Analytical Toxicology Introduction PDF

Analytical Toxicology Introduction By Dr. Nagwa M. Ghandour Professor of Forensic Medicine and Clinical Toxicology Faculty of medicine - Assiut University 2024 Table of contents 1 2 TOXICOLOGY WHA...

Analytical Toxicology Introduction By Dr. Nagwa M. Ghandour Professor of Forensic Medicine and Clinical Toxicology Faculty of medicine - Assiut University 2024 Table of contents 1 2 TOXICOLOGY WHAT IS A POISON? 3 4 TYPES OF POISONING CLASSIFICATION OF POISON  5 6 KINDS OF DOSE CONDITIONS MODIFYING THE ACTION OF POISONS 7 8 OUTCOME OF POISONING ENTRANCE OF POISON 9 DIAGNOSIS OF POISONING  TOXICOLOGY : is that branch of science which deals with the study of poisons. TOXIC – means poison OLOGY – means science Regarding: Origin Physical and chemical properties Physiological action Treatment of their effect and methods of detection.  What is a poison? ➔ POISON: is any substance, when introduced into the body and absorbed through the blood stream , can act chemically and produce dangerous effect or destroys life. ➔ Any agent may be poisonous at a given dose and route of administration  CLASSIFICATION OF POISON 1. According to the 2-According to 3-According to the origin, source or pharmacological action organs affected nature 4.According to Methods of Isolation  Plants: e.g. opium, atropine, strychnine and digitalis. Metals: e.g. Lead, mercury, antimony, arsenic, iron and phosphorus. Animal: e.g. Snake bite, scorpion sting and spiders. Synthetic: e.g. Barbiturates, tricyclic antidepressants, analgesics…etc 1-According to the origin, source or nature:  Local action : Corrosives Remote action: Plant Alkaloids Both local and remote actions: Some Organic acids 1. 2-According to pharmacological action:  Liver: Paracetamol, arsenic, phosphorus, iron…etc Heart: Digitalis, beta blockers, calcium channel blockers, aconite, antimony…etc. Kidney: Mercury, cadmium, phenol…etc. Neurotoxins: Convulsants & depressants. 1. Ocular: Methanol, nicotine and lead. Dermal: Corrosives, arsenic and mercury. Respiratory: Hydrocarbons & irritant 3-According to the organs gases. affected  Volatile Poisons and those isolated by distillation ( Alcohol, phenol, chloroform) Non Volatile Poisons – those that are isolated by extraction with organic solvents (Alkaloids, organic 1. Acid ) Metallic Poisons (Arsenic, mercury) And Other Substances for which special method of isolation are required ( some acids and alkali metals 4.According to Methods of are extracted with water). Isolation  Types Of Poisoning Poisoning: It is the phenomenon that occurs by the ingestion of any poisonous substances or coming in contact of any poisonous substances. 1. From medical point of view 2-From the Legal point of view  1. Acute Poisoning: Due to either taking a strong poison in single dose or several doses at a short interval. 2. Chronic Poisoning: It is produced by taking several small doses at long intervals From medical point 3.Acute on top of chronic: Acute poisoning of view with a background of chronic exposure to (Mode of Exposure) the toxin. a. Subacute toxicity (2-4 Weeks) b. Subchronic toxicity (≈3 months) c. Chronic toxicity (>3 months)  1. Accidental Poisoning – those in which the poison was taken without the intention to cause death. It may be taken by mistake or without knowing that it is poisonous. 2. Suicidal Poisoning – those in which the poison was taken by the victim voluntarily for the purpose of taking his own life From Legal point of 3.Homicidal Poisoning – those in which the view poison was given with intent to cause death to the victim. (circumstances) 4. Undetermined OR Therapeutic Errors – those in which the history is hazy as to how the person was obtained and why it was administered. CONDITIONS MODIFYING THE ACTION OF POISONS The individual the poisons 1. Age and sex 1.Physical State or form of 2. Health the poisons 3. Habit – repeated taking of 2. Dilution small dose of drug 3.Solubility of the poisons 4. Idiosyncrasy – a term applied 4. Modes of administration to the individuals who exhibit 5. Chemical combination unusual reactions to certain 6. Dose substances 5. Diseases 6. Food 7. Sleep  KINDS OF DOSE 1. Safe Dose –not cause harmful effect 2. Toxic or Poisonous Dose – is harmful to both healthy and sick 3. Lethal Dose – kills 4. Minimum Dose – is the smallest amount that will produce the therapeutic effect without causing harm 5. Maximum dose – is the largest amount that will cause no harm but at the same time produce the desired therapeutic effect. ENTRANCE OF POISON Poison May Enter the Body Through: 1. Mouth and are absorbed into the circulation after passing through the stomach and intestinal wall. 2. Nose and enter the blood from the upper respiratory passages or lungs. 3. Eyes, Transdermal 4. Rectum, vagina, urethra, bladder 5.Injection (SC,IM,IV)  Outcome of poisoning: Full recovery: The return to previous health without any sequalae after treatment. Delayed recovery: Recovery is delayed without sequalae after treatment of the acute phase. Sequalae: A persistent disability after recovery from poisoning. Death: Due to respiratory failure, cardiovascular collapse, seizures, hyperthermia, and /or other organ dysfunction. 17  DIAGNOSIS OF POISONING is very difficult because of: 1. The large number of poisons and the factors modifying them 2. Some of the symptoms observed in cases of poisoning are also seen in certain diseases.  The Forensic Laboratory is responsible for demonstrating the absence or presence of chemical substances in biological and non- biological specimens in connection with medico-legal investigations. The laboratory must be capable of analyzing a wide variety of toxic substances.  He must be a first-rate analytical chemist and be knowledgeable about the effects of poisons. He must know the 'older' techniques in addition to the newly evolving ones.  Information necessary for the laboratory Suspected agents: The content of toxicology screens varies among laboratories. Although a standard screen may not include the suspected agent, if alerted beforehand the laboratory may be able to modify procedures as needed in order to search for the suspected agents first. Suspected dose: Analytic sensitivities vary among laboratories, and some facilities may not be able to detect therapeutic concentrations of certain drugs in their routine screens. Knowledge of the approximate dose ingested is important because in certain cases the use of more sensitive analytic methods designed for therapeutic monitoring, not screening, may be necessary. Time of ingestion and sampling: knowledge of both the ingestion and sampling time is necessary to determine the degree of drug absorption Clinical presentation: knowledge of the clinical presentation helps the laboratory to select the most appropriate screening procedures. Location of the patient.  Choice of specimen Qualitative versus quantitative tests. No single specimen type is universally appropriate for identification of toxic agents. The selection of specimen type is based on both the pharmacokinetics of the suspected agent and laboratory methodology. In general, Quantitative tests are performed on serum or whole blood; qualitative tests are performed on urine and gastric contents. The major exception to this rule is quantitation of heavy metals, generally performed on urine, which must be collected in acid-washed, metal-free containers. PRESERVATION OF SPECIMENS FOR TOXICOLOGICAL EXAMINATION 1. Blood – place in test tube with a sodium oxalate or anticoagulant Refrigerated with solid carbon dioxide (dry ice) good for 72 hrs. ❖ Alcohol- Do not use alcohol or similar preservative since denaturants will give false and misleading results in the analysis. ❖ Formalin – extremely undesirable as preservative of specimen for toxicological examination since it will seriously interfere with the test for most organic poisons. 2.Urine: collect 50 to 75 ml in a plastic container with no preservative. Urine is well suited to toxicological and chemical analysis for a number of reasons. It is an aqueous, protein-free solution, noninvasive, collected in large quantities, and most drugs are concentrated in urine, both parent drug and the characteristic metabolite(s) are present in urine, aiding in qualitative identification.  3.Gastric contents: Collect 50 to 75 ml in a plastic container with no preservatives. 4.Nonbiologicals (pills, air samples, clothes…etc) : may contain higher concentrations of the suspected agent and may be simpler to analyze than body fluids.  Schemes for the detection of poisons 1.The examination will first be visual both by naked eyes and with the aid of a suitable magnifier. In this way recognizable fragments of seeds, leaves or other parts of poisonous plants may be picked out and after botanical identification, indicate the lines along which chemical analysis should proceed. Crystals of organic or inorganic substances may be identified and suggest the confirmatory tests to be applied. 2.Careful attention should made of any odor which may be associated with some chemical group for which search may be done. 3.The reaction of gastric and internal contents, urine or liquid in vessels suspected of containing a poison should be tested. For this a 'universal indicator' litmus, phenolphthalein, methylo orange are very useful. If this preliminary examination has given reasonably clear indications to the poison or class of poison used, the way is clear for appropriate chemical analysis. 4.Some Substances that require special methods of isolation such as essential oils and insecticides are treated in a special manner. I. A sample is submitted to distillation alone or with a current of steam. This process effects the separation of volatile poisons if present. II. The Reinsch test for the common metallic poisons, arsenic, antimony, bismuth, mercury and silver is applied on a part of the sample. III.The third step is the search for the organic poisons non-basic and basic compounds. The procedure is a purification, one in order to get a protein free residue from which the poison can be isolated from acidic medium for the non basic compounds or alkaline medium for the basic compounds by organic solvents. 4) After the separation of the non-basic and basic compound the somewhat pure substances are tested by: a. Color (spot test) tests. b. Crystal tests. c.Spectophotometric analysis d.Immunoassays. e.Chromatographic analysis.