1. General Toxicology By: Rajia Mahmoud Hejazy MD CLINICAL TOXICOLOGY
Assistant professor of clinical toxicology
Faculty Of Pharmacy, & Faculty of Medicine
Umm Al-Qura University, KSA
Benha University, EGYPT

2. GENERAL TOXICOLOGY Classification of poisons:
I- According to their mode of action:
a) Poisons with local action:
They act locally producing immediate destruction of the tissues with which they come in contact e.g corrosives (except organic acids).
b) Poisons with remote action:
They act only after absorption without any local effects e.g plant poisons which act mainly on CNS.
c) Poisons with both local and remote actions:
As irritant metallic poisons (lead, Mercury, arsenic,..etc) which have a local irritant action on the tissues they come in contact for sometime and a remote action (on parenchymatous organs) after absorption.

3. II- According to the organs affected:
The poison may be: Hepatotoxic: APAP, phosphorus, CCL4 and arsenic, Cardiotoxic: digitalis, Nephrotoxic:mercury, ASA Neurotoxic: alcohol …. etc.
III- According to the chemical nature:
Acids: like H2SO4, HNO3 and H2CL.
Alkalies: as caustic soda & caustic potash and ammonium hydroxide.
N.B. The source of the poison may be considered as in cases of plant and animal poisons.

4. VI- According to Labeling requirements
IV- According to Use
(e.g., pesticide, solvent, food additive)
V- According to Effects
- (e.g., cancer, mutation, liver injury)
VI- According to Labeling requirements
- (e.g., explosive, flammable, oxidizer)
VII- According to Poisoning potential
- (e.g., very or slightly toxic)

5. Factors affecting the severity of toxicity:
Factors related I- to the person II- to the poison
I- 1) Age of the person & individual suscptibility:
Children and old people generally are more susceptible to the toxic agents due to decrease detoxification power. However, children can tolerate the action of atropine, but not morphine.

6. 2) Genetic factors:
Persons suffering from glucose-6-phosphate dehydrogenase deficiency are susceptible at therapeutic doses to hemolytic effect of some drugs like vitamin K and sulphonamides.
Drug rash

7. 3) Personal hypersensitivity:
Very small harmless doses can produce severe symptoms in sensitive patients e.g. therapeutic dose of penicillin or iodine may produce anaphylaxis in some hypersensitive patients.
4) Tolerance:
Repeated intake of substances of abuse leading to the development of tolerance where the addicts can stand big dose without ill-effect. So, they have to increase the dose to get the same effect.

8. 5) Idiosyncrasy:
Abnormal response to some drugs e.g. morphine may produce convulsion instead of depression of CNS.
6) State of health :
Patients suffering from liver or kidney diseases may show signs of increased toxicity of the poisons.
7) Synergism:
The action of one drug may be increased if given with another drug e.g. alcohol and barbiturate.

9. 8) Condition of the stomach:
- Type of food:
Fatty foods delay the absorption of arsenic while they increase the absorption of some poisons as DDT and phosphorus.
- Gastric secretion:
Poisoning with potassium cyanide may not be fatal in case of achlorhydria as HCL in stomach is important to form the severely toxic hydrocyanic acid.
Empty or full stomach :
A poison taken on full stomach has slower action than the same dose of poison on empty stomach.

10. II- Factors related to the poisons:
1) State of the poison.
Poisons in gaseous form are more rapidly absorbed followed by liquid poisons, fine powder, then big lumps.
2) Routes of administration:
The quick.. inhalation followed by IV, IM, SC, ingestion, absorption through mucous membranes, lastly absorption through the intact skin which is minimal except in some poisons as organophosphates, phenol & tetraethyl lead.

11. 3) Dose of the poison:
The bigger the dose, the more toxic the effect. However, this is NOT a general rule as big doses of metallic poison may cause severe vomiting, so eliminate most of the poison.
4) Cumulation:
After repeated small doses of certain drugs, that are not readily metabolized, the effect of a single large dose is reached leading to poisoning e.g. digitalis.

12. Diagnosis of Poisoning:
1- History and circumstantial evidences.
2- Clinical manifestations.
3- Investigations.

13. 1- History and circumstantial evidences:
- Sudden appearance of toxic manifestations in a healthy person or a group of persons after taking certain food or drink (as food poisoning, methanol and carbon monoxide toxicity).
- History of intake a poison, financial problems, psychiatric troubles, previous attempts at suicide or threatening by somebody.
- Presence of bottle of tablets or insecticide near the victim .
- Patients rescued from fire (CO, cyanide).

14. 2- Clinical manifestations (signs and symptoms):
- Vital signs:
Temp, Pulse, BP,Respiratory rate Breath odour, Pupil, Skin
Recorded in initial evaluation & repeated regularly.

15. Temperature:
*Hyperthermia: a,ss,t
a: anticholinergics.
s: salicylate , sympathomimetics
t: tricyclic antidepressants.
*Hypothermia: in CNS depressants (a,bb,o)
a: alcohols
b: barbiturate+ benzodiazepines.
o: opiates.

16.    Pulse:
*Bradycardia: (a,b,c,d,o)
a: atropine (early),
b: beta blockers,
c: cholinergics, calcium channel blockers
d: digitalis,
o: opiates.
*Tachycardia: (It can occur late with any poison)
Anticholinergics.
Sympathomimetics.

17. Blood pressure:
*Hypertension: CNS stimulants (AC)
A:Amphetamine
C:cocaine
*Hypotension & tachycardia: occur late with any poison.+ theophylline and TCA
Respiratory rate:
*Tachypnea: ACT M
A:Aspiration pneumonia ( kerosine).
C:CNS stimulants ( cocaine,amphetamine),
T:Toxic hypoxia ( CO2, CO, cyanide),
M:Methemoglobinemia.
*Bradypnea: CNS depressants.(a bb o)

18. Breath smell:
Cyanide: (bitter almond)
Arsenic, OPC Garlic
Camphor Mothballs
Cyanide Bitter almond
Methyl salicylate Wintergreen
Paraldehyde Pears
Hemlock Carrots
Pupils:
*Miosis: OO, PP, CNE (D.D pontine hemorrhage).
OO: opiates, organophosphates,
PP: phenol (early stage), phenothiazine
C: carbamates
N: nicotine
E: ergot

19. *Mydriasis:
Dilated & reactive:
CNS stimulants
nicotine
opoid withdrawal
Dilated & fixed:
Anticholinergics
late in any poisoning
brain stem lesion

20. Skin:
*Needle tracks in IV drug abuse
*Bullous lesions in prolonged coma with prolonged pressure and skin hypoxia e.g. sedative hypnotics (especially barbiturates) & CO
*Flushing anticholinergics (flushed & hot),
alcohol (flushed & cold)
*Diaphoresis (CANOS)
C: carbamates
A: alcohol withdrawal
N: nicotine
O:organophosphates,
S: salicylates,
(D.D. hypoglycemia).

21. *Red: CO & cyanide
*Cyanosed: CNS depressants
*Jaundiced: (appi) arsenic, phosphorous, paracetamol, iron
*Petechiae & ecchymosis e.g. salicylates.
*Patches or eschars around the mouth in corrosives.

22. Clinical examination:
1-Respiratory system: Wheeze, pulmonary edema
*Wheezing: (due to bronchospasm) ipcco e.g. irritant gases & fumes, paraquate, carbamates , cholinergics organophosphates.
*Pulmonary edema: cardiogenic or non-cardiogenic
- Cardiogenic: (left ventricular failure) e.g. calcium channel blockers, beta blockers, tricyclic antidepressants.
- Non-cardiogenic: (due to factors increasing the pulmonary capillary permeability) ipcons
irritant gases & fumes, prolonged coma of CNS depressants as opiates & barbiturates (due to prolonged hypoxia) carbamates , organophosphates. nicotine, salicy.

23. CNS:
*Coma: abpo
a: alcohols, atropine
b: barbiturates
p :phenol
o:organophosphates, opiates
*Convulsion:
prolonged coma of CNS depressants as opiates & barbiturates (due to prolonged hypoxia)
lead, arsenic (encephalopathy)
oxalic acid (decalcification)
organophosphates (early stage of CNS stimulation)
CNS stimulants: strychnine; nicotine, cocaine. amphetamine
phenol, atropine, ergot, cyanide,

24. Abdomen:
*Adynamic ileus e.g. Anticholinergics
*Distened abdomen may indicate GIT perforation from inorganic corrosives.

25. 3- Investigations:
They are done to assess:
-base line of the patient
-follow up target organs
e.g. blood gases, electrolytes, glucose,
liver & renal function tests,
ECG and X-ray.

26. Common radiopaque medications: (BETA CHIP) B -Barium E -Enteric coated tablets: ASA, theoSR T-Tricyclic antidepressants A-Antihistamines. C-Chloral hydrate, cocaine, calcium, condoms (contains tablets, or Body Packers). H-Heavy metals I- Iodides P-Phenothiazines

27. b) Chemical detection: (Analytical toxicology)
The most important evidence of poisoning is by chemical analysis.
A) In the living:
Samples are taken from vomitus, gastric lavage, blood, urine and stool.
B) In the dead:
- Blood from femoral , axillary or iliac veins.
- Stomach and intestine.
- Organ samples
Vitreous humor if there is difficulty in blood sampling particularly in putrefaction.
CSF.

28. General lines of treatment of poisoned patient
(6)

29. Good supportive care is the backbone of any successful therapy of poisoned patients:
1- Prevent further exposure to the poisons.
2- Emergency and supportive measurements.
3- Decontamination.
4- Enhancement of excretion.
5- Administration of toxin-specific (physiological) antidotes.
6- Symptomatic treatment.

30. 1-Prevent Further Exposure To The Poisons:
1-Prevent Further Exposure To The Poisons: *In industrial or agricultural exposure → removed from the polluted area. *In cases of toxic inhalants → removal of the patient to fresh air and giving oxygen. *In suspected suicidal cases → the patient hospitalized and observed to prevent another trials. *During medical treatment if toxic manifestations appear → the drug should be stopped immediately

31. 2. Emergency and Supportive Measures:
ABCD’s

32. 2. Emergency and Supportive Measures: The first step is to recognize and treat life threatening conditions (A, B, C, D): A=Airway. B= Breathing. C= Circulation. D= Disability i.e. assess neurological status, level of consciousness and convulsion.

33. A) Airway opening & clearance:
Triple airway maneuver:
(Head tilt, jaw thrust, Mouth opening)
If there is any suspicion of neck injury:
Place the patient in left lateral position with the head downwards which allows the tongue to fall forwards and vomitus or secretions to drain out of the mouth.

34. Airway clearance:
a- Finger sweep technique to remove any F.B. or denture.
b- Suctioning of the mouth and oropharynx to remove secretions.

35. B) Breathing support:
a)  Airway devices
b) Assist ventillation by giving oxygen
c) Active ttt.

36. 1-Oropharyngeal or nasopharyngeal airway devices:
2-ETT,
3-Tracheostomy
1-Oropharyngeal or nasopharyngeal airway devices:
placed in the mouth or to lift the tongue and push it forward

37. Endotracheal intubation (ETT):
In Comatosed patient.
Advantages :
- It protects the airway & prevents aspiration and obstruction.
- It allows for mechanically-assisted ventilation.
Some emergency drugs can be given through it e.g. naloxone, atropine and epinephrine

38. -Cricothyrodotomy or tracheostomy: In upper airway obstruction (ETT can not be INSERTED)

39. PO2 < 60 mmHg & PCO2 > 60 mmHg. Don’t wait until apniec Methods:
b- Assist ventillation: (oxygen)
Indication
PO2 < 60 mmHg & PCO2 > 60 mmHg. Don’t wait until apniec
Methods:
1- Mouth-to-mouth ventilation.
2- Mouth-to-mask ventilation (this method is more hygienic).
3- Bag and mask ventilation
4-Bag and tube ventilation
5-Mechanical ventilation (used when resuscitative efforts are prolonged).

40. The greatest contributor to death from drug overdose or poisoning is respiratory failure
Toxic causes of respiratory failure:
I Central causes:
such as opiates, barbiturates, alcohols …..
II Peripheral causes due to
1-airway obstruction
2-Neuromuscular block
3-Paralysis of respiratory muscles

41. c- Active treatment:
Bronchospasm, pneumonia, pulmonary edema, specific antidote.
1-Administer bronchodilators if there is wheezing or ronchi:
- B2- agonists e.g. sulbutamol inhalation.
- Aminophylline slowly IV if the above is not effective.
2-Treat pneumonia with the following:
- Antibiotics if there is evidence of infection.
- Corticosteroids (if it is a chemical-induced pneumonia).
3-Treat pulmonary edema with the following:
-Avoid excessive fluid administration.
-Administer supplemental oxygen.
-Diuretics.
4-Consider specific antidotes e.g. Naloxone can reverse respiratory depression in a patient with opiate overdose.

42. C) Circulatory support: (5)
1-Check blood pressure and pulse rate and rhythm:
Perform CPR if there is no pulse.
Treat shock and arrhythmia if present.
Hypotension treatment:
Normal saline fluid challenge, 20 mL/kg up to 2 liter or S BLP 100 mm/Hg
Vasopressors if still hypotensive as dopamine or dobutrex
PRBC’s if bleeding or anemic
Hypertension treatment:
Nitroprusside, beta blocker, or nitroglycerin
With tachycardia: do not give BB alone, you can worsen HTN if it is caused by alpha adrenergic stimulation as with cocaine

43. C) Circulatory support: (5)
2-Begin continuous ECG monitoring:
This is essential for comatosed patients and patients with cardiotoxicity.
3-Establish an intravenous line .
4- Draw blood for routine studies.
5-Foly’s catheter is placed in the bladder if the patient is seriously ill (shocked, convulsing or comatosed).
Obtain urine for routine and toxicologic testing and measure hourly urine output

44. REASSESS frequently

45. D)Disability
Once ABC are addressed, the neurological status should be assessed, mainly:
level of consciousness & convulsions. 
I-level of consciousness: a)Coma and b)stupor
Stupor: is a grade of unconsciousness in which the patient can be aroused (awakened) only by painful stimuli.
Coma: is a state of prolonged unconsciousness in which the patient can not be aroused by painful stimuli.
The level of consiuosness is evaluated roughly by the responsive scale AVPU:
A=awake and alert.
V= respond to verbal stimuli.
P=respond to pain.
U= unresponsive

46. Reed’s classification of the level of consiousness
Circul.
Resp
Reflexes
Pain response
Consious level
stage
Normal
Intact
Arousable
Asleep
Withdrawal
Comatose I
None II
Absent
III
Shock
cyanosed IV

47. Causes of coma : (5)
*Toxic *Traumatic *Pathologic
*Environmental *Hysterical
Toxic causes:
Generalized CNS depression (e.g. ethanol, opiates, sedative-hypnotics).
As a postictal phenomenon (after a drug-induced seizure) (e.g. anticholinergics).
Hypoglycemia (e.g. insulin, oral hypoglycemic drugs).
Cellular hypoxia (e.g. CO, cyanide).
Traumatic Causes
head injures.
Pathologic causes:
Liver & renal failure. Infections as encephalitis or meningitis .

48. 4.Environmental causes:
Hypothermia or hyperthermia.
4. Hysterical:
No organic cause, normal vital signs, and negative investigations.
Complications of coma:
- Loss of protective airway reflexes, resulting in airway compromise which is a major cause of death.
-Hypotension.
-Hypothermia.
-Rhabdomyolysis.

49. Treatment of coma (7)
1- Support ABC.
2- Give coma Coktail: DONT
 Administer supplemental O2
Dextrose, Naloxone and Thiamine:

50.  a)     Dextrose is given to all patients with depressed consciousness.
Child : 25 % (1-2 ml/kg) I.V.
Adolescent/Adult: 50 % (1 ml/kg) I.V.
b)    Naloxone is given to all patients with depressed respiration.
-      Child: 0.01 mg/kg I.V.
-         Adolescent/Adult: 0.4 mg I.V. (amp= 200µgm/Kg) up to 2 mg I.V. can be repeated max 10 mg.
if no response, repeat the dose every 2 min. till a total dose of 10 mg.
c)    Thiamine is given to malnourished and chronic alcoholic patients.
-       It is not given routinely to children.
100 mg I.M.

51. 3-  Control convulsions if they are present:
4-  Correct any temperature, electrolyte, or acid-base disturbance.
5-  If suspecting a brain lesion, perform a CT scan and treat accordingly.
6- Continuous care of the comatosed:
a)Care of respiratory system: Frequent suctioning, antibiotics.
b)    Care of G.I.T.: Antacids, lactulose.
c)    Nutritional support: Tube feeding
d)    Removal of excreta: Urine and stools removal.
e)     Care of the skin: Frequent changing PP
f)      Care of the eyes: Antibiotic eye drops& ointment).
7-Consider specific antidotes e.g. flumazenil for benzo.

52.  II-Convulsions: (6)
*Toxic *Traumatic *Pathologic
*Metabolic *Idiopathic *Environmental
Toxic causes:
1-Convulsions due to Withdrawal from alcohol or sedative hypnotic drug.
2-Convulsions due to Decalcification of the blood e.g. oxalic acid poisoning → tetanic convulsions
3-Convulsions due to Poisons acting on CNS.

53. Poisons acting on the cerebrum → muscular hyperactivity.
E.g. Amphetamine, cocaine, caffeine & atropine.
- Poisons acting on the brain stem → clonic convulsions i.e. contraction and relaxation of the muscles.e.g. picrotoxinPb
- Poisons acting on the spinal cord → tonic convulsions i.e. sustained hypertonia of the muscles.e.g. as strychnine
- Poisons → cerebral anoxia .e.g. cyanide.

54. -Metabolic causes:
hypoglycemia, hyponatremia, hypocalcemia, or hypoxia.
-Traumatic causes:
head trauma with intracranial injury.
-Idiopathic epilepsy
-Exertional or environmental hyperthermia.
Pathologic causes:
-CNS infection: meningitis or encephalitis,febrile seizures in children.

55.  Complications of convulsions:
1- Any seizures can cause airway compromise, resulting in apnea or pulmonary aspiration.
2- Multiple or prolonged seizures may cause severe metabolic acidosis, hyperthermia, rhabdomyolysis, and brain damage.

56. Treatment of convulsions: 1-Maintain an open airway and assist ventilation. 2- Use one or more of the following anticonvulsants: Diazepam (Valuim): mg/kg IV (5-10 mg) IM or IV Lorazepam (ativan) 2 mg IV, may repeat as needed. Short acting barbiturates or ultrashort acting as Pentothal sodium: 0.5 – 1 gm, slowly IV. Phenobarbital: 10-15mg/kg slowly IV infusion over minutes. Phenytoin: the anticonvulsant of last choice for most drugs induced seizures. Dilantin (phenytoin)10 mg/kg IV

57. Any questions?

58. 3- Decontamination Lungs
Skin
Eye
Lungs
GIT

59.  I-Skin decontamination
Indications:
1-     Cases of Corrosives to prevent skin injury.
2-     Toxins that are readily absorbed through the skin (e.g. organophosphorous insecticides, paraquat, phenol, oxalic acid, …etc); to prevent systemic absorption.
  Steps of decontamination:
a)     Wear protective clothes & gloves.
b)    Remove the patient’s contaminated clothing.
c)Flush exposed areas with copious quantities of taped water or saline for at least 30 minutes. Use soap for oily substances.

61. II. Eyes Indications:
1- Corrosive agents and hydrocarbon solvents that can rapidly damage the cornea.
2-Toxins that are readily absorbed through the skin can also be absorbed through the conjunctiva.
Steps of decontamination:
a) Flush exposed eyes with copious quantities of taped water or saline for up to 20 minutes.
b)Ophthalmologic consultation is a must in patients with serious injury.

62. III. Inhalation
Indications:
1.    Irritating gases and fumes e.g. chlorine gas.
2.     Toxins that are absorbed thorugh the respiratory tract e.g. CO, cyanide, hydrogen sulphide, organophosphorus insecticides. ((هام

63. Steps of decontamination:
a) Ensure adequate respiratory protection for yourself and other care providers (wear protective mask).
b) Remove the victim from exposure to fresh air.
c) Care of respiration is started after cleaning the mouth, administer humidified O2 (if available) and assist ventilation (if necessary). Tracheostomy or ETT may be needed.
Observe for evidence of upper respiratory edema (manifested by stridor and hoarse voice) and a later non-cardiogenic pulmonary edema (manifested by dyspnea, tachypnea and hypoxemia).

64. Whole bowel irrigation
GIT decontamination
Emesis
Gastric lavage
Local antidotes
Catharsis
Whole bowel irrigation

65. A-Emesis:
This is one of the most convenient methods used to get rid of the poison from the stomach.
Emetic used : Syrup of ipecac
Syrup of ipecac is the emetic of choice in both children over the age of 6 months and in adults.
Ipecac is the dried root of Cephalus ipecaquanha plant that contains the active alkaloids emetine & cephaline.        

67.  It causes vomiting through 2 phases: Early vomiting (within 30 minutes): due to the direct local irritant action of ipecac on gastric mucosa,
Late vomiting (after another 30 minutes) is the result of central stimulation of the chemoreceptor trigger zone.
Dose: 30 ml for adults, 15 ml for children and 5 – 10 ml for children between 6 months and 2 years. If vomiting does not occur after 30 minutes, the dose is repeated.
If still no vomiting, gastric lavage should be carried out to remove ipecac from the stomach (as it is toxic).
NB: Manual digital stimulation or apomorphine are unsafe and should not be used.

68. Contraindications of emesis:
1) Substance:
-Convulsants Corrosives (inorganic)
- Hydrocarbons Sharp objects (needle, pin)
2) Patients:
-Unconscious or comatosed patient. -Decreased gag reflex.
-Severe CVS disease or emphysema or respiratory distress.
-Recent surgical intervention Hemorrhagic tendencies.
- Previous significant vomiting before this moment.
- Under 6 months of age (gag reflex not well developed).
-Pregnancy.

69. Advantages of emesis:
-It is generally less traumatic than gastric lavage which is unpleasant to most people and must be done by qualified trained physician.
-Emesis can recover particles that are too large to pass through the openings of gastric lavage tube.

70. Whole bowel irrigation
GIT decontamination
Emesis
Gastric lavage
Local antidotes
Catharsis
Whole bowel irrigation

72. Decrease Absorption: B. Gastric lavage
a. provides immediate recovery
of gastric contents.
It Does not reliably remove pills and pill fragments
b. Efficacy after the first hour or two is questionable
c. Risk of Aspiration, so airway has to be protected (LLD position with some Trendelenberg or for a lethargic patient with a depressed gag, endo-tracheal intubation).
d. Contraindicated as emesis (Rule of Except) in most hydrocarbon ingestions and in caustic ingestions

73. Decrease Absorption: C.Activated Charcoal
• Drug may adsorb into the charcoal and thereby prevent absorption in the first place.
• Useful for some drugs that undergo substantial enterohepatic recirculation, or small volume of distribution or low protein binding and are highly adsorbed by charcoal.
• Dose usually 1-2 g/kg orally or naso- gastric tube (Patient must be awake or intubated.

74. Decrease Absorption: C.Activated Charcoal
– Multiple doses may be given:
0.5 g/kg every 2h h or
20g every 2 h for up to 48 h
Indication of Repeat-dose activated charcoal
Very large ingestions of toxic substance
Sustained release and enteric coated preparations
Carbamazepine, phenobarbital, phenytoin
Salicylate, theophylline, digitoxin

75. Activated Charcoal Not good for: Lithium Iron Alcohols Lead
Hydrocarbons
Caustics
N.B. Recent studies suggest that activated charcoal alone is just as effective as gut emptying followed by charcoal (gut dialysis).

76. GI Decontamination Decrease Absorption: D. Cathartics
Hasten passage of ingestions or AC
Contraindications: obstruction , ileus, child 5y, corrosives
10% magnesium citrate 3ml/kg or 70% sorbitol 1-2 …./kg (not used now)
Severe fluid loss, hypernatremia, hyperosmolarity, renal failure with Mg catharatics, nausea & abdominal pain
Cathartics –
hasten passage ….. But no evidence that they decrease morbidity or mortality and they can cause
significant fluid loss and lyte imbalances.
Large ingestions, especially if not adsorbed to charcoal

77. GI Decontamination Decrease Absorption: E.Whole bowel irrigation
Poly Ethylene Glycol ( movicol)-1 to 2 liters/hour until the material is recovered or the effluent is clear
Used for: Large ingestions, SR or EC tablets, packers (ex. cocaine)
Contraindications: obstruction or ileus
Complications: Aspiration, nausea, may decrease effectiveness of charcoal
Cathartics –
hasten passage ….. But no evidence that they decrease morbidity or mortality and they can cause
significant fluid loss and lyte imbalances.
Large ingestions, especially if not adsorbed to charcoal

78. Enhanced Elimination Urinary manipulation
Forced diuresis can cause fluid overload(CHF, Pulm Edema)
Alkalinization as in salicylate poisoning
Hemodialysis, Hemoperfusion less dependent on molecular size, solubility, and protein binding, achieves greater clearance rates for most drugs
Forced diuresis can cause fluid overload
Alkalinization as in salicylate poisoning
Hemoperfusion – similar equipment and access, blood pumped through a column containing an adsorbant material like charcoal
less dependent on molecular size, solubility, and protein binding, achieves greater clearance rates for most drugs
Peritoneal dialysis and hemofiltration – less invasive than above, used for a continuous removal over time in a non-critical patient.
Role in acute poisonings is unclear.

79. Enhanced Elimination
Peritoneal dialysis, Hemofiltration less invasive than above, used for a continuous removal over time in a non-critical patient.
Role in acute poisonings is unclear.
Forced diuresis can cause fluid overload
Alkalinization as in salicylate poisoning
Hemoperfusion – similar equipment and access, blood pumped through a column containing an adsorbant material like charcoal
less dependent on molecular size, solubility, and protein binding, achieves greater clearance rates for most drugs
Peritoneal dialysis and hemofiltration – less invasive than above, used for a continuous removal over time in a non-critical patient.
Role in acute poisonings is unclear.

80. Enhanced Elimination Does the patient need it?
Severe intoxication with a deteriorating condition despite maximal supportive care
Usual route of elimination is impaired
A known lethal dose or lethal blood level
Underlying medical conditions that can increase complications
It the patient stable, will supportive care alone enable recovery, is there an antidote?
Indications include:
Usual route – lithium overdose in a patient with renal failure

81. Antidotes Acetaminophen N-acetylcysteine (Mucomyst)
Organophosphates Atropine, PAM (Toxoguanin)
Anticholinergic physostigmine
Arsenic, mercury dimercaprol (DMSA)
Benzodiazepines flumazenil (Anexate)
Beta blockers glucagon
Calcium channel block calcium
Carboxyhemoglobin (CO) 100% O2, HBO
Cyanide nitrite, Na thiosulfate (Lilly kit)
Digoxin digoxin antibodies (FAB)
Physostigmine:--
Side effects: seizures, vomiting, diarrhea, abdominal cramping
indications: tachydysrhythmias with hemodynamic compromise, intractable seizures or severe agitation or psychosis.
Contraindications: conduction disturbances, prolonged QRS, PR
Physostigmine – for CNS effects. Side effects: seizures, vomiting, diarrhea, abdominal cramping
indications: tachydysrhythmias with hemodynamic compromise, intractable seizures or
severe agitation or psychosis.
Contraindications: conduction disturbances, prolonged QRS, PR

82. Antidotes Ethylene glycol fomepizole, HD Heparin protamine sulfate
Iron deferoxamine (dysferal)
Isoniazid pyridoxime (Vit. B6)
Methanol fomepizole, HD
Methemoglobin methylene blue
Opioids naloxone (narcan)
Salicylate alkalinization, HD
TCA’s sodium bicarbonate
Warfarin FFP, vitamin K
Fresh Frozen Plasma

83. Toxidromes
A group of typical signs and symptoms consistently associated with exposure to a particular type of toxin

84. Cholinergic Toxidrome
Diarrhea Salivation Urination Lacrimation Miosis Urination Bradycardia Defecation Bronchospasm GI upset Emesis Emesis Lacrimation Limp paralysis, fasiculations, hyporeflexia Salivation, sweating
Limp – paralysis, fasiculations, hyporeflexia

85. Cholinergics Muscarinic only in 1-Organophosphates
Irreversibly bind cholinesterases
2- Carbamate
Reversibly bind cholinesterases, poor CNS penetration
Muscarinic and nicotinic effects
1-Pesticides, nerve agents
Military personnel
Field workers, crop dusters
Truckers
Pest control, custodial workers O
Irreversibly bind cholinesterases – acetylcholine supply increases and you exhaust the postsynaptic neuronal transmission in the CNS and PNS
Muscarinic – parasympathetic effects
Nicotinic – gives you muscular effects
OP – physostigmine, neostigmine
Carb – antihelmintic, insecticides

86. Cholinergics Antidote Atropine for muscarinic effects
Pralidoxime reverses phosphorylation of cholinesterase
Irreversibly bind cholinesterases – acetylcholine supply increases and you exhaust the postsynaptic neuronal transmission in the CNS and PNS
Muscarinic – parasympathetic effects
Nicotinic – gives you muscular effects O
Irreversibly bind cholinesterases – acetylcholine supply increases and you exhaust the postsynaptic neuronal transmission in the CNS and PNS
Muscarinic – parasympathetic effects
Nicotinic – gives you muscular effects
OP – physostigmine, neostigmine
Carb – antihelmintic, insecticides

87. Anticholinergics Atropine Scopolamine Antispasmotics Hyoscyamine TCAs
Mydriatics
Antihistamines
Chlorpheniramine
Diphenhydramine
Antipsychotics
Clozapine
Olanzapine
Thioridazine

88. Anticholinergic Toxidrome
DRY m.m (thirsty),& throat (hoarseness)
DRY Flushed skin
Mydriasis, blurred vision, loss of accommodation EYE
Fever HIGH
Tachycardia HIGH
Hypertension HIGH
Decreased bowel sounds S.Ms
Urinary retention S.Ms
Mental status changes
(hallucination, excitation) CNS St.
Seizures CNS St.
Ataxia CNS St.
Amanita muscaria mushroom
Amanita muscaria mushroom

89. Antihistamines Antidepressants Atropine Antipsychotic
(HOT as a hare) Hyperthermia
(RED as a beet) Flushed
(DRY as a bone) Dry skin
(BLIND as a bat) Dilated pupils
(MAD as a hatter) Hallucinations
(Flappy as a bird) Tachycardia
(Full as Container) Urinary retention

90. Toxidromes Opioids Respiratory depression Miosis
Hypoactive bowel sounds
Clinical Pearl: Sweating (diaphoresis) differentiates sympathomimetic
and
anticholinergic toxidromes
Sympathomimetics
Hypertension
Tachycardia
Hyperpyrexia
Mydriasis
Anxiety, delirium
Cocaine – Amphetamines - Phencyclidine - Pseudoephedrine

91. OPIOD WITHDRWAL TOXIDROME
& ...MY...
Mania
Mydriasis
Muscle twitch
Massive sweating
Metabolic acidosis
Male ejaculation & female orgasm.
....&….
Yawning with chillness alternating with flushing
Agitation
Anxiety
Insomnia
Irritability

92. SEROTONIN SYNDROME Altered Mental status: Autonomic Dysfunction:
(Agitation – Delirium – Coma)
Autonomic Dysfunction:
(Mydriasis – Diaphoresis – Hyperthermia – Tachycardia – Fluctuating B/P)
Abnormal neuromuscular activity
(Tremors – Rigidity – Seizures)

93. NICOTINIC TOXIDROME: (recalled by the days of the week):
Saturday: Seizures
Sunday: Somnolent
Monday: Miosis
Tuesday: Tachycardia
Wednesday: Weakness
Thursday: Tremors
Friday: Fasciculations

94. References
Poisoning & Drug Overdose, California Poison Control System. KR Olson, 3rd edition, Appleton & Lange, 2003.
Emergency Medicine Board Review Series. L Stead, Lippincott Williams & Wilkins, 2008.
Emergency Medicine, A comprehensive study guide. Tintinalli, 6th edition, McGraw Hill, 2008.

95. Hope after this lecture we know:
How to generally manage a toxic patient
The most famous toxidromes, & antidotes
Prescribe the ideal treatment for toxic patient