Toxicology

Created by

Gloria Msheri

Cards (133)

Toxicology 
A broad-based multidisciplinary science that examines the harmful effects of substances on living organisms, including humans
Subdivisions of toxicology 
Descriptive toxicology
Environmental toxicology
Forensic toxicology
Mechanistic toxicology
Regulatory toxicology
Medical or clinical toxicology
Descriptive toxicology 
Focuses on toxicity testing with the intent of defining the degree of risk associated with substances
Environmental toxicology 
Involves the detection and understanding of environmental pollutants and their effects on humans and other organisms
Forensic toxicology 
Is primarily concerned with detection and quantification of toxic substances for legal purposes
Mechanistic toxicology 
Is focused on determining the mechanisms by which substances exert toxic effects
Regulatory toxicology 
Uses toxicologic data to establish policies regarding exposure limits for toxic substances
Medical or clinical toxicology
Focuses on the diagnosis and treatment of toxic effects in humans
In principle, the concepts are similar to those of PK and PD
Paracelsus: '"All things are poison and nothing is without poison, only the dose permits something not to be poisonous."'
Even water in excess can exert toxic effects (water intoxication) by disrupting electrolyte balance
Poison 
Any substance that may disrupt biologic function and potentially kill an organism
Toxin 
A poison of biologic origin that does not have the ability to replicate
Venom 
A toxin that is injected into the victim by an organism (e.g., bee sting, snake bite)
Toxicant 
A general term that refers to any harmful substance and is generally interchangeable with poison
Drug overdose 
The ingestion or application of a drug in greater quantities than are recommended or generally practiced
Toxicokinetics 
Similar to PK, it refers to absorption, distribution, metabolism and excretion of toxic substances
Toxicodynamics 
Similar to PD, it refers to interaction between toxic substances and molecular targets to generate toxic effects
General mechanisms of toxicity
Physical
Chemical
Pharmacologic
Biochemical
Genomic (genotoxic)
Mutagenic (carcinogenic)
Immunologic
Teratogenic
Toxicity can be caused by both therapeutic and nontherapeutic substances
Toxic effect may be a direct extension of the drug's primary action, unrelated to the primary therapeutic effect but related to the general pharmacology of the drug, or have no relationship to the therapeutic action of the drug
Major toxic effect organs 
Liver
Kidney
Heart
Lungs
Brain
Liver 
Exposed to a high concentration of toxic substances, receives a large proportion of systemic blood flow, has high metabolic activity that generates reactive intermediates
Kidney 
Receives a high proportion of the cardiac output, many toxic substances are excreted by the kidney and concentrated in the urine
Heart 
Total blood volume passes through the heart, so it is exposed to all blood-borne toxicants
Lungs 
Have extremely large surface area for interaction with toxicants, particularly those airborne, and total cardiac output passes through the lungs
Brain 
A critical target organ because of its central role in homeostasis, so toxicants affecting the brain may influence multiple systems and result in widespread systemic toxicity
Poisoning remains a significant public health issue that affects up to approximately 5% of the population per year in industrialized countries
Many countries have established national poison control centers that can serve as valuable sources of information
Key questions in toxicology 
How much risk is associated with a particular substance?
Under what conditions does this risk become apparent?
The level of acceptable risk will vary, and very toxic substances may be used therapeutically if the benefits outweigh the risks
Factors in risk assessment
Hazard identification
Dose response
Exposure assessment
Clinical status
Patient characteristics
Many countries have established national poison control centers that can serve as valuable sources of information. The WHO maintains a directory of these centers (see Websites).
Risk Assessment 
Key questions in toxicology are: how much risk is associated with a particular substance and under what conditions does this risk become apparent? The level of acceptable risk will vary.
Key factors in risk assessment
Hazard identification
Dose response
Exposure assessment
Clinical status
Patient characteristics
Hazard identification 
What substances are involved and what are the adverse effects of each substance? Knowledge of the physicochemical properties, toxicokinetics, and toxicodynamics of the suspected toxicant(s) is invaluable in designing treatment strategies.
Dose response 
Is there a known dose response relationship for the toxic effects of the toxicant? Do toxic effects mirror [plasma]? At what [dose] do toxic effects appear?
Exposure assessment 
Includes estimation of the degree of exposure, whether the exposure was acute or chronic, the route of exposure, and the time since exposure.
Clinical status 
In many cases, information about the degree and time of exposure may be lacking. In such cases, careful determination of the clinical status of the patient coupled with knowledge of potential hazards can assist in determining the type of toxicant, the suspected time course, and the treatment protocol. Recognition of compromised airway, circulatory, or neural function requires immediate supportive measures.
Patient characteristics 
Specific characteristics such as anthropomorphic characteristics, genetic background, and preexisting conditions of each patient also factor into risk assessment. Some (e.g. weight) may affect the course of poisoning indirectly, whereas others (e.g. alcoholism) may have a more direct effect by influencing the production or elimination of toxic substances. Genetic polymorphisms may affect absorption, biotransformation, or elimination of toxicants.