*Dosage errors

 *Idiosyncratic reactions

 *Childhood poisoning

 *Environmental exposure

 *Exposure

  *Chemical warfare

  *Assault/homicide

  *Suicide attempts

3. Therapeutic Toxicology
 
       ->The purpose of this TDM educational guide is to:
->Provide an overview of the history of Therapeutic Drug Monitoring
->Define the role of TDM testing in patient care
->Highlight factors that affect results and interpretation
->Describe the drugs that are most frequently monitored and the methods used to monitor them.

 History:

 
The science of Therapeutic Drug Monitoring grew out of the recognition that:

*Certain drugs have a narrow therapeutic range.
*In concentrations above the upper limit of the range,the drug can be toxic.
*In concentrations below the lower limit of the range, the drug can be ineffective.
*Not all patients have the same response at similar dose.

 Introduction:

     Measuring the blood concentration of certain therapeutic drugs is only on of effective TDM monitoring. Because therapeutic ranges are not absolutes, in many instances expert clinical interpretation of the value is necessary to derive meaning from the result. True TDM testing takes
into consideration all the factors that can affect results, as well as all the factors that can affect interpretation, as described below.

 4. Industrial Toxicology

                       Industrial toxicology is a science that deals with potential harmful effects of materials, products and wastes on health and environments. Toxicology combines the knowledge from the following fields:

Chemistry
Biology
Pharmacology
Physiology
Pathology


 Methods for Assessing Toxicity:
                          Toxicity data for substances come from many sources, most often from controlled studies. Because all chemicals can become toxic under a specific condition, the studies manage not only the amount of chemical involved, but also the conditions of exposure. Nearly all substances fail to exhibit effects at very low exposure levels, but at some level, effects begin to appear. This suggests a threshold level for effects, above which increased concentrations will produce more severe effects. Also, as exposure levels increase, the effects are likely to occur in a larger portion of the population. The following is the list of methods used for the assessment of toxicity:

 Human Experimentation
 Human Experience
 Animal Studies
 Microorganism Testing Human Experimentation: One way to collect data on toxicity of materials is application of the experiment to human subjects. In general, this method is limited to the cases when a serious concern for some disease or illness is present. When a pharmaceutical substance appears to have high benefit and relatively low risk as a result of many other tests, the FDA may approve testing in humans. There is virtually no opportunity to perform general testing of substances on human subjects. Therefore, toxicity data must come from other than human tests.
Human Experience: Sometimes accidental exposures provide opportunities to compile data on the toxicity of a substance. The exposures may be acute or chronic. In accidental exposures there is no control over the exposure and generally it is difficult to draw a conclusion from a single occurrence. Researchers must estimate the exposure levels using epidemiological procedures. After a pattern of disease appears that could be related to some exposure, further testing will be necessary in order to draw a conclusion.
Animal Studies: Most toxicity data come from controlled and replicated animal studies. A problem in toxicity testing involves time. Some substances produce disease in a portion of a population after a long latency period or chronic exposure. To replicate slow exposure or wait for latency periods would be very expensive. As a result, many toxicity test procedures involve high dose rates.
Microorganism Testing: This is a short-term test for toxicity , which monitors the growth patterns of a bacteria with and without exposure to a toxic chemical. These test do not include the variables that animal studies do in the mathematical models for generalizing test results to humans.


5. Forensic Toxicology


                  The first comprehensive work on forensic toxicology was published in 1813 by Mathieu Orifila. He was a respected Spanish chemist and the physician who is often given the distinction of "father of toxicology." His work emphasized the need for adequate proof of identification and the need for quality assurance. It also recognized the application of forensic toxicology in pharmaceutical, clinical, industrial and environmental fields.

                   Forensic toxicology is a discipline of forensic science concerned with the study of toxic substances or poisons, of which there are many thousands. Toxicology encompasses theoretical considerations, methods and procedures from many disciplines including analytical chemistry, biochemistry, epidemiology, pharmacodynamics, pathology, and physiology.

                   Currently, forensic toxicology is the study of alcohol, drugs (licit and illicit) and poisons, including their chemical composition, preparations and identification. It includes knowledge about the absorption, distribution and elimination characteristics of such substances in the body, as well as the manner in which the body reponds to their presence and the factors which determine drug safety and effectiveness. To understand drug action one must know where and how the effects occur in the body.