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TOXICOLOGY I. The fate of poison in organism

TOXICOLOGY I. The fate of poison in organism. M. Balíková. What is the poison. The substance which after the resorption into the blood stream can induce the harmful effects to the organism Toxic effects : contemporary with permanent damage to organs fatal

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TOXICOLOGY I. The fate of poison in organism

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  1. TOXICOLOGYI. The fate of poison in organism M. Balíková M. Balíková: The Fate of Poison

  2. What is the poison The substance which after the resorption into the blood stream can induce the harmful effects to the organism Toxic effects: • contemporary • with permanent damage to organs • fatal Mutual action between poison and organism: PHARMACODYNAMICS (What does the poison to the organism?) PHARMACOKINETICS (What does the organism to the poison?) M. Balíková: The Fate of Poison

  3. The fate of poison in organism • Application mode and bioavailability,metabolism Inhalation-Sniffing-Injection-Ingestion-Dermal • Resorption into blood stream • Distribution into tissues • Biotransformation into metabolites • Elimination ways: a) Urine – polar compounds b) Feaces – lipophilic compounds c) Lungs – gases, volatiles d) Hair – deposits of basic compounds above all e) Saliva – hydrophilic/lipophilic f) Sweat – hydrophilic/lipophilic M. Balíková: The Fate of Poison

  4. OVERVIEW M. Balíková: The Fate of Poison

  5. The individual variation in pharmacokinetics and pharmacodynamics a) Variation in effects (receptors) b) Variation in metabolism (enzymes) • Genetics (e. g. variation among races) • Sex • Age • Actual health state • Life style, tolerance • The mode of application, drug mixtures M. Balíková: The Fate of Poison

  6. Biotransformation: Modification of the chemical structure of parent compound in organism, catalysed by enzymes • Metabolites with different potency • Most of enzymes bound in hepatocytes • The liver and the first pass metabolism • Lipophilic compounds – extensive metabolism • Polar metabolites – excreted by urine M. Balíková: The Fate of Poison

  7. 1st phase Oxidation (P450 system) Reduction Hydrolysis 2nd phase-conjugation Sulphuric acid Glucuronic ac. Glycine Cysteine Glutathione Biotransformation: M. Balíková: The Fate of Poison

  8. Oxidation of alcohols M. Balíková: The Fate of Poison

  9. Oxidation of unsaturated bonds M. Balíková: The Fate of Poison

  10. O-Dealkylation M. Balíková: The Fate of Poison

  11. N-Dealkylation M. Balíková: The Fate of Poison

  12. N-Oxidation M. Balíková: The Fate of Poison

  13. S-Oxidation M. Balíková: The Fate of Poison

  14. Oxidative desulphuration M. Balíková: The Fate of Poison

  15. Oxidative deamination M. Balíková: The Fate of Poison

  16. Reduction of aldehydes, ketones M. Balíková: The Fate of Poison

  17. Reduction of nitrogroups M. Balíková: The Fate of Poison

  18. Hydrolysis of esters M. Balíková: The Fate of Poison

  19. Hydrolysis of amides M. Balíková: The Fate of Poison

  20. Hydrolysis of benzodiazepines M. Balíková: The Fate of Poison

  21. Biotransformation of Salicylates CONJUGATION with GLYCINE M. Balíková: The Fate of Poison

  22. CONJUGATION of MORPHINE M. Balíková: The Fate of Poison

  23. Biotransformation of heroin, codeine cccc111111AAAAA M. Balíková: The Fate of Poison

  24. Biotransformationofcocaine M. Balíková: The Fate of Poison

  25. Biotransformation of methamphetamine M. Balíková: The Fate of Poison

  26. Biotransformation of 9-THC M. Balíková: The Fate of Poison

  27. Nonspecific metabolites of some benzodiazepines M. Balíková: The Fate of Poison

  28. Specific metabolites of flunitrazepam M. Balíková: The Fate of Poison

  29. Metabolism of paracetamol Acetaminophen (COLDREX, KORYLAN, PANADOL) Risk of hepatotoxicity Hepatoprotection Antidotum N-Acetylcystein M. Balíková: The Fate of Poison

  30. Why to care about biotransformation • Development of a toxicological method • Interpretation of toxicological findings • Understanding of drug effects • Correct and effective therapy, reduction of adverse drug effects M. Balíková: The Fate of Poison

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