Toxicokinetics- BE Flashcards
Change from one chemical to another by a chemical reaction within the body
Biotransformation
Terms that are frequently used for the biotransformation process
Metabolism or metabolic transformation
Vital to survival in transforming absorbed nutrients into substances required for normal body functions
Biotransformation
Example of drug undergo biotransformation
Phenoxybenzamine
Serve as an important defense mechanism in that toxic xenobiotics and body waste are converted into less harmful substances
Biotransformation
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
Example of body waste that must be eliminated is
Hemoglobin
This is released during the typical destruction of red blood cells
Hemoglobin
One of the several hemoglobin metabolites
Bilirubin
Toxic to the brain of newborn and in high concentration may cause irreversible brain inhury
Bilirubin
Biotransformation results in metabolites of lower toxicity
Detoxification
Metabolites are more toxic than the parent substance
Bioactivation
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
Frequently used to describe a process whereby a substance leaves the body
Excretion and elimination
Used in a broader sense and includes the removal of the absorbed xenobiotic by metabolism and excretion
Elimination
Elimination or ejection of the xenobiotic and its metabolite by specific excretory organs
Excretion
Main routes for excretion are via
Urine, feces and exhaled air
Primary organ systems in excretion are
Urinary, gastrointestinal and respiratory system
What poisons may do to the body
Toxicodynamics
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
Inflammation example
Terminal bronchioles and alveoli leading to chemical pneumonitis and pulmonary edema (from nitrogen dioxide No2)
Corrosive effects by contact
NaoH or acids such as sulphuric, nitric or hydrochloric acid
Will behave as anesthetics and cause drowsiness, nausea, headache, unconsciousness, and death
Fat soluble solvents
Example of gases that can cause asphyxiation
Carbon monoxide, Hydrogen cyanide, Hydrogen sulfide
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
