Toxicology: Analytical/forensic And Clinical Toxicology

Front 1

• Define analytic toxicology

Back 1

o Applies tools of analytic chem in order to estimate exposure to chemicals in living organisms. It can be qualitative and quantitative.

Front 2

• Define forensic toxicology

Back 2

o Utilizes toxicology for purposes of the law (usually done on the deceased).
o Usually the identification of a chemical that may have been served in inflicting death or injury.

Front 3

• What was the Elements de Toxicologie written by Chapuis in 1873?

Back 3

o It was a classification system for toxic agents. It included gases, volatile substances, metals, miscellaneous, etc.
o It described methods for separating toxic agent from matrix in which it is embedded to allow for analysis (ex. tissue or blood sample)

Front 4

• What doe postmortem investigations include?

Back 4

o Qualitative and quantitative analysis of drugs/poisons in biological specimens collected at autopsy and their interpretations.

Front 5

• Who is the cause of death determined by?

Back 5

o Medical examiner and coroner. But pathologist and toxicologist also helps to determine the correct conclusion.

Front 6

• In a tox investigation of lethal poisoning, what are the three steps that are needed? What kind of questions need to be answered?

Back 6

o Obtaining a case history and suitable specimens, conducting suitable toxicologic analyses on available specimens, and interpreting the analytical findings.
o What was the route of administration? What was the approx. dose? What was the concentration? Was it enough to cause death or alter actions leading to death?

Front 7

• What two reasons have forensic toxicologists become more involved in analysis of specimens from living victims of poisonings?

Back 7

o Administration of drugs to incapacitate victims of kidnapping, robber, sexual assault
o Poisoning as a form of child abuse

Front 8

• What is a forensic urine drug testing (FUDT) test for? How do people try to adultery these tests? What do these tests look at?

Back 8

o It is performed with immunoassays on high speed and are often used in work places and criminal cases.
o People try to ingest diuretics or alter the specimen with bleach, vinegar, etc. to avoid being caught for certain substances.
o However, the tests look at pH, creatinine, specific gravity, and specific/known chemical adulterations. These show whether the urine sample was adulterated or not.

Front 9

• What does a DUI test? What is the threshold concentration for diminished driving? What level is characterized as a DUI?

Back 9

o Driving under the influence of ethanol.
o The threshold BAC is 0.04 g/dL for diminished driving which is about 2 drinks/hour.
o 0.08-0.10 is considered DUI

Front 10

• How are forensic toxicologists used in the courtroom?

Back 10

o To provide an objective testimony describing the analytical methods and findings
o Providing an opinion about the interpretation of the results

Front 11

• What are common encountered agents in emergency toxicology?

Back 11

o Ethanol, methanol, isopropanol, ethylene glycol, drugs of abuse, etc.

Front 12

• How is analytic tox used in therapeutic monitoring?

Back 12

o Plasma monitoring is employed to verify that a patient is receiving the proper dose of the drug and that a steady state concentration is established.
o Monitoring of plasma or serum concentration at regular intervals will detect if certain variables have changed and needs correction..

Front 13

• What is the purpose of biological monitoring?

Back 13

o It is used commonly in factories to monitor workers directly which will show a better indication of what the exposure was and to separate the mixture of compounds or metabolites to see the toxic agent.

Front 14

• What is analytical toxicology used for?

Back 14

o Forensic tox with living and deceased individuals to determine presence of a chemical compound
o Routine drug screening of individuals
o Used to determine blood alcohol levels
o Used in clinical tox.
o Therapeutic monitoring.

Front 15

• What are the three cardinal rules of treating poisoning cases?

Back 15

o Remove any unabsorbed material
o Limit the absorption of additional poison
o Hasten the elimination of the poison. They have to monitor the amount remaining in circulation as well as monitor how much is excreted

Front 16

• What is the clinical strategy for treatment of the poisoned patient (expanding on the 3 cardinals)?

Back 16

o Stabilization of patient
o Clinical eval (history, physical examiniation, labs, etc.)
o Prevention of further toxin absorption
o Enhancement of toxin elimination
o Administration of antidote
o Supportive care and clinical follow-up

Front 17

• What is the first priority in dealing with poisoned patients?

Back 17

o Clinical stabilization and assessment of vital signs.

Front 18

• What is the purpose of getting a clinical history of the poisoned patient?

Back 18

o To determine the substance the individual was exposed to as well as the duration and general concentration.
o This can be a problem in cases of suicide because patients can lie.

Front 19

• How can exposures of the poisoned patients be estimated?

Back 19

o Estimates are always maximized (because it is better to be safe when you’re unsure). Literature is consulted to predict expected symptoms and their timelines.

Front 20

• What is the purpose of the physical examination of a poisoned patient?

Back 20

o It is a required step that allows for a clinical toxicologist to categorize the patient into a toxic syndrome.

Front 21

• Define toxic syndrome

Back 21

o It is a collection of clinical signs that, taken together, probably are associated with exposure to certain classes of toxic agents.

Front 22

• What symptoms would be exhibited if a patient was poisoned from sympathomimetics (cocaine)?

Back 22

o Increased bp, increased pulse, slightly increased temperature, mydriasis in pupils, no change in lungs, no change in abdomen, and neurologically hyperalert with increased reflexes.

Front 23

• What symptoms would be exhibited if a patient was poisoned from an anti-cholinergic toxin?

Back 23

o Slightly increased or no change in bp, increased pulse, increased temperature, mydriasis in pupils, no change in lungs, decreased bowel sounds in abdomen, and neurologically altered mental status.

Front 24

• What symptoms would be exhibited if a patient was poisoned from a cholinergic toxin?

Back 24

o Slightly decreased or no change in bp, decreased pulse, no change in temperature, miosis in pupils, increased bronchial sounds in lungs, increased bowel sounds in abdomen, and neurologically altered mental status.

Front 25

• What symptoms would be exhibited if a patient was poisoned from an opoid?

Back 25

o Decreased blood pressure, decreased pulse, decreased temperature, miosis in pupils, no change or rales in lungs, decreased bowel sounds in abdomen, and neurologically decreased level of consciousness.

Front 26

• In laboratory evaluations, what do action levels or toxic thresholds do?

Back 26

o They show toxicologists a certain level where under it, some symptoms might not show themselves while above it, there will be a presentation of these certain symptoms based on the toxin.

Front 27

• What is an anion gap? What is it used for? How is it taken?

Back 27

o It is a test that is done that helps to determine which poison may be in question. This is done through taking a blood sample.
o It tells you what the ratio of particles in blood should be and whether or not it is altered.
o It looks at h the difference between the serum Na concentration and the sum of the serum Cl and bicarbonate concentration.

Front 28

• What is a normal value for an anion gap? What does an elevated anion gap suggest?

Back 28

o A normal value would be less than 12.
o Elevated anion gap suggests systemic toxicity from AT MUD PILES

Front 29

• What does the acronym AT MUD PILES stand for?

Back 29

o Alcohol (ethanol), toluene, methanol, uremia, diabetic ketoacidosis, paraldehyde, iron/isoniazid, lactic acid, ethylene glycol, salicylate

Front 30

• What is an osmol gap? What is it used for? how is it taken?

Back 30

o It is a test that is done that helps to determine which poison may be in question. This is done through taking a blood sample.
o It measures the difference between serum osmolarity and serum osmolarity calculated from clinical chem measurements of Na ions, glucose, and BUN (blood urea nitrogen) concentrations.

Front 31

• What is a normal value for osmol gap? What does an elevated osmol gap tell you?

Back 31

o Normal is less than 10 mOsm.
o An elevated level suggests the presence of an osmotically active substance not accounted for by the tests.
o It could be from ethanol, ethylene glycol, isopropanol, or methanol

Front 32

• What do radiographic examinations like X-rays do for determining poisons?

Back 32

o It can help to identify meds that contain ferrous or potassium salts or stuff that have enteric coatings.
o It can detect paint ingestions, detect foreign bodies in GI tract
o CT scans can even detect CO exposure

Front 33

• How can toxicologists intervene to prevent further poison absorption?

Back 33

o For inhaled substances, they can remove patient from the toxic environment
o For topical exposures, they can remove the toxin from the skin
o For oral poisons, they can induce vomiting (used to use syrup of ipecac), gastric lavage, or giving them an oral administration of activated charcoal.

Front 34

• If the toxin has already been absorbed by the patient, how can toxicologists use alkalinizaiton of urine to increase survival? How is it done?

Back 34

o Preventing further absorption won’t help, so you’d have to enhance elimination.
o Done by alkalinizing urine which increases renal clearance of weak acids.
 You put a basic solution into blood and increase the pH of the urine filtrate causing the ionization of weak acids and preventing reabsorption of toxin by the renal tubules resulting in excretion. Acidification is not used because it can cause lots of problems

Front 35

• How can toxicologists use hemodialysis to increase chance of survival for patients who’ve already absorbed the poison? When is this not useful?

Back 35

o It is a filtration of the blood past a dialysis membrane. the fluid that runs through this membrane is discarded.
o It isn’t useful for situations where drugs are bound to plasma proteins or if the toxins accumulate in tissues.

Front 36

• How can toxicologists remove the toxins, especially those bound to plasma proteins, from the blood when dialysis isn’t useful?

Back 36

o Hemoperfusion- blood is filtered through a chamber containing activated charcoal or amberlite resin which allows for plasma protein bound toxins to be eliminated.
o Plasma exchange/transfusion/Pheresis- removal of patient’s plasma with replacement by donor. But this is rarely used.

Front 37

• How can serial oral activated charcoal help with elimination?

Back 37

o It increases systemic clearance of various drug substances by removing toxins in the blood even ones that are plasma bound and eliminating them through the GI tract. It is called non-renal clearance.

Front 38

• What are some examples of the MoAs of antidotes?

Back 38

o Chelators
o Receptor antagonists to prevent over stimulation
o Competitors to compete for binding sites
o Inducing the biological sites to increase binding sites for toxin to increase patient’s detoxifying capacity for that toxin

Front 39

• What kind of supportive care is provided for a poisoned patient?

Back 39

o Close clinical monitoring to check for delayed toxicity or multiple toxic phases.
o Psych evals especially in cases of suicidal patients.

Front 40

• Who invented the chromatography?

Back 40

o A Russian botanist named Mikail Tswett in 1903.

Front 41

• How do chromatography machines generally work?

Back 41

o They all have a mobile phase and a stationary phase.
o Chemicals separate one from another because they interact differently at the interface of the stationary and mobile phases.
o The mobile phase is pushed through a pump. There is a sample introduction site that mixes with the mobile phase and gets to the column which is the stationary phase. The columns separate certain substances depending on certain factors. The detector checks what comes out of the column and has a readout with the data

Front 42

• How do you read a chromatography data sheet?

Back 42

o You’ll have the detector’s response on the y-axis and the retention time on the x-axis. You’ll have different peaks presented at different times and at different heights that show the separated compounds. You can compare certain peak heights and retention times to known data to determine what a substance would be. It can also tell you how much of the substances are in the blood

Front 43

• What are the different High performance/pressure liquid chromatography (HPLC) modes?

Back 43

o Size exclusion
o Ion exchange
o Bonded phase with normal and reverse phases

Front 44

• What is size exclusion gel chromatography?

Back 44

o It has columns packed with material having precisely controlled pore sizes.
o The sample is simply screened or filtered in the column
o Larger molecules elute first as small molecules take a longer time to travel through the column

Front 45

• What is ion exchange chromatography?

Back 45

o It uses ionic/ionizable samples and separates them based on strength of charge.
o The stationary phase has an ionically charged surface of opposite charge to the sample.
o The stronger the charge of the sample, the stronger the attraction to the ionic stationary surface.

Front 46

• What is bonded phase chromatography?

Back 46

o It uses the differences in polarity and the like dissolves like principle to separate substances.

Front 47

• Describe the normal bonded phase chromatography procedure.

Back 47

o The stationary phase is polar
o A less polar or non-polar solvent is used as the mobile phase.
o The more polar compounds in the sample will be attracted to the stationary phase and the less polar compounds will elute first.

Front 48

• Describe the reverse bonded phase chromatography procedure.

Back 48

o The stationary phase is non-polar
o The mobile phase is more polar than the stationary phase.
o The less polar compounds in the sample will be attracted to the stationary phase and the more polar compounds will elute first.

Front 49

• What qualifications should the mobile phase have in chromatography?

Back 49

o It should lack contamination
o It should not react with the column packing
o It should be compatible with the detector
o It should dissolve the sample
o It should have a low viscosity

Front 50

• What are the advantages of HPLC?

Back 50

o It is fast, has good resolution, it is automated, quantitation is easy, great sensitivity, can run heat-liable and non-volatile compounds, and sample recovery is possible.