Toxicology Flashcards
What is the highest incidence of toxic exposure in the US?
young kids younger than 5 > teens > adults
Definition of toxicology
Study of adverse effects of xenobiotics in humans
Xenobiotics
Chemicals and drugs that are not normally found in or produced by the body. Describe the environmental exposure to chemicals or drugs.
What are the 3 major disciples of toxicology?
Mechanistic, Descriptive, and Regulatory
What is mechanistic toxicology?
Explain the cellular, molecular, and biochemical effects of xenobiotics within the context of a dose-response relationship between the xenobiotic and its adverse effects
What is descriptive toxicology?
Uses the results from animal experiments to predict what level of exposure will cause harm to humans (risk assessment)
What is regulatory toxicology?
Combines data from mechanistic and descriptive studies to establish standards that define the level of exposure that will not pose a risk to public health or safety
What are the three toxicology specialties?
Forensic, clinical, environmental
What is the purpose of forensic tox?
Primarily concerned with the medical and legal consequences of exposure
Major focus is establishing and validating the analytic performance of test methods used to generate evidence in legal situations—including cause of death
What is the purpose of clinical tox?
Focuses on relationships between xenobiotics and disease states
Emphasis on diagnostic testing and therapeutic intervention
What is the purpose of environmental tox?
The evaluation of environmental chemical pollutants and their impacts on human health
Which of the following is an exogenous substance?
Xenobiotics
Poisons
Toxins
Xenobiotics and Poisons
Poisons
Describe substances from an animal, plant, mineral, or gas
Toxins
Endogenous substance biologically synthesized either in living cells or in microorganisms. 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
Populations in which we see majority of poisoning cases
50% Suicide (highest mortality)
30% Accidental (most frequent in children)
20% Homicide/Occupational (industry or agriculture)
What are the most common routes of exposure/
Ingestion, inhalation, transdermal absorption
T/F:
Ionized substances can undergo passive diffusion
FALSE
Ionized CANNOT
Hydrophobic CAN
List some factors that can influence absorption
rate of dissolution, GI motility, resistance to degradation in GI tract, other substances
What is the central theme to toxicology?
The concept that all substances have the potential to cause harm
What is the purpose of the toxicity rating? (dose-response relationship of oral dose)
Useful system to compare relative toxicities of substances as the predicted endpoint is death. It evaluates data from a frequency histogram to toxic responses over a range of doses and will evaluate the responses over that wide range of concentration
5mg/kg can be lethal
What is TD50?
The toxic dose
the dose that would produce a toxic response in 50% of the population
What is LD50?
The lethal dose
the dose that would produce a lethal response in 50% of the population
What is ED50?
The effective dose
the dose that would produce a therapeutic/beneficial/effective response in 50% of the population
What is the therapeutic index?
Ratio of TD50 OR LD50 to the ED50
TD50:ED50
OR
LD50:ED50
What does it mean when you have a large therapeutic index?
That there are fewer toxic/adverse effects when the dose is in the TR
Does the following statement refer to Acute or Chronic toxicity:
Generally associated with repeated and frequent exposure for extended time periods at doses that are insufficient to cause an immediate acute response
Chronic
Acute refers to a single, short term exposure to a substance in which the dose can cause immediate toxic effects
T/F:
Signs and symptoms are often non-specific and relies on lab testing
TRUE
What are common specimen types for tox testing?
Urine and blood
Forensics often use serum, plasma, nails, hair, oral fluid
Define toxicokinetics
Toxic agents exhibit unique absorption, distribution, metabolism and elimination
Analysis of toxic agents is typically a two step process consisting of __1__ and __2__
1) screening (qualitative)
2) confirmatory (quantitative)
What are the methods used in toxic agent analysis?
Immunoassays (most common), GC, LC-MS, Inorganic compounds, NMR
State the most significant metabolism pathway for alcohols:
1) Alcohol
2) ADH (alcohol dehydrogenase)
3) Aldehyde
4) ALDH (hepatic aldehyde dehydrogenase)
5) Acid
What tubes are preferred for blood for toxic analysis?
Royal Blue trace free unless lead testing then we want a tan top
These are known to be free of certain chemicals
____ are known to have a common depressant effect on the CNS, mediated by changes in membrane properties
Alcohols
___ is in the top 10 causes of hospital admissions
ETOH (ethanol- most common)
What is fetal alcohol syndrome caused by and what is the result?
Ethanol consumption during pregnancy. It can result in delayed motor and mental capabilities
Chronic consumption of ___ affects the liver the most. What is the mechanism?
Ethanol
It causes an accumulation of lipids in hepatocytes and 20% develop toxic hepatitis. Cirrhosis is common
What is the mechanism that is used to mediate the pathological effects of long term ethanol use?
Adduct formation with the aide of acetaldehyde. The adducts can change the structure and function of various proteins
1) Ethanol
2) Acetaldehyde
3) Acetate
4) Acetaldehyde adducts
Methanol
Is a common lab solvent found in household cleaners
Accident consumption occurs from homemade alcohol (moonshine)
Neuropathy and blindness
Formic acid = severe metabolic acidosis
Isopropanol
Rubbing alcohol
CNS depressant similar to ethanol but can have severe acute phase symptoms
Ethylene glycol
Common component of hydraulic fluid and antifreeze. It has a sweet taste so you can see ingestion in kids and animals.
Severe metabolic acidosis
Alcohol determination for BAC can be performed on serum, whole blood, and plasma. Which of these is the most preferred specimen and why?
Serum is the preferred specimen of choice as it has a higher body water than whole blood and the ethanol is uniformly dispersed in total body water.
How is serum osmolality effected with serum ethanol?
Serum osmo increases 10 mOsm/kg per 60mg/dL increase in serum ethanol
(freezing point lowers with more alcohol)
How is carbon monoxide produced?
By the incomplete combustion of carbon-containing substances
CO and __ compete for the same binding sites
O2
What are the greatest hazards for CO poisoning?
Aspiration and ingestion
T/F:
CO is odorless but has a taste
FALSE
CO is odorless and tasteless
Cyanide
Very toxic substance in solid, liquid, or gas form. Binds to heme iron
Can be poisoned via inhalation, ingestion, transdermal. Used in industrial processes, insecticides, and rodenticides
High lactic levels are commonly found in ___ poisoning
Cyanide
Arsenic
Both natural and manmade substances and the toxicity depends on the valent state, solubility, rate of absorption and elimination.
What are the three major groups of arsenic?
Arsine gas, inorganic forms, organic forms (foods)
Cadmium
Used in electroplating and galvanizing. It is a significant environmental pollutant. SLOW half like of 30yr
What diseases/conditions are associated with Cadmium poisoning
- concomitant parathyroid dysfunction
- Vit D deficiency
- Itai-Itai disease
Lead
Component of byproduct of many industrial processes. Distributed in the body and mostly in the bone and soft tissues with a much longer half time in the bones.
T/F:
Children are more sensitive to lead than adults
TRUE
____ is a potent inhibitor of many enzymes
Lead
What are the 3 forms of mercury?
- Elemental (liquid at RT)
- Inorganic salts
- Component of organic compounds
Give an example for each form of mercury with its toxicity level
Elemental mercury (Hg0): no significant effects
Cationic mercury (Hg2+): moderately toxic
Organic mercury (methyl mercury CH3Hg+): extremely toxic
What is the most common route for mercury into the human body that is the primary factor that determines mercury toxicity in the human body?
GI absorbance
T/F:
The inorganic form of mercury is rapidly and efficiently absorbed
FALSE
the ORGANIC forms are
_____ binds with proteins and inhibits many enzymes
Mercury
Function of pesticides
Intentionally added to harm or kill something.
What is the primary concern with pesticides?
High level exposure. Those most at risk are people handling exposures without appropriate PPE
Salicylates
Acetylsalicylic (ASPIRIN)
Interference with PLT aggregation and GI function
Reye’s syndrome in viral infection in kids
Acute ingestion of high doses causes metabolic acidosis, hyperventilation, excess ketone formation, mixed acid-base disturbance
Acetaminophen
TYLENOL - common analgesic
Overdose associated with severe hepatotoxicity
Concern with MFO: more susceptible in alcoholics
MFO
Mixed-function oxidase
Hepatic system can become overwhelmed
T/F: DOA POSITIVE can tell us whether the patient has used the drug a single time or if they are a chronic user
FALSE, a positive result cannot tell us if this was a single use or a chronic substance abuse.
What is the typical method for a drugs of abuse screening
A urine screen to detect recent drug abuse
What are substances of abuse
OTC, prescription, illicit drugs
T/F:
DOA testing is a 2 tiered approach
TRUE: Screening and confirmation
What are things that can cause detection alteration
Urine tamp, pH, SG, and creatinine
The following statements describe which part of the DOA testing process:
- Simple, rapid, inexpensive
- “Spot tests:
- Lateral flow assays
Detects classes of drugs based on similarities in chemical configurations
SCREEN
What is a drawback of DOA test screening
May also detect chemical related substances with little to no abuse potential
Confirmation testing must use methods with high __a__ and __b__
Sensitivity and specificty
What is the reference method used the most for DOA confirmation?
GC-MS
T/F:
DOA confirmation can provide quantitative or qualitative information
TRUE
Amphetamines/Methamphetamines
Therapeutic drugs used for narcolepsy and ADD. These are stimulants with high abuse potential. Chronic use can lead to develop tolerance and physiological dependency
Sedatives-hypnotics
CNS depressants with a wide range of roles and abuse potential.
Serious toxic effect with respiratory depression and hypotension
Toxicity potentiated with ethanol use
Overdose symptoms include lethargy, slurred speech, and possible coma
Barbiturates
A sedative that has a high abuse potential
Originally a sleep inducer
Used as a “downer” after a cocaine or amphetamine “high”
Long half life
Benzodiazepines
A sedative that is more commonly found at a greater availability compared to barbiturates.
Metabolized quickly and long acting. Has a high efficacy, safety, and low addiction potential with minimal side effects.
Used as a sedative and for anti-anxiety uses
Tetrahydrocannabinol (THC)
Cannabinoid: psychoactive component of marijuana
Abundant and potent that causes a sense of well-being or euphoria
Lipophilic substance that is rapidly removed from circulation by passive diffusion into hydrophobic compartments (brain and fat)
Slow elimination
Cocaine
Low concentrations = local anesthetic
Higher concentration = potent CNS stimulator with a sense fo excitement and euphoria
Alkaloid salt that is administered directly or inhaled as a vapor (crack)
The primary factor that determines toxicity of cocaine is the __a__ and the __b__
a) dose
b) route of administration
What route of administration is the greatest hazard regarding cocaine use?
IV is the greatest hazard followed by smoking
Opioids
Capable of analgesia, sedation, and anesthesia
Derived from opium poppy
Naturally occurring, chemically modified, synthetic
High abuse potential that can cause physical and psychological dependence.
Acute overdose results in respiratory acidosis due to depression of respiratory centers, myoglobinuria, possibly including some cardiac markers
Opium, morphine, and codeine are collectively known as what?
Opiates (naturally occurring)
Tricyclic Antidepressants (TCA)
Used to treat depression and mood disorders
Commonly used in suicide attempts
Blocks the reabsorption and serotonin and norepinephrine, increasing the levels of those neurotransmitters in the brain
3 ring chemical structure
Methylenedioxymethamphetamine (MDMA)
Amphetamine derivative “ecstasy”
Administered orally but can be admin from inhalation, injection, and smoking
20% eliminated in the urine unchanged
Hallucination, euphoria, empathic and emotional responses, increased visual and tactile sensistivity
Phencyclidine (PCP)
“angel dust”
Illicit drug with stimulant, depressant, anesthetic, and hallucinogenic properties
Overdose cases stupor and coma
Ingested/inhaled by smoking PCP-laced tobacco or marjuana
LIPOPHILIC = dist into fat and brain
Slow elimination
Anabolic Steroid
Chemically related to testosterone
Used to increase muscle mass and improve athletic performance
Chronic use is associated with toxic hepatitis and accelerated atherosclerosis = abn aggregation of plts
MALE: testicular atrophy, sterility, impotence
FEMALES: development of masculine traits, breast reduction, sterility
