Pediatric Annals

The Use of the Clinical Laboratory in the Diagnosis and Treatment of Substance Abuse

Deborah C Stewart, MD

Abstract

The physician confronted with the emergency care of the patient suspected of substance abuse requires rapid and accurate information for critical diagnostic and therapeutic decision making. The initial approach to the patient must be based on information gathered from the history and physical examination, as the clinical laboratory usually becomes available only after initial supportive measures have been instituted. Despite this limitation, the clinical laboratory can be extremely useful to the clinician by providing qualitative screening for the presence or absence of toxic substances as well as quantitative data regarding drug levels in the biological fluids. By understanding the proper uses and limitations of the laboratory, the physician is able to order appropriate tests, obtain useful, timely results and interpret test results accurately.

Initial diagnostic efforts in suspected substance abuse should include:1-3

1. Brief problem-oriented history.

2. Physical examination.

3. Appropriate specimens for analysis (urine, blood, gastric contents, saliva, etc.).

4. Submitting specimens to the lab as they become available.

5. Requesting qualitative screening of urine for drugs as an initial diagnostic effort.

6. Requesting quantitative analysis of appropriate specimens, if necessary.

7. Obtaining other relevant data necessary for patient management (electrolytes, blood gases, etc.).

8. Interpreting laboratory data correctly.

The initial history in patients suspected of substance abuse often guides the subsequent diagnostic efforts. Information should be gathered from parents, friends, or other witnesses both about the current episode and past history of substance abuse. Data regarding substances used by friends, recent emotional upset, or behaviorsuggesting depression such as insomnia, anorexia, and lack of interest should be sought. The provider should attempt to determine what the substance looked like, how much was taken and by what route, and if any other medication or drug could have been taken. Past medical history of trauma should be elicited.

Physical examination should be meticulous and emphasize vital signs, mental status, level of consciousness, cardiovascular, and neuromuscular status. When the type or severity of the symptoms does not correlate with the amount, route, or type of drug allegedly ingested, mixed ingestions (particularly with alcohol), concomitant trauma, or a medical condition may be strongly suspected.

All available fluid should be obtained and sent to the laboratory, particularly urine, blood, vomitus, and gastric aspirate. Any available suspect substance or paraphernalia should also be included. Urine is usually the most readily available body fluid and should be sent to the lab as soon as it is obtained. Urine specimens are best used to qualitatively screen for the presence or absence of a drug, using thin layer chromatography.4'5 This method is relatively quick, inexpensive, and is able to detect the presence of most drugs of abuse (Table I). Results obtained by this method must be confirmed using another method such as gas liquid chromatography to eliminate the possibility of errors caused by metabolites or interferences by other substances. For instance, some drugs such as cocaine and heroin may be detected by the presence of their metabolites.6

In addition, some drugs are excreted only minimally in the urine and may not be found by urine screening unless very large doses were taken. These drugs include pentobarbital, secobarbital, and others which may be detected in gastric contents or the blood. If the patient was lavaged or an emetic given soon after the ingestion, the substance may not be in the urine in large amounts. In this case, the gastric contents should be screened. The first fluid obtained from emesis or lavage should be sent to the laboratory, as this generally contains the greatest drug content.7

The information obtained from the qualitative screen is usually adequate to guide initial treatment…

The physician confronted with the emergency care of the patient suspected of substance abuse requires rapid and accurate information for critical diagnostic and therapeutic decision making. The initial approach to the patient must be based on information gathered from the history and physical examination, as the clinical laboratory usually becomes available only after initial supportive measures have been instituted. Despite this limitation, the clinical laboratory can be extremely useful to the clinician by providing qualitative screening for the presence or absence of toxic substances as well as quantitative data regarding drug levels in the biological fluids. By understanding the proper uses and limitations of the laboratory, the physician is able to order appropriate tests, obtain useful, timely results and interpret test results accurately.

Initial diagnostic efforts in suspected substance abuse should include:1-3

1. Brief problem-oriented history.

2. Physical examination.

3. Appropriate specimens for analysis (urine, blood, gastric contents, saliva, etc.).

4. Submitting specimens to the lab as they become available.

5. Requesting qualitative screening of urine for drugs as an initial diagnostic effort.

6. Requesting quantitative analysis of appropriate specimens, if necessary.

7. Obtaining other relevant data necessary for patient management (electrolytes, blood gases, etc.).

8. Interpreting laboratory data correctly.

The initial history in patients suspected of substance abuse often guides the subsequent diagnostic efforts. Information should be gathered from parents, friends, or other witnesses both about the current episode and past history of substance abuse. Data regarding substances used by friends, recent emotional upset, or behaviorsuggesting depression such as insomnia, anorexia, and lack of interest should be sought. The provider should attempt to determine what the substance looked like, how much was taken and by what route, and if any other medication or drug could have been taken. Past medical history of trauma should be elicited.

Physical examination should be meticulous and emphasize vital signs, mental status, level of consciousness, cardiovascular, and neuromuscular status. When the type or severity of the symptoms does not correlate with the amount, route, or type of drug allegedly ingested, mixed ingestions (particularly with alcohol), concomitant trauma, or a medical condition may be strongly suspected.

All available fluid should be obtained and sent to the laboratory, particularly urine, blood, vomitus, and gastric aspirate. Any available suspect substance or paraphernalia should also be included. Urine is usually the most readily available body fluid and should be sent to the lab as soon as it is obtained. Urine specimens are best used to qualitatively screen for the presence or absence of a drug, using thin layer chromatography.4'5 This method is relatively quick, inexpensive, and is able to detect the presence of most drugs of abuse (Table I). Results obtained by this method must be confirmed using another method such as gas liquid chromatography to eliminate the possibility of errors caused by metabolites or interferences by other substances. For instance, some drugs such as cocaine and heroin may be detected by the presence of their metabolites.6

In addition, some drugs are excreted only minimally in the urine and may not be found by urine screening unless very large doses were taken. These drugs include pentobarbital, secobarbital, and others which may be detected in gastric contents or the blood. If the patient was lavaged or an emetic given soon after the ingestion, the substance may not be in the urine in large amounts. In this case, the gastric contents should be screened. The first fluid obtained from emesis or lavage should be sent to the laboratory, as this generally contains the greatest drug content.7

The information obtained from the qualitative screen is usually adequate to guide initial treatment or to aid in the differential diagnosis of stupor or coma. The identification of a broad category of substances is often all that is needed even in those circumstances where specific medications are available for intervention. Examples of these situations include: naloxone for narcotic overdose, be nza t r opine for the treatment of extrapyramidal manifestations of phenothiazine overdose, physostigmine for anticholinergic symptoms of tricyclic overdose, and sedatives or haloperidol for severe amphetamine toxicity.8

When submitting specimens for qualitative analysis, it is important to indicate to the laboratory the clinical history of the patient, the source of the specimen, the time of collection, as well as the class of drugs suspected. Brief one-word histories such as "comatose," "OD," and "stuporous" are inadequate. This information can speed the turn-around time by directing the laboratory toward more specific analytic methods. In addition, it is extremely important that the urgency of the analysis be clearly indicated to the laboratory. "Stat" results should be requested only if the result will aid in the initial management of the patient. Also, there is usually a significant additional fee to the patient for "stai" procedures; often in the range of $100 or more, depending on the laboratory.

Table

TABLE 1DRUG SCREEN CHILDREN'S HOSPITAL OF LOS ANGELES

TABLE 1

DRUG SCREEN CHILDREN'S HOSPITAL OF LOS ANGELES

Once a qualitative determination has been performed on urine, then, if necessary and appropriate, the amount of drug is quantified (Table 2). Serum is preferred for quantitative analysis, as urine varies in amount, concentration, and acidity. However, occasionally, it is possible to draw certain inferences from urine levels. Ingenerai, for acute ingestions, low levels generally indicate either a low dosage or a considerable lapse of time since abuse. On the other hand, low urine levels in a chronic abuser may signify increased metabolic clearance of the substance. Serum levels are more costly and time consuming and should be ordered only when indicated for therapeutic decision making.

Table

TABLE 2SOME INDICATIONS FOR QUANTITATIVE ANALYSIS IN DRUG OVERDOSE

TABLE 2

SOME INDICATIONS FOR QUANTITATIVE ANALYSIS IN DRUG OVERDOSE

Table

TABLE 3ACIDIC, NEUTRAL AND BASIC DRUGS OF ABUSE

TABLE 3

ACIDIC, NEUTRAL AND BASIC DRUGS OF ABUSE

Quantitative drug levels may be extremely useful if there is a specific antidote with severe side effects of its own whose use must be judiciously considered. Quantitative levels can also be of great assistance in aiding decisions regarding the use of extraordinary life-saving measures such as hemodialysis. For example, in barbiturate overdose, particularly with the longer acting drugs, serial determinations of serum levels may indicate the necessity for dialysis. In acetaminophen poisoning, the decision to administer acetylcysteine therapy is based on serum levels. In methanol intoxication, quantitative levels may be helpful in several ways: first, to determine the necessity for hemodialysis and second, to monitor the need for ethanol therapy. Serum levels may also be extremely useful in mixed drug overdoses, or when concomitant trauma is suspected. Lower serum levels than expected to account for observed symptomatology suggest an alternate drug, concomitant disease, or traumatic etiology. The frequent adulteration of street drugs with other substances (e.g., PCP in mescaline, amphetamine in cocaine, etc.) make this an important consideration.

Quantitative drug levels are frequently important in forensic medicine. In these cases, it is essential that the specimens be handled in a "chain-of-e vid enee" manner to ensure that the results will be valid evidence in a court of law. Every laboratory should have an established protocol for handling medicolegal specimens. Appropriate handling of such specimens includes the following:9

1. the appropriate specimen should be submitted in sufficient quantity;

2. the exact time a specimen is collected must be recorded as well as the relationship ofthat time to the time of ingestion;

3. specimen collection, labeling, and preservation techniques should be noted and should adhere to laboratory standards;

4. the specimen should be transported in a sealed container, usually a sealed envelope; and

5. the specimen must maintain "integrity."

To maintain integrity, the specimen collected, analyzed, and reported as evidence must be one and the same without alteration. This requires that all personnel handling the specimen must indicate in writing that they have received the specimen intact and without alteration. Finally, the analytical method employed should be the most accurate available to the laboratory.

To accurately interpret quantitative drug data, one must consider those factors which affect serum levels, patient response, and the ability of the lab to detect the biologically active forms of the drug. Patient factors such as age, sex, adiposity, concurrent disease state, drug tolerance, and hereditary metabolic differences all may considerably affect drug response.3'10 For example, neonates have increased drug susceptibility because of decreased plasma protein binding, reduced rate of hepatic biotransformation and a lower glomerular filtration rate.9 Women are generally thought to be more susceptible to certain drug effects than men, partly because of smaller size and slight differences in hepatic enzyme activity." Obese people tend to have prolonged effects of certain lipid soluble drugs such as the barbiturates and PCP, as the body fat serves as an important storage depot. Chronic disease states may considerably modify drug effects. !0 Patients with chronic pulmonary disease are exceptionally sensitive to respiratory depressants. Hyperthyroid individuals may tolerate more morphine, but are less tolerant of a stimulant drug. Renal disease, with decreased glomerular filtration rate may cause prolonged action and increased drug levels. Uremie patients may also have decreased protein binding of certain drugs leading to increased toxicity. Certain types of hepatic diseases may alter hepatic microsome function, with resultant reduced metabolic clearance.

Prolonged administration of certain drugs, particularly those affecting the central nervous system, can result in the development of drug tolerance. This may be due to increased biotransformation of the drug or decreased receptor responsiveness. Patients using opiates, amphetamines, barbiturates, and alcohol may have plasma drug levels which poorly correlate with clinical signs.6 Genetic factors may also have powerful influences on drug effects. Differences in INH metabolism by the liver or prolonged apnea following succinylcholine administration are two prototypic examples. The field of pharmacogenetics is young and it is expected that individual variation in drug effects will be due increasingly to genetic factors. This will help to explain not only those idiosyncratic clinical responses, but also the atypical responses often seen with "street drugs."

Drug related factors are also of extreme importance in the correct interpretation of toxicologtcal data. Such factors as drug dose, route of administration, drug formulation, ionizability, tissue and protein binding, presence of pharmacologically active metabolites or interfering substances, and routes of elimination must be considered. Drug dosage may often be quite difficult to determine. Methods such as pill counting and toxicological analysts of ingested substances can be quite helpful, but often this data is not available. In addition, many street drugs have variable drug concentrations, are often mixed with adulterants, or contaminants, or may not contain any of the purported drug. For example, street methaqualone (Quaalude) is often Valium and street THC is virtually always another drug such as mescaline or PCP.12

Route of administration is strongly related to both intensity and duration of drug effects. GI absorption after oral administration is dependent on such factors as drug pH, lipid solubility, and gastric emptying time. Drugs in the non-ionized, lipid soluble state pass through cell membranes most rapidly. Therefore acidic drugs such as barbiturates will be most easily absorbed in the acid environment of the stomach. Basic drugs such as morphine and amphetamine will be poorly absorbed in the stomach, but well absorbed in the alkaline environment of the small intestine (Table 3).13 Conversely, drug excretion is enhanced when drugs are ionized. This is the basis for acidifying the urine pH to enhance excretion. For example, phencyclidine is an alkaline, lipid soluble drug whose excretion can be enhanced by urine acidification (Table 4).14

The degree to which a drug is bound to serum proteins is an extremely important consideration when analyzing drug data. For a given drug concentration, it is the amount of free, unbound drug rather than the total amount of drug present which determines the drug's effectiveness. Abusable drugs which are predominantly protein bound include barbiturates, benzodiazepines, and methadone.10 These drugs can be displaced by substances with greater affinity for serum proteins such as bilirubin or free fatty acids. Also, changes in serum protein concentration can significantly alter the amount of free drug. Since most drug assays measure the total amount of the drug present in the body, any changes in protein binding with resultant changes in pharmacological activity will not be reflected by changed serum drug levels.

Many drugs have pharmacologically active metabolites. Measurement of the parent drug alone may be deceiving. The parent drug may not be detected in a drug assay, while its metabolites may be present. In general, metabolites persist longer than the parent drug, and are often responsible for some drug effects. For example, diazepam levels measured by ultraviolet spectrophotometry are much higher than those measured by gas chromatography. UV spectrophotometry measures both parent drug and metabolites, while gas chromatography measures the parent drug alone. Table 5 lists some of these drugs and their active metabolites. Most drug assay techniques attempt to measure active metabolites, but in case of discrepancy between clinical findings and laboratory findings, the possibility of a missed metabolite should be considered.

The route of elimination of a drug clearly affects the measurement of drug concentrations. The "breath test" for ethanol intoxication provides a reliable index of blood levels. Highly ionized, and therefore water soluble drugs are more easily excreted. For example, in PCP intoxication, the urine to blood ratio of PCP is 97 times greater than 7.5.14 Clearly, it is important to obtain the appropriate fluids for analysis, as well as to be aware of the variables such as pH, urine flow, GI motility, etc., which affect elimination, and therefore detection.

Finally, the ability of the laboratory to detect the drug is an important consideration in the interpretation of drug data. The clinician should have a general knowledge of the common laboratory methods employed for toxicological analysis, and their advantages and disadvantages. A brief review of the various laboratory methods follows, outlining the possible technical interferences which may occur in the laboratory.

Methods of drug analysis used by individual laboratories vary greatly depending on local abuse patterns, availability of equipment and trained technical personnel, accuracy, turn-around time (TAT), and cost. Optimal analysis methods are accurate, sensitive, specific, and have a short TAT, thus increasing clinical usefulness. The more sensitive and specific a method is, the more costly. Less specific techniques can identify broad categories of drugs such as amphetamines or narcotics and are quite inexpensive, but can lead to many false positive and false negative results. One should consider, for a given assay, whether or not certain metabolites are also measured or if there are interfering substances. For example, nicotine found in the blood of heavy smokers interferes with certain commonly used analysis methods for methadone. It is known that this group has a particularly high incidence of heavy smokers. Detection limits (sensitivity) also vary greatly between the methods, but a limit of 0.5 ¿ig/ml is considered good for most labs.7 This is generally the limit for amphetamine, methamphetamine, rapid acting barbiturates, codeine and morphine in drug screens. The detection limit is generally 0.7 Mg/ml for phenobarbital and 1.0 Mg/ml for methadone, propoxyphene, cocaine, and methaqualone. If quantitation is indicated, the accuracy of drug concentration determination should be ±10%.5 Both accuracy and specificity can be improved by using more timeconsuming methods. However, there are certain drugs for which a short TAT is crucial, particularly those which produce life-threatening emergencies. Turnaround time also increases with the number of drugs requested to be screened. It is therefore important for the physician requesting the drug screen to specify to the lab the classes of substances under consideration, the sensitivity needed, and the urgency of the analysis.

Table

TABLE 4PH OF URINE AND GASTRIC FLUID VS. PHENCYCLIDINE CONCENTRATION

TABLE 4

PH OF URINE AND GASTRIC FLUID VS. PHENCYCLIDINE CONCENTRATION

Table

TABLE 5SOME DRUGS OF ABUSE WITH PHARMACOLOGICALLY ACTIVE METABOLITES

TABLE 5

SOME DRUGS OF ABUSE WITH PHARMACOLOGICALLY ACTIVE METABOLITES

There are many procedures in use today for toxicological analysis. The most common include Chromatographic, spectrophotometric, and immunological techniques. Chromatographie techniques have traditionally been the cornerstone for drug analysis and are particularly useful for drug screening. The three types in general use are thin layer (TLC), gas (GC), and high pressure liquid chromatography (HPLC). All Chromatographie techniques are based on the separation of a mobile, drug unknown carrying phase from a stationary phase. This separation is based on specific differences in the physicalchemical characteristics of the two phases. The mobile phase separates a given distance (termed the Rf) from the stationary phase in comparison to a known standard.

In TLC, a Chromatographie plate is coated with silica gel to form the stationary phase while the mobile phase rises up the plate by capillary action. The unknown is then detected by applying a reagent, causing it to become visible as a spot with a characteristic color and Rr value.8 The main usefulness of TLC is as an initial qualitative screening method for urine samples. It is also used to separate various components of drug mixtures prior to a more definitive analysis by another technique. One major advantage of TLC is that the spot may be scraped from the plate, easily redissolved, and then analyzed using another method. Other advantages are its relative simplicity, rapidity (separation is completed within 30 to 90 minutes), and relative low cost. In addition, it can often readily identify metabolites in relation to parent compounds. The major disadvantage of this method is the lack of specificity, as TLC often will give a spot similar in appearance to more than one of the standards. In this case, other confirmatory methods such as GLC must be used. For example, methaqualone and meclaqualone (a chemical analog of methaqualone) appear as identical spots on TLC, but on GLC they can easily be separated.12

Gas liquid chromatography involves the volatilization of the substance in question which is carried by a carrier gas through a column packed with oil-coated inert material. The gas moves through the column at different rates depending on solubility and is then detected at the other end and recorded as a series of peaks on a strip chart. The length of time it takes each substance from injection to detection by peak formation is generally characteristic and allows qualitative determinations. Quantitative results are obtained from the area under each peak.12 Advantages of GLC include a sensitivity (ability to measure nanogram and picogram amounts), rapidity, and accuracy, as well as an ability to give quantitative and qualitative results in a .single step. The major disadvantages to GLC are that the sample must be able to volatilize and that different substances require different and often quite expensive detector types.

High pressure liquid chromatography is a relatively recent addition to Chromatographie methods. It too is based on a column of packed beads coated with a nonpolar substance, through which a mobile solvent continuously streams. The unknown is then added and detected at the other end with a spectrophotometer or flourometer. Results are recorded and quantified on a strip chart.9 The major advantages of this method are that it is able to clearly separate similar compounds and that it permits the assay of multiple substances at once. However, HPLC is being supplanted in many laboratories by newer immunoassay techniques as they become available.

Current interest is focused on immunological assay techniques which are becoming widely used because they are both highly sensitive and specific. Sensitivity results from the affinity for binding between the antigen and antibody. Specificity results from the unique fit between an antigen and its corresponding antibody. Measurement of the degree and the extent of antigen-antibody binding is done by labeling either the antigen or the antibody with tracers such as radionuclides, enzymes or fiourescent compounds, which are then measured.

In the radioimmunoassay (RIA) specific antibody is added to a mixture of the patient's serum containing the drug (unlabeled antigen) and a known quantity of radioactively labeled drug (labeled antigen). The radioactivity of the unbound antigen (not bound to antibody) is then measured against a standard and antigen concentration is determined.9 However, despite exquisite sensitivity, RIA techniques are currently being replaced by enzyme linked (ELISA) and fiourescent immunoassays which do not require the handling of radioactive materials.

The principle of both the ELISA and fiourescent antibody techniques is that the purified enzyme is linked to antigen (drug) or antibody, and that the combination of antigen and antibody results in a change in enzyme activity or flourescence. This change is proportional to the concentration of the drug in the biological fluid.9 Currently, commercial kits using the enzyme immunoassay techniques are available for many of the drugs of abuse. Results from this technique using drugs of abuse currently are only semiquantitative. They are becoming increasingly popular because they are sensitive, require only minutes, require little training, are easily automated, and require minimum sample preparation and size. The major disadvantages of these methods is their impracticality for large scale screening (since they generally only measure one drug at a time), their high cost (up to $15 per determination), inability to detect metabolites and their current limitation of providing only semiquantitative results for drugs of abuse. Table 6 lists the availability of one brand of enzyme immunoassay widely in use called EMIT (enzyme multiplied immunoassay technique by SYVA). Despite these disadvantages, the future technology in drug abuse analysis seems to be aimed at enzyme immunoassays.

Finally, the clinician must be aware of drug interference with certain clinical laboratory tests which, if unrecognized, can lead to confusion regarding the patient's status. Drugs can interfere with laboratory tests in two ways: 1) interference due to inherent pharmacological action of the drug (e.g., the well known effect of ethanol causing hypoglycemia); or 2) interference with laboratory analysis procedures (e.g., interference of phenothiazines with testing procedures for urobilinogen, falsely elevating the determination). Table 7 presents the more commonly involved drugs and their influences on serum or urine analysis.3,13

In summary, the clinical laboratory can be an invaluable aid in the diagnosis and treatment of substance abuse. However, to optimize the usefulness of the laboratory, the clinician must keep the following principles in mind:

1. Initial supportive management of the patient suspected of substance abuse relies on data obtained from the history and physical examination.

Table

TABLE 6DRUGS CURRENTLY ANALYZED BY EMIT(R)

TABLE 6

DRUGS CURRENTLY ANALYZED BY EMIT(R)

Table

TABLE 7DRUG EFFECTS ON LABORATORY TESTS

TABLE 7

DRUG EFFECTS ON LABORATORY TESTS

Table

TABLE 7DRUG EFFECTS ON LABORATORY TESTS

TABLE 7

DRUG EFFECTS ON LABORATORY TESTS

2. All specimens suspected of containing the unknown substance should be submitted (blood, urine, vomitus, gastric aspirate, and any substance found on or around the patient).

3. In most instances, qualitative urine screening is all that is necessary to guide therapy.

4. Quantitative results should be requested only when there are specific implications for patient management, such as antidotes or hemodialysis.

5. The presence of a drug in the body does not negate possible metabolic or traumatic causes of an altered state of consciousness. Trauma following drug ingestion is common.

6. Medicolegal specimens must be handled in a "chain of evidence" manner.

7. The clinician should be familiar with the laboratory's scope, sensitivity, and specificity in analysis.

8. The clinician should be aware of potential interferences with drug analysis to avoid additional confusion regarding the patient's status.

9. A negative drug screen does not mean that the drugs are absent, as a positive screen does not prove that the drug was responsible for the patient's illness.

Effective communication between the clinician and the lab is essential.7

ACKNOWLEDGMENT

The author gratefully acknowledges the assistance of William Temple, M. D., Department of Pathology, Martin Luther King Hospital, for his assistance in preparing this manuscript.

REFERENCES

1. Dreisbach R: Handbook of Poisoning, ed IO. Los Altos, California, Lange Medical Publications. 1980. pp 33-41.

2. Diagnosis and management of reactions to drug abuse. Medical Letter 22:18, 1980.

3. Meyers F, Jawelz E, Goldiein A; Review of Medico! Pharmacology, ed 1.' Los Allos, California. Lange Medical Publications, 1980, p 797.

4. Baseet R: Analytical Procedures for Therapeutic Drug Monitoring and Emergence Toxicology. New York, Biomédical Publications, 1980. pp 8690.

5. Kaiman S. Clark D: Drag Assay: The Strategy of Therapeutic Drug Monitoring. New York. Masson Publishing USA, 1979.

6. Cohen S: The Substance Abuse Problem. New York, H a won h Press, 1981.

7. Green; Use of the toxicology laboratory. Critical Care Quarterly 2:19-23, 1982.

8. Kaye S: Handbook of Emergency Toxicology, ed 4. Springfield, Illinois. Charles C Thomas, 1980.

9. Baer D, Dito W (eds): Interpretations in Therapeutic Drug Monitoring. Chicago, American Society of Clinical Pathologisis, 1981. pp 317-327.

10. Lemberger L, Ru A: Physiologic Disposition of Drugs of Abuse. New York. Spectrum Publications. 1976.

11. Goodman L. Oilman A (eds): The Pharmacological Basis of Therapeulics, ed 4. New York. Macmillan Publishing Co Inc. 1970, pp 20-31.

12. Tucker J: How analysis anonymous works. The Pharm Chem Newsletter 10:1-9, 1981.

13. Pribor H. Morrei G. Sehen G: Drug Monitoring and Pharmacokinetü Data. Park Forest South, Illinois, Pathotox Publishers, 1980.

14. McAdams M. Lindner R, et al: Phencyclidine Abuse Manual. Los Angeles. University of California Extension, 1980, p 227.

TABLE 1

DRUG SCREEN CHILDREN'S HOSPITAL OF LOS ANGELES

TABLE 2

SOME INDICATIONS FOR QUANTITATIVE ANALYSIS IN DRUG OVERDOSE

TABLE 3

ACIDIC, NEUTRAL AND BASIC DRUGS OF ABUSE

TABLE 4

PH OF URINE AND GASTRIC FLUID VS. PHENCYCLIDINE CONCENTRATION

TABLE 5

SOME DRUGS OF ABUSE WITH PHARMACOLOGICALLY ACTIVE METABOLITES

TABLE 6

DRUGS CURRENTLY ANALYZED BY EMIT(R)

TABLE 7

DRUG EFFECTS ON LABORATORY TESTS

TABLE 7

DRUG EFFECTS ON LABORATORY TESTS

10.3928/0090-4481-19820801-08

Sign up to receive

Journal E-contents