Medical Laboratory Science Review Harr 5.9 Chemistry - Toxicology and Terapeutic Drug Monitoring

In which of the following cases is qualitative analysis of the drug usually adequate?

A. To determine whether the dose of a drug with a low therapeutic index is likely to be toxic

B. To determine whether a patient is complying with the physician's instructions

C. To adjust dose if individual differences or disease alter expected response

D. To determine whether the patient has been taking amphetamines

D. To determine whether the patient has been taking amphetamines

D The purpose of therapeutic drug monitoring is to achieve a therapeutic blood drug level rapidly and minimize the risk of drug toxicity caused by overdose. Therapeutic drug monitoring is a quantitative procedure performed for drugs with a narrow therapeutic index (ratio of the concentration producing the desired effect to the concentration producing toxicity). Drug groups that require monitoring because of high risk of toxicity include aminoglycoside antibiotics, anticonvulsants, antiarrhythmics, antiasthmatics, immunosuppressive

agents used for transplant rejection, and psychoactive drugs. When testing for abuse substances, the goal is usually to determine whether the drug is present or absent. The most common approach is to compare the result to a cutoff determined by measuring a standard containing the lowest level of drug that is considered significant

The term pharmacokinetics refers to the:

A. Relationship between drug dose and the drug blood level

B. Concentration of drug at its sites of action

C. Relationship between blood concentration and therapeutic response

D. The relationship between blood and tissue drug levels

A. Relationship between drug dose and the drug blood level

A Pharmacokinetics is the mathematical expression of the relationship between drug dose and drug blood level. When the appropriate formula is applied to quantitative measures of drug dose, absorption, distribution, and elimination, the blood concentration can be accurately determined

The term pharmacodynamics is an expression of the relationship between:

A. Dose and physiological effect

B. Drug concentration at target sites and physiological effect

C. Time and serum drug concentration

D. Blood and tissue drug levels

B. Drug concentration at target sites and physiological effect

B Pharmacodynamics is the relationship between the drug concentration at the receptor site (tissue concentration) and the response of the tissue to that drug. For example, the relationship between lidocaine concentration in the heart muscle and the duration of the action potential of Purkinje fibers.

The study of pharmacogenomics involves which type of testing?

A. Family studies to determine the inheritance of drug resistance

B. Testing drugs with cell cultures to determine the minimum toxic dosage

C. Testing for single nucleotide polymorphisms known to affect drug metabolism

D. Comparison of dose-response curves between family members

C. Testing for single nucleotide polymorphisms known to affect drug metabolism

C Pharmacogenomics refers to the study of genes that affect the performance of a drug in an individual. One

method is to test for single nucleotide polymorphisms (SNPs) using DNA microarrays in genes such as those that code for the cytochrome P450 enzymes involved in the metabolism of many drugs. Genetic variations of one such enzyme may account for individual pharmacokinetic differences and can be used to predict the efficacy of the drug

Select the five pharmacological parameters that determine serum drug concentration.

A. Absorption, anabolism, perfusion, bioactivation, excretion

B. Liberation, equilibration, biotransformation, reabsorption, elimination

C. Liberation, absorption, distribution, metabolism, excretion

D. Ingestion, conjugation, integration, metabolism, elimination

C. Liberation, absorption, distribution, metabolism, excretion

C Liberation is the release of the drug and absorption is the transport of drug from the site of administration to the blood. The percent of drug absorption and the rate of absorption determine the bioavailable fraction, f. This is the fraction of the dose that reaches the blood. Distribution refers to the delivery of the drug to the tissues. It involves dilution and equilibration of the drug in various fluid compartments including the blood, and is influenced by binding to proteins and blood cells. Metabolism is the process of chemical modification of the drug by cells. This results in production of metabolites with altered activity and solubility. Excretion is the process by which the drug and its metabolites are removed from the body.

Which route of administration is associated with 100% bioavailability?

A. Sublingual

B. Intramuscular

C. Oral

D. Intravenous

D. Intravenous

D When a drug is administered intravenously, all the drug enters the bloodstream, and therefore, the bioavailable fraction is 1.0. All other routes of administration require absorption through cells, and this process reduces the bioavailable fraction. The bioavailable fraction for a drug given orally can be calculated by dividing the peak blood concentration after oral administration by the peak drug concentration after IV administration. A value of 0.7 or higher is desired for drugs given orally

The phrase "first-pass hepatic metabolism" means that:

A. One hundred percent of a drug is excreted by the liver

B. All drug is inactivated by hepatic enzymes after one pass through the liver

C. Some drug is metabolized from the portal circulation, reducing bioavailability

D. The drug must be metabolized in the liver to an active form

C. Some drug is metabolized from the portal circulation, reducing bioavailability

C Drugs given orally enter the blood via the portal circulation and are transported directly to the liver. Some drugs are excreted by the liver, and a fraction will be lost by hepatic excretion before the drug reaches the general circulation. An example is propranolol, a β-blocker that reduces heart rate and hypertension. The bioavailable fraction is 0.2-0.4 when given orally because much of the drug is removed by first-pass hepatic metabolism.

Which formula can be used to estimate dosage needed to give a desired steady-state blood level?

A. Dose per hour = clearance (milligrams per hour) × average concentration at steady state ÷ f

B. Dose per day = fraction absorbed - fraction excreted

C. Dose = fraction absorbed × (1/protein-bound fraction)

D. Dose per day = half-life × log Vd (volume distribution)

A. Dose per hour = clearance (milligrams per hour) × average concentration at steady state ÷ f

A After a patient receives a loading dose to rapidly bring the drug level up to the desired therapeutic range, a maintenance dose must be given at consistent intervals to maintain the blood drug level at the desired concentration. The dose per hour is determined by multiplying the clearance per hour by the desired average steady-state concentration,

then dividing by f (bioavailable fraction).

Which statement is true regarding the volume distribution (Vd) of a drug?

A. Vd is equal to the peak blood concentration divided by the dose given

B. Vd is the theoretical volume in liters into which the drug distributes

C. The higher the Vd, the lower the dose needed to reach the desired blood level of drug

D. The Vd is the principal determinant of the dosing interval

B. Vd is the theoretical volume in liters into which the drug distributes

B The Vd of a drug represents the dilution of the drug after it has been distributed in the body. The Vd is used to estimate the peak drug blood level expected after a loading dose is given. The peak blood level equals the dose multiplied by f ÷ Vd. The Vd can be calculated by dividing the dose, Xo, by the initial plasma drug concentration, Co, (Vd = Xo/Co) or by dividing the clearance rate by K, the elimination rate constant (K = 0.693 divided by drug half-life). The greater the Vd, the higher the dose that will be needed to achieve the desired blood concentration of drug. The Vd is the principal determinant of the dose, and the clearance rate is the principal determinant of the dosing interval.

For drugs with first-order elimination, which statement about drug clearance is true?

A. Clearance = elimination rate ÷ serum level

B. It is most often performed by the liver

C. It is directly related to half-life

D. Clearance rate is independent of dose

A. Clearance = elimination rate ÷ serum level

A First-order elimination represents a linear relationship between the amount of drug eliminated per hour and the blood level of drug. For drugs following linear kinetics, clearance equals the elimination rate divided by the drug concentration in blood. When clearance (in milligrams per hour) and f are known, the dose per hour needed to give a desired average drug level at steady state can be calculated. Clearance is inversely related to the drug's half-life and is accomplished mainly by the kidneys.

Which statement about steady-state drug levels is true?

A. The absorbed drug must be greater than the amount excreted

B. Steady state can be measured after two elimination half-lives

C. Constant intravenous infusion will give the same minima and maxima as an oral dose

D. Oral dosing intervals give peaks and troughs in the dose-response curve

D. Oral dosing intervals give peaks and troughs in the dose-response curve

D When drugs are infused intravenously, both the distribution and elimination rates are constant. This eliminates the peaks and troughs seen in the dose-response curve. Peak and trough levels are characteristics of intermittent dosing regimens. The steady state is reached when drug in the next dose is sufficient only to replace the drug eliminated since the last dose. Steady state can be measured after five drug half-lives because blood levels will have reached 97% of steady state

If too small a peak-trough difference is seen for a drug given orally, then:

A. The dose should be decreased

B. Time between doses should be decreased

C. Dose interval should be increased

D. Dose per day and time between doses should be decreased

C. Dose interval should be increased

C Increasing the dosing interval will reduce the trough concentration of the drug, and increasing the dose will increase the peak concentration of the drug, resulting in a greater peak trough difference. The peak-trough ratio is usually adjusted to 2 with the dose interval set to equal the drug half-life. Under these conditions, both peak and trough levels often fall within the therapeutic range.

If the peak level is appropriate but the trough level too low at steady state, then the dose interval should:

A. Be lengthened without changing the dose per day

B. Be lengthened and dose rate decreased

C. Not be changed, but dose per day increased

D. Be shortened, but dose per day not changed

D. Be shortened, but dose per day not changed

D Increasing the dose rate may result in peak drug levels in the toxic range. Decreasing the dosing interval will raise the trough level so that it is maintained in the therapeutic range. The trough level is affected by the drug clearance rate. If clearance increases, then trough level decreases

If the steady-state drug level is too high, the best course of action is to:

A. Decrease the dose

B. Decrease the dose interval

C. Decrease the dose and decrease the dose interval

D. Change the route of administration

A. Decrease the dose

A Decreasing both dose and dosing interval will have offsetting effects on peak and trough blood levels. The appropriate dose can be calculated if the clearance or Vd and f are known. For example, the initial dose is calculated by multiplying the desired peak blood drug concentration by the Vd.

When should blood samples for trough drug levels be collected?

A. 30 minutes after peak levels

B. 45 minutes before the next dose

C. 1-2 hours after the last dose

D. Immediately before the next dose is given

D. Immediately before the next dose is given

D The trough concentration of a drug is the lowest concentration obtained in the dosing interval. This occurs immediately before the absorption of the next dose given. Trough levels are usually collected just before the next dose is given

Blood sample collection time for peak drug levels:

A. Varies with the drug, depending on its rate of absorption

B. Is independent of drug formulation

C. Is independent of the route of administration

D. Is 30 minutes after a bolus intravenous injection is completed

A. Varies with the drug, depending on its rate of absorption

A The peak concentration of a drug is the highest concentration obtained in the dosing interval. For oral drugs, the time of peak concentration is dependent upon their rates of absorption and elimination and is determined by serial blood measurements. Peak levels for oral drugs are usually drawn 1-2 hours after administration of the dose. For drugs given intravenously, peak levels are

measured immediately after the infusion is completed.

Which could account for drug toxicity following a normally prescribed dose?

A. Decreased renal clearance caused by kidney disease

B. Discontinuance or administration of another drug

C. Altered serum protein binding caused by disease

D. All of these options

D. All of these options

Decreased renal clearance caused by kidney disease, Discontinuance or administration of another drug, and Altered serum protein binding caused by disease

D Therapeutic drug monitoring is necessary for drugs that have a narrow therapeutic index. Individual differences alter pharmacokinetics, causing lack of correlation between dose and drug blood level. These include age, diet, ingestion with or without food, genetic factors, exercise, smoking, pregnancy, metabolism of other drugs, protein binding, and disease states.

Select the elimination model that best describes most oral drugs.

A. One compartment, linear first-order elimination

B. Michaelis-Menton or concentration-dependent elimination

C. Two compartment with a biphasic elimination curve

D. Logarithmic elimination

A. One compartment, linear first-order elimination

A Most drugs given orally distribute uniformly through the tissues reaching rapid equilibrium, so both blood and tissues can be viewed as a single compartment. Elimination according to Michaelis-Menton kinetics is nonlinear because at high concentrations, the hepatic enzyme system becomes saturated, reducing the elimination efficiency.

Drugs rapidly infused intravenously usually follow which elimination model?

A. One compartment, first order

B. One compartment, logarithmic

C. Biphasic or two compartment with serum level rapidly falling in the first phase

D. Michaelis-Menton or concentration-dependent elimination

C. Biphasic or two compartment with serum level rapidly falling in the first phase

C Drugs rapidly infused intravenously follow a

two-compartment model of elimination. The central

compartment is the blood and tissues that are

well perfused. The second consists of tissues for

which distribution of drug is time dependent. In

determining the loading dose, the desired serum

concentration should be multiplied by the volume

of the central compartment to avoid toxic levels.

Which fact must be considered when evaluating a patient who displays signs of drug toxicity?

A. Drug metabolites (e.g., N-acetylprocainamide) may need to be measured as well as parent drug

B. If the concentration of total drug is within therapeutic limits, the concentration of free drug cannot be toxic

C. If the drug has a wide therapeutic index, then it will not be toxic

D. A drug level cannot be toxic if the trough is within the published therapeutic range

A. Drug metabolites (e.g., N-acetylprocainamide) may need to be measured as well as parent drug

A Altered drug pharmacokinetics may result in toxicity even when the dose of drug is within the accepted therapeutic range. Two common causes of this are the presence of unmeasured metabolites that arephysiologically active, and the presence of a higher than expected concentration of free drug. Because only free drug is physiologically active, decreased binding protein or factors that shift the equilibrium favoring more unbound drug can result in toxicity when the total drug concentration is within the therapeutic range. Some drugs with a wide therapeutic index are potentially toxic because they may be ingested in great excess with little or no initial toxicity. For example, acetaminophen overdose does not usually become apparent until 3-5 days after the overdose. This creates the potential for hepatic damage to occur from continued use, especially in patients who have decreased hepatic or renal function because the drug half-life is extended

When a therapeutic drug is suspected of causing toxicity, which specimen is the most appropriate for an initial investigation?

A. Trough blood sample

B. Peak blood sample

C. Urine at the time of symptoms

D. Gastric fluid at the time of symptoms

B. Peak blood sample

B When a drug is suspected of toxicity, the peak blood sample (sample after absorption and distribution are complete) should be obtained because it is most likely to exceed the therapeutic limit. If the peak level is above the upper therapeutic limit, then toxicity is confirmed, and the drug dose is lowered. If the peak drug concentration is within the therapeutic range, toxicity is less likely, but cannot be ruled out. A high concentration of free drug, the presence of active metabolites, and abnormal response to the drug are causes of drug toxicity that may occur when the blood drug level is within the published therapeutic range.

For a drug that follows first-order pharmacokinetics, adjustment of dosage to achieve the desired blood level can be made using which formula?

A. New dose = current dose /concentration at steady state × (desired concentration)

B. New dose = current dose/desired concentration × (concentration at steady state)

C. New dose = concentration at steady state/ desired concentration × (half-life)

D. New dose = concentration at steady state/ current dose × (desired concentration)

A. New dose = current dose /concentration at steady state × (desired concentration)

A Most drugs follow first-order pharmacokinetics, meaning the clearance of drug is linearly related to the drug dose. The dose of such drugs can be adjusted by multiplying the ratio of the current dose to blood concentration by the desired drug concentration, provided the blood concentration is measured at steady state.

For which drug group are both peak and trough measurements usually required?

A. Antiarrhythmics

B. Analgesics

C. Tricyclic antidepressants

D. Aminoglycoside antibiotics

D. Aminoglycoside antibiotics

D Aminoglycoside antibiotics cause damage to the eighth cranial nerve at toxic levels, resulting in hearing loss. When given at subtherapeutic doses, they fail to resolve infection. Most drugs falling in the other classes have a narrow peak-trough difference but are highly toxic when blood levels exceed the therapeutic range. Usually, these can be safely

monitored by measuring trough levels.

Which of the following statements about TLC for drug screening is true?

A. Acidic drugs are extracted in an alkaline nonpolar solvent

B. A drug is identified by comparing its Rf value and staining to standards

C. Testing must be performed using a urine sample

D. Opiates and other alkaloids are extracted at an acid pH

B. A drug is identified by comparing its Rf value and staining to standards

B TLC can be performed on urine, serum, or gastric fluid and qualitatively identifies most drugs. Each has a characteristic Rf, which is the ratio of the distance migrated by the drug to the solvent. The Rf of the sample must match the Rf of the drug standard. Extraction of drugs for TLC is highly pH dependent. The pH must be adjusted to reduce the solubility (ionization) of the drug in the aqueous phase. Usually, alkaline drugs (e.g., opiates) are extracted at pH 9.0 and acidic drugs (e.g., barbiturates) at pH 4.5

The EMIT for drugs of abuse uses an:

A. Antibody conjugated to a drug

B. Enzyme conjugated to an antibody

C. Enzyme conjugated to a drug

D. Antibody bound to a solid phase

C. Enzyme conjugated to a drug

C In EMIT, enzyme-labeled drug competes with drug in the sample for a limited amount of reagent antibodies. When antibody binds to the enzyme-drug conjugate, it blocks the catalytic site of the enzyme. Enzyme activity is directly proportional to sample drug concentration because the quantity of unbound drug-enzyme conjugate will be highest when drug is present in the sample.

Which statement about EMIT is true?

A. Enzyme activity is inversely proportional to drug level

B. Formation of NADH is monitored at 340 nm

C. ALP is the commonly used conjugate

D. Assay use is restricted to serum

B. Formation of NADH is monitored at 340 nm

B EMIT is a homogenous immunoassay, meaning that free antigen does not have to be separated from bound antigen. Most EMIT assays use a two-reagent system. Reagent A contains substrate (usually glucose-6-PO4), coenzyme (NAD+), and antibody to the drug. Reagent B contains enzyme-labeled drug (usually G-6-PD-drug) and buffer. The rate of NADH production is proportional to the drug concentration. EMIT assays are commonly used to test for drugs of abuse in urine. In such cases, the enzyme activity of the low calibrator (drug concentration equal to U.S. Substance Abuse and Mental Health Services Administration minimum for a positive test) is used as the cutoff.

Which statement regarding cloned enzyme donor immunoassay (CEDIA) is true?

A. The enzyme used is glucose-6-phosphate dehydrogenase

B. The enzyme donor and acceptor molecules are fragments of β-galactosidase

C. Drug concentration is inversely related to fluorescence

D. The antibody is covalently linked to the enzyme donor

B. The enzyme donor and acceptor molecules are fragments of β-galactosidase

B CEDIA is a homogenous enzyme immunoassay that is commonly used to measure drugs of abuse. Drug conjugated to a fragment of β-galactosidase that is catalytically inactive competes with drug in the sample for a limited number of antibodies to the drug. The fragment, called the enzyme donor (ED), and substrate (chlorophenol red-β-D-galactopyranose) are mixed with the sample. A second reagent containing monoclonal antibody and a second fragment of β-galactosidase called the enzyme acceptor (EA) is added. If the antibody is neutralized by drug from the sample, the ED and EA combine forming an active enzyme. The concentration of drug in the sample is directly proportional to the amount of chlorophenol red formed.

Which statement is true regarding particle-enhanced turbidimetric inhibition immunoassay methods for therapeutic drugs?

A. Drug concentration is proportional to light scatter

B. Magnetic separation is needed to remove unbound conjugate

C. When particle-bound drug binds to antibody, light scattering is increased

D. Two antibodies to the drug are needed

C. When particle-bound drug binds to antibody, light scattering is increased

C Particle-enhanced turbidimetric inhibition immunoassays are homogenous immunoassays

frequently used to measure proteins and therapeutic

drugs in serum or plasma. Polystyrene-modified latex

particles conjugated to the drug (particle-bound drug) compete with drug in the sample for a limited number of antibodies. If drug concentration is low, more of the antibody binds to the particle-bound drug, increasing the turbidity of the reaction. Therefore, light scattering is inversely proportional to the drug concentration.

Quantitation of a drug by gas chromatography-mass spectroscopy (GC-MS) is usually performed in which mode?

A. Total ion chromatography

B. Selective ion monitoring

C. Ion subtraction

D. Selective reaction monitoring

B. Selective ion monitoring

B Most GC-MS instruments use an electron beam to split the drug emerging from the column into its component ions. These are drawn into the mass analyzer, usually a vacuum chamber containing two pairs of charged rods (a positive pair and a negative pair) called a quadrupole analyzer. By changing the potential and radio frequency applied to the rods, the travel of ions will vary depending upon their mass to charge (m/z) ratio. As ions emerge from the mass filter, they are detected by an electron multiplier tube. CG-MS instruments can be operated in two modes, total ion chromatography and selective ion monitoring. A total ion chromatograph displays the retention time of all ions detected and their abundance. It is primarily used for identification of unknown compounds. SIM mode measures the abundance of one or more principal ions that provides sufficient specificity to eliminate potential interfering substances and greater quantitative sensitivity. For example, tetrahydrocannabinol (THC) can be identified by ions m/z 371.3, 372.3, and 473.3

SITUATION: A urine sample is received in the laboratory with the appropriate custody control form, and a request for drug of abuse screening. Which test result would be cause for rejecting the sample?

A. Temperature after collection 95°F

B. pH 5.0

C. Specific gravity 1.005

D. Creatinine 5 mg/dL

D. Creatinine 5 mg/dL

D Approximately 5 per 1,000 urine samples received for DAU testing have been adulterated by either dilution, substitution, or addition of substances such as glutaraldehyde that interfere with testing. The majority of these situations can be detected by determining temperature (90°F-100°F) pH (4.5-8.0), specific gravity (1.003-1.019), and creatinine (≥20 mg/dL). All of the values listed are within the limits of an acceptable sample with the exception of creatinine. Dry reagent strips are available that test for pH, specific gravity, creatinine, nitrite, peroxide, pyridinium, and glutaraldehyde.

Which substance has the longest detection time?

A. Amphetamines

B. Cocaine

C. Benzodiazepines

D. Marijuana

D. Marijuana

D Some drugs have a long half-life, and can be detected for longer periods after use, but the detection window also depends on other variables such as dosage, frequency of use, and method sensitivity. Marijuana is stored in fatty tissue and is metabolized slowly. In persons who use marijuana several times per week, cannabinoids can be detected several weeks after last use. For chronic daily users, this extends to months after discontinuation. Other drugs with detection windows of a week or more include long-acting barbiturates, LSD, anabolic steroids, and phencyclidine (PCP)

Which statement about the measurement of carboxyhemoglobin is true?

A. Treatment with alkaline dithionite is used to convert carboxyhemoglobin to oxyhemoglobin

B. Oxyhemoglobin has no absorbance at 540 nm, but carboxyhemoglobin does

C. Bichromatic analysis is required in order to eliminate interference by oxyhemoglobin

D. Carboxyhemoglobin can be measured by potentiometry

C. Bichromatic analysis is required in order to eliminate interference by oxyhemoglobin

C The absorbance spectras of oxy- and carboxyhemoglobin pigments overlap, and bichromatic or multichromatic analysis is required in order to accurately measure carboxyhemoglobin. In bichromatic analysis, oxyhemoglobin and methemoglobin are converted to deoxyhemoglobin by the addition of alkaline sodium dithionite. The ratio of absorbance at 541:555 nm is directly proportional to

carboxyhemoglobin concentration. Percent

carboxyhemoglobin is commonly determined

from simultaneous absorbance measurements

at 548, 568, and 578 nm, or other wavelength

combinations, a process called oximetry.

Which of the following statements about blood alcohol measurement is correct?

A. Symptoms of intoxication usually begin when the level exceeds 0.05% w/v

B. The skin puncture site should be disinfected with isopropanol

C. The reference method is based upon enzymatic oxidation of ethanol by alcohol dehydrogenase

D. Gas chromatography methods require extraction of ethanol from serum

A. Symptoms of intoxication usually begin when the level exceeds 0.05% w/v

A Alcohol dehydrogenase is not specific for ethanol, and in vitro interference can occur with some ADH methods when skin is disinfected with other alcohols. For this reason, and to avoid interference with the

interpretation of chromatograms for volatiles, blood samples are collected after disinfecting the skin site with benzalkonium chloride or other nonalcohol antiseptic. GLC is the legally accepted method of ethanol analysis. The low boiling point of ethanol permits direct analysis on blood or plasma diluted with water containing 1-propanol or other suitable internal standard.

Which specimen is the sample of choice for lead screening?

A. Whole blood

B. Hair

C. Serum

D. Urine

A. Whole blood

A Lead accumulates in RBCs, bones, and neural tissues, and whole blood, hair, and urine are suitable for demonstrating lead toxicity. Greatest sensitivity is obtained by using whole blood, which can detect exposure over time. Because lead is rapidly eliminated from plasma, serum or plasma should not be used to test for lead exposure. Lead binds to sulfhydryl groups of proteins such as delta-aminolevulinic acid (∆-ALA) dehydratase and ferrochelatase and interferes with heme synthesis. This results in increased free erythrocyte protoporphyrin, erythrocyte zinc protoporphyrin, urinary coproporphyrin III, and δ aminolevulinic acid, which are also useful markers for lead poisoning. When screening for lead poisoning in children, the method of choice is graphite furnace atomic

absorption spectrophotometry or inductively coupled plasma mass spectroscopy because they offer the best analytical sensitivity. The CDC cutoff for normal lead in children is less than 5.0 μg/dL

Which of the following enzymes can be used to measure plasma or serum salicylate?

A. Peroxidase

B. Salicylate esterase

C. Salicylate hydroxylase

D. p-Aminosalicylate oxidase

C. Salicylate hydroxylase

C The enzymatic assay of salicylate uses salicylate hydroxylase, which reduces salicylate with NADH and forms catechol and NAD+. Salicylate can also be measured by HPLC and various immunoassays including EMIT. Salicylate toxicity causes an initial respiratory alkalosis because the drug stimulates the respiratory center. However, this is followed by metabolic acidosis as the drug is metabolized. Therefore, it is imperative to identify salicylate as the cause of toxicity before treatment of an acid-base imbalance caused by aspirin overdose.

Which of the following tests is least essential to the operation of an emergency department at a general hospital?

A. Carboxyhemoglobin

B. Osmolality

C. Salicylate

D. Lead

D. Lead

D The vast majority of acute toxicology situations seen in the emergency department (ED) involve poisoning with alcohol, acetaminophen, salicylate, abuse substances, or carbon monoxide. Emergency departments should offer a minimum of these tests. In the absence of specific tests for abuse substances or a comprehensive drug screen, the serum osmolality measured by freezing point depression is a sensitive surrogate test for drug and alcohol overdose. In the ED environment, a difference between measured and calculated osmolality greater than 10 mOsm/Kg almost always indicates drug or alcohol poisoning. Toxicity from lead poisoning and most other trace metals is usually a chronic condition that does not often require immediate access to laboratory testing.

Which of the following trace elements is considered an essential micronutrient?

A. Thallium

B. Aluminum

C. Mercury

D. Selenium

D. Selenium

D Trace elements can be divided into two categories, those that have no known biological purpose and those that do. The former include thallium, mercury, lead, cadmium, and aluminum. All others can be considered essential, including arsenic that has been shown necessary for normal methionine metabolism. Most trace elements are of medical importance because excessive levels lead to toxicity. However, a deficiency of trace elements such as selenium, zinc, and copper are commonly caused by total parenteral nutrition and are medically important.

When measuring trace metals in blood other than lead, what type of tube should be used?

A. Navy blue top

B. Green top

C. Purple top

D. Red top

A. Navy blue top

A In order to avoid trace contamination by metals present in the stopper lubricants, a tube with a navy blue top is used for measuring trace metals. These tubes are validated for most but not all trace metals. Such tubes are available with or without EDTA for serum or whole-blood analysis, respectively. Tubes with tan stoppers containing EDTA are used for lead assay because they are certified to contain no more than 0.25 μg/dL lead. In addition, type 1 purity water (10 Mohm, 10 or less CFU/mL) and analytical reagent grade chemicals are always used to prepare reagents such as matrix modifiers. Although most trace metals are measured in whole blood or serum, arsenic is usually measured in urine because it is metabolized and excreted within hours of ingestion.

Which whole-blood level is suggestive of excessive exposure to lead in children but not adults?

A. 4 µg/dL

B. 14 µg/dL

C. 28 µg/dL

D. 32 µg/dL

B. 14 µg/dL

B Because lead exposure in children leads to learning impairment, the cutoff for exposure recommended by the Centers for Disease Control is 5 μg/dL in venous whole blood. Values of 5 μg/dL or more should be monitored closely with follow-up testing, and if they increase, steps should be taken to remove lead contamination from the home and environment. For adults the recommended cutoff is 25 μg/dL. Because lead readily enters the red blood cells, and passes from plasma to urine quickly, whole blood is a more sensitive measure of exposure than plasma. Because lead from the fingers may contaminate the specimen, a venous sample is preferred over a capillary sample collected by finger stick.

What are the likely laboratory findings in a person suspected of having Wilson's disease?

A. Blood copper and ceruloplasmin low, urinary copper excretion high

B. Blood and urine copper concentration high, ceruloplasmin low

C. Blood and urine copper concentration high, ceruloplasmin high

D. Blood and urine copper concentration low, ceruloplasmin low

A. Blood copper and ceruloplasmin low, urinary copper excretion high

A Wilson's disease is an autosomal recessive disease in which copper transport is abnormal. The gene causing the disease codes for an ATPase (called Wilson's protein or ATP7B) that is needed to excrete copper into bile and incorporate copper into ceruloplasmin. There are over 200 reported mutations of this gene. The absence of Wilson's protein results in failure to load ceruloplasmin with copper, dramatically reducing its half-life in blood. Therefore, blood levels of ceruloplasmin are low, and blood levels of copper are usually low because there is little ceruloplasmin to bind it. Copper deposits in tissues, particularly the liver and brain, causing necrosis, and excess is excreted in the urine.