Toxicology Flashcards
True or False
Labs help identify and quantitate specific toxic substances like
-household items that can be considered toxic/poison
-illicit drugs / prescription drugs
-Heavy metals
-Miscellaneous materials
True
Highest incidence of toxic substances occurs in which set of population
Highest in kids(less than 5yrs old)>teens (tide-pods)>adults
What are Xenobiotics?
Chemicals/ drugs that are NOT normally found or produced in the body
Define Toxicology
The study of adverse effects of Xenobiotics in humans
Scope of toxicity is broad. What are the 3 Major Disciplines
last one starts with an R
Mechanistic
Descriptive
Regulatory
Explain the Mechanistic discipline
-To make explain the molecular/cellular/biochemical effects of Xenobiotics
w/in the context of a dose-response relationship
between the xenobiotics and its adverse effects
-It the basis of rational therapy
&
the development of lab tests to asses the degree of exposure
Explain the Descriptive discipline
-Risk assessment
-Uses animal (results) to experiments to predict the level of exposure that will cause harm to humans
Explain the Regulatory discipline
Data from both mechanistic & Descriptive
are used to establish STANDARDS that define the level of exposure that will NOT pose a risk to public health/safety
-Most regulatory toxicologist work w/ the government.
What are the specialties w/in toxicology
Forensic
Clinical
Environmental
Forensic speciality does what?
-Primary concern with the medical & legal consequences of exposure
-Focus on the establishing & validating the analytic performance of test methods
which are used to generate legal situations
including cases of death
Clinical speciality does what?
-Focus on relationship between xenobiotics & disease states
-Emphasis on diagnostic testing & therapeutic intervention
Environmental speciality does what?
-Evaluates the environmental chemical pollutants & their impacts on human health
True or False
Toxicology is usually NOT part of the clinical chemistry as a specialty
False: It is usually considered part of clinical chemistry
True or False
Xenobiotics, Poisons, and Toxins
are used interchangeably
True
What is the commonality between Xenobiotics and poisons?
Both exogenous agents that can have an adverse effect on a living organism
What are Xenobiotics?
Describe environmental exposure to chemicals or drugs
(antibiotics, antidepressants,
perfluorinated &
brominated compounds)
What are Poisons?
Describe substances from an animal/ plant/ mineral, or gas
(venoms from snakes or spiders, poison hemlock,
arsenic, lead,
carbon monoxide)
What are Toxins?
Endogenous substances that are biologically synthesized in living cells or microorganisms
Ex:
Botulinum toxin from Clostridium Botulinum
Hemotoxins from snakes
Mycotoxins produced from fungi
What are Toxicant and toxic?
Refers to substances that are NOT produced within a living cell or microorganism
AND
are more commonly used to describe environmental chemicals
True or False
50% are due to accidental exposures
&
30% are poisoning cases are due to suicide attempts
&
the rest are homicidal & occupational exposure
FALSE:
50% are suicide attempts (highest mortality rate)
30% are due to accidental exposures (frequent in kids/teens & seen w/ adults for therapeutic & illicit drugs instances)
the rest, is True (homicidal & occupational)
True or False
Ingestion is one of the most common routes of exposure and must be absorbed into circulation to exert a systemic effect.
True
Which of the following are is NOT true when it comes to passive diffusion
A. Must be able to cross cellular barriers
B. Hydrophobic can
C. Ionized can’t
D. Weak acids become protonated in gastric acid—becomes ionized- and are absorbed in stomach
E. Weak bases—absorbed in intestine
D. It becomes NONionized- and gets absorbed in stomach
Which of the following factors ALSO influence the rate of diffusion
A. Rate of dissolution
B. GI motility
C. Resistance to degradation in GI tract
D. Interaction with other substances
E. Only A
F. All of the above
F. All of the above
True or False
Toxins not absorbed in GI tract can produce local effects like diarrhea, bleeding, and malabsorption
True
Which is NOT true for the Dose-response Relationship
A. central theme to toxicology
B. assessing a substance potential to cause pathological effects
C. require an index of the relative toxicity of substances
D. most xenobiotics can produce pathological effects other than death
E. must correlate the dose of a xenobiotic that will result in harmful effects
F. correlates to a single oral dose to probability of a lethal outcome in an average 80kg male
G. all true
F. Should be average 70kg male
Which is true regarding Dose-response relationship
A. Used to evaluate responses over a narrow range of concentrations
B. toxic responses OR response associated with a pathological effects, increases the the lethal dose
C. Evaluates data from a cumulative frequency histogram to toxic responses over a range of doses
D. Determined to be the indicator of the toxic effects specific for many toxins
E. All the above
Answer
C. Evaluates data from a cumulative frequency histogram to toxic responses over a rang of doses
Corrected versions
A. Used to evaluate responses over a wide range of concentrations
B. toxic responses & pathological effects, lowers the the lethal dose
D. Determined to be the indicator of the toxic effects specific for that toxin
What does TD50 mean?
The predicted dose that would produce a Toxic response in 50% of the population
Toxic dose
What does ED50 mean?
The predicted dose to have a therapeutic benefit or be effective in 50% of the population
Effective dose
What does LD50 mean?
The predicted does that would result in death for 50% of the population
Lethal dose
What is the therapeutic index? (TI)
Ratio of TD or LD over ED
TI= TD50/ED50
or
TI= LD50/ED50
What is the benefit of a large therapeutic index (TI)?
Fewer adverse effects/toxic effects when dose is within therapeutic range (T.R.)
True or False
The measure of GGT or ALT can be used to evaluate liver cells?
True
True or False
All individuals respond display the same response to the same dose
False
What is the Quantal dose-relationship
Describes the changes in health effects
of a defined population
Based on
the exposure to the xenobiotic
What is acute toxicity?
Usually single, short-term exposure
to a substance in which the dose is sufficient to cause
immediate toxic effects
What is chronic toxicity?
Generally associated with repeated & frequent exposure for extended time periods (months to years)
at doses that are insufficient to cause an immediate acute response
True of False
Chronic toxicity can affect different systems than acute?
True
True or False
Signs and symptoms of toxicity are specific and don’r rely on lab testing?
False
They are NONspecific and DO require lab testing
Which is not a reason for toxic testing
A. Drug screen
B. Heavy metal panels
C. Environmental risk of exposure
D. Support investigation of exposure or confirm clinical suspicion of poisonings
E. Comply with occupational regulations/guidelines
F. All are true
F. ALL are reasons for testing
Which is not used for specimen type testing
A. Blood/urine
B. Serum/ plasma
C. Hair
D. Nails
E. synovial/ oral fluid
E. Oral fluid is a specimen type, but not synovial fluid.
What is Toxicokinetics?
When toxic agents exhibit unique absorption, distribution, metabolism, and elimination
Pre-analytic variables excludes which of the following?
A. Elimination patterns
B. Analyte stability
C. Specimen collection procedures
D. Urine collected at 24hrs is the preference
E. Dose of xenobiotic
E. is excluded
The rest ARE pre-analytical variables
what are challenges when collecting specimen?
Risk of contamination such as
-patient clothing
-skin
-hair
-collection environment
-specimen handling variables
What color tube do you use for collection samples?
Royal blue top - Meaning: the tube is “trace element free” / no other chemical w/in the tube
True or False
Royal blue top tube is also used for the collection of lead testing
False
Tan top tube is specifically used for Pb
What is the process of toxic analysis? How many steps does it involve?
It is a two step process: Includes screening & confirmation
Which is true of the screening process
A. Rapid/simple, QUALITATIVE
B. Mainly intended to rule out presence of specific substances
C. Good analytic sensitivity but lack specificity
D. All are true
E. Only A & C
E. Both A & C
B.- Intended to detect the presence of specific substances
True or False
Confirmatory testing is Quantitative AND includes reporting the concentration of the substance?
True
Which of the following is not a method of quantitative testing?
A. Immunoassay
B. Gas chromatography (GC) w/ mass spectrometry (MS)
C. Liquid chromatography (LC-MS)
D. Organic compounds w/ plasma mass spec (ICP-MS) or atomic absorption (AA) methods.
E. Nuclear magnetic resonance (NMR)
D. INorganic compounds
Immunoassays are most commonly used for what type of screens?
Drug screens
Which quantitative test method is best used for organic compounds
GC & MS
Know the common toxicology of alcohol
Initial effects -> disorientation/ confusion/ euphoria
Can progress-> unconsciousness/ paralysis/ death
Alcohols have similar effects at equivalent concentrations
Common depressant effect on CNS
What is the biotransformation of alcohol/ what is the metabolism pathway
Alcohol->(ADH)-> Aldehyde->(ALDH)-> Acid
What is false regarding Ethanol
A. Common exposure that make top 10 causes of hospital admissions
B. 50% of hospital admission have an alcohol related issue
C. 80K american die each year to alcohol related causes
D. Can cause Fetal alcohol syndrome (Drinking while prego’s)
E. legal limit is 80mg/dl
B. 20% of hospital admission have an alcohol related issue
&
50% of motor vehicle death include alcohol
Chronic consumption affects liver more than other tissues/cells
how does it affect it?
-Accumulation of lipids in hepatocytes - 20% develop toxic hepatitis (w/ long term abuse)
-Cirrhosis is common results
-GGT can increase w/ ethanol abuse (BUT also unrelated to ethanol use)
-AST/ALT ratio is >2.0 (highly specific for ethanol related disease)
Can HDL increase with Ethanol consumption?
YES, weird but happens
Know the 2 step Ethanol hepatic metabolism process
Ethanol->Acetaldehyde->acetate->acetaldehyde adducts
Adduct formation w/ acetaldehyde.
-Most acetaldehyde is converted to acetate but some is released in the free state
-Adduct change the structure & function of various proteins
What is makes Methanol more dangerous than other alcohols?
A. Common lab solvent & found in household cleaners
B. Accidental ingestion from homemade liquors
C. Metabolized by hepatic alcohol dehydrogenase (ADH) to formaldehyde, then Aldehyde dehydrogenase (ALDH) converts to formic acid (acid - leads to METABOLIC acidosis)
D. Can cause optic neuropathy ->Blindness
What is Isopropanol?
How is it metabolized?
-Rubbing alcohol
-by alcohol dehydrogenase (ADH)
True or False?
Isopropanol & acetone are CNS depressants?
True
Acetone has long half life & intoxication can lead to extended periods of ethanol like symptoms
What is false regarding to Ethylene glycol
A. Common hydraulic fluid/ antifreeze
B. Ingestion bc alcohol dependency & kids bc its sweet taste
C. immediate effects similar to Acetone
D. Can result in metabolic alkalosis
E. D & C
E.
Immediate effects similar to ethanol
Can result in metabolic acidosis
The use of alcohol dehydrogenase (ADH) & Aldehyde dehydrogenase (ALDH) results in
formation of Oxalic acid and glycolic acid which lead to
oxalate crystals in the renal tubes = tubular damage
B/c Ethanol distributes uniformly in total body water, serum has higher conc.
what is considered in the determination of alcohols?
-Pre-analytical factors
-Analytic methods- must be accurate & precise like gas chromatography (GC)
What are the Pre-analytical considerations?
-Venipuncture side cleaned w/ NON-alcohol (iodine/ chlorohexidine)
-specimens must be capped & sealed (stored for 14days)
-When non-sterile (or >14days), the specimen Must be preserved w/ sodium fluoride (gray top) to prevent bacterial fermentation
What happens to serum osmolality in terms of Ethanol concentration?
-Increase in serum osmo correlates w/ increase in serum ethanol.
-Difference between measured osmolality & calculated osmo
gives the degree of increase due to ethanol
(Will be BIGGER w/ increase ethanol)
-serum osmo increased
10mOsm/kg
per
60mg/dL
increase in serum ethanol
True or False
Enzymatic method of alcohol determination doesn’t require specialized equipment?
True
They use NON-human form of ADH to oxidize ethanol to acetaldehyde and reduction of NAD to NADH
What is False in terms of alcohol determination w/ headspace of GC.
A. Has established reference method
B. Undiluted sample w/ saturated sodium chloride
C.Volatile move into headspace of the closed container
D. Sample the headspace and construction of a standard curve (or compared to standard n-propanol)
B. Diluted sample w/ saturated sodium chloride
Carbon monoxide is produced when?
-Is the incomplete combustion of carbon-containing substances
It’s colorless, orderless, tasteless gas
What does carbon monoxide cause in blood?
-creates carboxyhemoglobin (COHb) that has 200x higher affinity to Hgb than O2
-half life of 6-90min (treat w/ 100% O2 or Hyperbaric chambers)
What are caustic agents?
Found in many household products and occupations settings
-exposure to strong acids (metabolic acidosis) or bases (metabolic alkalosis) associated w/ injury …duh
Which type of exposure has the greatest hazard?
Aspiration and ingestion
Aspiration associated w/ pulmonary edema & shock
Ingestion = GI lesions (mouth-butt) & can perforate the GI
Can result in hematemesis, abdominal pain, shock,
Where is Cyanide used & what does it do?
Can be used in industrial/ insecticides/ rodenticides/ pyrolysis (plastic burning)
Super Toxic - binds to heme iron (headache/ dizzy/ respiration depression)
Inhalation, ingestion, transdermal - (seizure/ coma/ death)
where is Arsenic found?
Toxicity dependent on valent state, solubility, rate of absorption/ elimination
3 major groups w/ different absorption depending on form
-Arsine gas (smelting & agriculture)
-inorganic forms (homicide/ suicide agent)
-organic forms (less harmful- clams/scallops/mussels/ bottom feeding fish)
know how Organic forms of arsenic are processed in the body
They are rapidly absorbed by **GI **& cleared by Renal filtration
Chronic toxicity (Bioaccumulation) due to low level BUT persistent exposure
Binds to protein & changes its structure. Most are only detectable for a few hours.
90% of arsenic is found in urine w/ 6 days
What are Mee’s lines and what causes them?
They are white lines in nails caused by some arsenic binding to sulfhydryl groups in KERATIN (skin & nail)
where is Cadmium found & what does it cause to the bod
Environmental pollutant from nickle-cadmium batteries (or pigments in paint/plastics or electroplating/ galvanizing) -> can be taken up by crops (tobacco)
Toxic to Kidneys (tubular dysfunction)
parathyroid dysfunction & vitamin D deficiency
Itai-itai disease
Elimination is veeery slooooow ~ 30years
where is lead found & what does it do to the body?
Industrial byproduct (pain/gasoline) & is widely distributed thru body (bone/BM, soft tissue, kidneys, nerves, erythrocytes)
GI absorption (adults absorb 5-15%, kids higher, infants 30-40%)
Elimination by Renal filtration (@ slow rate)
What is the treatment for lead?
Stopping lead exposure, then therapeutic chelation (EDTA) which can remove lead (from Bone/tissue) by forming complexes, which are cleared by kideys
What is the average adult intake of Lead
Lead content is variable in food
75-120ug BUT not associated w/ toxicity
True or False
Children are more sensitive than adults?
True, 11 states w/ mandated lead lvls for Medicaid programs
Both adults and kids can have abdominal or neurological symptoms after acute exposure
toxicity is multifaceted & dose dependent
Which is False in regards to lead
A. Potent inhibitor of many enzymes
B. Can cause basophilic stippling
C. Does not affect vitamin D
D. Affects heme synthesis
E. can cause Hypertension, carcinogenesis, birth defects, renal damage
C. Does affect vitamin D
How many forms of Mercury are there?
3 forms & each w/ different toxicities
Elemental (liquid at room temp)
Inorganic (can cause toxic levels in industrial settings)
Components of Organic compounds (food can be contaminated w/ it = major source of exposure)
True or False
Ingestion or Inhalation of elemental mercury can have severe effects to the GI system and respiratory system?
False
ELEMENTAL mercury (Hg0) Ingestion can happen without significant effects
Inhalation of ELEMENTAL is also insignificant bc of low vapor pressure
True or False
Cationic mercury (Hg2+) is extremely toxic
False
It is MODERATELY toxic
True or False
Organic mercury is extremely toxic
True.
Organic is extremely toxic (MOST common route- primary factor that determines toxicity is absorbance by GI)
Cationic is moderately toxic
Elemental can have insignificant effects
what happens to absorbed organic mercury?
Gets concentrated in brain & peripheral nerves (tremors)
Also binds to protein which inhibits enzymes
symptoms include GI issues (ulcers, bloody poop, necrosis), Heart issues (tachycardia), Renal issues
Chronic exposure has cumulative effect w/ slow elimination rate
Where are Pesticides found & how are people exposed?
Found in environment b/c of insecticides & others. Can also be found in occupational/ home settings
Primary concern with high lvl of exposure (ppl w/out PPE)
Contaminated food is frequent route of exposure
What are Salicylates & what can they cause in kids?
Acetylsalicyclic acid/ aspirin - interfere w/ PLT aggregation & GI function
Reye’s syndrome with viral infections in kids
Acute ingestion of Salicylates cause what?
-Metabolic acidosis
-hyperventilation
-can end up w/ mixed acid-base disturbance
-excess ketone formation
How are high doses of Salicylates treated
Treatment involves neutralizing/ eliminating excess acid & maintaining electrolyte balance
What are the TR for Salicylate acid
&
what is the TR for anti-inflammatory effects
2-10 mg/dl for pain relief
10-30mg/dl for anti-inflammatory effects
True or False
40mg/dl is the dose for toxic effects
False
Toxicity >50mg/dl
True or False
A Trinder reaction is a chromogenic assay (color changing)
True
(used for quantitation of Salicylates?)
what is Acetaminophen
Tylenol - common analgesic
Can overdose w/ sever hepatotoxicity. It has a high affinity to proteins, (low free fraction)
True or False
Kidney filtrate & excrete most of the acetaminophen
False
Renal filtration of parent drug is minimal
MOST is eliminated by HEPATIC uptake
Bio-transfomation conjugation, excretion
True or False
Mixed-function oxidase (MFO) system can be overwhelmed by acetaminophen
TRUE
What is the time frame for onset of hepatic damage by acetaminophen
3-5 days
acetaminophen is then rapidly cleared from serum BUT will see increased liver enzymes too
True or False
An alcoholic is more susceptible for acetaminophen toxicity
&
you would reference the levels w/ high performance liquid chromatography (HPLC) over an immunoassay
FALSE
Bc Immunoassay is most common
BUT
Alcoholics are indeed more susceptible to acetaminophen toxicity
What are the therapeutic levels for acetaminophen
10-30 ug/ml
What are the toxic levels of Acetaminophen
> 150 ug/ml,
4hrs after ingestion
What is true in regards to Drugs of abuse (DOA)
A. typically urine screen for few substance by qualitative
B. detects recent & past drug abuse
C. abstaining for a period of time can avoid detection
D. Can tell b/w single use & chronic substance abuse
E. Determines time from & dose
C. is true
a. many substances
b. only detects recent
d. can’t tell difference
e. doesn’t determine time or dose
Substance abuse can happen with which of the following
more than one choice is possible
A. OTC drugs
B. Prescription drugs
C. Illicit drugs
D. Vitamins
E. All of the above
A, B, C
What percent of adults use illicit drugs
24% of adults
in terms of recreational or performance enhancement
what is true in terms of Confirmatory testing
A. Must use methods with high sensitivity & specificity
B. many provide quantitative or qualitative
C. must use different method than screen
D. GC-MS reference method for most
E. All of the above
E. All of the above
True or False
Immunoassays are common for screening & provide a high degree of specificity?
False: They provide a high degree of sensitivity
and are easily automated
Chromogenic (qualitative ID & quantification)
immunoassay
GC & LC
are all examples of what kind of testing?
They are general analytic procedures
What drugs does the typical screening panel include?
Aphetamines, barbiturates, benzodiazepenes, cocain, opioids, THC, tricyclic antidepressants
