毒物分析 Clinical Toxicology 授課教師:賴滄海教授 03-30-2009 The categories with the largest number of deaths are as follows: Salicylate Aspirin (Acetylsalicylic acid) has analgesic, antipyretic and antiinflammatory properties. Therapeutic concentration: analgesic-antipyretic (lower than 60 mg/L) anti-inflammatory (150 to 300 mg/L) Aspirin interferes with platelet aggregation and thus prolongs bleeding times. Pharmacologic effect of salicylates Stimulate central respiratory center Uncoupling of oxidative phosphorylation Enhance anaerobic glycolysis, Inhibite Kreb’s cycle and transaminase enzyme. Respiratory alkalosis predominates in children over age 4 and in adults. Fig.25-13. Nomogram for estimating the severity of acute salicylate intoxication.(From Done, A.K.:salicylate intoxication: Significance of measurements of salicylate in blood in cases of acute ingestion. Pediatrics, 26:800, 1960. Reproduced by permission of Pediatrics.) Symptoms of salicylate intoxication Tinnitus (耳鳴) Diaphoresis (出汗) Hyperthermia Hyperventilation Nausea, vomiting Acid-base disturbances CNS effects lethargy, disorientation, coma and seizures. Respiratory alkalosis (19%) Metabolic acidemia (15%) Combined (61%) Treatment Ipecac to induce vomiting Correction of acid-base and electrolyte imbalance, activated charcoal to prevent absorption Hemodialysis Screening Assay for Acetaminophen and Salicylate Acetaminophen After acid hydrolysis, the sample was reacted with ocresol in basic solution to show blue color. Salicylate Salicylates reacted with Ferric chloride solution to produce a violet color reaction. (Interferant: Diflunisal, labetalol, keto acids) Methemoglobin Less than 1.5%of total hemoglobin in normal blood Caused by methhemoglobin reductase deficiency or ingestion of nitrites, nitrates, phenacetin, phenazopyridine, sulfonamides, sulfones, aniline dyes. Determined spectrophotometrically at 630mm Alcohols Ethanol Methanol Ethyleneglycol Isopropylalcohol Ethyleneglycol 資料來源: 2007年5月7日自由時報 Effects of Ethanol Cardiovascular system—Increase high-density lipoprotein Central nervous system-CNS depression (Respiratory center, coma, death) Gastrointestinal tract-Stimulate the production of gastric juices Kidney-Diuretics ( Inhibit the secretion of ADH) Liver-Fatty liver,Cirrhosis Fetal alcohol syndrome Determination of Ethanols 1. 2. 3. Enzymatic Headspace-GC Breath-testing device (amount of ethanol in 1mL of blood equals to 2100mL of breath air) Henry’s law Carbon Monoxide Lithium Use to treat manic-depressive illness. It enhances reuptake of neurotransmitters, thus produces sedating effect on the CNS Toxicity apathy, sluggishness, drowsiness, lethargy, speech difficulties, irregular tremors, muscle weakness, ataxia, epileptic seizures. Determined with ISE or Atomic Absorption Spectrometry, Flame emission photometry Lead Toxicity Inhibits amino levulinic acid dehydratase (causes accumulation of protoporphyrin in RBC) Forms covalent bonds with the-SH group of cysteine in proteins (Nerve cells are particular susceptible) Determination whole blood was analyzed with atomic absorption spectrometry •Fig.25-27. Effects of inorganic lead on children and adults (lowest observable adverse effect levels). (From Royce, S.E., Needleman, H. L., Eds.: Case Studies in Environmental Medicine: Lead Toxicity. U.S. Public Health Service, ATSDR, 1990.) Iron Toxicity Severe irritation of the epithelial lining of the GI tract and results in hemosiderosis, which may develop into hepatic cirrhosis. Hemosiderosis A term used to imply iron overload without associated tissue injury Determined spectrophotometrically after reaction with Bathophenanthroline or Ferrozine