Special Topic Pharmacology
Principles of Toxicology and Specific Antidotes
Prepared by
Marc Imhotep Cray, M.D.
Pharmacolog...
Marc Imhotep Cray, M.D.
12 LEARNING OBJECTIVES
1. To understand the general principles of
clinical toxicology
2. To know g...
Marc Imhotep Cray, M.D.
12 LEARNING OBJECTIVES
5. To know what aspects of the physical
examination and what diagnostic tes...
Marc Imhotep Cray, M.D.
12 LEARNING OBJECTIVES
9. To know how to counteract toxicological
effects at receptor sites, if po...
Marc Imhotep Cray, M.D.
Common Causes of Death in
Acutely Poisoned Patient
 Comatose patient:
 Loss of protective reflex...
Marc Imhotep Cray, M.D.
Common Causes of Death in
the Acutely Poisoned Patient
 Shock – due to hemorrhage or internal
ble...
Marc Imhotep Cray, M.D.
Common Causes of Death in
the Acutely Poisoned Patient
 Seizures – may result in pulmonary
aspira...
Marc Imhotep Cray, M.D.
Common Causes of Death in
the Acutely Poisoned Patient
 Massive damage to a specific organ
system...
Marc Imhotep Cray, M.D.
APPROACH TO THE POISONED
PATIENT
 History; Oral statements concerning
details
 Call Poison Contr...
Marc Imhotep Cray, M.D.
APPROACH TO THE POISONED
PATIENT
 Examination of the skin
 Mouth examination
 Lab (clinical che...
Marc Imhotep Cray, M.D.
TREATMENT OF ACUTE
POISONING
 Treat the patient, not the poison", promptly
 Supportive therapy e...
Marc Imhotep Cray, M.D.
TREATMENT OF ACUTE
POISONING
 - 1st Goal - keep concentration of
poison as low as possible by pre...
Marc Imhotep Cray, M.D.
Prevention of Absorption of
Poison
 Decontamination from skin surface
 Emesis: indicated after o...
Marc Imhotep Cray, M.D.
Prevention of Absorption of
Poison
 Induce emesis in the following ways:
1. mechanically by strok...
Marc Imhotep Cray, M.D.
Prevention of Absorption of
Poison
 Gastric lavage: insert tube into
stomach and wash stomach wit...
Marc Imhotep Cray, M.D.
Prevention of Absorption of
Poison
 Chemical Adsorption
 activated charcoal will adsorb many
poi...
Marc Imhotep Cray, M.D.
Prevention of Absorption of
Poison
 Purgation
 Used for ingestion of enteric coated tablets
when...
Marc Imhotep Cray, M.D.
Prevention of Absorption of
Poison
 Alteration of biotransformation
 Interfere with metabolic co...
Marc Imhotep Cray, M.D.
Prevention of Absorption of
Poison
 Decreasing passive resorption
from nephron lumen
1. Diuresis
...
Marc Imhotep Cray, M.D.
Antagonism of the absorbed
poison (see PDF Notes)
 If poisoning is due to agonist acting at
recep...
Marc Imhotep Cray, M.D.
Strategies for Treatment of
the Poisoned Patient
 Evaluate and stabilize vital signs
 Give suppo...
Marc Imhotep Cray, M.D.
Strategies for Treatment of
the Poisoned Patient
 Use the drug dissociation constant, presumed
pH...
Marc Imhotep Cray, M.D.
Strategies for Treatment of
the Poisoned Patient
 If volume of distribution is very large; do not...
Marc Imhotep Cray, M.D.
Acute organophosphate
pesticide toxicity
Click for: CASE PRESENTATION
A 6 month-old girl is irrita...
Marc Imhotep Cray, M.D.
Acute organophosphate pesticide
toxicity
 Mechanism of acute OP pesticide toxicity
discerned from...
Marc Imhotep Cray, M.D.
Acute organophosphate
pesticide toxicity (see notes page)
 Acute organophosphate toxicity occurs
...
Marc Imhotep Cray, M.D.
SIGNS AND SYMPTOMS
 M-U-D-D-L-E-S:
 miosis,
 urination,
 diarrhea,
 diaphoresis,
 lacrimatio...
Marc Imhotep Cray, M.D.
SIGNS AND SYMPTOMS
CHILDREN VS. ADULTS
 Reviews of case series indicate that
pediatric organophos...
Marc Imhotep Cray, M.D.
DIAGNOSIS AND TREATMENT
 Diagnosis of organophosphate poisoning is
often made based on the histor...
Marc Imhotep Cray, M.D.
DIAGNOSIS AND TREATMENT
Cholinesterase(ChE) Depression as a
Diagnostic Tool
 Remember: Individual...
Marc Imhotep Cray, M.D.
DIAGNOSIS AND TREATMENT
 Treatments for OP Poisoning
 Supportive Care
 Atropine
 2-PAM
31
Marc Imhotep Cray, M.D.
eMedicine Toxicology Articles
 Toxicity, Acetaminophen
 Toxicity, Amphetamine
 Toxicity, Antich...
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Principles of Toxicology and Anidotes:IN IVMS Special Topics Pharmacology

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Principles of Toxicology and Anidotes:IN IVMS Special Topics Pharmacology

  1. 1. Special Topic Pharmacology Principles of Toxicology and Specific Antidotes Prepared by Marc Imhotep Cray, M.D. Pharmacology Teacher Companion Learning tools Reading: Lecture PDF Notes / Epidemiology of Poisoning and Antidotes Used In Toxicology Video: IVMS-General Principles of Pharmacology Animations Playlist Clinical: E-Medicine Article Toxicity, Carbon Monoxide Full article table at the end
  2. 2. Marc Imhotep Cray, M.D. 12 LEARNING OBJECTIVES 1. To understand the general principles of clinical toxicology 2. To know general factors that influence toxicity 3. To understand the initial approach to the poisoned patient in terms of setting immediate priorities 4. To appreciate the necessity to conduct, as the first order of business, those procedures that evaluate and preserve vital signs 2
  3. 3. Marc Imhotep Cray, M.D. 12 LEARNING OBJECTIVES 5. 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 6. To understand the goals of treatment e.g. to treat the patient, not the poison, promptly 7. To know and understand strategies for treatment 8. To know and understand specific approaches for reducing the body burden of various poisons 3
  4. 4. Marc Imhotep Cray, M.D. 12 LEARNING OBJECTIVES 9. To know how to counteract toxicological effects at receptor sites, if possible 10.To know and understand important treatment contraindications that prevent serious injury or death of patients 11. To be aware of newer approaches and treatment modalities 12.To know where to rapidly obtain facts, specific antidotes, or other information on poison control needed immediately to treat the patient 4
  5. 5. Marc Imhotep Cray, M.D. Common Causes of Death in 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 5
  6. 6. Marc Imhotep Cray, M.D. 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 6
  7. 7. Marc Imhotep Cray, M.D. 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 from fights, accidents, fall from high places. Suicides, etc 7
  8. 8. Marc Imhotep Cray, M.D. 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 (domoic acid)  Kidney (ethylene glycol)  Heart (cobalt salts)  Note: death may occur in 48 – 72 hrs 8
  9. 9. Marc Imhotep Cray, M.D. 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 9
  10. 10. Marc Imhotep Cray, M.D. 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 10
  11. 11. Marc Imhotep Cray, M.D. 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 11
  12. 12. Marc Imhotep Cray, M.D. 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 12
  13. 13. Marc Imhotep Cray, M.D. 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 13
  14. 14. Marc Imhotep Cray, M.D. Prevention of Absorption of Poison  Induce emesis in the following ways: 1. mechanically by stroking posterior pharynx; 2. use of syrup of ipecac, 1 oz followed by one glass of water; 3. use of apomorphine parenterally 14
  15. 15. Marc Imhotep Cray, M.D. 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 15
  16. 16. Marc Imhotep Cray, M.D. 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 16
  17. 17. Marc Imhotep Cray, M.D. 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 17
  18. 18. Marc Imhotep Cray, M.D. Prevention of Absorption of Poison  Alteration of biotransformation  Interfere with metabolic conversion of compound to toxic metabolite  Increasing urinary excretion by acidification or alkalinization 18
  19. 19. Marc Imhotep Cray, M.D. Prevention of Absorption of Poison  Decreasing passive resorption from nephron lumen 1. Diuresis 2. Cathartics 3. Peritoneal dialysis 4. Hemodialysis 5. Hemoperfusion 19
  20. 20. Marc Imhotep Cray, M.D. Antagonism of the absorbed poison (see PDF Notes)  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 20
  21. 21. Marc Imhotep Cray, M.D. 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 for the poison 21
  22. 22. Marc Imhotep Cray, M.D. 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  Initiate body burden reduction procedures or specific antidotes based on the above information 22
  23. 23. Marc Imhotep Cray, M.D. 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 23
  24. 24. Marc Imhotep Cray, M.D. Acute organophosphate pesticide toxicity Click for: CASE PRESENTATION A 6 month-old girl is irritable and congested. Rosa brings her 6 month-old daughter to your rural clinic. She is new to the community, having arrived from Mexico about one month ago. She came to join her husband who recently established a steady job as a pesticide applicator on a large orchard… 24
  25. 25. Marc Imhotep Cray, M.D. Acute organophosphate pesticide toxicity  Mechanism of acute OP pesticide toxicity discerned from clinical diagnostic tools and antidotes used to treat organophosphate poisonings.  Namely, determination of red blood cell and plasma pseudocholinesterase activity 25
  26. 26. Marc Imhotep Cray, M.D. Acute organophosphate pesticide toxicity (see notes page)  Acute organophosphate toxicity occurs through inhibition of acetylcholinesterase 26
  27. 27. Marc Imhotep Cray, M.D. SIGNS AND SYMPTOMS  M-U-D-D-L-E-S:  miosis,  urination,  diarrhea,  diaphoresis,  lacrimation,  excitation of the central nervous system, and  salivation. This works reasonably well in adults 27
  28. 28. Marc Imhotep Cray, M.D. SIGNS AND SYMPTOMS CHILDREN VS. ADULTS  Reviews of case series indicate that pediatric organophosphate poisonings often manifest with hypotonia or mental status changes such as lethargy and coma, as well as seizures, the latter being relatively rare in adult OP poisoning 28
  29. 29. Marc Imhotep Cray, M.D. DIAGNOSIS AND TREATMENT  Diagnosis of organophosphate poisoning is often made based on the history of significant exposure and consistent symptoms, as in the case described. If probable organophosphate poisoning is suspected, immediate treatment is recommended without waiting for laboratory confirmation. Early consultation with a poisoning specialist is recommended 29
  30. 30. Marc Imhotep Cray, M.D. DIAGNOSIS AND TREATMENT Cholinesterase(ChE) Depression as a Diagnostic Tool  Remember: Individual baseline ChE levels are variable  To confirm suspected OP poisoning:  Compare post-exposure ChE levels to those at time of illness  Clinically significant OP exposure:  20% depression of plasma pseudocholinesterase  15% depression of RBC ChE 30
  31. 31. Marc Imhotep Cray, M.D. DIAGNOSIS AND TREATMENT  Treatments for OP Poisoning  Supportive Care  Atropine  2-PAM 31
  32. 32. Marc Imhotep Cray, M.D. eMedicine Toxicology Articles  Toxicity, Acetaminophen  Toxicity, Amphetamine  Toxicity, Anticholinergic  Toxicity, Antidepressant  Toxicity, Antidysrhythmic  Toxicity, Antihistamine  Toxicity, Arsenic  Toxicity, Barbiturate  Toxicity, Benzodiazepine  Toxicity, Beta-blocker  Toxicity, Calcium Channel Blocker  Toxicity, Carbon Monoxide  Toxicity, Caustic Ingestions  Toxicity, Clonidine  Toxicity, Cocaine  Toxicity, Cyanide  Toxicity, Cyclic Antidepressants  Toxicity, Digitalis  Toxicity, Lead  Toxicity, Medication-Induced  Toxicity, Narcotics  Toxicity, Salicylate 32

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