(F) Lec 1: Intro to Toxicology Flashcards
Definitions of Toxicology
- The study of the (quantitative/qualitative) effects of chemicals on biologic tissue
- The study of the effects of chemicals on biologic systems with emphasis on the ____ of their harmful effects and the conditions under which these occur
- The study of the adverse effects of ____ in humans
- The study of substances or xenobiotics (exogenously/endogenously) introduced into the body
- Quantitative
- Mechanisms
- Xenobiotics
- Exogenously
Definition of Terms
Substances that are foreign and are not normally found in the body as they can have adverse effects on living organisms
Xenobiotics
Definition of Terms
Exogenous agents that can have adverse effects on living organisms that are often of animal, plant, mineral, or gas origin
Poisons
Definition of Terms
Endogenous substances biologically synthesized in living cells and microorganisms (e.g. Botulinum)
Toxins
Background of Toxicology
Who is the Father of Modern Toxicology?
Mateu Joseph Bonaventura Orfila
Contributions of Mateu Joseph Bonaventura Orfila
- He introduced (quantitative/qualitative) methodology into the study of the actions of chemicals on animals
- He was the first to point out the valuable use of ____ analyses as proof that existing symptoms were related to the presence of a particular chemical in the body
- He was able to make the process ____ and ____
- Quantitative
- Chemical
- Systematic and Measureable
Background of Toxicology
He emphasized the value of experimentation in Toxicology as well as the Dose-Response concept
Paracelcus
Contributions of Paracelcus
βAnything can be poisoned and it is the ____ or amount that makes the poisonβ
Dose
Contributions of Paracelcus
With his famous line, βanything can be poisoned and it is the dose or amount that makes the poisonβ, he concludes that any substance can be considered as what?
Toxic
Give the 3 aspects of Toxicology
- Environmental
- Economic
- Medical
Among the ff. fields/disciplines: Physiology, Biology, Chemistry, Pharmacology, Pathology, Engineering, Public Health, and Immunology
Which is the most closely related to Toxicology?
Pharmacology
TOF: The general idea about the major disciplines of Toxicology is to try and study different toxic substances on how it can affect our body and get to know different ways on how it can be prevented
True
3 Major Disciplines of Toxicology
- This focuses on the cellular, molecular, and biochemical effects of xenobiotics
- It focuses more on in-vitro tests
Mechanistic
3 Major Disciplines of Toxicology
- Uses results from animal experiments to predict what level of exposure will cause harm in humans
- Also known as βrisk assessmentβ
- This is what was mostly used before the discovery of cellular and molecular components
Descriptive
3 Major Disciplines of Toxicology
- This uses the combined data from the mechanistic and descriptive discipline to establish standards that define the level of exposure that will not pose a risk to public health or safety
Regulatory
Specialties under Toxicology
- Deals with medico-legal cases
- Establishes and validates test methods used for legal situations
Forensic
Specialties under Toxicology
- It focuses on the relationship of xenobiotics and disease states
- It evaluates diagnostic testing and therapeutic interventions
- Is more commonly used in the field
Clinical
Specialties under Toxicology
- Involves the evaluation of environmental chemical pollutants and their impact on human health
- An example would be the Minamata disease in Japan, caused by methyl mercury
Environmental
Fundamental Principles of Toxicology
- The chemical must get to the ____ site in a biologic system to produce an effect or become toxic
- Not all chemical-induced biologic effects are ____ as proven by the use of therapeutic drugs
- The effects of chemicals on ____, if properly qualified, may also be applicable to humans
- The occurrence and intensity of chemical-induced biologic effects are ____-related
- Effector
- Harmful
- Animals
- Dose
Fundamental Principles of Toxicology
- A lot of tests in toxicology are done through ____ testing
- The results can be applicable to humans due to the variation of ____ among different species
- For example, the product of purine metabolism in humans and mammals is uric acid while for other organisms itβs ____
- Animal
- Metabolism
- Allantoin
Familiarize yourself with the 6 factors that influence toxicity
- Biologic
- Chemical
- Genetic
- Route of administration
- Dose response relationship
- Human immune system
Biologic Factors
A toxic effect happens when the substance successfully enters the body
Absorption and Translocation
Biologic Factors
An example of this is: when someone is exposed to hepatotoxic chemicals, the liver is still seen to function up until 80% of it is destroyed
There will not be any manifestations unless a huge part of the liver is destroyed
Reserve Functional Capacity
Biologic Factors
- This is a very helpful guide when it comes to testing for the presence of toxic substances
- Knowledge in drug metabolism gives us an idea on where we can find it most abundant in the body leading to the determination on which specimen is best used
Accumulation and Storage
Biologic Factors
What are the 2 most common specimens used in toxicology studies?
Urine and Blood
Biologic Factors
- Refers to the ability to show less response to a specific dose of a chemical than what was shown on a prior occasion from the same dose
- In their peak exposure, along with the same dose, there was less of a response
Tolerance
Biologic Factors
The tolerance aspect is very much exemplified by drugs of ____ in that some people develop tolerance therefore their bodies require more of the substance to obtain the desired effects
Abuse
Biologic Factors
Tolerance or Resistance?
1. No response, develops rapidly, and can be genetic
2. There is less of a response and it takes time
- Resistance
- Tolerance
Give the four (4) aspects of the biologic factors
- Absorption and Translocation
- Reserve Functional Capacity
- Accumulation and Storage
- Tolerance
Chemical Factors
For example, a very strong acid can be corrosive and is able to burn regardless of what part of the body it is in contact with
Non-Specific Chemical Action
Chemical Factors
- Some chemicals have specific actions based on the concept of a target and receptor
- It focuses more on the substance gaining entry into the body and reaching the target tissue
Selective Chemical Action
Chemical Factors
This is influenced by pH; it determines whether a substance is absorbed, metabolized, or stored
Ionization
Chemical Factors
Drugs are processed similarly to ____. If they are
bound, there is a (smaller/bigger) likelihood that they will exert their action more effectively as compared to when they are free
- Hormones
- Smaller
Chemical Factors
Some substances are ____-soluble while some are ____-soluble; wherever they are more soluble, that is where they exist more
- Water
- Lipid
Chemical Factors
This is aka Metabolic Transformation wherein if something enters the body, the body metabolizes it to get rid of it
Biotransformation
Chemical Factors
TOF: If the substance itself is toxic, the body can only convert it to a less toxic substance
False (it can also convert it into a more toxic substance)
Chemical Factors
In methanol toxicity, harm to the body is (induced/reduced) upon its metabolism
Induced
Chemical Factors
Methanol is an alcohol and since the liver has the alcohol
dehydrogenase enzyme that is known to metabolize
alcohols and glycols, if methanol is combined with
alcohol dehydrogenase, what two (2) substances are formed?
- Formaldehyde
- Formic Acid
Chemical Factors
Effects of Formic Acid:
1. Some form of metabolic (alkalosis/acidoses)
2. It produces ____ toxicity which damages the eyes leading to blindness
- Acidosis
- Ocular
Chemical Factors
What is an intervention to methanol toxicity that uses a competitor for alcohol dehydrogenase to prevent the conversion of methanol to formic acid?
Ethanol
Chemical Factors
If ethanol is able to compete for the same enzyme that methanol uses, it now produces what two (2) substances?
- Acetaldehyde
- Acetic Acid
Note: The focus is that it tries to prevent possible blindness
Give the five (5) aspects of the chemical factors
- Non-Specific Chemical Action
- Specific Chemical Action
- Ionization
- Solubility
- Biotransformation
Genetic Factors
An example of this is the anesthetic effect of succinylcholine on pseudocholinesterase deficiency wherein people with this deficiency present with prolonged apnea when administered with succinylcholine whereas normal people do not experience any adverse reactions
Prolongation of Chemical Action due to Deficient Biotransformation
Genetic Factors
In the case of succinylcholine and pseudocholineasterase deficiency, what reaction do patients with the deficiency manifest upon receiving a dose of succinylcholine?
Prolonged apnea
Genetic Factors
An example of this is Dicumarol dosing that occurs in patients with deficiencies in their metabolic transformation pathways leading to bleeding
Note: Dicumarol is an oral anticoagulant metabolized in the liver
Accumulation of a Chemical due to Deficient or Absent Metabolic Transformation
Genetic Factors
An example of this is the case of Primaquine-induced hemolytic anemia in G6PD deficiency
Hypersensitivity
Genetic Factors
What kind of drug is primaquine?
An anti-malarial drug
Genetic Factors
A lot of genetic factors are due to ____ deficiencies, specifically enzyme deficiencies
Metabolic
Give the three (3) aspects of the genetic factors
- Prolongation of Chemical Action due to Deficient Biotransformation
- Accumulation of a Chemical due to Deficient or Absent Metabolic Transformation
- Hypersensitivity
Immunologic Factors
Refers to the amount or quantity of a substance which can be toxic or effective
Dose
Immunologic Factors
____ is a more general term while ____ relates more to the harmfulness of a particular substance
Potency; Toxicity
Immunologic Factors
This is determined by the amount needed to exert whatever is the expected effect for that substance
Potency
Immunologic Factors
TOF: A substance that is more potent is a substance that needs a smaller amount to produce an effect
True
Immunologic Factors
TOF: A more toxic substance usually requires a larger amount to produce its harmful effects
False (smaller amount)
Immunologic Factors
Acute vs Chronic?
1. A single short-term exposure at a dose sufficient to cause immediate toxic effects
2. A repeated and frequent exposure for an extended period at doses insufficient to cause an immediate response
- Acute
- Chronic
Immunologic Factors
When it comes to therapy and management, certain substances require distinct ____ for acute poisoning and chronic exposure
Antidotes
Immunologic Factors
Refers to how substances best gain access to the body at certain routes
Routes of Administration
Routes of Administration (no choices)
- Through the skin
- Difficult to determine (based on lung activity)
- One of the most common routes for patients brought into the ER
- Done through injections whether intradermal, subcutaneous, intramuscular, or intravenous
- This is associated with having the highest bioavailability for most substances
- Percutaneous
- Inhalation
- Oral
- Parenteral
- Intravenous
Dose-Response Relationship
TOF: Toxic response increases as the dose increases
True
Dose-Response Relationship (Terminologies)
The dose predicted to be effective or have therapeutic benefits in 50% of the population
Effective Dose 50 (ED50)
Dose-Response Relationship (Terminologies)
The dose predicted to produce a toxic response in 50% of the population
Toxic Dose 50 (TD50)
Dose-Response Relationship (Terminologies)
The dose predicted to result in death in 50% of the population
Lethal Dose 50 (LD50)
Dose-Response Relationship
TOF: It is safe to assume that the highest dose can always result in death
False (possibly, not always)
- Defined as a ratio of Toxic Dose 50 (TD50) to Effective Dose 50 (ED50)
- A higher value means fewer toxic effects when the dose is within the therapeutic range
- It means that it would take a higher dose for that substance to reach the toxic dose
Therapeutic Index
Dose-Response Relationship Plot
As you move further to the right (higher dose), that is the time when you first reach the ____ dose, then ____ dose, and finally the ____ dose
Effective (ED50) > Toxic (TD50) > Lethal (LD50)
Toxicity Ratings
- < 5 mg/kg
- 5 to 50 mg/kg
- 50 to 500 mg/kg
- 0.5 to 5.0 g/kg
- 5 to 15 g/kg
- > 15.0 g/kg
A. Extremely toxic
B. Super toxic
C. Practically non-toxic
D. Very toxic
E. Moderately toxic
F. Slightly toxic
- B - Super
- A - Extremely
- D - Very
- E - Moderately
- F - Slightly
- C - Non-toxic
Areas of Concern in the Toxicology Laboratory
- These were initially discovered or manufactured for therapeutic use
- However, people found ways to take pleasure out of it
Drugs of Abuse (DoA)
Areas of Concern in the Toxicology Laboratory
- Refers to the desirable and undesirable effects of therapeutic drugs
- The laboratory makes sure that it is the beneficial effects that are taken advantage of
Therapeutic Drug Monitoring (TDM)
What are the four (4) areas of concern in the Toxicology Laboratory?
- Drugs of Abuse (DoA)
- Therapeutic Drug Monitoring (TDM)
- Environmental Carcinogens and Mutagens
- Poisons and Toxins
The clinical laboratory collaborates with the entire ____ team to gather information relevant to health with regards to toxins
Healthcare
Considerations
- The ____ and ____ of suspected exposure along with that of specimen collection
- Patient ____
- ____ examination
- Time and Date
- History
- Physical
Considerations
TOF: Both the time and place of exposure and specimen collection should agree because substances can be metabolized and some of them when collected too late may decrease and disappear from the sample
True
Specimen Collection and Consideration
Aside from urine and blood, what two (2) samples can be used especially for arsenic toxicity?
Hair or Fingernails
Specimen Collection and Consideration
In general, if the suspected substance to be detected is a Drug of Abuse, what samples are submitted?
Urine
Specimen Collection and Consideration
If the purpose of specimen collection is for therapeutic drug monitoring, what sample is used?
Blood (serum)
Specimen Collection and Consideration
In cases of toxicity with trace metals/elements, a specialized tube with what color stopper is used?
Royal Blue (it is trace element-free)
Specimen Collection and Consideration
For lead detection, what colored tube is used?
Tan top
Screening Procedures
This test is applicable for the study of methemoglobinemia and carboxyhemoglobinemia that are induced by certain drugs
Spot Test
Screening Procedures
This test gives physicians an idea of what the offending agent could be especially if it potentially causes rapid heart rate or bradycardia as symptoms
ECG
Screening Procedures
- This test is part of a basic metabolic panel
- It is sometimes called βChemistry 7β because it includes 7 substances to be measured
Anion Gap
Screening Procedures
In βChemistry 7β or the Anion Gap, what are the seven (7) substances included?
- Sodium
- Potassium
- Chloride
- Bicarbonate
- BUN
- Creatinine
- Glucose
Screening Procedures
Familiarize yourself with how the anion gap is computed
π΄πΊ = ππ β (πΆπ + π»πΆπ3) or
π΄πΊ = (ππ + πΎ) β (πΆπ + π»πΆπ3)
Screening Procedures
This is calculated by determining the difference between the sodium level and sum of the chloride and bicarbonate
Anion Gap
Screening Procedures
Since we have electrical neutrality in our bodies, the sum of all cations and anions should be?
Zero (0)
Screening Procedures
TOF: If we perform anion gap calculation, we include all the ions
False (only the major ones)
Note: This difference accounts for those that we did not measure
Screening Procedures
Give the reference range for the anion gap
8 to 16 mmol/L
Screening Procedures
An increased anion gap is paired with metabolic ____
Acidosis
Screening Procedures
TOF: Computation of the anion gap is time-dependent
True
Screening Procedures
Familiarize yourself with the conditions associated with increased anion gap with metabolic acidosis
- MUDPILES
- GOLD MARK
Note: Look up the conditions correspondent to these acronyms
Screening Procedures
This is the difference in measured osmolality, by freezing point depression, and calculated serum osmolality
Osmolal Gap
Screening Procedures
The difference of the osmolal gap should be around what value?
Β± 10
Screening Procedures
In an ideal setting, the measured osmolality should be ____ with the calculated serum osmolality
The same (no difference)
Screening Procedures
TOF: The calculated serum osmolality does not account for all substances that contribute to its measurement
True
Screening Procedures
What 2 forms of toxicity are associated with a high osmolal gap?
Alcohol and Ethylene Glycol Toxicity
Screening Procedures
Familiarize yourself with the formula for the osmolal gap
ππΊ = ππ ππ + ππ ππ
Screening Procedures
In computing for the osmolal gap:
1. This measurement is obtained by the instrument
2. This measurement is obtained from measuring sodium, glucose, and urea
- Measured one (Osmm)
- Calculated one (Osmc)
Screening Procedures
Familiarize yourself with the formula for calculated osmolality
Check the transes/PPT (formula cannot be transcribed)
Screening Procedures
In computing for the osmolal gap, what unit is universally used?
mmol/L
Screening Procedures
Most drug screenings are done using rapid ____ tests
Immunoassay
Screening Procedures
Refers to the collective term for GCMS, HPLC, and LCMS
Chromatography
Screening Procedures
What is the gold standard for drug detection and quantitation in general?
Gas ChromatographyβMass Spectrometry (GCMS)
Management
Initial management for patients suspected of acute toxicity follow the ABCDE acronym which stands for?
- A - airway
- B - breathing
- C - circulation
- D - disability
- E - exposure
Management
What are the four (4) management aspects for acute toxicity?
- The ABCDE acronym
- It is collaborative
- Revolves around the timely removal of the toxin or its effects
- The clinical laboratory
According to Paracelsus:
βAll substances are ____, there is none that is not a poison. The right dose differentiates a poison and a ____β
Poison; Remedy
