Intro to General Toxicology Flashcards by michelle anne

the study of the adverse effects of chemicals and other substances on living organisms

toxicology

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the science of poisons, their adverse effects, and the treatment of the disorders.

toxicology

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HISTORY OF TOXICOLOGY

Plants and fish poisons

ANTIQUITY - Chinese Journals

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HISTORY OF TOXICOLOGY

Aconite - chinese arrow poison

ANTIQUITY - Chinese Journals

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HISTORY OF TOXICOLOGY

________ - chinese arrow poison

Aconite

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HISTORY OF TOXICOLOGY

Focus primarily on venoms

ANTIQUITY - Chinese Journals

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HISTORY OF TOXICOLOGY

Chinese Journals focus primarily on __________

venoms

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HISTORY OF TOXICOLOGY

Ebers Papyrus

ANTIQUITY - Egyptian Documents

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HISTORY OF TOXICOLOGY

Contains information pertaining to
many recognized poisons like hemlock, aconite, opium, and metals such as lead, copper, and antimony

Ebers Papyrus

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HISTORY OF TOXICOLOGY

Most extensive and preserved record of Ancient Egypt

Ebers Papyrus

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HISTORY OF TOXICOLOGY

Poisons and antidotes

ANTIQUITY - Hindu Medicine

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HISTORY OF TOXICOLOGY

Classified 600 plant, animal, and mineral poisons

ANTIQUITY - Greek Physicians

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HISTORY OF TOXICOLOGY

Most popular: hemlock, a state poison; e.g., for death penalty

ANTIQUITY - Greek Physicians

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HISTORY OF TOXICOLOGY

active ingredient of hemlock

coniine, a piperidine alkaloid

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HISTORY OF TOXICOLOGY

Introduced bioavailability in
therapy and overdosage

Hippocrates

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HISTORY OF TOXICOLOGY

Inhibits the nervous system, leading to paralysis, causing death by suffocation w/c is the cause of death of Socrates

hemlock

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HISTORY OF TOXICOLOGY

“Father of Botany”

Theophrastus

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HISTORY OF TOXICOLOGY

Added a number of poisons and
clinical toxicology principles pertaining to bioavailability and overdosage

Hippocrates

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HISTORY OF TOXICOLOGY

Student of Aristotle

Theophrastus

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HISTORY OF TOXICOLOGY

Poisonous plants in De Historia
Plantarum

Theophrastus

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HISTORY OF TOXICOLOGY

1st to attempt to classify poisons; e.g., under plants, animals, or minerals

Dioscorides

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HISTORY OF TOXICOLOGY

Five volume compilation
containing 600 plants and
1000 different medications

De Materia Medica

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HISTORY OF TOXICOLOGY

First systemic pharmacopoeia; also one of the oldest

De Materia Medica

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HISTORY OF TOXICOLOGY

Ingested a mixture of 36
ingredients as protection against
assassination

King Mithridates VI

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HISTORY OF TOXICOLOGY meaning antidote or protective mixture

Mithridatic

HISTORY OF TOXICOLOGY Poisons used for assassinations or executions

Romans

HISTORY OF TOXICOLOGY first law against poisoning

Lex Cornelia

HISTORY OF TOXICOLOGY wrote Lex Cornelia

Sulla

HISTORY OF TOXICOLOGY Spannish rabbi

MIDDLE AGE - Maimonides

HISTORY OF TOXICOLOGY Poisons and their Antidotes

MIDDLE AGE - Maimonides

HISTORY OF TOXICOLOGY “Moses ben Maimon”

MIDDLE AGE - Maimonides

HISTORY OF TOXICOLOGY He included a treatise on the treatment of poisoning from insects, snakes, and mad dogs

MIDDLE AGE - Maimonides

HISTORY OF TOXICOLOGY Milk, butter, and cream could affect the bioavailability by delaying intestinal absorption

MIDDLE AGE - Maimonides

HISTORY OF TOXICOLOGY Tested toxic concoctions

MIDDLE AGES - Catherine de Medici

HISTORY OF TOXICOLOGY Noted the following: ■ Rapidity of the toxic response or onset of action ■ Effectiveness of the compound or potency ■ Degree of response of the parts of the body or specificity and site of action ■ Complaints of the victim or clinical signs and symptoms

MIDDLE AGES - Catherine de Medici

HISTORY OF TOXICOLOGY Philippus Aureolus Theophrastus Bombastus von Hohenheim-Paracelsus

RENAISSANCE - Paracelsus

HISTORY OF TOXICOLOGY A physician-alchemist

RENAISSANCE - Paracelsus

HISTORY OF TOXICOLOGY He focused on primary toxic agent as a chemical entity

RENAISSANCE - Paracelsus

HISTORY OF TOXICOLOGY He formulated the Dose of Response as a bulwark of toxicology

RENAISSANCE - Paracelsus

HISTORY OF TOXICOLOGY “All substances known to man are poison, there is none which is not a poison, and only the dose determines the effect.”

RENAISSANCE - Paracelsus

HISTORY OF TOXICOLOGY According to Paracelsus, _____ is essential in the examination of responses to chemicals

Experimentation

HISTORY OF TOXICOLOGY According to Paracelsus, One should make a distinction between the ______ and _____ properties of chemicals These properties are sometimes but not always indistinguishable except by _______

therapeutic and toxic; dose

HISTORY OF TOXICOLOGY He held this: One can ascertain a degree of specificity of chemicals and their therapeutic or toxic effects

RENAISSANCE - Paracelsus

HISTORY OF TOXICOLOGY Discovered Hg and Pb toxicity from goldsmithing

RENAISSANCE - Ellenbog

HISTORY OF TOXICOLOGY Ellenbog Discovered Hg and Pb toxicity from __________

goldsmithing

HISTORY OF TOXICOLOGY “On the Miners’ Sickness and Other Diseases of Miners” where he depicted the etiology of miners’ diseases and the treatment and preventive strategies

RENAISSANCE - Agricola

HISTORY OF TOXICOLOGY Occupational Toxicology - 2 people

Bernardino Ramanzzini, Percival Pott

HISTORY OF TOXICOLOGY Discourse on the disease of workers

RENAISSANCE - Bernardino Ramanzzini

HISTORY OF TOXICOLOGY Poly-aromatic hydrocarbon carinogenicity

RENAISSANCE - Percival Pott

HISTORY OF TOXICOLOGY Soots from chimney causes scrotal cancer

RENAISSANCE - Percival Pott

HISTORY OF TOXICOLOGY Experimental Toxicology

AGE OF ENLIGHTENMENT

HISTORY OF TOXICOLOGY MOA of emetine and strychnine

AGE OF ENLIGHTENMENT - Magendie

HISTORY OF TOXICOLOGY Orfila is a _____

physician

HISTORY OF TOXICOLOGY First toxicologist to use autopsy

AGE OF ENLIGHTENMENT - Orfila

HISTORY OF TOXICOLOGY “Father of Modern Toxicology”

AGE OF ENLIGHTENMENT - Orfila

HISTORY OF TOXICOLOGY Magendie’s student

AGE OF ENLIGHTENMENT - Bernard

HISTORY OF TOXICOLOGY “Introduction to the Study of Experimental Medicine”

AGE OF ENLIGHTENMENT - Bernard

HISTORY OF TOXICOLOGY Trained 120 students who later populated the most important laboratories of pharmacology and toxicology worldwide

AGE OF ENLIGHTENMENT - Oswald Schmiedeberg

HISTORY OF TOXICOLOGY Synthesis of hippuric acid which is fundamental for liver function

AGE OF ENLIGHTENMENT - Oswald Schmiedeberg

HISTORY OF TOXICOLOGY Chronic toxicity of narcotics and other alkaloids

AGE OF ENLIGHTENMENT - Louis Lewin

HISTORY OF TOXICOLOGY Prevalent use of “patent” medicines led to several incidents of poisoning from these medicaments

MODERN ERA - 20th Century

HISTORY OF TOXICOLOGY Upton Sinclair exposé of the meat packing industry in ______

The Jungle

HISTORY OF TOXICOLOGY Passage of Wiley Bill in 1906

US Pure Food and Drug Laws

HISTORY OF TOXICOLOGY One of the first journals of experimental toxicology

Archiv fur Toxikologie i.e., Archives of Toxicology

HISTORY OF TOXICOLOGY vital amines

vitamins

HISTORY OF TOXICOLOGY This led to the use of the first large-scale bioassays or multiple animal studies

DISCOVERY OF RADIOACTIVITY AND VITAMINS

LAWS ESTABLISHED DURING THE 20TH CENTURY Utilized The Jungle of Upton Sinclair

Wiley Bill

LAWS ESTABLISHED DURING THE 20TH CENTURY First of the U.S. pure food and drug laws

Wiley Bill

LAWS ESTABLISHED DURING THE 20TH CENTURY As reponse to the consequence of acute kidney failure after taking sulfanilamide in glycols solutions

Establishment of the National Insitute of Health

LAWS ESTABLISHED DURING THE 20TH CENTURY ○ Was passed into a Law ○ Second bill involving the establishment of Food and Drug Authority

Copeland Bill

LAWS ESTABLISHED DURING THE 20TH CENTURY Includes substances that was neither a drug nor a food had to be shown to be safe and efficacious for approval

Federal Insecticide, Fungicide, and Rodenticide Act

HISTORY OF TOXICOLOGY Any chemical found to be carcinogenic in laboratory animals or humans could not be added to the US Food Supply

AFTER WORLD WAR II - The Delaney Clause

HISTORY OF TOXICOLOGY First American journal dedicated to toxicology

AFTER WORLD WAR II - Toxicology and Applied Pharmacology

HISTORY OF TOXICOLOGY Developed staining procedures to observe cell and tissues

AFTER WORLD WAR II - Paul Erlich

HISTORY OF TOXICOLOGY Pioneered the understanding of how toxicants influence living organisms

AFTER WORLD WAR II - Paul Erlich

HISTORY OF TOXICOLOGY Attempts to understand the effects of chemicals on the embryo and fetus and on the environment as a whole gained momentum

AFTER WORLD WAR II - 1960s

HISTORY OF TOXICOLOGY __________ developed as a subdiscipline and risk assessment become a major product of toxicologic investigations

Cellular and molecular toxicology

HISTORY OF TOXICOLOGY used for morning sickness in pregnant women, but caused deformities in babies, affecting the extremities

Thalidomide

HISTORY OF TOXICOLOGY by Rachel Carson

Silent Spring

HISTORY OF TOXICOLOGY Convulsions jumping and involuntary

Minamata Disease: Dancing cat fever

HISTORY OF TOXICOLOGY Caused by exposure of people to methylmercury which targets the central nervous system, kidney, and liver

AFTER WORLD WAR II - Minamata Disease

HISTORY OF TOXICOLOGY People ate the fish that were exposed to methylmercury

AFTER WORLD WAR II - Minamata Disease

HISTORY OF TOXICOLOGY what era was Sequencing of Human Genome under?

21ST CENTURY TOXICOLOGY

HISTORY OF TOXICOLOGY 3 organisms possessing orthologs of human genes:

○ Zebra fish - Danio rerio, ○ Roundworms - Caenorhabditis elegans, and ○ Fruit flies - Drosophila melanogaster

HISTORY OF TOXICOLOGY identify common name: Danio rerio

Zebra fish

HISTORY OF TOXICOLOGY identify common name: Drosophila melanogaster

Fruit flies

HISTORY OF TOXICOLOGY identify common name: Caenorhabditis elegans

Roundworms

HISTORY OF TOXICOLOGY Novel approaches to studying the fetal origin of adult diseases

21st CENTURY TOXICOLOGY - Epigenetics

HISTORY OF TOXICOLOGY Study of the adverse effects of xenobiotics

21st CENTURY TOXICOLOGY - Toxicology

HISTORY OF TOXICOLOGY Toxicology is the study of the adverse effects of ________

21st CENTURY TOXICOLOGY - xenobiotics

DEFINITION OF TERMS substances produced naturally

Toxins

DEFINITION OF TERMS synthetic, weakened, or inactivated toxins

Toxoids

DEFINITION OF TERMS produced or a by-product of human activities

Toxicants

DEFINITION OF TERMS “corpus delicti” or “body of evidence”

poison

DEFINITION OF TERMS Any substance which can cause injury, disease, and death, when applied, introduced into, or developed within the body

poison

DEFINITION OF TERMS Clinical toxicity secondary to accidental exposure

poisoning

DEFINITION OF TERMS Any foreign substance - not normally found in the body ○ E.g., cosmetics, vaccines, pesticides

xenobiotic

DEFINITION OF TERMS The toxicity associated with any chemical substance

intoxication

DEFINITION OF TERMS An intentional exposure with the intent of causing injury or death

overdose

DEFINITION OF TERMS Frequency of occurrence of adverse reactions upon exposure to the poison

risk

DEFINITION OF TERMS The likelihood that injury will occur in a given situation or setting

hazard

DEFINITION OF TERMS Ability of a substance to cause biological change leading to adverse effects

toxicity

DEFINITION OF TERMS The probability that harm will not occur under specified conditions

safety

DEFINITION OF TERMS A collection of signs and symptoms which characterizes a specific toxicant

toxidrome

AREAS OF TOXICOLOGY Deals with investigation of the toxic effect of the substance on the biological system

experimental toxicology

AREAS OF TOXICOLOGY Use of a living organism; e.g., animal models – mice, rat, rabbit

experimental toxicology

What is the most commonly used animal model in experimental toxicology?

Guinea pig - Cavia porcellus

TYPE OF DOSE Smallest dose that kills 50% of the population

median lethal dose or LD50 & median lethal concentration or LC50

TYPE OF DOSE Poisons administered at any route except inhalation

LD50

T/F: The term LC50 is only used for poisons administered via inhalation or aquatic exposure

True

Maximum amount of drug considered safe

threshold limit value

T/F: The lower the TLV, the more dangerous the substance as it would have a narrow therapeutic index

True

TYPE OF DOSE Dose which produces the desired effect in 50% of subjects

median effective dose or ED50

Measure of safety or the ratio of the LD50 to ED50

therapeutic index

AREAS OF TOXICOLOGY Involves the diagnosis/treatment or antidote of poisoning cases with emphasis on medical sciences, including signs and symptoms or toxidromes

clinical toxicology

CLASS OF DRUG Atropine

anticholinergics - dry

CLASS OF DRUG organophosphate

cholinergics - wet

CLASS OF DRUG carbamates

cholinergics - wet

CLASS OF DRUG amphetamine

sympathomimetics

CLASS OF DRUG cocaine

sympathomimetics

CLASS OF DRUG morphine

opiates

CLASS OF DRUG heroin

opiates

TOXIDROME anticholinergics aka alice in the wonderland symptoms

dry mucosa, hyperthermia, mydriasis, delirium, flushed skin due to vasodilation

TOXIDROME cholinergics

DUMBBLESS / SLUDGE

TOXIDROME sympathomimetics

mydriasis, tachycardia, HTN, seizures

TOXIDROME opiates

tria: miosis, hypotension, coma hyperventilation, bradycardia

AREAS OF TOXICOLOGY Deals with deleterious effects and impact of chemicals present as toxins of the environment, to the living organism

environmental toxicology

AREAS OF TOXICOLOGY Specialized area within environment toxicology that focuses more specifically on the impacts of toxic substances on population dynamics in an ecosystem

ecotoxicology

AREAS OF TOXICOLOGY Concerned with sampling and toxicity testing which provide information for safety evaluation and regulatory requirements

regulatory toxicology

AREAS OF TOXICOLOGY Deals with the medical and legal aspects of poisoning

forensic toxicology

AREAS OF TOXICOLOGY Deals with the mechanisms by which chemicals exert their toxic effects on organisms

mechanistic toxicology

AREAS OF TOXICOLOGY Deals with the chemicals found in the workplace

occupational toxicology

What is the major route of poisoning under occupational toxicology?

inhalational

AREAS OF TOXICOLOGY Concerned directly with toxicity testing

descriptive toxicology

AREAS OF TOXICOLOGY Concerned with diseases caused by or uniquely associated with toxic substances

clinical toxicology

DEFINITION something that can cause HARM

hazard

DEFINITION chance -- high or low -- that any hazard will actually cause somebody harm

risk

Enumerate the types of hazards

1. biological 2. chemical 3. ergonomic 4. physical 5. psychological 6. safety

TYPE OF HAZARD include virus, bacteria, insects, animals

biologic

TYPE OF HAZARD nature of this hazard will depend on the properties of the chemicals used and stored on the premises

chemical

TYPE OF HAZARD result of physical factors that can lead to MUSCULOSKELETAL INJURIES

ergonomic

TYPE OF HAZARD result of environmental factors and include heights, vibration, radiation, and pressure

physical

TYPE OF HAZARD include hazards that can have an adverse effect on an individual’s mental health or wellbeing

psychological

TYPE OF HAZARD hazard that create unsafe working conditions

safety

A _______ is the likelihood of a person being injured or receiving an adverse health effect due to a _____________ occurrence

risk; hazard

What are the factors that can influence risk?

1. frequency of exposure 2. route of exposure 3. severity

What are the major routes of exposure?

1. GIT - ingestion 2. lungs - inhalation 3. skin - topical, percutaneous, dermal 4. parenteral - IV, IM, or SQ

Arrange the routes of exposure according to decreasing severity

IV > IH > I > SQ > IM > ID > PO

What are the categories of exposure?

1. acute 2. subacute 3. subchronic 4. chronic

How many hours of exposure to be considered acute, subacute, subchronic, or chronic?

single exposure: acute - <24h repeated exposures: subacute - 1 mos or less subchronic - 1 to 3 mos chronic - >3mos

What is the most often route of repeated exposure?

What are the types of poisoning effects?

1. local 2. remote 3. combined

POISONING EFFECTS impression made by the poison is to the body part it made contact with

local effect

LOCAL EFFECTS upon contact to body, what type of effect do acids -- e.g., H2SO4 on cornea -- produce?

corrosive effect that can lead to coagulative necrosis aka solidification

LOCAL EFFECTS upon contact to body, what type of effect do bases/alkalis -- e.g., NaOH on cornea -- produce?

caustic effect that can lead to liquefactive necrosis aka perforation

POISONING EFFECTS effect is produced in an area other than the site of application

remote

COMBINED EFFECTS state the local & systemic effects of phosphorus

local: cutaneous burns systemic: hepatic and renal failure

COMBINED EFFECTS state the local & systemic effects of cantharidin from sting of Spanish fly

local: vesicant or blister systemic: aphrodisiac/genitourinary irritant that can lead to renal dysfunction

EXAMPLES OF SPECIFIC EFFECTS irritants

acids and alkalis

EXAMPLES OF SPECIFIC EFFECTS neurotics

hallucinogens

EXAMPLES OF SPECIFIC EFFECTS carcinogenic

nitrosamines, aflatoxins found in molds in crops

EXAMPLES OF SPECIFIC EFFECTS asphyxiants

CO, methane gas

EXAMPLES OF SPECIFIC EFFECTS lacrimators

cholinergics, carbamates, organophosphates

EXAMPLES OF SPECIFIC EFFECTS sternutators

strychnine, veratrine

EXAMPLES OF SPECIFIC EFFECTS asthenics

tubocurarine, NM blocers

EXAMPLES OF SPECIFIC EFFECTS narcotics

opioids

Specify the classification of toxic agents

1. use 2. source 3. target organ 4. effect 5. physical state 6. chemical stability 7. general chemical structure 8. poisoning potencial 9. label requirements 10. biochemical MOA

DEFINITION concentration of a substance that may produce a toxic effect

dose

DEFINITION effect that a dose can produce ; may be positive or negative

response

What are the two types of dose-response relationship?

1. individual or graded 2. quantal

What are the types of quantal dose-response relationship?

1. normal or gaussian distribution 2. cumulative quantal 3. probit quantal

Specify the types of graphs associated with the different types of quantal dose-response relationships

1. normal or gaussian distribution - normal frequency curve/bell-shaped curve 2. cumulative - sigmoidal or S-shaped 3. probit - straight line

T/F: Hormesis is bi-phasic

True

HORMESIS at low doses: at high doses:

low doses: beneficial, can stimulate high doses: harmful, can inhibit

VARIATION IN TOXIC RESPONSES it means that a chemical produces injury to one kind of living matter without harming another form of life even though the two may exist in intimate contact

selective toxicity

SELECTIVE TOXICITY antibiotics

bacteria and human

SELECTIVE TOXICITY ergosterol

fungi and human

SELECTIVE TOXICITY birds can excrete uric acid but humans cannot -- it accumulates and leads to gout

birds and human

VARIATION IN TOXIC RESPONSES experimental results in animals when properly qualified are applicable to humans

specific differences

VARIATION IN TOXIC RESPONSES contributes for the idiosyncratic reactions to chemicals and for interindividual differences in toxic responses

individual differences