-soluble interfering substances. Extraction also serves to concentrate the drugs. In general, a pH of nine promotes extraction of alkaline and neutral drugs, and a pH of 4.5 promotes extraction of neutral or acidic drugs. Most abuse drugs with the exception of barbiturates and some benzodiazepines are extracted at an alkaline p H. Chromatography is a method used to separate molecules of similar structure. The process of separation depends upon nature of the chromatographic medium. Separation can result from partitioning (solubility differences), adsorption, size exclusion, ion exchange, and affinity bonding.
Gas chromatography is performed using a glass column packed with a liquid separation medium such as polyethylene glycol or an open glass capillary that is coated with a liquid polymer separation medium. GC measures only those substances that are volatile or can be separated into volatile compounds. GC separates molecules primarily on the basis of solubility. The sample is introduced into the instrument injection port and is vaporized by a high temperature. The vapors are carried by an inert gas (usually nitrogen) into a temperature-controlled column where they separate based upon their boiling point. Molecules of low boiling move faster through the column and elute first. When the drugs leave the column they are most often detected by a process called flame ionization. A small hydrogen-air flame is used to excite the molecule, causing release of an outer shell electron. This produces a current that is proportional to the concentration of the molecules. The instrument produces a recorder tracing of a peak when a compound is detected. The peak height or area is proportional to the drug concentration. The time between introduction of the sample and the appearance of the peak is called the retention time. Under standardized conditions, the retention times of unknown substances can be compared to those of drug standards to identify the drug in the sample. GC is the reference method for measuring ethanol in blood and is sufficiently sensitive and specific to identify most drugs extracted from biological samples.
GC-MS is a form of gas chromatography. The detector used is a mass spectrometer. This device usually uses an electron beam to break the eluted drug into ion fragments. The ions are kept apart by application of a vacuum and are separated according to their mass to charge (m/z) ratio in the mass analyzer, which is usually a quadrupole mass filter. This device produces alternating direct current voltage and radio frequency waves that attract and repel the ions. Ions of different m/z ratios move at different rates as the frequencies change and leave the filter at different times. The ions are detected by a dynode as they leave the filter. When the ion strikes the dynode it causes the element to release a shower of electrons. This current is used to produce a peak corresponding in height to the concentration of the ion. A recorder tracing of all of the ion fragments constitute the mass spectrum of the drug. As no two drugs have the identical mass spectrum this method conclusively identifies the drug. For drug identification the GC-MS is used in a mode called total ion chromatography, which displays the complete mass spectrum of the eluate and allows comparison to a computerized library of drug standards. For quantitative analysis the selected ion monitoring (SIM) mode is used. This mode measures the principal ions of the drug and can more accurately quantify the drug at lower concentrations.
When testing for abuse substances the timing of specimen collection is very important because drugs are metabolized and eliminated at different rates. Dosage, length of use, and individual differences in absorption, metabolism, and elimination cause the window of detection to vary. Approximate detection times are shown below for some commonly abused drugs:
- amphetamines: one to two days
- short acting barbiturates (eg. Seconal): one day
- long-acting barbiturates (eg. Phenobarbital): two to three weeks
- benzodiazepines: three days
- THC: three days for acute intermittent use; up to one month for heavy, chronic use
- cocaine: two to four days
- ethanol: three to four hours
- morphine and codeine: two days
- phencyclidine: one to two days
- propoxyphene: six to 48 hours
Therapeutic drug monitoring (TDM)
The same dose and dosing schedule for a drug can be therapeutic for some patients, and subtherapeutic or toxic for others. Age, gender, smoking, genetics, protein binding, concurrent medications, and renal and hepatic function cause variation in drug absorption, distribution, and clearance, which affects blood levels of the drug. The study of the behavior of a drug in the body is called pharmacokinetics. Pharmacokinetics describes the relationship between drug dose and blood concentrations. When two or more measurements are made after the drug reaches steady state, the results can be used to determine the dose and dosing interval needed to achieve the desired blood level. Tests for therapeutic drugs are performed for four reasons. 1) To determine whether the dose and dosing interval are able to maintain the desired blood level of the drug. 2) To permit empirical adjustment of the dose when the drug level falls outside the therapeutic range. 3) To verify that the patient is complying with the prescribed treatment. 4) To evaluate the magnitude of an intentional or accidental drug overdose.
In practice, only those drugs that have toxic potential near the therapeutic range need to be monitored. Drugs that should be monitored include many anticonvulsants, aminoglycoside antibiotics, antiasthmatics, antiarrhythmics, antineoplastics, antidepressants, and immunosuppressive drugs used in organ transplantation. As orally ingested drugs are metabolized and eliminated between doses, blood levels are time dependent. Shortly following absorption and distribution of the drug in the body, the blood level will peak. As the drug is metabolized and eliminated the blood level will fall until replaced by the next oral dose. When serial measurements of drug are plotted, the result is a dose response curve made up of repeating peaks and troughs. Accurate timing of sample collection is required to properly interpret blood drug test results. For most drugs, there is not a great difference between peak and trough blood drug levels, and measurement of trough drug concentration is sufficient to evaluate the patient. In cases where the trough-peak range is large, both trough and peak levels need to be considered. This is the case when monitoring aminoglycoside antibiotics. When measuring trough blood levels of a drug the sample should be collected just before the next dose is given. Collection time for peak blood levels depends upon the drug and route of administration. For aminoglycoside antibiotics peak levels are usually drawn 30 minutes following an IV (intravenous) dose and 60 minutes following an IM (intramuscular) dose.
Immunoassay method for measuring biological substances such as drugs, proteins, and hormones. It utilizes antibodies specific for the substance being tested.
Enzyme protein that accelerates the rate of a biochemical reaction.
Enzyme immunoassay procedure employing an enzyme bound to an antigen or antibody. The antibody binds to the antigen of interest and the enzymatic reaction measures the concentration of the antigen.
Chromatography technique used to separate closely related biological molecules which exploits one or more of the following differences: solubility, molecular size, adsorption, ion exchange, affinity bonding.
Gas chromatography chromatographic method that utilizes a gas for the carrier or mobile phase and a liquid for the stationary phase.
Gas chromatography with mass spectroscopy method that employs a gas chromatograph to separate the molecules and a mass spectrometer to identify and quantify the separated compounds.
High performance liquid chromatography chromatographic method that utilizes a liquid mobile phase or carrier and a liquid stationary phase. Sample is forced through the stationary phase by a high pressure pump.
Thin layer chromatography chromatographic method that uses a thin layer of silica gel and a liquid mobile phase which migrates upward through the silica gel by capillary action. Molecules are carried by the mobile phase and separate on the basis of solubility.
Therapeutic drug monitoringhe measurement of a drug in blood serum or plasma in order to determine the adequacy of dosing and prevent drug toxicity.
Trough level drug assay performed on a sample collected before the next dose is absorbed.
Peak level drug assay performed on a sample following complete absorption and distribution.
Therapeutic drug measurements
Both immunoassay and chromatographic methods are used to quantify therapeutic drugs. EMIT, CEDIA, and FPIA assays are the most commonly used immunoassays. Gas chromatography and high-performance liquid chromatography are the most commonly used chromatographic methods.
FLUORESCENCE POLARIZATION IMMUNOASSAY (FPIA). This method measures the plane polarized fluorescence of fluorscein-labeled antigen without the need for an enzyme conjugate. Fluorscein conjugated to a drug competes with the drug in the sample for a limited number of antibody molcecules. Plane-polarized UV light is transmitted through the sample. Both the unbound and antibody-bound, fluorscein-labeled drug absorb the UV light and the fluorescein becomes excited. The unbound labeled drug is rotating rapidly and emits light that is unpolarized. The labeled drug that is bound by antibody rotates more slowly and will emit light that is plane polarized. The detector responds to plane-polarized light only because a polarizing filter is placed between the cuvet and detector. Antibody binds to more fluorescein labeled drug when there is less drug in the patient's serum. This slows down its rotation giving a greater plane polarized signal. Therefore, plane-polarized fluorescent intensity is inversely proportional to the drug concentration in the patient's sample.
CLONED ENZYME DONOR IMMUNOASSAY (CEDIA). A technique related to EMIT is CEDIA (cloned enzyme donor immunoassay). The method uses a drug conjugated to a fragment of the enzyme [.beta]-galactosidase which is called the enzyme donor (ED). The ED reagent also contains the substrate, cholorophenol red-[.beta]-D-galactopyranose. This is mixed with urine or serum and a second reagent containing a monoclonal antibody against the drug and a second fragment of [.beta]-galactosidase called the enzyme acceptor (EA). If drug is present in the sample it neutralizes the antibody. The two enzyme fragments associate forming an active enzyme which splits the substrate, liberating the red dye. Absorbance is directly proportional to drug concentration. If drug is not present, the antibody binds to the ED fragment preventing formation of active enzyme.
HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC). HPLC is a chromatography method that uses liquid mobile and stationary phases. The mobile phase is usually a buffer to which a polarity modifier such as acetonitrile has been added. The stationary phase consists of a stainless steel column of silica gel that is bonded to a nonpolar liquid. The most common column packing for clinical use is octadecylsilane (C18). The stationary phase is less polar than the mobile phase, and this causes compounds which are lower in polarity to be retained longer than more polar molecules. The column is packed very tightly to give thousands of surfaces upon which partitioning can occur. Therefore, a pump is used to move the mobile phase through the column. To obtain a flow rate of 1.5 2.0 mL/min it is not uncommon to develop a pressure of 1,200-2,500 pounds per square inch at the start of the column. The separated molecules enter an optical flowcell after eluting from the column. UV (ultra-violet) light is passed through the flowcell and a photo-multiplier tube or photodiode array detects the transmitted light. When a drug enters the flowcell it will absorb a portion of the incident UV light causing an increase in absorbance (optical density). This signal is applied to a chart recorder, which produces a peak that is proportional in height and area to the concentration of the drug. HPLC is time consuming and is usually reserved for assays of drugs for which there is no available immunoassay. It has the advantage of being able to separate drug metabolites from parent compounds and separate compounds that are nonvolatile (for example, anabolic steroids).
Results for drug of abuse tests should be negative (ie. below the low calibrator cutoff). Results for therapeutic drugs should fall within the published therapeutic range for the drug and treatment. Some typical therapeutic limits for commonly measured drugs are shown below:
- Acetaminophen: 10-30 mg/L; toxic level >200 mg/L.
- Amikacin: trough 1-4 mg/L; peak 25-35 mg/L; toxic trough >10 mg/L; toxic peak >35 mg/L.
- Carbamazepine: 4-12 mg/L; toxic level >15 mg/L.
- Digoxin: 1.5-2.0 [.mu]g/L; toxic level >2.5 [.mu]g/L.
- Ethosuximide: 40-100 mg/L; toxic level >150 mg/L.
- Gentamicin: trough 1-2 mg/L; peak 8-10 mg/L; toxic trough >2 mg/L; toxic peak >12 mg/L.
- Kanamycin: trough 4-8 mg/L; peak 25-35 mg/L; toxic trough >10 mg/L; toxic peak >35 mg/L.
- Lidocaine: 1.5 - 6 mg/L: toxic level >6 mg/L.
- Netilmicin: trough 1-2 mg/L; peak 8-10 mg/L; toxic trough >2 mg/L; toxic peak >12 mg/L.
- Phenobarbital: 15-40 mg/L; toxic level >40 mg/L.
- Primidone: 5-12 mg/L; toxic level >15 mg/L.
- Procainamide: 4-10 mg/L; toxic level >12 mg/L.
- Salicylates: 100-300 mg/L; toxic level >400 mg/L.
- Theophylline: 8-20 mg/L; toxic level >20 mg/L.
- Tobramycin: trough 1-2 mg/L; peak 8-10 mg/L; toxic trough >2 mg/L; toxic peak >12 mg/L
- Valproic acid: 50 - 100 mg/L; toxic level >100 mg/L.
- Vancomycin: trough 5-10 mg/L; peak 20-40 mg/L: toxic peak >80 mg/L.
Health care team roles
Therapeutic drug tests are ordered by physicians. Blood and urine samples may be collected by a nurse or phlebotomist. In the case of drug of abuse testing performed on behalf of an employer or government agency, drug testing is supervised by a medical officer appointed by the institution. Urine samples are collected and transported by nontesting personnel who should have special training in chain-of-custody procedures. Drug testing is performed by a clinical laboratory scientist, CLS (NCA) or medical technologist, MT (ASCP) or by a clinical laboratory technician, CLT (NCA) or medical laboratory technician, MLT (ASCP). Clinical toxicologists, clinical chemists, and clinical pharmacologists may be responsible for interpreting therapeutic drug tests and recommending doseage adjustments to the physician. Psychiatrists, psychologists, nurses, and social workers who are trained in drug abuse treatment are involved in evaluation, treatment, and counseling of drug abusers.
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Substance Abuse and Mental Health Services Administration. <<a href="http://www.samhsa.gov/public/public.html">http://www.samhsa.gov/public/public.html>.
Drug Testing (Encyclopedia of Small Business)
Drug testing is the process wherein companies utilize the resources of scientific laboratories to determine whether any of their employees use illegal drugs. Drug testing, which most commonly requires workers to submit urine samples for analysis, is utilized in businesses and industries throughout the United States, although the practice continues to generate controversy. Proponents argue that it has been an effective deterrent, and that employers have the right to know if their employees are engaging in behavior that can damage the company. Opponents contend, however, that the practice violates fundamental individual rights and can have a corrosive effect on workplace morale.
Drug testing became a popular element of corporate safety and productivity policies during the 1970s and 1980s, as awareness heightened of the serious impact that substance abuse can have on business efficiency and profitability. During this period, companies of all shapes and sizes began to turn to drug testing as a method of curbing substance abuse among the members of their workforce. Large corporations were by and large the leaders in this trend, but many small-and mid-sized companies implemented drug testing policies as well. By 1996, an American Management Association survey indicated that more than 80 percent of responding employers required workers to submit to drug tests on at least a "random testing" basis. That percentage dropped by more than 10 percent by 1999, and observers believe that the number is actually lower since small companies, which were not part of the survey, are less likely to use drug testing. But many analysts believe that this downward trend was primarily a reflection of the nation's tight labor market for skilled employees. They contend that use of drug testing policies will rise again when unemployment rates rise and businesses can afford to be more selective and deliberate in their hiring processes.
THE DEBATE OVER TESTING
Supporters of workplace drug testing note that over the past several years, as drug testing has become more prevalent in American businesses, cases of workplace substance abuse have undergone a significant drop. Proponents of the practice argue that there is a clear correlation between these two trends. Business owners who use drug testing also point to cost-benefit analysis as a factor in their thinking; they note that the expense (typically $15 per test, with confirmatory tests costing approximately $60) of a testing policy, while potentially expensive over the long term, can be absorbed much more easily than the litigation costs that might stem from a single incident featuring a drug-impaired employee.
Moreover, some researchers and business owners claim that the introduction of drug testing in the work environment has actually improved the morale of the larger workforce, since the majority of employees are more interested in ensuring that their workplace is a safe and productive one. And of course, proponents of drug testing note that studies clearly show that companies are far more likely to enjoy financial healthhich also benefits employeesf they are able to establish and maintain an environment in which substance abuse is not tolerated.
Nonetheless, detractors claim that the practice is not all that it is cracked up to be. "Despite the fact that the constitutional right to privacy does not apply to private-sector employees, many people feel strongly that drug testing is too 'invasive' and violates an important right," wrote George R. Gray and Darrel R. Brown in HR Focus. In addition, they charged that "testing current employees seems to promote a statement that employers do not trust their workers to behave responsibly regarding drug use." Gray and Brown did point out, however, that businesses can take steps to minimize this impression: "Careful education efforts about the need for testing can help prepare workers for a new program. A program directed toward sensitive positions or departments, tailored to a company's specific problems, and carefully designed to avoid communicating a feeling of mistrust among all employees appears to be the company's best approach in drug testing."
Another common criticism leveled against drug testing is that it does not spot more commonplace causes of workplace accidents and inefficiency, such as fatigue or alcohol use. Critics on this point argue that performance-based testing (also known as impairment testing or fitness for duty testing) is actually more valuable. Impairment testing measures whether workers are alert and fit for tackling their duties by tracking eye movement reactions to various stimuli. Evelyn Beck notes in Workforce that supporters of these types of testing argue "because impairment tests measure involuntary responses, cheating is less a concern than it is with urine tests, which unsupervised employees have been known to dilute or substitute."
Critics also argue that the findings of many drug-testing laboratories, which operate according to varying levels of regulation around the country, are simply not reliable. More detailed testing has proven effective in significantly reducing the number of errors made by testing laboratories, but observers note that additional testing is more expensive, and that this added cost could prove prohibitive to smaller companies in particular. Finally, even advocates of drug testing admit that companies who maintain worksites in more than one state face potential employment practice liability exposures, because privacy laws vary from state to state. As a result, employers in this situation often shape their practices differently from site to site, and in the process open themselves up to charges that they are not maintaining uniform employment practices.
THE FUTURE OF DRUG TESTING
Drug testing will continue to be employed on a widespread basis for the foreseeable future, as concerns over safety, productivity, and liability continue to trump privacy concerns in the minds of many business owners, executives, and managers. Moreover, many analysts predict that the practice will become even more pervasive in the next decade or so. By 2003, the U.S. Department of Health and Human Services is expected to implement new mandatory guidelines changing many aspects of regulated workplace drug testing. These changes will initially impact only the 20 percent of workplaces that mandate regulated testing, but observers predict that unregulated industries will quickly follow suit in most meaningful areas. The most important new provisions contained in these revised HHS guidelines will govern collection points and expanded specimen sample possibilities. In the former area, laboratories will be able to test at the point of collection with hand-held kits and automated equipment. In the latter realm, laboratories will be able to test using specimens other than urine. "Proposed additional specimens include oral fluids, sweat, and hair," wrote Kathy Hitchens in Medical Laboratory Observer. All of these specimens can be collected immediately and under direct observation, eliminating the possibility of employee contamination or substitution of the specimen.
Beck, Evelyn. "Is the Time Right for Impairment Testing?" Workforce. February 2001.
Cranford, Michael. "Drug Testing and the Right to Privacy: Arguing the Ethics of Workplace Drug Testing." Journal of Business Ethics. December 1998.
Fletcher, Lee. "Employer Drug Testing Has Pitfalls." Business Insurance. October 23, 2000.
Gray, George R., and Darrel R. Brown. "Issues in Drug Testing for the Private Sector." HR Focus. November 1992.
Hitchens, Kathy. "Workplace Drug Testing: How is it Changing?" Medical Laboratory Observer. February 2001.
Peters, Tom. "Why Workplace Drug tests Send Workers Bad Message." Washington Business Journal. October 21, 1994.
Solomon, Robert M., and Sydney J. Usprich. "Employment Drug Testing." Business Quarterly. Winter 1993.
"Substance Abuse in the Workplace." HR Focus. February 1997.
Taurone, Dominic. "What to Do When an Employee Tests Positive for Drugs." Employee Benefit News. October 1, 2000.
SEE ALSO: Employee Rights