Clinical toxicology

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Clinical toxicology

  1. 1. CLINICALCLINICAL TOXICOLOGYTOXICOLOGY Joseph Hanig, Ph.D.Joseph Hanig, Ph.D.
  2. 2. LEARNING OBJECTIVESLEARNING OBJECTIVES  To understand the general principles ofTo understand the general principles of clinical toxicologyclinical toxicology  To know general factors that influenceTo know general factors that influence toxicitytoxicity  To understand the initial approach to theTo understand the initial approach to the poisoned patient in terms of settingpoisoned patient in terms of setting immediate prioritiesimmediate priorities  To appreciate the necessity to conduct, asTo appreciate the necessity to conduct, as the first order of business, thosethe first order of business, those procedures that evaluate and preserveprocedures that evaluate and preserve vital signsvital signs
  3. 3. LEARNING OBJECTIVESLEARNING OBJECTIVES  To know what aspects of the physicalTo know what aspects of the physical examination and what diagnostic tests areexamination and what diagnostic tests are to be conducted to evaluate the generalto be conducted to evaluate the general type as well as the specifics of thetype as well as the specifics of the poisoningpoisoning  To understand the goals of treatment e.g.To understand the goals of treatment e.g. to treat the patient, not the poison,to treat the patient, not the poison, promptlypromptly  To know and understand strategies forTo know and understand strategies for treatmenttreatment  To know and understand specificTo know and understand specific approaches for reducing the body burdenapproaches for reducing the body burden of various poisonsof various poisons
  4. 4. LEARNING OBJECTIVESLEARNING OBJECTIVES  To know how to counteract toxicologicalTo know how to counteract toxicological effects at receptor sites, if possibleeffects at receptor sites, if possible  To know and understand importantTo know and understand important treatment contraindications that preventtreatment contraindications that prevent serious injury or death of patientsserious injury or death of patients  To be aware of newer approaches andTo be aware of newer approaches and treatment modalitiestreatment modalities  To know where to rapidly obtain facts,To know where to rapidly obtain facts, specific antidotes, or other information onspecific antidotes, or other information on poison control needed immediately topoison control needed immediately to treat the patienttreat the patient
  5. 5. Common Causes of Death in theCommon Causes of Death in the Acutely Poisoned PatientAcutely Poisoned Patient  Comatose patient:Comatose patient: – Loss of protective reflexesLoss of protective reflexes – Airway obstruction by flaccid tongueAirway obstruction by flaccid tongue – Aspiration of gastric contents intoAspiration of gastric contents into tracheobronchial treetracheobronchial tree – Loss of respiratory driveLoss of respiratory drive – Respiratory arrestRespiratory arrest  Hypotension – due to depression ofHypotension – due to depression of cardiac contractilitycardiac contractility
  6. 6. Common Causes of Death in theCommon Causes of Death in the Acutely Poisoned PatientAcutely Poisoned Patient  Shock – due to hemorrhage or internalShock – due to hemorrhage or internal bleedingbleeding  Hypovolemia – due to vomiting, diarrheaHypovolemia – due to vomiting, diarrhea or vascular collapseor vascular collapse  Hypothermia – worsened by i.v. fluidsHypothermia – worsened by i.v. fluids administered rapidly at room temperatureadministered rapidly at room temperature  Cellular hypoxia – in spite of adequateCellular hypoxia – in spite of adequate ventilation and Oventilation and O22 admin. – due to CN, COadmin. – due to CN, CO or Hor H22S poisoningS poisoning
  7. 7. Common Causes of Death in theCommon Causes of Death in the Acutely Poisoned PatientAcutely Poisoned Patient  Seizures – may result in pulmonarySeizures – may result in pulmonary aspiration;asphyxiaaspiration;asphyxia  Muscular hyperactivity resulting inMuscular hyperactivity resulting in hyperthermia, muscle breakdown,hyperthermia, muscle breakdown, myoglobinemia, renal failure, lacticmyoglobinemia, renal failure, lactic acidosis and hyperkalemiaacidosis and hyperkalemia  Behavioral effects –traumatic injuryBehavioral effects –traumatic injury ferom fights, accidents, fall from hihferom fights, accidents, fall from hih places. Suicides, etcplaces. Suicides, etc
  8. 8. Common Causes of Death in theCommon Causes of Death in the Acutely Poisoned PatientAcutely Poisoned Patient  Massive damage to a specific organMassive damage to a specific organ system:system: – Liver (acetaminophen; amanitaLiver (acetaminophen; amanita phylloides [poison mushroom]phylloides [poison mushroom] – Lungs (paraquat)Lungs (paraquat) – Brain (demoic acid)Brain (demoic acid) – Kidney (ethylene glycol)Kidney (ethylene glycol) – Heart (cobalt salts)Heart (cobalt salts) Note: death may occur in 48 – 72 hrsNote: death may occur in 48 – 72 hrs
  9. 9. APPROACH TO THE POISONEDAPPROACH TO THE POISONED PATIENTPATIENT  History; Oral statements concerningHistory; Oral statements concerning detailsdetails  Call Poison Control Center re: drugCall Poison Control Center re: drug labelinglabeling  Initial physical examinationInitial physical examination  Assessment of vital signsAssessment of vital signs  Eye examinationEye examination  CNS and mental status examinationCNS and mental status examination
  10. 10. APPROACH TO THE POISONEDAPPROACH TO THE POISONED PATIENTPATIENT  Examination of the skinExamination of the skin  Mouth examinationMouth examination  Lab (clinical chemistry and x-rayLab (clinical chemistry and x-ray proceduresprocedures  Renal function testsRenal function tests  EKGEKG  Other screening testsOther screening tests
  11. 11. TREATMENT OF ACUTETREATMENT OF ACUTE POISONINGPOISONING  Treat the patient, not the poison",Treat the patient, not the poison", promptlypromptly  Supportive therapy essentialSupportive therapy essential  Maintain respiration and circulation –Maintain respiration and circulation – primaryprimary  Judge progress of intoxication by:Judge progress of intoxication by: Measuring and charting vital signs andMeasuring and charting vital signs and reflexesreflexes
  12. 12. TREATMENT OF ACUTETREATMENT OF ACUTE POISONINGPOISONING  - 1st Goal - keep concentration of- 1st Goal - keep concentration of poison as low as possible bypoison as low as possible by preventing absorption and increasingpreventing absorption and increasing eliminationelimination  - 2nd Goal - counteract toxicological- 2nd Goal - counteract toxicological effects at effector site, if possibleeffects at effector site, if possible
  13. 13. PREVENTION OF ABSORPTIONPREVENTION OF ABSORPTION OF POISONOF POISON  Decontamination from skin surfaceDecontamination from skin surface  Emesis: indicated after oral ingestion ofEmesis: indicated after oral ingestion of most chemicals;most chemicals; – must consider time since chemical ingestedmust consider time since chemical ingested  Contraindications:Contraindications:  ingestion of corrosives such as strong acid or alkali;ingestion of corrosives such as strong acid or alkali;  if patient is comatose or delirious;if patient is comatose or delirious;  if patient has ingested a CNS stimulant or isif patient has ingested a CNS stimulant or is convulsing;convulsing;  if patient has ingested a petroleum distillateif patient has ingested a petroleum distillate
  14. 14. PREVENTION OF ABSORPTIONPREVENTION OF ABSORPTION OF POISONOF POISON  Induce emesis in the followingInduce emesis in the following ways:ways:  mechanically by stroking posteriormechanically by stroking posterior pharynx;pharynx;  use of syrup of ipecac, 1 oz followed byuse of syrup of ipecac, 1 oz followed by one glass of water;one glass of water;  use of apomorphine parenterallyuse of apomorphine parenterally
  15. 15. PREVENTION OF ABSORPTIONPREVENTION OF ABSORPTION OF POISONOF POISON  Gastric lavage: insert tube intoGastric lavage: insert tube into stomach and wash stomach withstomach and wash stomach with water or ½ normal saline to removewater or ½ normal saline to remove unabsorbed poisonunabsorbed poison  Contraindications are the same asContraindications are the same as for emesis except that thefor emesis except that the procedure should not be attemptedprocedure should not be attempted with young childrenwith young children
  16. 16. PREVENTION OF ABSORPTIONPREVENTION OF ABSORPTION OF POISONOF POISON  Chemical AdsorptionChemical Adsorption  activated charcoal will adsorb manyactivated charcoal will adsorb many poisons thus preventing their absorptionpoisons thus preventing their absorption  do not use simultaneously with ipecac ifdo not use simultaneously with ipecac if poison is excreted into bile in active formpoison is excreted into bile in active form  adsorbent in intestines may interruptadsorbent in intestines may interrupt enterohepatic circulationenterohepatic circulation
  17. 17. PREVENTION OF ABSORPTIONPREVENTION OF ABSORPTION OF POISONOF POISON  PurgationPurgation  Used for ingestion of enteric coated tabletsUsed for ingestion of enteric coated tablets when time after ingestion is longer thanwhen time after ingestion is longer than one hourone hour  Use saline cathartics such as sodium orUse saline cathartics such as sodium or magnesium sulfatemagnesium sulfate  Chemical InactivationChemical Inactivation  Not generally done, particularly for acids orNot generally done, particularly for acids or bases or inhalation exposurebases or inhalation exposure  For ocular and dermal exposure as well asFor ocular and dermal exposure as well as burns on skin; treat with copious waterburns on skin; treat with copious water
  18. 18. PREVENTION OF ABSORPTIONPREVENTION OF ABSORPTION OF POISONOF POISON  Alteration of biotransformationAlteration of biotransformation  Interfere with metabolic conversion ofInterfere with metabolic conversion of compound to toxic metabolitecompound to toxic metabolite  Metabolism of some compoundsMetabolism of some compounds produces highly reactive electrophilicproduces highly reactive electrophilic intermediates; if nucleophiles present,intermediates; if nucleophiles present, toxicity is minimal; if nucleophilestoxicity is minimal; if nucleophiles depleted, toxicity resultsdepleted, toxicity results  Increasing urinary excretion byIncreasing urinary excretion by acidification or alkalinizationacidification or alkalinization
  19. 19. PREVENTION OF ABSORPTIONPREVENTION OF ABSORPTION OF POISONOF POISON  Decreasing passive resorption fromDecreasing passive resorption from nephron lumennephron lumen  DiuresisDiuresis  CatharticsCathartics  Peritoneal dialysisPeritoneal dialysis  HemodialysisHemodialysis  HemoperfusionHemoperfusion
  20. 20. Antagonism of the absorbed poisonAntagonism of the absorbed poison  If poisoning is due to agonist actingIf poisoning is due to agonist acting at receptors for which specificat receptors for which specific antagonist is available; antagonistantagonist is available; antagonist may be availablemay be available  Drugs that stimulate antagonisticDrugs that stimulate antagonistic physiologic mechanisms may of littlephysiologic mechanisms may of little clinical value; titration difficultclinical value; titration difficult  Use of antibodiesUse of antibodies
  21. 21. Strategies for Treatment of theStrategies for Treatment of the Poisoned PatientPoisoned Patient  Evaluate and stabilize vital signsEvaluate and stabilize vital signs  Give supportive therapy, if neededGive supportive therapy, if needed  Determine the type and specifics ofDetermine the type and specifics of the poisonthe poison  Time of exposureTime of exposure  Determine the presumed currentDetermine the presumed current location of the poisonlocation of the poison  Determine Volume of DistributionDetermine Volume of Distribution and Kand Kii for the poisonfor the poison
  22. 22. Strategies for Treatment of theStrategies for Treatment of the Poisoned PatientPoisoned Patient  Use the drug dissociation constant,Use the drug dissociation constant, presumed pH based on location and thepresumed pH based on location and the Henderson-Hasselbach equation toHenderson-Hasselbach equation to determine the ratio of ionized to non-determine the ratio of ionized to non- ionized poisonionized poison  Determine the immediate (real time) riskDetermine the immediate (real time) risk or hazard for absorptionor hazard for absorption  Intiate body burden reduction proceduresIntiate body burden reduction procedures or specific antidotes based on the aboveor specific antidotes based on the above informationinformation
  23. 23. Strategies for Treatment of theStrategies for Treatment of the Poisoned PatientPoisoned Patient  If volume of distribution is very large; doIf volume of distribution is very large; do not waste time on any type of dialysisnot waste time on any type of dialysis  X-ray for location of enteric coated pillsX-ray for location of enteric coated pills and use cathartics if in the stomachand use cathartics if in the stomach  Use hypocholesteremics for poisonsUse hypocholesteremics for poisons trapped in enterohepatic biliary systemtrapped in enterohepatic biliary system
  24. 24. SPECIFIC ANTIDOTESSPECIFIC ANTIDOTES PoisonPoison AcetaminophenAcetaminophen Acetylcholinesterases,Acetylcholinesterases, OP’s, physostigmineOP’s, physostigmine Iron saltsIron salts Methanol, EthyleneMethanol, Ethylene glycolglycol Mercury, leadMercury, lead Narcotic drugsNarcotic drugs Anti/muscarinics-Anti/muscarinics- cholinergicscholinergics OP anticholinergicsOP anticholinergics AntidoteAntidote AcetylcysteineAcetylcysteine AtropineAtropine DeferoximeDeferoxime EthanolEthanol Metal ChelatorsMetal Chelators NaloxoneNaloxone PhysostigminePhysostigmine Praladoxime (2-PAM)Praladoxime (2-PAM)

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