1. CLINICAL TOXICOLOGY Lecture 1 & 2 Introduction
Dr. Tavga A. Baban

2. Introduction
Clinical toxicology:- is concerned with diseases and illnesses associated with short term or long term exposure to toxic chemicals.

3. Who is more prone to toxicity? Children less than 5 years old. Why?

4. The environment: includes the area around the home.
Children are curious and investigative.
Many household products are marked in attractive packages.

5. 4. The natural tendency of children to place everything into their mouth.

6. 5. Taking medication in the presence of children “If I see it, I can do it,” 6. Dosing errors 7. Poisons are often left in easy view and accessible. Poisoning also occur because many products are used in unvented areas. Another factor that increase toxicity is the absence of information about the constituents of many products.

7. 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

8. 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

9. 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

10. 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

12. APPROACH TO THE POISONED PATIENT
Table 3.1 page 42
History; Oral statements concerning details
Call Poison Control Center
Initial physical examination
Assessment of vital signs
Eye examination (miosis or mydriasis, nystagmus, and vision disturbance)
CNS and mental status examination

14. APPROACH TO THE POISONED PATIENT
Examination of the skin
Mouth examination
Lab (clinical chemistry and x-ray procedures
Renal function tests
ECG
Other screening tests

18. 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

19. 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

20. 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
if patient has ingested sharp object
if patient less than 6 months

21. PREVENTION OF ABSORPTION OF POISON
Induce emesis in the following ways:
mechanically by stroking posterior pharynx;
use of syrup of ipecac, 15ml for children and 30ml for adults followed by one glass of water;
use of apomorphine parenterally

22. PREVENTION OF ABSORPTION OF POISON
Gastric lavage: insert tube into stomach and wash stomach with water or normal saline to remove unabsorbed poison
Contraindications are the same as for emesis except that the procedure should not be attempted with young children

23. PREVENTION OF ABSORPTION OF POISON
Chemical Adsorption
activated charcoal will adsorb many poisons thus preventing their absorption
adsorbent in intestines may interrupt enterohepatic circulation

24. 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

25. Metabolism of some compounds produces highly reactive electrophilic intermediates; if nucleophiles present, toxicity is minimal; if nucleophiles depleted, toxicity results

26. Increase Elimination Of Toxic Agents
Increasing urinary excretion by acidification or alkalinization
Decreasing passive resorption from nephron lumen
Diuresis
Cathartics
Peritoneal dialysis
Hemodialysis
Hemoperfusion

27. Forced diuresis and pH alteration
It is useful when compounds or active metabolites are eliminated by the kidney and diuresis enhances their excretion.
Mannitol and furosemide are generally used.
This method is no longer indicated because it increase the excretion of chemical only two fold.
Alkaline diuresis is achieved by administration of sodium bicarbonate, 1-2 mEq/kg every 3-4 hr.

28. The potential uses of urine alkalinization have been with weak acid such as salicylates and phenobarbital.
Acid diuresis is possible by using ammonium chloride, 75mg/kg/24hr.
Acid diuresis increase the elimination of weak bases, such as amphetamine, phencyclidine, and quinidine. This procedure is no longer recommended.

29. Dialysis and hemoperfusion
Peritoneal Dialysis
The procedure is undertaken by inserting a tube through a small incision made in the abdominal area into the peritoneum.
The peritoneal membrane serves as the semipermeable (dialyzing) membrane. The dialyzable chemical diffuses from blood across the peritoneal membrane into the dialyzing fluid (from higher concentration to lower concentration).

30. Peritoneal Dialysis Advantages:- Easy. Lowest risk for complications.
Disadvantages:-
The least effective method for removing most poisons. It is 5-10 time less efficient than hemodialysis.
Not suitable when rapid removal of a toxic substance is needed.
Complications include:- abdominal pain, intraperitoneal bleeding, intestinal, bladder, liver, or spleen perforation; peritonitis; water and electrolyte imbalance; and protein loss.

31. Procedure for peritoneal dialysis

32. Hemodialysis
Two catheters are inserted into the patient’s femoral vein. Blood is pumped from one catheter through the dialysis unit, across the semipermeable membrane, and back through the other catheter.
The procedure is continued for 6-8 hr. the solubilized chemical diffuses across the semipermeable membrane into the dialysis solution.
Clearance of the toxic agent is based on differences in osmotic and concentration gradients.

33. Procedure for hemodialysis

34. Procedure for hemodialysis

35. Disadvantages
The chemical that removed by this way must have a low molecular size.
Less effective for drug that are highly protein-bound.
Useless for chemicals that are extensively taken by the tissues.
Complications include clotting, and seepage of blood from around connections, hypotension, convulsions, arrhythmias, infection, and hematologic defects.

36. Hemoperfusion
The passage of blood through columns of adsorptive material, such as activated charcoal, to remove toxic substances from the blood.
It is more effective than peritoneal dialysis and hemodialysis for removing compound that are:
lipid soluble.
protein bound.
Poorly dialyzable.
Complications include:- trapping of white blood cells and platelets and microembolization. Newer systems solved this problem.

37. Procedure for hemoperfusion

39. Antagonism of the absorbed poison
Chemical antagonism e.g. protamine sulfate + heparin, chelators of metal ions
Functional or physiological antagonism e.g. glucagon + B-blockers

40. C. Pharmacological or receptor antagonism e.g. naloxone + opioid
D. Dispositional antagonism (pharmacokinetic interaction)

41. 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

42. Strategies for Treatment of the Poisoned Patient
Determine the immediate (real time) risk or hazard for absorption
Initiate body burden reduction procedures or specific antidotes based on the above information

43. 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

44. SPECIFIC ANTIDOTES Antidote Poison Acetylcysteine Atropine Deferoxime
Ethanol
Metal Chelators
Naloxone
Physostigmine
Praladoxime (2-PAM)
Poison
Acetaminophen
Acetylcholinesterases, OP’s, physostigmine
Iron salts
Methanol, Ethylene glycol
Mercury, lead
Narcotic drugs
Anti/muscarinics-cholinergics
OP anticholinergics

45. Poison
Warfarin
Digoxin
INH
BZD
Chloroquin
Heparin
Snake bite
B-blockers
TCA
Antidote
Vit. K
Fab AB
Vit. B6
Flumazenil
Diazepam
Protamine sulphate
Antivenom
Glucagon
Physostigmine, NaHCO3