Clinical and Forensic Toxicology. Roger L. Bertholf, Ph.D. Associate Professor of Pathology Chief of Clinical Chemistry & Toxicology. Toxicology Disciplines. Industrial Toxicology Toxic exposures in the workplace Product testing Molecular Toxicology Veterinary Toxicology
Une image / un lien ci-dessous est fourni (tel quel) pour télécharger la présentation
Politique de téléchargement : le contenu du site vous est fourni TEL QUEL pour votre information et votre usage personnel ; il ne peut être vendu, concédé sous licence ni partagé sur d’autres sites sans l’accord de son auteur.Le contenu vous est fourni TEL QUEL, pour votre information et votre usage personnel uniquement.Téléchargez la présentation en cliquant sur ce lien.Lors du téléchargement, si vous ne parvenez pas à télécharger une présentation, l’éditeur a peut-être supprimé le fichier de son serveur.Pendant le téléchargement, si vous ne parvenez pas à obtenir une présentation, le fichier a peut-être été supprimé par l’éditeur.
F I N
Plus de contenu associé
Transcription de la présentation
Clinical and Forensic Toxicology Roger L. Bertholf, Ph.D. Associate Professor of Pathology Chief of Clinical Chemistry & Toxicology
Clinical Toxicology • The branch of toxicology that is concerned with human poisoning • Drug overdoses • Pharmaceuticals • Drugs of abuse • Toxic exposures • Environmental • Occupational • Accidental
Anticholinergic Poisoning • Belladonna, Jimsonweed, antihistamines, phenothiazines, certain mushrooms (Group V), scopolamine, tricylics, OTC sleeping pills • Mnemonic: Red as a beet, dry as a bone, mad as a hatter, hot as a stone, bowel and bladder lose their tone, and the heart runs alone. • Physostigmine is antidote
Nicotinic Poisoning • Insecticides, tobacco, black widow spider venom • Tachycardia, hypertension, muscle fasciculations, weakness, paralysis • d-turbocurarine is antidote
Ethanol • Most common (by far) toxic exposure • Often associated with: • Trauma • Loss of consciousness • Other drug exposure • Frequently involves medico-legal interventions
Ethanol Pharmacodynamics Loss of consciousness Staggering gait CNS impairment Slurred speech Blood alcohol concentration (mg/dL, %) Impaired motor coordination Loss of inhibition 0 0.05 0.10 0.15 0.20 0.25 0.30 0.35
Ethanol distribution Cells 82% H2O Serum 95% H2O EtOH Serum (or plasma) ethanol is 5 – 15% higher than whole blood ethanol
Enzymatic Ethanol Methods • ADH is selective, but not specific for ethanol • Other enzymes that involve NADH can potentially interfere
Non-ethanol Alcohol Poisoning • Alcohol toxicity is primarily related to metabolites • Ethanol Acetaldehyde Acetate • Isopropanol Acetone • Methanol Formaldehyde Formic acid • Ethylene Glycol Oxalate and Hippuric acid • Non-ethanol alcohol exposures can be detected by an increase in the osmol gap
The Osmol Gap • Colligative properties depend on the number of of dissolved particles • Boiling point • Freezing point • Osmolality is usually determined by freezing point depression • The difference between the calculated and measured osmolality is the Osmol Gap
Salicylate Poisoning • Toxic symptoms develop at serum concentrations exceeding 250 mg/L • Serum concentrations exceeding 1000 mg/L can be fatal • Symptoms are tinnitus, hyperventilation, respiratory failure, convulsions, coma • Lab results reveal mixed metabolic acidosis/respiratory alkalosis • Acidification of urine enhances elimination
Acetaminophen Poisoning • Toxic symptoms develop at serum concentrations exceeding 100 mg/L • Serum concentrations exceeding 450-500 mg/L result in severe liver damage • Symptoms may not appear until hepatic failure is evident and irreversible • Antidote is N-acetylcysteine
Carbon Monoxide Poisoning • Can be deliberate or accidental • CO is odorless • CO binds irreversibly to hemoglobin, displacing oxygen • CO-Hb (carboxyhemoglobin) can be measured on a co-oximeter • Different max than O2-Hb (oxyhemoglobin) • Hyperbaric oxygen may be indicated
Metal Poisonings • Iron is most common (particularly in kids) • Ferritin • Deferoxamine is antidote • Arsenic is most notorious • Acute vs. chronic • Inorganic vs. arsine gas • BAL (dimercaprol) is antidote
Metal Poisonings • Lead • Most cases in children exposed to lead paint • Blood lead >10 g/L is considered risk • Monitor with -aminolevulinic acid dehydratase • EDTA is antidote • Mercury • Organic vs. inorganic • Neurotoxic, nephrotoxic, teratogenic
Spot Tests for Metal Poisoning • Reinsch Test: Copper wire turns. . . • Shiny silver: Mercury • Dull black: Arsenic • Shiny black: Bismuth • Dark purple sheen: Antimony • Gutzeit test for arsenic • Acidification produces arsine gas, which discolors silver nitrate paper • Iron reacts with potassium ferricyanide and ferrous sulfate to produce Prussian Blue
TLC Stains • Ninhydrin: 1o or 2o amines (sympathomimetics) • Mercuric Sulfate: barbiturates, glutethimide, phenytoin (white ppt) • Diphenylcarbazone: same as mercuric sulfate (blue or purple spot) • Iodoplatinate: 3o amines • Dragendorf's reagent: methaqualone • UV absorption at 254 nm: benzodiazepines, barbiturates, methaqualone • Fluorescence at 366: Benzodiazepines, quinine, quinidine
Patient consent not required Identity of specimen is presumed Screening result is sufficient for medical decision Results are used for medical evaluation Subject must consent to be tested Identity of specimen must be proved Only confirmed results can be considered positive Results are used for legal action Medical vs. forensic drug testing
Illegal Drug Use in the U.S.(1998 Household Survey) • 13.6 million Americans use illicit drugs • 25 million in 1979 • 8.3% of youths age 12-17 use marijuana • 14.2% in 1979 • 1.8 million Americans use cocaine • 5.7 million in 1985
History of workplace drug testing • 1960s – 1970s: The Department of Defense begins testing military personnel for illegal drug use. • 1986: President Reagan establishes the “Federal Drug-Free Workplace”. • 1988: Mandatory Guidelines for Federal Workplace Drug Testing Programs is published in the Federal Register.
The “NIDA” program • NIDA (now SAMHSA) requirements for drug testing were drafted by Research Triangle Institute • The RTI established the National Laboratory Certification Program (NLCP) • Drug testing for federal agencies (DOT, NRC, etc.) must be performed in a NLCP-certified laboratory
Florida Drug-Free Workplace • The Florida HRS (now AHCA) established a drug-free workplace program in 1990 • Specifications for the State of Florida program are similar to federal requirements, but there are notable differences • Employees of Florida Drug-Free Workplace-compliant businesses must be tested in AHCA-licensed laboratories
Low cost Fast Semi-quantitative High sensitivity Low specificity High cost Slow Quantitative High sensitivity High specificity Screening vs. Confirmation
A confirmatory method should . . . • Utilize the most accurate (specific) testing method available • Have sensitivity equal to or better than the screening method • Be economically feasible • Be simple enough to standardize across many laboratories • Produce results that are legally defensible
GC/Mass Spectrometry Detector Injector Ionizer Mass Filter GC Column Data System
Focusing lens From GC + + To MS + Ion volume (or source) (-) Electron impact ionization Power supply Filament e- e- Collector (+)
