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119 Cards in this Set
- Front
- Back
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What is a toxicant?
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Toxicant (poison) is any substance that causes a harmful effect (sickness or death) upon sufficient exposure.
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What percent of toxin exposure can be attibuted to suicide attempts?
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50% suicide attempts
30% accidental overdose 20% homicide or occupational exposure |
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What are the routes of exposure to toxins?
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Ingestion, inhalation and transdermal absorption
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What is toxicity?
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Toxicity is a relative term used to compare harmful effects of one substance with another.
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What are the four factors that influence toxicity?
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Exposure variables of toxicant – dose dependency and route, rate and duration of exposure
Nature of toxicant--solubility and physical state of toxicant Biological variables of individual ingesting toxicant –age, genetic makeup, ability to metabolize certain drugs Toxicokinetics-- drug transformation by metabolic processes before exerting an effect on the ingestor |
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What are some "benefits" to toxicology?
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Screen for presence of substance
Qualitative is sufficient Non invasive (urine) Fast TAT Metabolites can be detected Cheap Minimum analytical sensitivity = symptomatic (minimum diagnostic sensitivity) |
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What are some "benefits" to TDM?
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Assume substance is present
Need quantitative result Invasive (serum) Slow TAT Metabolites may interfere Expensive Dynamic range should include therapeutic range |
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What is minimum analytical sensitivity?
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Minimum amount that gives a positive result
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What is minimum diagnostic sensitivity?
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minimum amount that shows symptoms
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Screening for drugs of abuse (toxicology)
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Screening is the first step of DOA testing
Rapid, simple, qualitative testing Very sensitive, lacks specificity Negative result can rule out toxicant Positive result should be considered presumptive until confirmed by a more specific method. Most common method is immunoassay |
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What is the screening test for DOA?
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immunoassay
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What is the confirmatory test for DOA?
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Gas Chromatography
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Confirmatory tests
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Positive drug screens are almost always followed up with a confirmatory test
Confirmatory test detects same drug but relies on a different drug property Eg: if screening test is done by immunoassay, confirmatory must use gas chromatography Confirmatory test must be very specific and at least as sensitive as the screening test Quantitative, expensive, takes longer to perform, often done in batches in toxicology labs. |
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What are some examples of toxic substances?
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Analgesics – Aspirin and Tylenol
Barbiturates -- sedatives Drugs of abuse –Amp, Cocaine, THC etc. Pesticides Alcohols Carbon Monoxide Metals – lead, mercury etc. |
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(TPQ) What is the most commonly abused substance in the U.S.?
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alcohol
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What is another name for salicylate?
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Aspirin (acetylsalicylic acid = ASA)
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What is the active ingredient in aspirin?
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salicylic acid
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What is aspirin used for?
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Aspirin (acetylsalicylic acid = ASA) is a commonly used analgesic, antipyretic and anti-inflammatory drug.Adverse effects: interference with platelet aggregation and gastrointestinal function.
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What happens in aspirin overdose?
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Salicylate overdose stimulates respiratory center initial respiratory alkalosis which causes conversion of pyruvate to lactate and breakdown of fatty acids to produce ketoacids which causes metabolic acidosis
Net: mixed acid base disorder |
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What is the theruaputic range for salicylate?
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15-30 mg/dL
500 mg/dL lethal |
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How do you treat salicylate overdose?
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Overdose treatment: neutralization and elimination of excessive acid and maintenance of electrolyte balance.
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How do you measure salicylate levels in blood?
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Trinder rxn –purple color with FeCl3
Enzymatic—NADH linked rxn measured at A340 |
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What is the common name for Acetaminophen?
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Tylenol
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What is Acetaminophen?
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Analgesic
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What does an overdose cause?
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Severe hepatotoxicity
Metabolized, conjugated and eliminated by liver Hepatic damage is indicated 3-5 days after ingestion >150 ug/mL @ 4hrs is toxic |
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What condition is caused by intoxication of Acetaminophen?
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Intoxication results in hepatocytstic necrosis due to inability of liver to adequately conjugate the metabolite of acetominophen, acetamidoquinone (a reactive intermediate) by glutathione.
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In acetaminophen overdose, glutathione can be depleted (GSH pathway is exhausted) but reactive intermediates continue to be produced. (T/F)
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True.
Result: excess N-acetylbenzoquinoneimine can cause hepatic necrosis |
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What is an antidote for acetaminophen overdose?
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Antidote: N-acetylcysteine (NAC)
Cause more glutathione in the reduced state |
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What is carbon monoxide?
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Colorless, odorless and tasteless gas
has ~ 200 – 250 times more affinity for hemoglobin than O2 |
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What happens during carbon monoxide poisoning?
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During CO poisoning, hemoglobin cannot adequately exchange CO2 for O2 because of the increased amount of CO which causes an increase in COHb and decrease oxyhemoglobin
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% COHb and symptoms
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Normal value in the city, non smokers ~ 0 - 5%
Smokers up to 15% -- headache and SOB (shortness of breath) if not accustomed 30% -- severe headaches, SOB, fatigue, impairment of judgment 40-50% -- confusion, loss of consciousness 60 – 70% -- unconsciousness, respiratory failure, death with continuous exposure 70 -80% -- lethal, immediately fatal |
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What are the different methods for measuring COHb?
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Spot CO check
Spectrophotometry Differential spectrophotometry |
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How does the Spot CO Check work?
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5mL of 40 % NaOH + 5 mL of 1:20 diluted blood
Persistence of pink solution = ≥ 20% COHb *Cyanide poisoning gives same appearance |
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How does spectrophotometry for COHb work?
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measure at 4 – 7 λ’s. Old method
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How does differential spectrophotometry for COHb work?
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A hemolysate of WB is treated with a reducing agent (sodium hydrosulfite) to reduce oxyhemoglobin and methemoglobin but does not react with COHb only COHb and reduced Hb in soln.
Absorption spectrum at 555nm (both) and 541 nm (more Abs by COHb) |
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(TPQ) ______________ is a consequence of tylenol overdose.
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Hepatocystic necrosis
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What is the most common toxic exposure?
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Alcohol
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How does the body rid itself of alcohol?
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Liver
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Are alcohols polar or non polar?
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Relatively non polar
Absorbed though stomach |
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How long does it take for alcohol to peak?
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About 1 hour after consumption
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What liver enzymes detoxify alcohol?
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Alcohol dehydrogenase;
Ethanol+NAD -> acetaldehyde+NADH Acid aldehydrogenase Acetaldehyde -> acetate |
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What are some effects of a ethanol blood level of 50 - 100 mg/dL?
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Reduced inhibitions, disorientation, confusion
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What are some effects of a ethanol blood level of 100 - 200 mg/dL?
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progressive impairment of motor abilities
Ethanol blood level of 0.1 g/dL defined as toxic |
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What are some effects of a ethanol blood level of 200 - 400 mg/dL?
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approaching unconsciousness
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What is the legal limit of ethanol blood level in most states?
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80 - 100 mg/dL
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What does long term consumption of alcohol cause to the liver?
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alcoholic (toxic) hepatitis leads to cirrhosis
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What lab result are indicative of alcoholic cirrhosis?
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Hepatitis: Normally Alt > AST
Alcohol hep: increase enzymes and bili AST:ALT = >2.0 (2X AST) b/c AST mostly mitochondrial Inc GGT |
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What happens during methanol poisoning?
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methanol -> formaldehyde -> formic acid -> severe metabolic acidosis
pancreatic necrosis and visual impairment More toxic than ethanol IV ethanol administered to use up liver enzymes b/c ethanol metabolites are less harmful |
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What is isopropanol metabolized to in the liver?
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isopropanol (rubbing alcohol) -> acetone (not usually in toxic amounts)
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What is ethylene glycol metabolized to in the liver?
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ethylene glycol or 1,2 ethanediol (antifreeze) -> formic acid, glycolic acid and oxalic acid -> renal failure
SEE several Calcium oxalate crystals in every field |
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What is the enzymatic alcohol dehydrogenase (ADH) method
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Ethanol + NAD+ + ADH -> acetaldehyde + NADH
Measure absorbance of NADH produced at 340 nm. Methanol or isopropanol produces a negative or low result. |
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How is osmolality measured?
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Freezing point osmometer
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How do you calculate osmolal gap?
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osmo gap = measured osmo - calculated osmo
(normal value = up to ~10 mOsm/Kg) |
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How much does serum osmolality increase for each 60 mg/dL of ethanol increase?
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10 mOsm/Kg
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How do we calculate osmolality to detect alcohols other than ethanol?
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calc osmo = 1.86 (Na+) + (glucose/18) + (BUN/2.8) + (ETOH/5)
In this case, osmolal gap will be increase for only non ethanol alcohols or other compounds. |
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What is the gold standard for detecting alcohols in serum?
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Gas Liquid Chromatography
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What are some sources of error in GLC?
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Change in flow rate of mobile (gas) phase
Change in oven temp causes change in solubility of stationary (liquid) phase Change in null voltage of FID Change in precise volume of sample injected |
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What is the internal standard GLC?
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n-Propanol
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How is the IS used in GLC?
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Internal standard (lS) is used to correct problems
IS is pure, in liquid form, analyzed by same characteristics as analyte of interest, never found in patient’s sample Every sample (standard, qc and patient) is mixed with same amount of IS. Ratio of IS in calibration run and IS in patient run is used |
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Which alcohol will contribute the most to osmolality?
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Ethanol Toxic: 300 Osmolality added: 0.22
Methanol Toxic: 50 Osmolality added 0.31 |
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How do you calculate osmolal gap?
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osmo gap = measured osmo - calculated osmo
(normal value = up to ~10 mOsm/Kg) |
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How much does each 60 mg/dL of ethanol increase serum osmolality?
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10 mOsm/Kg
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What is the formula used to calculate osmolal gap taking ethanol into account?
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calc osmo = 1.86 (Na+) + (glucose/18) + (BUN/2.8) + (ETOH/5)
In this case, osmolal gap will be increase for only non ethanol alcohols or other compounds. |
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If a patient comes to the ER and has normal-decreased blood pH and no acetone (ketone) is present, what should you expect?
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Ethanol
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If a patient comes to the ER and has normal-decreased blood pH and acetone (ketone) is present, what should you expect?
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Isopropanol
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If a patient comes to the ER and has severly decreased blood pH and no acetone (ketone) is present, what should you expect?
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Methanol
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What is the gold standard for measurement of alcohols?
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Gas liquid chromatography
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What is retention time?
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The time from injection of sample to measurement.
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The IS is only mixed with the patient's sample. (T/F)
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False. Mix the IS with everything. Peaks should match.
QC. Std. Control. |
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In gas liquid chromatography, what does retention time determine?
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Identification
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In gas liquid chromatography, What does peak height determine?
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Quantification
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(TPQ) The gold standard for confirmation drug screening is what?
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GCMS
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Ethanol ingestion inhibits glucose production. (T/F)
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True
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What are the effects of chronic alcohol poisoning?
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toxicity of acetaldehyde, or failure of homeostatic or synthetic mechanisms in liver
One early sign is hepatomegaly, caused by triglyceride accumulation due to metabolism of ethanol in preference to fatty acids |
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What are some effects of chronic high alcohol poisoning?
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- impaired glucose tolerance & diabetes mellitus
- hypertriglyceridemia - liver cirrhosis & decreased serum albumin - portal hypertension - coagulation defects - cardiomyopathy - peripheral neuropathy |
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What tests can be used to diagnose chronic alcohol poisoning?
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Increased plasma uric acid, GT (not specific), triglycerides
* Increased WBC count in gout only |
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What nutrition markers will be decreased in if an alcoholic practices poor nutrition?
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Decreased plasma folate, calcium, magnesium, phosphate
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How many grams of ethanol or in 1 unit?
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1 unit = 10mL EtOH = 8g EtOH
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What are the important stimulants?
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Amphetamine, Cocaine, Methamphetamine, Nicotine, Theophyliline
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What are the important hallucinogens?
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Phencyclidine, THC
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What are the important opiates?
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Codeine, Heroin, Methadone, Morphine, Oxycodone
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What are the important barbiturates (sleeping pills)?
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"all the barbital's"
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What are the important benzodiazepines (tranquilizer)?
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Diazepam
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What are barbiturates?
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Barbiturates are sedatives that exert a tranquilizing effect through their depressant effect on the CNS. Controls epilepsy.
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What is the treatment for barbiturates?
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None except establishment of an open airway , aiding is respiration and maintaining cardiac output.
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What are narcotics?
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Narcotics or opioids are compounds that produce sleep and pain relief. Overdose amounts can depress the CNS, decreased respiration and coma.
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What are some examples of narcotics?
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heroin, morphine, codeine and methadone. Heroin is metabolized by the liver to form morphine and is excreted by the kidney as morphine glucuronide.
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What is the treatment for Naloxone?
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Treatment is Naloxone, a narcotic antagonist
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What is the largest group of pesticide?
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Organophosphates
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How do pesticides work?
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Inhibit acetylcholinesterase (RBC membrane) which results in specific effect on heart and respiratory centers, cramps and CNS effects
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What do we measure to determine the affect of the pesticides?
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Measure plasma psuedocholinesterase (an isoenzyme of acetylcholinesterase). Pesticides have same effect on psuedocholinesterase as acetylcholinesterase (inhibit) but we have better immunoassays for psuedocholinesterase.
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How do amphetamines affect the body?
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CNS stimulant that blocks dopamine receptors in the brain
Produces an initial sense of increased mental and physical capacity and a perception of well being followed by restlessness, irrritability and possibly psychosis. |
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what are amphetamines used for?
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treat narcolepsy and ADD
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What is the metabolite of amphetamines?
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Metabolism occurs in liver and produces benzoic acid.
Overdose results in hypertension, cardiac arrhythmias and possibly death |
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What is cocaine?
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Local anesthetic and CNS stimulant (high dose) that elicits a sense of euphoria and excitement
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Does cocaine have a short or long half life?
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Short (0.5 - 1.0)
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What is the metabolite of cocaine?
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Metabolized by cholinesterase to benzoylecognine (inactive) which is excreted by the kidney. Metabolite is measured in urine (confirmed by GCMS)
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What are the symptoms of cocaine toxicity?
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Toxicity leads to hypertension, arrhythmia, seizure and myocardial infarction.
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Drug screens measure only the metabolite? (T/F)
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False. Parent drug and metabolite are measured?
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What are cannabinoids?
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Group of psychoactive compounds found in Marijuana (processed product is Hashish)
tetrahydrocannabinol (THC) is most potent and abundant |
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What are the side effects of cannabinoids?
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Produces psychological effects (euphoria, sense of well being, short term memory impairment) and are stored in fat cells (lipophilic)
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THC is excreted in urine over an extended period of time. (T/F)
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True. Major urinary metabolite is THC-COOH
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What is phencyclidine (PCP)?
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Anesthetic that is illegally used as a hallucinogen
Adverse effects include violence in subject, seizures, respiratory depression and death. Identification of PCP occurs by detection of parent drug in urine |
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(TPQ) Which test will assess opiate abuse?
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Methadone
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Where is arsenic found?
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Found in pesticides, weed killers and some paints
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Cocaine is metabolized to what?
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Benzolyecgonide
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Few proteins bind to arsenic. (T/F)
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Many proteins bind to Arsenic (sulfhydryl groups in particular), the free, ionized form is rapidly cleared through renal system
Bound stays in system |
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What are some toxic symptoms arsenic poisoning?
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Toxic symptoms: gastroenteritis, shredding of the stomach lining, lines in the fingernails due to keratin binding and death
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What is the specimen of choice for arsenic poisoning?
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Urine is the specimen of choice for analysis. Hair and fingernails can be tested for assessment of long term exposure
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Where is mercury found?
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Found in antibacterial agents, photographic reagents, pesticides and batteries. Poisoning is typically the result of inhalation or ingestion (contaminated food is a major source in the general public)
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What are the toxic effects of mercury poisoning?
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Toxic effects: GI irritation, severe kidney damage and neurological symptoms.
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What is the treatment for mercury poisoning?
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Treatment: Chelators such as EDTA and Penicillamine bind mercury
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How is lead introduced into the body?
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Poisoning is typically due to lead paint ingestion or continuous exposure to lead in the soil.
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How does lead affect the body?
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Lead is a potent inhibitor of many enzymes
Effects vitamin D metabolism and results in changes in bone and calcium metabolism which causes a decreased conc. of 25-hydroxy and 1,25 dihidroxy Vitamin D Decreases heme synthesis (anemia) by inhibiting enzyme PBG synthase and ferrochelatase which leads to increased conc. of intermediates ALA (aminolevulinic acid) and Protoporphyrin. increased protoporphyrin leads to increased zinc protoporphyrin in circulating erythrocytes (fluorescent compound) |
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What are some toxic effects of lead poisoning
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Toxic effects: GI irritation, weight loss, kidney damage and in children, altered cognition and encephalopathy. Death can occur due to peripheral vascular collapse or brain involvement.
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What kind of lab result would you see in a patient with lead poisoning?
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Serum and urine lead levels
Increased urinary ALA is a highly sensitive and specific indicator of lead poisoning –correlates well with blood levels. RBC protoporphyrins Basophillic stippling in erythrocytes |
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What is the treatment for lead poisoning?
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Treatment: lead chelators such as EDTA and penicillamine bind lead and allow it to be excreted by the kidney
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Why is metal analysis performed in specialty lab?
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Requires specially clean equipment and room
Special vacutainer tubes for blood and specially cleaned jugs for 24 hour urines. Lead analysis is commonly performed in clinical laboratories because of high exposure |
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What is the reference method for metal analysis?
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Atomic absorption spectrometry
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