Toxicology Exam 1

Who is considered the father of toxicology?

Mathew Orfila.

What is toxicology?

The study of how natural or man-made poisons cause undesirable effects in living organisms.

What does 'ED50' represent?

The dose that would be predicted to be effective or have a therapeutic benefit in 50% of the population.

What distinguishes a coroner from a medical examiner?

A coroner is an elected position, while a medical examiner is a medical doctor.

What is the significance of vitreous fluid in toxicology?

It is the gold standard sample when testing for alcohol, remaining for days after death.

What do the initials STA stand for?

Systematic Toxicological Analysis.

What is pharmacokinetics?

The study of what the body does to the drug.

How does ionization of drugs affect their absorption?

It influences whether a drug is absorbed in the stomach or gastrointestinal membrane; non-ionized drugs are absorbed better.

What is the first-pass effect?

The amount of drug reaching systemic circulation is less than the amount absorbed due to metabolic breakdown in the liver.

What is selective toxicity?

A chemical's ability to produce injury to one kind of living matter without harming another form of life.

What is the significance of CYP450 in drug metabolism?

these enzymes significantly alter the rate at which a drug is broken down by the body.

What is the importance of P450 enzyme inhibition in drug interactions?

It can lead to increased drug levels and potential toxicity by slowing down metabolic processes.

What does Tmax stand for?

The time taken to reach the maximum concentration of a drug in the bloodstream.

How can you evaluate the volume of distribution (Vd)?

Dose administered/plasma concentration.

What factors affect bioavailability?

Route of administration, formulation, chemical properties of the substance, solubility, concentration, surface area, blood supply, and pH.

What is the functional unit of the kidney?

The nephron.

What are the mechanisms of renal excretion of a drug?

Glomerular filtration, tubular secretion, and tubular reabsorption.

What is the role of NADPH in Phase I metabolism?

NADPH donates electrons in reactions catalyzed by cytochrome P450 enzymes.

What is the general role of Phase I metabolism?

It primarily involves the oxidation of xenobiotics, introducing functional groups.

What is the primary difference between Phase I and Phase II metabolism?

Phase I primarily involves oxidation, while Phase II involves conjugation reactions.

What is a toxic metabolite?

It is a byproduct of drug metabolism that can cause harmful effects.

What is the significance of LD50?

LD50 is the lethal dose required to kill 50% of a tested population; a measure of acute toxicity.

What are the primary routes of drug administration?

oral, intravenous, intramuscular, subcutaneous, and topical.

What factors can influence a drug's half-life?

Factors include age, weight, organ function, route of administration, and interactions with other drugs.

What role do transport proteins play in pharmacokinetics?

They help in the absorption, distribution, and elimination of drugs across cell membranes.

What is the purpose of determining the therapeutic index?

This measures the safety of a drug, comparing the effective dose to the toxic dose.

What impacts renal clearance of a drug?

This is impacted by glomerular filtration rate, tubular secretion, and reabsorption.

What is chemical induction in drug metabolism?

This refers to the process where a substance increases the production of enzymes that metabolize drugs.

What does 'first-pass metabolism' refer to?

This is the process where the concentration of a drug is significantly reduced before it reaches systemic circulation during its first use.

What is biotransformation?

This is the chemical modification made by an organism on a chemical compound.

What is the difference between acute and chronic toxicity?

This refers to harmful effects occurring shortly after exposure, while chronic toxicity refers to long-term effects resulting from prolonged exposure.

What is a dose-response relationship?

This relationship is the relationship between the amount of a substance and the intensity of its effect.

What are the phases of drug metabolism?

Phase I (modification) and Phase II (conjugation or synthesis).

What role do cytochrome P450 enzymes play in drug metabolism?

These enzymes are important for the oxidation of drugs and other xenobiotics.

What is systemic circulation?

This is the pathway of blood flow from the heart to the body and back, distributing oxygenated blood and nutrients.

What is the difference between a poison and a toxicant?

A poison is any substance that can produce a harmful effect, while a toxicant specifically refers to man-made or natural substances causing toxicity.

What does 'half-life' mean in pharmacokinetics?

The time required for the concentration of a drug in the bloodstream to reduce by half.

How do environmental factors influence toxicity?

Environmental factors such as temperature, humidity, and exposure duration can affect the toxicity of substances.

What are biomarkers of exposure?

These are biological indicators that can be measured to determine the presence of toxic substances in the body.

What is the role of the liver in drug metabolism?

This is the primary organ responsible for metabolizing drugs, breaking them down into inactive metabolites or active forms.

What is pharmacodynamics?

This is the study of the effects of drugs on biological systems and their mechanisms of action.

What is the significance of protein binding in pharmacokinetics?

This affects the distribution and efficacy of a drug; only unbound drugs can exert therapeutic effects.

What does 'clearance' mean in pharmacokinetics?

This is the volume of plasma from which a substance is completely removed per unit time.

What factors influence drug solubility?

Chemical structure, temperature, pH, and presence of solvents all influence it.

What is the purpose of therapeutic drug monitoring?

This aims to optimize drug therapy by ensuring adequate concentrations while avoiding toxicity.

What is meant by 'bioequivalence'?

This refers to the absence of a significant difference in the bioavailability of two formulations of the same drug.

What are active metabolites?

These are drug byproducts that are pharmacologically active and can contribute to the drug's effects.

What is the action of chelating agents?

These bind to heavy metals and facilitate their excretion from the body, helping to counteract toxicity.

Mechanistic Toxicology

elucidates the cellular and biochemical effects of toxins.

Descriptive Toxicology

uses results of animal experiments to predict harmful effects to humans

Occupational Toxicology

Combines occupational medicine and occupational hygiene

Environmental Toxicology

Integrates toxicology with sub-disciplines such as ecology, wildlife, and aquatic biology.

Food Toxicology

Is involved in delivering a safe and edible food supply to the consumer

Regulatory Toxicology

Gathers and evaluates existing toxicological information to establish concentration-based standards of “safe” exposure.

Clinical Toxicology

The study of interrelationships between toxin exposure and disease states

Forensic Toxicology

Concerned with medico-legal consequences of exposure to a toxic substance or a toxin.

When to use gastric content

this specimen type is useful after overdoses

When to use organs/tissues

This specimen is useful when the body is found after the blood has already clotted.

When to use bile

This specimen is useful when blood and urine are not available since we prefer to work with biological fluids.

When to use vitreous fluid

Good for testing alcohol levels post-mortem, since it remains in a sterile cavity.

When to use hair

This specimen is good for long-term use of substances.

Which specimen correlates to the concentration of a drug with the impairment of the person?

Urine/Blood correlate to _____.

Which biospecimen is important in the case of the sudden death of a person who has large quantities of a lethal agent in the stomach?

Gastric Content

Steps of STA for a biological sample

Screening/General unknown screening —> MS analysis (if possible) —> qualitative/quantitative measures

Meaning of PTS

Proficiency Testing Scheme

How many half-lives are required for a drug to be sequentially administered in order to achieve steady-state concentrations in a patient’s plasma?

Four to five half-lives.

What is the difference between one and two compartment systems in pharmacokinetics.

One compartment hypothesizes that after absorption is distributed equally throughout the body. Two compartment assumes that first a drug is distributed to highly perfused tissues and then to less perfused tissues.

Bioavailability

The actual amount of the drug which enters into the bloodstream.

Factors that affect bioavailability:

1. Route of Administration

2. Formulation

   1. chemical properties of the substance

   2. type: chalky powder vs gel capsule

Which route of administration provides 100% bioavailability of a drug.

Intravenous

How hydrophobicity of a drug affects the distribution

It controls how much of the dug absorbs into the tissues (higher lipid solubility) versus into the blood (lower lipid solubility)

The importance of free and protein binding of a drug in blood

This reduces the concentration of free drugs available for diffusion across membranes.

The name of the enzyme responsible for drugs’ metabolism.

P450: monooxygenases

The mechanism of action for Monoamine Oxidase and its inhibitors.

MAOIs block the monooamine oxidase enzyme which is what breaks down many neurotransmitters in the brain.

How does O2 participate in phase I metabolism

In Phase I metabolism, O2 acts as a reactant in the oxidation reaction catalyzed by cytochrome P450 enzymes, combining with the substrate and electrons to introduce an oxygen atom.

Phase I Metabolism Example with Tylenol

Substrate: Acetaminophen (Tylenol)
Enzyme: Cytochrome P450 (CYP450)

further conjugation is seen in phase II

Phase II Metabolism Example with Tylenol

Substrate: Acetaminophen (from Phase I)
Enzyme: Glucuronosyltransferase

How phase II glucuronidation affects the excretion of a drug from urine.

converting the drug molecule into a more water-soluble conjugate (glucuronide), which allows for easier filtration and elimination through the kidneys

Toxicant

Any chemical that can injure or kill humans, animals, or plants; a poison

Toxic

Poisonous or deadly effects on the body caused by any form of consumptiion

Toxin

Toxic substances produced naturally

Toxicity

The degree to which a substance is poisonous or can cause injury

Toxic symptoms

Any feeling or sign indicating the presence of poison in the system

Toxic effects

Health effects that occur due to exposure to a toxic substance

Tolerance

A person’s diminished response to a drug due to repeated use over time causing the body to adapt.

Selective toxicity

Means that a chemical will produce injury to one kind of living matter without harming another form of life

NOAEL

No Observed Adverse Effect Level; used in experimental toxicology for risk assessment

Additive adverse effect

4+4=8

Potentiate adverse effect

4+4=5

Antagonistic/Synergistic adverse effect

4+4=20