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CLINICAL
TOXICOLOGY
Joseph Hanig, Ph.D.
LEARNING OBJECTIVES
 To understand the general principles of
  clinical toxicology
 To know general factors that influence
  toxicity
 To understand the initial approach to the
  poisoned patient in terms of setting
  immediate priorities
 To appreciate the necessity to conduct, as
  the first order of business, those
  procedures that evaluate and preserve
  vital signs
LEARNING OBJECTIVES
 To know what aspects of the physical
  examination and what diagnostic tests are
  to be conducted to evaluate the general
  type as well as the specifics of the
  poisoning
 To understand the goals of treatment e.g.
  to treat the patient, not the poison,
  promptly
 To know and understand strategies for
  treatment
 To know and understand specific
  approaches for reducing the body burden
  of various poisons
LEARNING OBJECTIVES
 To know how to counteract toxicological
  effects at receptor sites, if possible
 To know and understand important
  treatment contraindications that prevent
  serious injury or death of patients
 To be aware of newer approaches and
  treatment modalities
 To know where to rapidly obtain facts,
  specific antidotes, or other information on
  poison control needed immediately to
  treat the patient
Common Causes of Death in the
    Acutely Poisoned Patient
 Comatose   patient:
  – Loss of protective reflexes
  – Airway obstruction by flaccid tongue
  – Aspiration of gastric contents into
    tracheobronchial tree
  – Loss of respiratory drive
  – Respiratory arrest
 Hypotension – due to depression of
    cardiac contractility
Common Causes of Death in the
       Acutely Poisoned Patient
 Shock – due to hemorrhage or internal
  bleeding
 Hypovolemia – due to vomiting, diarrhea
  or vascular collapse
 Hypothermia – worsened by i.v. fluids
  administered rapidly at room temperature
 Cellular hypoxia – in spite of adequate
  ventilation and O2 admin. – due to CN, CO
  or H2S poisoning
Common Causes of Death in the
    Acutely Poisoned Patient
 Seizures  – may result in pulmonary
  aspiration;asphyxia
 Muscular hyperactivity resulting in
  hyperthermia, muscle breakdown,
  myoglobinemia, renal failure, lactic
  acidosis and hyperkalemia
 Behavioral effects –traumatic injury
  ferom fights, accidents, fall from hih
  places. Suicides, etc
Common Causes of Death in the
    Acutely Poisoned Patient
 Massive     damage to a specific organ
 system:
  – Liver (acetaminophen; amanita
    phylloides [poison mushroom]
  – Lungs (paraquat)
  – Brain (demoic acid)
  – Kidney (ethylene glycol)
  – Heart (cobalt salts)
     Note:   death may occur in 48 – 72 hrs
APPROACH TO THE POISONED
        PATIENT
 History;   Oral statements concerning
  details
 Call Poison Control Center re: drug
  labeling
 Initial physical examination

 Assessment of vital signs

 Eye examination

 CNS and mental status examination
APPROACH TO THE POISONED
        PATIENT
 Examination   of the skin
 Mouth examination

 Lab (clinical chemistry and x-ray
  procedures
 Renal function tests

 EKG

 Other screening tests
TREATMENT OF ACUTE
            POISONING
   Treat the patient, not the poison",
    promptly

   Supportive therapy essential

   Maintain respiration and circulation –
    primary

   Judge progress of intoxication by:
      Measuring and charting vital signs and
    reflexes
TREATMENT OF ACUTE
         POISONING
- 1st Goal - keep concentration of
 poison as low as possible by
 preventing absorption and increasing
 elimination

- 2nd Goal - counteract toxicological
 effects at effector site, if possible
PREVENTION OF ABSORPTION
       OF POISON
   Decontamination from skin surface
   Emesis: indicated after oral ingestion of
    most chemicals;
    – must consider time since chemical ingested
   Contraindications:
         ingestion of corrosives such as strong acid or alkali;
         if patient is comatose or delirious;
         if patient has ingested a CNS stimulant or is
          convulsing;
         if patient has ingested a petroleum distillate
PREVENTION OF ABSORPTION
       OF POISON

   Induce emesis in the following
    ways:
        mechanically by stroking posterior
         pharynx;
        use of syrup of ipecac, 1 oz followed by
         one glass of water;
        use of apomorphine parenterally
PREVENTION OF ABSORPTION
       OF POISON
   Gastric lavage: insert tube into
    stomach and wash stomach with
    water or ½ normal saline to remove
    unabsorbed poison
    Contraindications are the same as
    for emesis except that the
    procedure should not be attempted
    with young children
PREVENTION OF ABSORPTION
       OF POISON
   Chemical Adsorption
        activated charcoal will adsorb many
         poisons thus preventing their absorption

        do not use simultaneously with ipecac if
         poison is excreted into bile in active form

        adsorbent in intestines may interrupt
         enterohepatic circulation
PREVENTION OF ABSORPTION
       OF POISON
   Purgation
        Used for ingestion of enteric coated tablets
         when time after ingestion is longer than
         one hour
        Use saline cathartics such as sodium or
         magnesium sulfate
    Chemical Inactivation
        Not generally done, particularly for acids or
         bases or inhalation exposure
        For ocular and dermal exposure as well as
         burns on skin; treat with copious water
PREVENTION OF ABSORPTION
       OF POISON
   Alteration of biotransformation
   Interfere with metabolic conversion of
    compound to toxic metabolite
   Metabolism of some compounds
    produces highly reactive electrophilic
    intermediates; if nucleophiles present,
    toxicity is minimal; if nucleophiles
    depleted, toxicity results
   Increasing urinary excretion by
    acidification or alkalinization
PREVENTION OF ABSORPTION
       OF POISON
   Decreasing passive resorption from
    nephron lumen
   Diuresis
   Cathartics
   Peritoneal dialysis
   Hemodialysis
   Hemoperfusion
Antagonism of the absorbed poison
 If poisoning is due to agonist acting
  at receptors for which specific
  antagonist is available; antagonist
  may be available
 Drugs that stimulate antagonistic
  physiologic mechanisms may of little
  clinical value; titration difficult
 Use of antibodies
Strategies for Treatment of the
         Poisoned Patient
 Evaluate  and stabilize vital signs
 Give supportive therapy, if needed
 Determine the type and specifics of
  the poison
 Time of exposure
 Determine the presumed current
  location of the poison
 Determine Volume of Distribution
  and Ki for the poison
Strategies for Treatment of the
           Poisoned Patient
   Use the drug dissociation constant,
    presumed pH based on location and the
    Henderson-Hasselbach equation to
    determine the ratio of ionized to non-
    ionized poison

   Determine the immediate (real time) risk
    or hazard for absorption

   Intiate body burden reduction procedures
    or specific antidotes based on the above
    information
Strategies for Treatment of the
           Poisoned Patient

   If volume of distribution is very large; do
    not waste time on any type of dialysis

   X-ray for location of enteric coated pills
    and use cathartics if in the stomach

   Use hypocholesteremics for poisons
    trapped in enterohepatic biliary system
SPECIFIC ANTIDOTES
      Poison                 Antidote
   Acetaminophen            Acetylcysteine
Acetylcholinesterases,        Atropine
  OP’s, physostigmine
      Iron salts            Deferoxime
 Methanol, Ethylene           Ethanol
         glycol
                           Metal Chelators
    Mercury, lead
                             Naloxone
   Narcotic drugs
  Anti/muscarinics-
      cholinergics          Physostigmine
 OP anticholinergics     Praladoxime (2-PAM)

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Clinical toxicology

  • 2. LEARNING OBJECTIVES  To understand the general principles of clinical toxicology  To know general factors that influence toxicity  To understand the initial approach to the poisoned patient in terms of setting immediate priorities  To appreciate the necessity to conduct, as the first order of business, those procedures that evaluate and preserve vital signs
  • 3. LEARNING OBJECTIVES  To know what aspects of the physical examination and what diagnostic tests are to be conducted to evaluate the general type as well as the specifics of the poisoning  To understand the goals of treatment e.g. to treat the patient, not the poison, promptly  To know and understand strategies for treatment  To know and understand specific approaches for reducing the body burden of various poisons
  • 4. LEARNING OBJECTIVES  To know how to counteract toxicological effects at receptor sites, if possible  To know and understand important treatment contraindications that prevent serious injury or death of patients  To be aware of newer approaches and treatment modalities  To know where to rapidly obtain facts, specific antidotes, or other information on poison control needed immediately to treat the patient
  • 5.
  • 6. Common Causes of Death in the Acutely Poisoned Patient  Comatose patient: – Loss of protective reflexes – Airway obstruction by flaccid tongue – Aspiration of gastric contents into tracheobronchial tree – Loss of respiratory drive – Respiratory arrest  Hypotension – due to depression of cardiac contractility
  • 7. Common Causes of Death in the Acutely Poisoned Patient  Shock – due to hemorrhage or internal bleeding  Hypovolemia – due to vomiting, diarrhea or vascular collapse  Hypothermia – worsened by i.v. fluids administered rapidly at room temperature  Cellular hypoxia – in spite of adequate ventilation and O2 admin. – due to CN, CO or H2S poisoning
  • 8. Common Causes of Death in the Acutely Poisoned Patient  Seizures – may result in pulmonary aspiration;asphyxia  Muscular hyperactivity resulting in hyperthermia, muscle breakdown, myoglobinemia, renal failure, lactic acidosis and hyperkalemia  Behavioral effects –traumatic injury ferom fights, accidents, fall from hih places. Suicides, etc
  • 9. Common Causes of Death in the Acutely Poisoned Patient  Massive damage to a specific organ system: – Liver (acetaminophen; amanita phylloides [poison mushroom] – Lungs (paraquat) – Brain (demoic acid) – Kidney (ethylene glycol) – Heart (cobalt salts)  Note: death may occur in 48 – 72 hrs
  • 10.
  • 11.
  • 12. APPROACH TO THE POISONED PATIENT  History; Oral statements concerning details  Call Poison Control Center re: drug labeling  Initial physical examination  Assessment of vital signs  Eye examination  CNS and mental status examination
  • 13. APPROACH TO THE POISONED PATIENT  Examination of the skin  Mouth examination  Lab (clinical chemistry and x-ray procedures  Renal function tests  EKG  Other screening tests
  • 14. TREATMENT OF ACUTE POISONING  Treat the patient, not the poison", promptly  Supportive therapy essential  Maintain respiration and circulation – primary  Judge progress of intoxication by: Measuring and charting vital signs and reflexes
  • 15.
  • 16. TREATMENT OF ACUTE POISONING - 1st Goal - keep concentration of poison as low as possible by preventing absorption and increasing elimination - 2nd Goal - counteract toxicological effects at effector site, if possible
  • 17. PREVENTION OF ABSORPTION OF POISON  Decontamination from skin surface  Emesis: indicated after oral ingestion of most chemicals; – must consider time since chemical ingested  Contraindications:  ingestion of corrosives such as strong acid or alkali;  if patient is comatose or delirious;  if patient has ingested a CNS stimulant or is convulsing;  if patient has ingested a petroleum distillate
  • 18. PREVENTION OF ABSORPTION OF POISON  Induce emesis in the following ways:  mechanically by stroking posterior pharynx;  use of syrup of ipecac, 1 oz followed by one glass of water;  use of apomorphine parenterally
  • 19. PREVENTION OF ABSORPTION OF POISON  Gastric lavage: insert tube into stomach and wash stomach with water or ½ normal saline to remove unabsorbed poison  Contraindications are the same as for emesis except that the procedure should not be attempted with young children
  • 20. PREVENTION OF ABSORPTION OF POISON  Chemical Adsorption  activated charcoal will adsorb many poisons thus preventing their absorption  do not use simultaneously with ipecac if poison is excreted into bile in active form  adsorbent in intestines may interrupt enterohepatic circulation
  • 21. PREVENTION OF ABSORPTION OF POISON  Purgation  Used for ingestion of enteric coated tablets when time after ingestion is longer than one hour  Use saline cathartics such as sodium or magnesium sulfate  Chemical Inactivation  Not generally done, particularly for acids or bases or inhalation exposure  For ocular and dermal exposure as well as burns on skin; treat with copious water
  • 22. PREVENTION OF ABSORPTION OF POISON  Alteration of biotransformation  Interfere with metabolic conversion of compound to toxic metabolite  Metabolism of some compounds produces highly reactive electrophilic intermediates; if nucleophiles present, toxicity is minimal; if nucleophiles depleted, toxicity results  Increasing urinary excretion by acidification or alkalinization
  • 23. PREVENTION OF ABSORPTION OF POISON  Decreasing passive resorption from nephron lumen  Diuresis  Cathartics  Peritoneal dialysis  Hemodialysis  Hemoperfusion
  • 24.
  • 25. Antagonism of the absorbed poison  If poisoning is due to agonist acting at receptors for which specific antagonist is available; antagonist may be available  Drugs that stimulate antagonistic physiologic mechanisms may of little clinical value; titration difficult  Use of antibodies
  • 26. Strategies for Treatment of the Poisoned Patient  Evaluate and stabilize vital signs  Give supportive therapy, if needed  Determine the type and specifics of the poison  Time of exposure  Determine the presumed current location of the poison  Determine Volume of Distribution and Ki for the poison
  • 27. Strategies for Treatment of the Poisoned Patient  Use the drug dissociation constant, presumed pH based on location and the Henderson-Hasselbach equation to determine the ratio of ionized to non- ionized poison  Determine the immediate (real time) risk or hazard for absorption  Intiate body burden reduction procedures or specific antidotes based on the above information
  • 28. Strategies for Treatment of the Poisoned Patient  If volume of distribution is very large; do not waste time on any type of dialysis  X-ray for location of enteric coated pills and use cathartics if in the stomach  Use hypocholesteremics for poisons trapped in enterohepatic biliary system
  • 29. SPECIFIC ANTIDOTES Poison Antidote Acetaminophen Acetylcysteine Acetylcholinesterases, Atropine OP’s, physostigmine Iron salts Deferoxime Methanol, Ethylene Ethanol glycol Metal Chelators Mercury, lead Naloxone Narcotic drugs Anti/muscarinics- cholinergics Physostigmine OP anticholinergics Praladoxime (2-PAM)