Understanding Intoxications: The Dose Makes the Poison

1. INTOXICATIONS Prof. Özge Köner Anesthesiology Dept

2. Paracelsus(1493–1541) "Poison is in everything, and no thing is without poison. The dosage makes it either a poison or a remedy." Dose make the poison

3. THE POISONOUS APPLE

4. War & terrorism Suicide Biological factors Occupational Home accident Environment

5. Children 1)Gas, smoke & vapor 2) Drugs: Fe preparates Analgesics Cleaning material 3)Toxic plant & animal venom Adults 1)Gas, smoke & vapor 2) Drugs: Tricyclic Antidepressants Narcotics Teophyllin 3)Toxic plant & animal venom Toxins

6. POISON RESPIRATORY SYS SKIN GIS BLOOD ORGAN & TISSUE DISTRIBUTION TOXICITY Storage Elimination Metabolism Active Metabolite

7. Asetaminophen Etilen glikol Metanol Arsenic Benzen Kloral hidrate Chloroform Codein Anilin Isopropanol Parathion Sulfanilamid Tri-o-kresol fosfat Heptachlor Imipramin Dimetil nitrozamid Karbon tetrachlorur Metabolism into a more toxic substance

8. Skin - Gastrointestinal System Scrotum>Forehead>Axilla>Head > Abdomen > Dorsum of hand-foot (Stratum corneum of dorsum of the hand & foot is 100-400 times thicker). • Esophageus epitelium prevents absorbsion. • Maximum absorbsion is from Small Bowel (pH=6), stomach follows SB (pH=1-3).

9. Respiratory System • Gases, solvents, vapor • Aerosol, particules, smoke a) Mucous trap in trachea b) Phagositosis in lungs lymphatic system. Clara cells: • Clara cell protein • Prevent airway collapse • Increased serum levels decrease LUNG DAMAGE. Detoxification of the toxic subtances (Along with CYP-450)

10. Death of Sokrates with“Hemlock” Death penalty by poison Jacques-Louis David

11. Basics of evaluation • Mental status: agitated vs Sedated? • Pupils • Skin • Vital signs • Mucous membranes • Odors

12. Lab evaluation • ECG • Blood glucose • Blood gas • Chemistry • Complete Blood Count • Paracetamol, aspirin, Ethanol blood level • Urinary analysis • Chest XR,

13. Basics of treatment • NO ANTIEMETICS • Gastric decontamination • Active charcoal • Give within 1 hr. Ineffective in alcohols, metals, caustic agents • Aggressive supportive therapy • Iv line, fluids, monitorization • Antidotes • Dialysis

14. Baldıran otu, Ağu otu, Yılan otu(Conium Maculatum, Hemlock) • Piperidine alkaloid coniine. • 6-8 gr fresh leave lead to death.Lethal dose:12 gr/kg. • Nausea, vomiting, hypersalivation, midriasis, diplopia, numbness, tachycardia-bradycardia, respiratory insufficiency., • Neurotoxin: CNS depression. • Hepatotoxicity, nephrotoxicity

15. Grayanotoxin poisoning(Deli Bal Zehirlenmesi) • Flowers of the Rhododendron plant. “Rhododendrondisease”. • Rhododendron Ponticais a plant of Black Sea region. It is also grown in China, North America, Korea, Caucasia, Georgia, British islands, Spain & Portugal.

16. Grayanotoxin poisoning • Severity of the intoxication depends on the ingested amount of honey. Intake < 30 g may be safe. • Toxin binds to Na channels of the cellular wall. Incessant depolarization fascilitates calcium entry into the cell. Toxineffects • Skeletal & cardiac muscles, nerves and CNS. • Confusion, AV block, hypotension, shock.

17. Grayanotoxin poisoning Lord Blackwood

18. Snake Poisoning • There are 12 poisonous and 29 nonpoisonous snake species in Turkey. • Poisonous snakes: Viperidae,Elapidae(Engerek, Kobra)

19. Snake Poisoning • Skin Necrosis: Local swelling, lenf node enlargement & compartment syn, rhabdomyolysis • Renal insufficiency • Hematoxin: Prevents clotting: Bleeding & DIC. • Neurotoxin: Prevents neurotransmitter release from presinaptic motor nerve endings; blocks postsynaptic Ach receptors. Respiratory insufficiency • Cardiotoxin: Hypotension & cardiac arest.

20. LEAD POISONING • CNS: Encephalopathy, Coma, convulsion • Nephropathy • Hypertension • Blocks heme synthesis: • Microcytic anemia • Reticulocytosis • Increased urinary δ-ALA • Gingival bands • Opaque metaphyseal bands in upper and lower tibia & femur *Science vol.315,1669.2007 *Troeska W. Great Water pipe Disaster,2006

22. Lead POISONING Symptoms: Digestivesystemdisorders, Irritability, Deafness. • Hairand bone sampleanalysis of thecomposer has revealedthatLudwig van Beethovenwasdied of chronicleadintoxication. 1770-1827

23. Lead poisoning • Leaded gasoline • Food (Spice, herbs) • Pica • Lead pigmented paints • Occupational • Retained bullet • Pipes, ceramic, glass • IV fluid (09% saline) • Seizure control, brain edema treatment • Chelating agents: intestinal irrigation with “polyethylene glycol” • Encephalopathy Ca-EDTA, BAL (British anti-lewisite) • No encephalopathy Ca-EDTA, DMSA (succimer) • Oral d-penicillamine ? More side effects THERAPY:

24. MERCURY POISONING • Composition of dental amalgam • 49% Mercury • 35% Silver • 9% Zinc • 6% Copper Seafood,batteries,thermometers • > 1000 died in Minnamata (Japan) between1932-68 due to sea food which was contaminated with mercury., • 459 died in Irak in1971 due to the seed grains treated with a mercury based fungucide. • Methyl mercury inhibits Piruvat Dehydrogenase irreversibly.

25. MERCURY POISONING Neurotoxicity: Ataxia, tremor, seizures Psychiatric: Anxiety, agitation Visual deficits Respiratory distress syndrome (mercury vapor) Nephrotoxicity Nausea, vomiting, diarrhoea

26. MERCURY POISONING TREATMENT • Chelating agents: • Oral DMSA/Succimer (2,3-dimercaptosuccinic acid) may enhance urinary Hg excretion; (penicillamine more side effect) • IMBAL (British Anti-Lewisite) avoid if metallic or organic mercury intox • GIS decontamination (in acute events): Active Charcoal Gastric lavage (solutions containing milk, egg white) • Whole bowel irrigation along with polyethylene glycol solution

27. Tetrachloro-dibenzo-dioksin (TCDD) • Accumulates in fat • Half life is 7 years • Contaminated water, food; • >90% of human exposure is through food (meat & dairy products, fish, shellfish, egg, milk cheese) • Chloracne • Carcinogen in high dose • Thyroid disease • CNS-Peripheric nerve pathology • Diabetes • Immune system defects

28. Tetraklorodibenzo-p-Dioksin (TCDD) by-product of industrial waste. • Coal fired utilities • Burning treated wood • Municipal waste incinerators • Trash burn barrels • Metal smelting • Diesel trucks • Manufacturing of some herbicides and pesticides

29. Agent Orange(TCDD) • USA airforce released 45 million L“Agent Orange” to kill the Vietkongs hiding into the forest for 6 years during Vietnam war. JM Stellmann, Nature, 17 April 2003, p.681

30. PARACETAMOL POISONING • Max daily adult dose: 4 gr. • 90% metabolized in liver, excreted in urine. • 10% metab via CYP2E1 to toxic NAPQI (N-acetyl-p-benzoquinone imine), which binds to hepatocytes, lead to hepatic cell lysis. • Fatal/non-fatal liver necrosis. • Chronic alcohol use increases the toxicity incidence. Peak effect occurs within 1 hour

31. PARACETAMOL POISONING Treatment: • GASTRIC LAVAGE • ACTIVE CHARCOAL: Single dose via NG route 1 g/kg within 1, 2 hrs after ingestion. • İV NAC: N-asetilsistein increases Glutathion synthesis. • Symptomsoccur 2- 12 hrsafteringestion: • Nausea, vomiting, diaphoresis, pallor, lethargy, malaise, abdominalpain • Hepotomegaly, increasedliverenzyme, prolonged PT. • Serum levelshould be measured.

32. PARACETAMOL • NAC: should be startedwithinfirst 8-10 hrs • NAC Continueduntil: 36 hrsafteringestion& plasmaparacetamollevelsareundetectable & transaminasenormal, discontinue NAC therapy. • NAC iv: 150 mg/kg loading in 200 mL 5%DW over 15 min • Maintenance: 50 mg/kg in 500 mL 5%DW over 4 hrs 100 mg/kg in 1000 mL 5%DW over 16 hrs

33. RUMACK-MATTHEW NOMOGRAM

34. ULUSAL ZEHİR DANIŞMA MERKEZİ NATIONAL POISON CONTROL CENTER CALL

35. ETHANOL POISONING • Lethal adult dose 5-8 g/kg. %80 %20

36. Treatment • IV access • Fluid therapy • Airway maintenance, respiratory support (if required) • In coma: Thiamin 100 mg (to prevent Wernicke- Korsakof syn & hypoglycemia)

37. METHANOL • Minimal lethal dose: 30 mL (150-200 mg/dL). • Toxic metabolites: Formaldehide & formic acid. • Symptoms occur within 1-24 hrs.

38. Methanol poisoningTreatment • IV access, fluid therapy • Gastric lavage within 2-4 hrs. • Metabolic acidosis treatment: folinic acid • Ethanolto saturate alcohol dehyrogenase(blood level 100-150 mg/dL) • Fomepizole: 4-methylpyrazole (alcohol dehyrogenase inhibitor) • Hemodialysis

39. CARBON MONOXIDE • Fires, malfunctioning stoves, exhaust systems, heaters, suicide • High affinity to Hb (240 times higher than O2) • Impairs O2 delivery: hypoxia. Diagnosis: • SpO2 is not sensitive • Blood COHb level (normal < 3%) should be assessed. • Smoke inhalation: detect blood cyanide levels.

40. CARBON MONOXIDE Headache, Nausea, Dizziness, Vertigo, Fatigue, Confusion, COMA, CONVULSION, STROKE. Angina pectoris, Myocardial ischemia/infarction, Troponin , Hypotension, Supraventricular/Ventricular dysrhythmia

41. CARBON MONOXIDE THERAPY: • 100% O2 inhalation • Hemodynamic Monitorization • IV access • Hyperbaric O2

42. LETHAL INJECTION BY GOVERMENT THIOPENTAL : 2-5 g PANCURONIUM POTASSIUM USA: Executions since 1976: 1429 Prisoners on death row: 3,108 (as of April, 2013)