Toxicokinetics- BE Flashcards by Scelene Macalintal

Change from one chemical to another by a chemical reaction within the body

Biotransformation

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Terms that are frequently used for the biotransformation process

Metabolism or metabolic transformation

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Vital to survival in transforming absorbed nutrients into substances required for normal body functions

Biotransformation

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Example of drug undergo biotransformation

Phenoxybenzamine

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Serve as an important defense mechanism in that toxic xenobiotics and body waste are converted into less harmful substances

Biotransformation

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Physical and chemical properties that control the distribution of a chemical throughout the body and its penetration to tissue cells

Nonpolar
Lipophilic
Low molecular weight

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Example of body waste that must be eliminated is

Hemoglobin

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This is released during the typical destruction of red blood cells

Hemoglobin

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One of the several hemoglobin metabolites

Bilirubin

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Toxic to the brain of newborn and in high concentration may cause irreversible brain inhury

Bilirubin

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Biotransformation results in metabolites of lower toxicity

Detoxification

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Metabolites are more toxic than the parent substance

Bioactivation

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Example of metabolite that interact with cellular macromolecules

Biotransformation of vinyl chloride to vinyl chloride epoxide, which covalently binds to DNA and RNA leading to liver cancer

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Frequently used to describe a process whereby a substance leaves the body

Excretion and elimination

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Used in a broader sense and includes the removal of the absorbed xenobiotic by metabolism and excretion

Elimination

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Elimination or ejection of the xenobiotic and its metabolite by specific excretory organs

Excretion

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Main routes for excretion are via

Urine, feces and exhaled air

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Primary organ systems in excretion are

Urinary, gastrointestinal and respiratory system

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What poisons may do to the body

Toxicodynamics

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Irritant effects example

May remove fat from the skin and cause dermatitis
Being alkaline, may irritate the skin and cause more severe damage
In low concentration may cause respiratory irritation

Detergents
Cement dust
Formaldehyde

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Inflammation example

Terminal bronchioles and alveoli leading to chemical pneumonitis and pulmonary edema (from nitrogen dioxide No2)

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Corrosive effects by contact

NaoH or acids such as sulphuric, nitric or hydrochloric acid

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Will behave as anesthetics and cause drowsiness, nausea, headache, unconsciousness, and death

Fat soluble solvents

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Example of gases that can cause asphyxiation

Carbon monoxide, Hydrogen cyanide, Hydrogen sulfide

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These gases poison cytochromes at low concentration and cause the rapid onset of headaches, dizziness, vomiting and confusion

Hydrogen cyanide

Heavy metals (enumerate) binds to this groups in enzymes and other proteins and cause damage in various parts of the body

Lead, Cadmium, Mercury Sulfhydryl groups

A poison that often subject of damage is lungs

Paraquat poisoning

This can caused cardiovascular effect such as arrhythmias

Trichloroethane or by carbon disulfide

This kind of pesticide inhibit acetylcholinesterase and lead to accumulation of Ach (can cause muscle weakness and paralysis, including respiration)

Organophosphate and carbamate pesticides

Provoke ab immune response (sensitization) resulting in asthma, rhinitis, and allergic rhinitis

Diisocyanates, glutaraldehyde, nickel

Example of carcinogens that causes hepatic hemangiosarcoma

Vinyl chloride

This increase the likelihood of individuals developing leukemia

Benzene

Mutagenic effects which is inherited defects by DNA damage

Alkylating agents (Mechloretamine)

Descending order of effectiveness

Inhalation Intravenous Subcutaneous Intramuscular Intradermal Oral Dermal

Route of exposure Ingestion Inhalation Topical, percutaneous, dermal

GIT Lungs Skin

Duration of exposure Acute Subacute Subchronic Chronic

Less than 24 hours, inhalation - less than 4 hours 1 month or less 1-3 months more than 3 moths

Frequency of exposure Acute Subchronic Chronic

Single episode/incident repeatedly over weeks or months months or years

What are the 5 effects of toxicity

ASCAD Acute effect Subacute effect Chronic effect Accumulative effect Delayed effect

It is rapidly developing, it reaches a maximum with a severe symptoms

Acute effect

Not as sever, but toxic effects are often same as acute

Subacute effect

Progresses at a slow varying rate; maybe mistaken for other diseases. Often difficult to address unless in the laboratory Cite examples:

Chronic effect

Accumulative effects occurs in two ways; __ and __ (Give example)

Accumulation of toxin (heavy metal) Of effect (organophosphate pesticides)

May only occur after prolonged exposure; the agent cannot be found in blood or tissues. Damage to system already done

Delayed effects

Classification of toxicants

PUCMET Physical state Use Chemistry Mechanism Effects Target organ toxicity

Use - Example Pesticide Solvent Food additives

Atrazine Benzene NutraSweet

Effects: Example Carcinogen Mutagen

Benzo-a-pyrene Methyl nitrosamine

Physical state: Example Oxidant Gas dust Liquid

Ozone Carbon dioxide iron oxide water

Chemistry: Example Aromatic amine Halogenated hydrocarbon

Aniline methylene chloride

Mechanism: Example Cholinesterase inhibitor Methemoglobin producer

Malathion Nitrate

Many toxin do not produce general effects but are SPECIFC to only a few organs

Target organ toxicity

Target organ toxicity Liver cancer Mesothelioma Lung toxicity Kidney toxicity

Vinyl chloride Asbestos Paraquat Cadmium

Lead concentrate in __ but its effect are mainly seen in __

Bone soft tissues (liver kidney and blood cells)

DDT accumulates in __ but effects is primarily in

Adipose tissue Central nervous system toxin

Target organs most frequently affected by toxicants

CCVM Central nervous system Circulatory system Visceral organs (liver, kidney, lung) Muscle and bone

Possible mechanism of tissue sensitivity

Preferential accumulation Selective metabolic activation Characteristic of tissue repair Specific receptors and function Physiological sensitivity

Enzymes needed to convert a compound to the active form may be present in the highest quantities in a particular organ Example...

Selective metabolic activation; Carbon tetrachloride, nitrosamine in liver

Toxicants may accumulate in only specific tissues and cause toxicity

Preferential accumulation

Example of some tissues that may be susceptible because they lack sufficiently repair capabilities

nitrosamines in liver

Toxicant may interact with receptors in a given tissue

Specific receptor activation

Example of specific receptor activation in which it is a neuromuscular blocker that is used in dart poisons

Curare

The nervous system is susceptible to agents that block the utilization of oxygen

Physiological sensitivity

Physiological sensitivity example Nitrite oxidizes __ Cyanides inhibits __ Barbiturates interfere with __

hemoglobin cytochrome enzyme sensors for oxygen and carbon dioxide content in blood