Monday, July 16, 2012

Toxicology







How much do you know about toxicology? Before proceeding try to answer any of these questions first:



. Interesting right?


So what is toxicology?



Toxicology is the study of the adverse effects of chemicals or biological agents on living organisms. It is the study of symptoms, mechanisms, treatments and detection of poisoning.


HISTORY OF TOXICOLOGY


I. Early history: Romans, Greeks, Chinese
Knew of human and animal poisons.
Categorized and studied poisons.
Royal "tasters"…


II. Socrates (470-399 B.C.):
Most celebrated poisoning victim.
Executed by poison hemlock.
Active principle: coniine.


III. 15th Century Europe: Italians developed poisoning into an art form


poisoning became a normal hazard of life.....


1. Venice's "Council of Ten" (City Council)
Put out poisoning contracts on political enemies.
Council transactions: detailed records with name of victim, contractor, type and amount of poison given, results…


2. Borgia: prominent family who practiced "applied toxicology"
Cesare, Lucretia and others.
Killed husbands, wives, lovers, political opponents, churchmen….


3. Catherine de Medici (1519-1589)
Wife of Henry II of France, mother of three French kings, ruler of France.
Early "experimental toxicologist".
Poisoned poor and sick street people under guise of "feeding" and assistance".
Killed political enemies for hire....
Documented signs and symptoms.


IV. Paracelsus full name: Philipus Aurelius Theophastrus Bombastus von Hohenheim-Paracelsus (1493-1514)
Instrumental in logical development of toxicology as science.
Developed concept of "dose".
Action a result of chemical entity -- toxicon.


V. Orfila (1787-1853) Spaniard--personal physician to Louis XVIII


"The Father of Modern Toxicology"
Developed toxicology into a science.
Compiled chemical and biological information on most known poisons.
Proposed the necessity of chemical analysis to prove cause-and-effect.


VI. Mid 1800s:
Analytical methods developed for As, Hg and miscellaneous alkaloids.






Divisions of Toxicology



Forensic toxicology is a combination of analytical chemistry and general principles of toxicology. This is a branch of medicine that focuses on medical evidence of poisoning, and tries to establish the extent to which poisons were involved in human deaths. Forensic toxicology is in many ways a kind of detective work that assembles the subtle clues found in the tissues of the body during autopsy.





Clinical toxicology is the study of diseases and disease states caused by exposure to toxins. This differs from forensic toxicology in that it is most often a study of the living, rather than only the dead. It often involves a study of toxicokinetics, the study of how the levels of toxicants and their metabolites change over time, the time that it takes to eliminate toxicants after exposure, and ways in which the toxic effects of various poisons can be reduced in persons who have been exposed, or how elimination of the toxicant can be increased.





Descriptive toxicology is concerned directly with toxicity testing. In descriptive toxicology, the toxic properties of chemical agents are systematically studied for various endpoints using a variety of different organisms. At what point does a chemical agent cause death to 50% of the animals under study? To what extent are various agents irritating to the eyes? How frequent are birth defects in the offspring when mothers are exposed during pregnancy? Descriptive toxicology is an attempt to characterize the toxic potential of various agents in a wide array of systems.






Mechanistic toxicology is the study of the many mechanisms by which toxins exert their effects on living systems. This is the identification of the targets to which toxins may bind, the tracking of the toxin as it is absorbed and distributed throughout the body, and the process as it is metabolized and altered by the body. This includes study of the stepwise manner in which toxicants enter the system, find their targets, and make incremental changes on the natural system. Mechanistic toxicology also involves the study of how these agents are metabolized and excreted after exposure has occurred.





Regulatory toxicology is the translation of laboratory testing data into policies concerning the applications and uses of chemicals in society, and the limits of allowable exposure in various settings. The regulatory toxicologist compares the toxicity profile with other known toxicants and tries to establish standards for allowable limits that are consistent with other agents with similar effects. Regulatory toxicology is the primary basis for laws that limit exposures for people and for the environment.






Biochemical toxicology is the study of the interactions toxicants have within living systems. Many of the aspects of mechanistic toxicology are found in the study of biochemical toxicology. What are the portals of entry into the living system? How is the agent distributed and metabolized once it is taken in? How does toxicity vary by age, sex, diet, and during pregnancy? What are the sites of action of the toxicant? How is the toxicant eventually metabolized and eliminated











What happens inside the body?


Toxicokinetics is essentially the study of "how a substance gets into the body and what happens to it in the body". Four processes are involved in toxicokinetics.









The study of the kinetics (movement) of chemicals was originally conducted with pharmaceuticals and thus the term pharmacokinetics became commonly used. In addition, toxicology studies were initially conducted with drugs. However, the science of toxicology has evolved to include environmental and occupational chemicals as well as drugs. Toxicokinetics is thus the appropriate term for the study of the kinetics of all toxic substances.




Frequently the terms toxicokinetics, pharmacokinetics, or disposition may be found in the literature to have the same meaning. Disposition is often used in place of toxicokinetics to describe the time-course of movement of chemicals through the body (that is, how does the body dispose of a xenobiotic?).




The disposition of a toxicant along with its biological reactivity are the factors that determine the severity of toxicity that results when a xenobiotic enters the body. Specific aspects of disposition of greatest importance are:

· duration and concentration of substance at the portal of entry
· rate and amount that can be absorbed
· distribution in the body and concentration at specific body sites
· efficiency of biotransformation and nature of the metabolites
· the ability of the substance or it's metabolites to pass through cell membranes and come into contact with specific cell components (e.g., DNA).
· the amount and duration of storage of the substance (or its metabolites) in body tissues
· the rate and sites of excretion







Types Of Toxic Effects


Mutagenicity – ability or capacity of a substance to cause gene alteration (e.g. ionizing radiation, ultraviolet).












Carcinogenicity – ability of a substance to cause abnormal proliferation or reproduction of an abnormal or genetically altered cell (e.g. benzene, asbestos)











Teratogenicity – ability to cause disturbance on the development of embryo causing birth defects (e.g.warfarin)










Toxicology of Drug Abuse



Amphetamines – stimulants which causes mood “high” ,increases concentration and reduce fatigue. In large quantities convulsions and death can occur.



Cocaine – it can be inhaled or injected directly into the bloodstream in small quantities it produces profound psychological well being, increase confidence and alertness through the neurotransmitter dopamine. In extreme cases it produces hallucination and death.



Cannabis – causes euphoria and relaxed inhibitions, increase appetite. In severe cases it include panic, paranoia, fatigue and dangerous behavior.



Opiates – derived from opium poppy plant. Can cause analgesia sedation and anesthesia.










“All substances are poisons. There is none which is not a poison. The right dose differentiates a poison & a remedy.”


- Paracelsus 1532




References:


Bishop, Michael. 2010. Clinical Chemistry, Techniques, Principles, Correlations, 6th Edition, Lippincott Williams and Willkins


Feldman, Robert,2008, Understanding Psychology Eighth edition


Images:


http://www.eoearth.org/article/Toxicokinetics


http://ucanr.org/repository/CAO/landingpage.cfm?article=ca.v065n03p118&fulltext=yes


http://dicksdiet.blogspot.com/2012/06/is-your-toxic-body-poisoning-you.html


http://www.web-books.com/eLibrary/ON/B0/B19/29MB19.html


http://totalpict.com/alcohol%20as%20a%20teratogen