POISONING AND TOXIC EXPOSURES – TYPES , DIAGNOSIS AND GENERAL PRINCIPLES OF MANAGEMENT

1. POISONING AND TOXIC EXPOSURES – TYPES , DIAGNOSIS AND GENERAL PRINCIPLES OF MANAGEMENT Department of Pharmacy Practice Chalapathi Institute of Pharmaceutical Sciences, Guntur

2. What is a Poison ? “Poison is a substance ( solid/ liquid or gaseous ), which if introducedin the living body, or brought into contact with any part there of, will produce ill health or death, by its constitutional or local effects or both.” Ref- The Essentials of Forensic Medicine and Toxicology Dr. K. Reddy

3. Poisoning “The development of dose related adverse effects following exposure to chemicals, drugs or other xenobiotics.” Ref- The Essentials of Forensic Medicine and Toxicology Dr. K. Reddy

4. EPIDEMIOLOGY • WHO (2004) - 3,46,000 deaths in a year d/t poisoning. • In 2005 – In India 1,13,914 estimated cases of poisoning with insecticides • Commonest cause in INDIA – Pesticides • Reasons – Agriculture based economy - Easy availability pesticides - Poverty

5. Types of poisoning • Acute poisoning – excessive single dose, or several smaller doses of a poison taken over a short interval of time. • Chronic poisoning – smaller doses over a period of time, resulting in gradual worsening eg. Arsenic , Phosphorus , Antimony etc.

6. Nature of poisoning • Homicidal– killing of a human being by another human being by administering poisonous substance deliberately. • Suicidal – when a person administer poison himself to end his/ her life. • Accidental – Eg. Household poisons- nail polish remover , acetone . Depilatories- Barium sulphide 4. Occupational– in professional workers. Eg. insecticides, noxious fumes.

7. Classification of poisons • According to the chief symptoms produced :- • Corrosives . Systemic • Irritants . Miscellaneous • Corrosives • Strong acids- H2SO4 , HNO3 , HCl • Strong alkalis- Hydrates & Carbonates of Na+ , K+ & NH3 • Metallic salts – Zinc chloride, Ferric chloride, KCN , Silver nitrate, Copper sulphate.

8. Classification continued…. • Irritants • Inorganic –i) Nonmetallic – Phosphorus, Iodine Chlorine. ii) Metallic – Arsenic, Antimony, Lead. iii) Mechanical – Powdered glass, hair b) Organic Vegetable – Abrusprecatorius, Castor, Croton, Calotropis. Animal – Snake & insect venom, Cantharides

9. Classification continued……. 3.Systemic • Cerebral • CNS depressants – Alcohol, opioids, hypnotics, general anesthetics. • CNS stimulants – Amphetamines, Caffeine • Deliriant – Datura, Cannabis, Cocaine b) Spinal – Nuxvomica c)Peripheral – Conium, Curare d) Cardiovascular - Aconite, Quinine, HCN e)Asphyxiants– CO, CO2 , H2S 4)Miscellaneous –Food poisoning, Botulism.

10. Routes of administration • Inhalational volatile gas, chemical dust, smoke, aerosol. • Injectable • Intra venous – Benzodiazepines, barbiturates, tricyclic antidepressants etc. • Intramuscular – Benzodiazepines, opioids etc • Subcutaneous – Botulinum toxin • Intra- dermal – Local anaesthetics, organophosphates

11. 3. Oral – Corrosives, organophosphorus 4.Through natural orifices- rectum/ vagina/ urethra Abrusprecatorius, croton, calotropis 5. Through unbroken skin – organophosphorus, Mercury, Lead

12. Diagnosis of poisoning • History – patient witness • Circumstantional evidence • suicide note • containers & potential toxins at scene of discovery • Physical examination • Investigations -Biochemical investigations -ECG abnormalities -Radiology -Toxicologic screening

13. History • Patient • If person is conscious , & immediately brought to the ED, history may be relevant • Mostly patient estimates of drug/ nature of substance ingested are inaccurate. • Witness • What substance/ substances ? • What route/ routes ? • What dose/ doses ? • When and for how long? • H /O psychiatric illness?

14. Circumstantial evidence • Unconscious adults • Empty drug containers/ wrappers /tablet neraby ↓ some sort of poisoning • Tablet particles staining mouth / clothing • Suicide note ↓ Assumption of poisoning

15. Following conditions should arouse suspicion of poisoning :- • Sudden appearance of symptoms after food or drink in an otherwise healthy person • Symptoms – uniform in character, rapidity • Sudden onset delirium, paralysis, cyanosis, collapse etc.

16. Physical examination • General appearance • Neurological status-conscious, confused, comatose. • Glassgow coma scale • Pupillary examination • Normal – Celphos poisoning • Miosis – Opioids, OP poisoning • Mydriasis – TCA, Theophylline, Dhatura, Methanol • Convulsions- Ethylene glycol, Lithium, SSRI • Muscular fasciculations– OP poisoning

17. Vital parameters – • Cardiorespiratory system - PR, BP, RR, Temp • Hypotension with bradycardia :- • Beta blockers, Cyanide, Benzodiazepines, Barbiturates, Opioids, Alchohol , OP insecticides • Hypotension with tachycardia :- • Beta -2 stimulants, Caffeine ,Theophylline, Amatoxin containing mushroom

18. Vital parameters contd…. • Hypertension with tachycardia :- • Sympathomimetics, Ergot alkaloids, Anticholinergics, Alcohol withdrawal • Respiratory depression with failure:- • Barbiturates, Benzodiazepines, Opiates, Sedative- hypnotics, Snake venom • Hyperventilation :- • Amphetamines , Salicylates, Hallucinogens, Cyanide, CO, H2S

19. Vital parameters contd…….. Body tempearture • Hypothermia :- • Barbiturates, Benzodiazepines, Ethanol, Opiates, Cyclic antidepressants • Hyperthermia:- • Amphetamines, Alcohol withdrawal, MAO inhibitors, Anticholinergic agents, Salicylates

20. Examination of Skin colour and lesions • ColourToxin/ poison • Pink Cyanide • Yellow ( jaundice) Phosphorus ,hepatotoxins (Acetaminophen, mushroom ) • Red Rifampicin • Blue (cyanosis) Aniline, Nitrites, . . Methemoglobinemia • Diaphoresis – • Salicylate, OP poisoning • Sympathomimetics, serotonin syndrome • Phencyclidine, alcohol or sedative withdrawal

21. Examination of Skin colour and lesions contd…. c. Bruising • Diffuse ecchymosis:- • Anticoagulant poisoning • Rodenticides d. Needle tracks • I/V abuse :- • Opiates • Amphetamines • Cocaine • May be hidden in groin or interdigital spaces

22. Examination of Skin colour and lesions contd…. e. Hair • Hair loss – Chemotheapuetic agents Thallium f. Nails • Mee’s lines – Arsenic poisoning Thallium

23. MEE’S LINES

24. Odours • Most common odour detected- Alcohol

25. Urine colour

26. Biochemical investigations • Hematologic • CBC, Platelet count, Coagulation profile • Hemolytic anemia- lead, NSAIDS, Quinidine • Thrombocytopenia- Aspirin, Phenytoin, Procanamide • Coagulopathy- snake venoms, warfarin • Liver function tests • S. bilirubin , enzymes – AST,ALT , ALP, coagulation profile • Acetaaminophen, sulfonamides, rifampicin, TCA, INH, • Renal functions tests • Aspirin, lead, barbiturates, alcohol, amphetamines, copper sulphate

27. Other Abnormalities Hyperkalemia • Digoxin, Cardiac glycosides, Rhabdomyolysis, K + sparing diuretics Hypokalemia • Theophylline, Amphetamines, Sympathomimetics Hypernatremia • Uncommon in clinical toxicology • Large dose of NaHCO3 for TCA overdose • Correction of life threatening metabolic acidosis Hyponatremia • Rare

28. Biochemical abnormalities contd…… Metabolic acidosis • Acetaaminophen, Ethanol, Methyl alcohol, Toulene Metabolic alkalosis • Calcium carbonate, Furosemide, Laxative Anion Gap • Anion Gap = [ Na+ ] – { [ Cl] +[ HCO3 ] } • Normal – 8- 12 mmol/ l • Increased anion gap :- • Ethylene glycol • Methanol • Salicylate poisoning

29. Biochemical abnormalities contd….. Osmolar gap • Detects the presence of osmotically active susbstances in serum or plasma • Calculated osmolality = 2 [ Na+] + [ urea] + glucose 2.8 18 Eg Ethanol - Osmolality = 2 [ Na+] + [ urea] + glucose + Ethanol 2.8 18 4.6

30. Biochemical abnormalities contd….. • Increased osmolar gap:- • Acetone • Ethanol • Ethylene glycol • Methanol

31. ECG abnormalities • Usually non specific

32. Radiological studies • Not particularly helpful in diagnosis. • May be useful in confirming :- • Ingestion of metallic objects. • Packets of heroin / cocaine ( body packing) • Serial chest X-ray - Aspiration pneumonitis, ARDS Bio assays of drugs • Acetaminophen • Acetone • Ethylene glycol • Methanol • Salicylate • Phenobarbital • Theophylline • Lithium

33. Toxicologic analysis • Urine , blood, gastric contents – confirm or rule out suspected poisoning. • Interpretation requires various methods:- • Thin layer chromatography – Acetaminophen • Gas liquid chromatography – BZD, Amphetamines • HPLC- BZD • Mass spectrometry- Anticonvulsant • Enzyme assays • RBC cholinestrase , serum cholinestrase – OP poisoning • Pseudocholinestrase levels – OP poisoning

34. Fundamentals of poisoning management • Initial resuscitation and stabilization • Removal of toxin from the body • Prevention of further poison absorption • Enhancement of poison elimination • Administration of antidote • Supportive treatment • Prevention of re - exposure

35. Management of poisoning contd…. • Initial resuscitation and stabilization – • I/V access – I/V fluids • Endo tracheal intubation - to prevent aspiration • Unconscious patients • Respiratory depression/ failure • Convulsions- give anticonvulsants • Removal of toxin from the body • Copious flushing with water or saline of the body including skin folds, hair • Inhalational exposure • Fresh air or oxygen inhalation

36. Prevention of poison absorption • G I decontamination • Performed selectively, not routinely • Gastric lavage • Useful IF DONE BEFORE 3 hr of ingestion of a poison • Done with water ( except infants – NS), 1:5000 potassium permangnate , 4% Tannic acid, saturated lime water or starch solution • Administering & aspirating 5ml/kg through a No. 40 F orogastric tube ( No. 28 F – children) or Ewald’s tube • Position – Trendelenburge & left lateral position • Performed until clear fluid is obtained or a maximum of 3 L

37. Prevention of poison absorption contd…. • Complications • Aspiration (common) • Esophageal / gastric perforation • Tube misplacement in the trachea Ewald’s gastric tube

38. Prevention of poison absorption contd…. • Contraindications • Corrosive poisoning – GE perforation • Petroleum distillate ingestants- Aspiration pneumonia • Compromised unprotected airway • Esophageal / gastric pathology • Recent esophageal / gastric surgery • Lavagedecreasesingestant absorption by an average of :- • 52 % - if performed within 5 minsof ingestion • 26 % - if performed at 30 mins • 16 % - if performed at 60 mins

39. Prevention of poison absorption contd…. 2. Ipecac Syrup induced emesis • Used for home management of patients with :- • Accidental ingestions • Reliable history • Mild predicted toxicity • Aministered orally • Dose :- • 30 ml – adults • 15 ml – children • 10 ml – small infants

40. MOA • Ipecac irritates the stomach & stimulates CTZ centre. • Vomiting occurs about 20 min after administration • Dose may be repeated if vomiting does not occur • Side effects • Protracted vomiting • Contraindications • Gastric / esophageal tears or perforation • Corrosives • CNS depression or seizures • Rapidly acting CNS poisons ( cyanide, strychnine, camphor )

41. Prevention of poison absorption contd……. 3. Activated charcoal • Greater efficacy • Less invasive • Given orally as a suspension ( in water ) or through NG tube • Dose – 1 g/kg body wt. • Charcoal adsorbs ingested poisons within gut lumen allowing charcoal- toxin complex to be evacuated with stool or removed by induced emesis / lavage

42. Prevention of poison absorption contd… • Indications- Barbiturates, Atropine , Opiates, Strychnine • Contraindications- Mineral acids, alkalis, cyanide, fluoride ,iron • Side effects • Nausea , vomiting, diarrhoea or constipation • May prevent absorption of orally administered therapeutic agents • Complications • Aspiration – vomiting • Bowel obstruction

43. Prevention of poison absorption contd…. 4. Whole bowel irrigation • Administration of bowel cleansing solution containing electrolytes & polyethylene glycol • Orally or through gastric tube • Rate – 2 L/ hr ( 0.5 L /hr in children) • End point- rectal fluid is clear • Position – sitting • Indication :- • Slow or enteric coated medications • Packets of illicit drugs • Heavy metals • Iron , Lithium

44. Contraindications • Bowel obstruction • Ileus • Unprotected airway • Complications: • Bloating • Cramping • Rectal irritation

45. 5. Cathartics • Promote rectal evacuation of GI contents • Most effective – Sorbitol • Dose – 1-2 g/kg • Salts – Disodium phosphate, Magnesium citrate & sulfate, Sodium sulfate • Saccharides – Mannitol, Sorbitol • Side effects – Abdominal cramps, nausea vomiting • Complications– Excessive diarrhoea, Hypermagnesemia • C/I– Corrosives Pre existing diarrhoea

46. Enhancement of elimination of poison 1.Alkalization of urine • Urine pH ≥ 7.5 • Urine output 3-6 ml/kg • 5% Dextrose in 0.45 NS containing 20 – 35 meq /L Of NaHCO3 to an IV solution • Uses – Chlorpropamide, Phenobarbital, Sulfonamides, Salicylates • C/I :- • Congestive heart failure • Renal failure • Cerebral edema

47. 2. Acidification of urine • Enhance elimination of weak bases such as Phencyclidine & Amphetamine • Not used anymore • S /E-Metabolic acidosis, Renal damage 3.Extra corporeal removal • Dialysis • Acetone, Barbiturates, Bromide, Ethanol, Ethylene glycol, Salicylates, Lithium • Less effective when toxin has large volume of distribution (>1 L/kg), has large molecular weight, or highly protein bound

48. Elimination of poison contd…. • Peritoneal dialysis • Alcohols , long acting salicylates, Lithium • Exchange transfusion • Indications • Fatal , irreversible toxicity • Deteriorating despite aggressive supportive therapy • Dangerous blood levels of toxins • Liver or renal failure • Eg. Arsine or Sodium Chlorate poisoning

49. Elimination of poison contd…. 4. Chelation • Heavy metal poisoning • Complex of agent & metal is water soluble & excreted by kidneys • Eg . BAL, EDTA, Desferrioxamine, DMSA • BAL – Arsenic, Lead, Copper, Mercury • EDTA- Cobalt, Iron, Cadmium • Desferrioxamine – Iron • DMSA- Lead, Mercury

50. Administration of Antidotes • Not all poisons have antidotes.