Clinical toxicology

29
CLINICAL CLINICAL TOXICOLOGY TOXICOLOGY Joseph Hanig, Ph.D. Joseph Hanig, Ph.D.

description

 

Transcript of Clinical toxicology

Page 1: Clinical toxicology

CLINICAL CLINICAL TOXICOLOGYTOXICOLOGY

Joseph Hanig, Ph.D.Joseph Hanig, Ph.D.

Page 2: Clinical toxicology

LEARNING OBJECTIVESLEARNING OBJECTIVES To understand the general principles of To understand the general principles of

clinical toxicologyclinical toxicology To know general factors that influence To know general factors that influence

toxicitytoxicity To understand the initial approach to the To understand the initial approach to the

poisoned patient in terms of setting poisoned patient in terms of setting immediate prioritiesimmediate priorities

To appreciate the necessity to conduct, as To appreciate the necessity to conduct, as the first order of business, those the first order of business, those procedures that evaluate and preserve procedures that evaluate and preserve vital signsvital signs

Page 3: Clinical toxicology

LEARNING OBJECTIVESLEARNING OBJECTIVES To know what aspects of the physical To know what aspects of the physical

examination and what diagnostic tests are examination and what diagnostic tests are to be conducted to evaluate the general to be conducted to evaluate the general type as well as the specifics of the type 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 for To know and understand strategies for treatmenttreatment

To know and understand specific To know and understand specific approaches for reducing the body burden approaches for reducing the body burden of various poisonsof various poisons

Page 4: Clinical toxicology

LEARNING OBJECTIVESLEARNING OBJECTIVES To know how to counteract toxicological To know how to counteract toxicological

effects at receptor sites, if possibleeffects at receptor sites, if possible To know and understand important To know and understand important

treatment contraindications that prevent treatment contraindications that prevent serious injury or death of patientsserious injury or death of patients

To be aware of newer approaches and To 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 on specific antidotes, or other information on poison control needed immediately to poison control needed immediately to treat the patienttreat the patient

Page 5: Clinical toxicology
Page 6: Clinical toxicology

Common Causes of Death in the Common 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 into Aspiration of gastric contents into

tracheobronchial treetracheobronchial tree– Loss of respiratory driveLoss of respiratory drive– Respiratory arrestRespiratory arrest

Hypotension – due to depression of Hypotension – due to depression of cardiac contractilitycardiac contractility

Page 7: Clinical toxicology

Common Causes of Death in the Common Causes of Death in the Acutely Poisoned PatientAcutely Poisoned Patient

Shock – due to hemorrhage or internal Shock – due to hemorrhage or internal bleedingbleeding

Hypovolemia – due to vomiting, diarrhea Hypovolemia – due to vomiting, diarrhea or vascular collapseor vascular collapse

Hypothermia – worsened by i.v. fluids Hypothermia – worsened by i.v. fluids administered rapidly at room temperatureadministered rapidly at room temperature

Cellular hypoxia – in spite of adequate Cellular hypoxia – in spite of adequate ventilation and Oventilation and O22 admin. – due to CN, CO admin. – due to CN, CO or Hor H22S poisoningS poisoning

Page 8: Clinical toxicology

Common Causes of Death in the Common Causes of Death in the Acutely Poisoned PatientAcutely Poisoned Patient

Seizures – may result in pulmonary Seizures – may result in pulmonary aspiration;asphyxiaaspiration;asphyxia

Muscular hyperactivity resulting in Muscular hyperactivity resulting in hyperthermia, muscle breakdown, hyperthermia, muscle breakdown, myoglobinemia, renal failure, lactic myoglobinemia, renal failure, lactic acidosis and hyperkalemiaacidosis and hyperkalemia

Behavioral effects –traumatic injury Behavioral effects –traumatic injury ferom fights, accidents, fall from hih ferom fights, accidents, fall from hih places. Suicides, etcplaces. Suicides, etc

Page 9: Clinical toxicology

Common Causes of Death in the Common Causes of Death in the Acutely Poisoned PatientAcutely Poisoned Patient

Massive damage to a specific organ Massive damage to a specific organ system:system:– Liver (acetaminophen; amanita Liver (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

Page 10: Clinical toxicology
Page 11: Clinical toxicology
Page 12: Clinical toxicology

APPROACH TO THE POISONED APPROACH TO THE POISONED PATIENTPATIENT

History; Oral statements concerning History; Oral statements concerning details details

Call Poison Control Center re: drug Call Poison Control Center re: drug labeling labeling

Initial physical examinationInitial physical examination Assessment of vital signs Assessment of vital signs Eye examination Eye examination CNS and mental status examinationCNS and mental status examination

Page 13: Clinical toxicology

APPROACH TO THE POISONED APPROACH TO THE POISONED PATIENTPATIENT

Examination of the skin Examination of the skin Mouth examination Mouth examination Lab (clinical chemistry and x-ray Lab (clinical chemistry and x-ray

procedures procedures Renal function tests Renal function tests EKG EKG Other screening testsOther screening tests

Page 14: Clinical toxicology

TREATMENT OF ACUTE TREATMENT OF ACUTE POISONINGPOISONING

Treat the patient, not the poison", Treat the patient, not the poison", promptlypromptly

Supportive therapy essential Supportive 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 and Measuring and charting vital signs and

reflexes reflexes

Page 15: Clinical toxicology
Page 16: Clinical toxicology

TREATMENT OF ACUTE TREATMENT OF ACUTE POISONINGPOISONING

- 1st Goal - keep concentration of - 1st Goal - keep concentration of poison as low as possible by poison as low as possible by preventing absorption and increasing preventing absorption and increasing elimination elimination

- 2nd Goal - counteract toxicological - 2nd Goal - counteract toxicological effects at effector site, if possible effects at effector site, if possible

  

Page 17: Clinical toxicology

PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION OF POISONOF POISON

Decontamination from skin surfaceDecontamination from skin surface Emesis: indicated after oral ingestion of Emesis: 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 is if patient has ingested a CNS stimulant or is

convulsing; convulsing; if patient has ingested a petroleum distillate if patient has ingested a petroleum distillate

Page 18: Clinical toxicology

PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION OF POISONOF POISON

Induce emesis in the following Induce emesis in the following ways: ways:

mechanically by stroking posterior mechanically by stroking posterior pharynx; pharynx;

use of syrup of ipecac, 1 oz followed by use of syrup of ipecac, 1 oz followed by one glass of water; one glass of water;

use of apomorphine parenterallyuse of apomorphine parenterally

Page 19: Clinical toxicology

PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION OF POISONOF POISON

Gastric lavage: insert tube into Gastric lavage: insert tube into stomach and wash stomach with stomach and wash stomach with water or ½ normal saline to remove water or ½ normal saline to remove unabsorbed poisonunabsorbed poison

Contraindications are the same as Contraindications are the same as for emesis except that the for emesis except that the procedure should not be attempted procedure should not be attempted with young childrenwith young children

Page 20: Clinical toxicology

PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION OF POISONOF POISON

Chemical Adsorption Chemical Adsorption activated charcoal will adsorb many activated charcoal will adsorb many

poisons thus preventing their absorptionpoisons thus preventing their absorption

do not use simultaneously with ipecac if do 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 interrupt adsorbent in intestines may interrupt

enterohepatic circulationenterohepatic circulation

Page 21: Clinical toxicology

PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION OF POISONOF POISON

Purgation Purgation Used for ingestion of enteric coated tablets Used for ingestion of enteric coated tablets

when time after ingestion is longer than when time after ingestion is longer than one hour one hour

Use saline cathartics such as sodium or Use saline cathartics such as sodium or magnesium sulfatemagnesium sulfate

Chemical InactivationChemical Inactivation Not generally done, particularly for acids or Not generally done, particularly for acids or

bases or inhalation exposure bases or inhalation exposure For ocular and dermal exposure as well as For ocular and dermal exposure as well as

burns on skin; treat with copious water burns on skin; treat with copious water

Page 22: Clinical toxicology

PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION OF POISONOF POISON

Alteration of biotransformation Alteration of biotransformation Interfere with metabolic conversion of Interfere with metabolic conversion of

compound to toxic metabolite compound to toxic metabolite Metabolism of some compounds Metabolism of some compounds

produces highly reactive electrophilic produces highly reactive electrophilic intermediates; if nucleophiles present, intermediates; if nucleophiles present, toxicity is minimal; if nucleophiles toxicity is minimal; if nucleophiles depleted, toxicity results depleted, toxicity results

Increasing urinary excretion by Increasing urinary excretion by acidification or alkalinization acidification or alkalinization

Page 23: Clinical toxicology

PREVENTION OF ABSORPTION PREVENTION OF ABSORPTION OF POISONOF POISON

Decreasing passive resorption from Decreasing passive resorption from nephron lumennephron lumen

DiuresisDiuresis CatharticsCathartics Peritoneal dialysis Peritoneal dialysis Hemodialysis Hemodialysis Hemoperfusion Hemoperfusion

Page 24: Clinical toxicology
Page 25: Clinical toxicology

Antagonism of the absorbed poison Antagonism of the absorbed poison

If poisoning is due to agonist acting If poisoning is due to agonist acting at receptors for which specific at receptors for which specific antagonist is available; antagonist antagonist is available; antagonist may be available may be available

Drugs that stimulate antagonistic Drugs that stimulate antagonistic physiologic mechanisms may of little physiologic mechanisms may of little clinical value; titration difficult clinical value; titration difficult

Use of antibodiesUse of antibodies

Page 26: Clinical toxicology

Strategies for Treatment of the Strategies 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 of Determine the type and specifics of

the poisonthe poison Time of exposureTime of exposure Determine the presumed current Determine the presumed current

location of the poisonlocation of the poison Determine Volume of Distribution Determine Volume of Distribution

and Kand Ki i for the poisonfor the poison

Page 27: Clinical toxicology

Strategies for Treatment of the Strategies for Treatment of the Poisoned PatientPoisoned Patient

Use the drug dissociation constant, Use the drug dissociation constant, presumed pH based on location and the presumed pH based on location and the Henderson-Hasselbach equation to Henderson-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) risk Determine the immediate (real time) risk or hazard for absorptionor hazard for absorption

Intiate body burden reduction procedures Intiate body burden reduction procedures or specific antidotes based on the above or specific antidotes based on the above informationinformation

Page 28: Clinical toxicology

Strategies for Treatment of the Strategies for Treatment of the Poisoned PatientPoisoned Patient

If volume of distribution is very large; do If 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 pills X-ray for location of enteric coated pills and use cathartics if in the stomachand use cathartics if in the stomach

Use hypocholesteremics for poisons Use hypocholesteremics for poisons trapped in enterohepatic biliary systemtrapped in enterohepatic biliary system

Page 29: Clinical toxicology

SPECIFIC ANTIDOTESSPECIFIC ANTIDOTESPoisonPoison

AcetaminophenAcetaminophenAcetylcholinesterases, Acetylcholinesterases,

OP’s, physostigmineOP’s, physostigmineIron saltsIron salts

Methanol, Ethylene Methanol, Ethylene glycolglycol

Mercury, leadMercury, leadNarcotic drugsNarcotic drugs

Anti/muscarinics-Anti/muscarinics-cholinergicscholinergics

OP anticholinergicsOP anticholinergics

AntidoteAntidoteAcetylcysteineAcetylcysteine

AtropineAtropine

DeferoximeDeferoximeEthanolEthanol

Metal ChelatorsMetal ChelatorsNaloxoneNaloxone

PhysostigminePhysostigminePraladoxime (2-PAM)Praladoxime (2-PAM)