1. Acids and Alkalis Caustic Agents

2. Acids and Alkalis Corrosives - denotes an acidic substance
Caustics - denotes an alkaline substance
Federal Hazardous Substance Act of 1967
Cause tissue injury by a chemical reaction - accept (base) or donate (acid) a proton.
Severity of tissue injury is determined by:
the substances pH or pKa,
concentration,
duration of contact and
volume of contact.

3. Acids and Alkalis
Ingestion is an extremely common event, accounts 229,500
alkali drain cleaners and acidic toilet bowl cleaners are responsible for most fatalities
10% of caustic ingestions result in severe injury requiring treatment
between 1-2% result in stricture formation
80% of ingestions are in children > 5 years
most adult ingestions are intentional

4. Acids Mechanism of action - denature proteins coagulative necrosis
cell morphology not grossly altered, destruction of enzymatic proteins
acid burns cause formation of tough leathery eschar or coagulum (which sloughs in 3-4 days)
little to no systemic absorption
stomach is most commonly involved organ

5. Acids, cont.
Management - any ingestion constitutes a medical emergency
skin or eye contact -
flush with copious amounts of water. remove contact lens and jewelry
wash skin with mild soap
do not apply topical ointments, creams, or dressings

6. Acids, cont.
Ingestion
serious solid ingestions are rare as the particles usually stick to the oropharynx, but liquid exposures can be severe
burning is so severe patient probably can not swallow
do not give carbonated beverages
do not give water, water + acid explosive release of steam - exothermic reaction
do not induce vomiting
maintain airway

7. Acids, cont. Clinical concerns:
perforation may occur after the third to fourth day as eschar sloughs
gastric outlet obstruction may develop over a 2-4 week period
upper GIT hemorrhage

8. Acids, cont. Common acid containing sources toilet bowl cleaners
automotive batteries
rust removal porducts
metal cleaning products
drain cleaning products

9. Acids, cont. Boric acid - H3BO3 weak bacteriostatic agent
used as an insecticide for roaches (roach motels)
do not apply to open wounds
toxic to the kidneys
can cause a severe dermatitis - boiled lobster rash - seen on palmar and plantar surfaces and buttocks

10. Acids, cont. Carbolic acid - phenol
one of the oldest disinfectants known
used as a deodorizer - Lysol
absorbed through intact skin
Signs - nausea, diaphoresis, CNS stimulation, hypotension, renal failure
Treatment - demulcents, activated charcoal

11. Alkalis More common cause of toxicity than acids
Most common alkaline agents causing toxicity
Ammonia
Sodium hydroxide
both of these are found in household cleaners and drain cleaners
Most cases are in children under the age of five years

12. Alkalis, cont. Mechanism of action
tissue injury causes by liquefactive necrosis (saponification of fats and solubilization of proteins)
cell death occurs from emulsification and disruption of cell membranes
OH ion reacts with tissue collagen causing it to swell and shorten
most severe injured tissues are the squamous epithelial cells of the oropharynx and esophagus (the most commonly involved organ)
alkali burns to the skin are yellow, soapy and soft

13. Acids, cont. Clinical concerns
tissue edema - leading to possible airway obstruction
erythema
ulceration
necrosis of tissues with possible stricture formation (depends on depth of burn)
perforation can occur

14. Alkalis, cont. Management of toxicity
eye and skin contamination - flush with copious amounts of water
ingestion - any ingestion constitutes a medical emergency
do not induce vomiting
give demulcents (milk, water or egg whites)

15. Alkalis, cont. Common base containing sources drain cleaning products
ammonia - containing products
over cleaning products
swimming pool cleaning products
automatic dishwasher detergent
hair relaxers
clinitest tablets
bleaches
cement

16. Alkalis, cont. Disc batteries Soaps - most are non toxic
usually pass through GIT in 48 hours
can become lodged
pressure necrosis
leak out potassium or sodium hydroxide
Soaps - most are non toxic
have emetic action so vomiting is spontaneous
automatic dishwashing soap - highly corrosive

17. Alkalis, cont.
Ammonia - NH3 - at room temp is a highly H2O soluble, colorless, irritant gas with a pungent odor.
1993 anhydrous ammonia was the 3rd most produced chemical in the US
farmers use 1/3 for fertilizer and animal feed
A component of may household cleaning products - glass cleaners, toilet bowl cleaners, metal polishes, etc.)
highly alkaline and corrosive
household ammonia - not as corrosive

18. Alkalis, cont.
Most common mechanism is exposure to anhydrous ammonia - liquid or gas
NH3 + H2O NH4OH
this reaction is exothermic - causes significant thermal injury
Ammonium hydroxide also causes severe alkaline burns
1998, US PCC reported 6,000 cases, 95% accidental, 13% resulted in moderate to severe outcomes
Ingestion of household solutions is usually accidental and occurs in young children, adult ingestions are usually suicide attempts

19. Alkalis, cont. Typical household ammonia
contain 3-10% ammonia hydroxide
pH less than caustic burns usually only seen with pH’s >12.5 so household products do not typically lead to significant burns
patients present with oropharyngeal and epigastric pain
may cause aspiration pneumonitis
kids may bite smelling salts - 20% ammonia - can cause esophageal burns and mild respiratory symptoms

20. Alkalies, cont. Bleach - sodium hypochlorite - NaOCl
taste terrible and spontaneously vomited
never mix bleach with acid or alkaline cleaning agents - release of chlorine gas
good to apply topically for any bites

21. Hydrocarbons

22. Hydrocarbons Organic compounds containing H and C
Derived from plants or from petroleum distillates
3 basic types
aliphatic
aromatic
halogenated
Petroleum distillates - produced from fractional distillation of crude petroleum
Terpenes - distillates of pinewood

23. Hydrocarbons, cont. Examples of petroleum distillates kerosene
gasoline
mineral spirits
naphtha
mineral seal oil
diesel oil
fuel oil

24. Hydrocarbons, cont. Characteristics
surface tension - cohesiveness of molecules on the surface of a liquid
volatility - tendency of a liquid to change into a gas or vapor
viscosity - resistance of a substance to flow over a surface, directly relates to the aspiration hazard
low verses high viscosity

25. Hydrocarbons, cont. Mechanism of Toxicity
64, 634 cases of HC exposure in 1994, as reported by the American Association of Poison Control Centers
24% required hospital treatment
more than 1/2 of all exposures occur in children under the age of 6 years
most exposures are accidental
22 people died in 1994

26. Hydrocarbons, cont. Mechanism of toxicity, cont.
major threat is danger of aspiration pneumonitis
vomiting increases the risk of aspiration
when aspirated, petroleum distillates :
inhibit surfactant - causing alveolar collapse and resultant hypoxemia
cause bronchospasm and capillary damage
cause hemorrhagic bronchitis
cause pulmonary edema

27. Hydrocarbons, cont. Mechanism of toxicity, cont.
Systemic toxicity can occur after oral ingestion
CNS depression, GIT irritation, liver and kidney damage, cardiovascular toxicity

28. Hydrocarbons, cont.
Characteristics of poisoning, 3 organ systems usually involved:
Pulmonary, GI & CNS
Signs and symptoms of pulmonary involvement
coughing, gasping and choking
smell of gasoline to the breath
rales and wheezing upon auscultation
hemoptysis and pulmonary edema

29. Hydrocarbons, cont. Signs and symptoms of GIT involvement
irritation of oropharynx
nausea and vomiting
abdominal pain
Signs and symptoms of CNS involvement
cerebral hypoxemia
lethargy
somnolence
coma or seizures

30. Hydrocarbons, cont. Management of poisoning
To induce vomiting or not to induce vomiting
Do not induce vomiting in patients who have ingested low viscosity petroleum distillate hydrocarbons ingestion as it increases the risk of aspiration pneumonitis
Do Maintain airway and support respiration

31. Hydrocarbons, cont. Do induce vomiting in patients who have ingested:
halogenated hydrocarbons
insecticides
turpentine
aromatic hydrocarbons
or ones which contain of heavy metals - must protect airway (endotracheal intubation)

32. Hydrocarbons, cont. Terpenes include pine oil, turpentine, and camphor
pine oil - product of pine trees (Pine Sol)
turpentine is a distillate from pine trees
camphor - distillate of the camphor tree
Have lower volatility and higher viscosity therefore less of a risk of aspiration than the petroleum distillates

33. Hydrocarbons, cont. Mechanism of Action of Turpentine and Pine oil
Systemic toxicity results in GIT irritation and CNS depression
see nausea, vomiting, diarrhea, weakness, somnolence, stupor and coma
Treatment:
GI tract decontamination - induce vomiting
maintain airway
transport

34. Hydrocarbons, cont. Camphor
uses - OTC preparations such as local anesthetics, chest cold inhalants, etc.
basically no therapeutic value, but still used
problem occurs if it is ingested
can cause CNS excitation and seizures, mechanism of action is unknown
causes irritation of upper airway and mucous membranes
Treatment - supportive care

35. Toxic Gases

36. Carbon Monoxide The most common form of poisoning
From 1979 to 1988, 56,000 people died from CO
Colorless, odorless, nonirritating gas
Produced by incomplete combustion of carbon containing compounds
Combines with Hb to form carboxyhemoglobin
CO-Hb will not transport O2
T 1/2 of CO-Hb is 5-6 hours in room air, 90 min in pure O2 at 1 atm, 23 min in O2 at 3 atm

37. Carbon monoxide, cont. Sources: propane powered engines
natural gas appliances - space heaters
automobile exhaust
gas log fireplaces
kerosene heaters
hibachi grills
portable generators

38. Carbon monoxide, cont. Mechanism of action:
Competes with O2 for active sites on Hb (220x the affinity for Hb as O2)
Interference with cellular respiration at the mitochondria level, binds to cytochrome oxidase
Induces smooth muscle relaxation
Hypoxemia, tissue hypoxia, no cyanosis, CO-Hb is cherry red in color

39. Carbon monoxide, cont.
Diagnosis based on patient presentation and a good history
Signs and symptoms vary widely
Signs depend on % CO-Hb levels in the blood
Presence of cherry red blood is pathognomonic

40. Carbon monoxide, cont. Clinical grading of CO poisoning Mild
headache, nausea, dizziness, vomiting, flu like symptoms
Moderate
confusion, slow thinking, shortness of breath, blurred vision, tachycardia, tachypnea, ataxia, weakness
Severe
chest pain, palpitations, severe drowsiness, disorientation, hypotension, syncope, myocardial ischemia, pulmonary edema

41. Carbon monoxide, cont. Exposure during pregnancy can be teratogenic
Chronic low level exposure can cause:
tiredness
lethargy
irritability
visual impairment
increased incidence of heart disease on atherosclerosis

42. Carbon monoxide, cont. Management of Toxicity:
The antidote for CO poisoning is 100% oxygen
hyperbaric chambers should be used more frequently than they currently are in the treatment of CO poisoning

43. Hydrogen sulfide poisoning
Highly toxic, malodorous, intensely irritating gas
Sources:
decaying organic materials
natural gas
volcanic gas
petroleum
sulfur deposits
sulfur springs
Most exposures are occupational

44. Hydrogen sulfide, cont. Mechanism of action:
inhibits mitochondrial cytochrome oxidase
paralyzes the electron transport system
inhibits cellular utilization of O2
metabolic acidosis secondary to anaerobic metabolism
plenty of O2 in the bloodstream, cells can not utilize it, so no hypoxemia but tissue hypoxia

45. Hydrogen sulfide, cont. Mechanism of action, cont.:
more potent cytochrome oxidase inhibitor than cyanide
rapidly absorbed through the inhalation route
metabolized by the liver and excreted through the kidneys
cause of death is respiratory paralysis due to toxic effects of H2S on respiratory centers in the brain

46. Hydrogen sulfide, cont. Concentration (ppm) Clinical effect
odor threshold
nose/eye irritation, olfactory nerve paralysis
sore throat, cough, keratoconjunctivits, chest
tightness, pulmonary edema
headache, disorientation, loss of reasoning, coma, convulsions
> death

47. Hydrogen sulfide, cont. Treatment: rescuer protection
basic life support
give O2, hyperbaric oxygenation is beneficial
nitrates are antidotal by inducing Meth-Hb - providing a large available source of ferric-heme which has a greater affinity for H2S than does cytochrome oxidase, sequestering sulfide ions freeing cytochrome oxidase

48. Cyanide Hydrocyanic acid, Prussic acid
In 1994 only 360 cases of cyanide poisoning (300 were unintentional, 9 patients died)
Sources:
electroplating, jewelry and metal cleaners
photographic processing
fumigant rodenticide
criminal tampering with OTC capsules
Amygdalin - pits of peaches, cherries, apricots, apples, plums
laetrile

49. Cyanide, cont. Mechanism of action:
causes tissue hypoxia by binding with ferric iron of mitochondrial cytochrome oxidase, thus inhibiting the functioning of the electron transport chain and the cells ability to utilize O2 in oxidative phosphorylation
substantial decrease in ATP production
see a shift to anaerobic metabolism
increased lactic acid production - metabolic acidosis

50. Cyanide, cont. Clinical presentation:
tissue hypoxia, especially of the heart and brain (plenty of O2 in the bloodstream, cells can not utilize what is there)
signs depend upon route and dose
inhalation of cyanide gas usually produces
rapid death
delayed onset after exposure to Amygdalin

51. Cyanide, cont. Clinical presentations, cont.
Patients who do not experience sudden collapse you will see anxiety, hyperventilation, CNS stimulation, tachycardia, palpitations
Late signs of poisoning include nausea, vomiting, hypotension, generalized seizures, coma, apnea, a variety of cardiac dysrhythmias
Smell of bitter almonds to the breath
Absence of cyanosis

52. Cyanide, cont. Treatment:
amyl nitrate - to induce Meth-Hb (same as with H2S)
give O2

53. Heavy Metal Toxicity

54. Mechanism of Action Most common route of exposure is oral
secondary is inhalation of fumes
Toxicity is expressed biologically because of their ability to bind to one or more ligands of biologic enzyme systems which then inactivates the enzyme system

55. One of the few poisons that we have a chemical antidote for:

56. Chelating Agents Chemical antidotes - chemically inactivate the poison
Compete with enzyme systems for the metals
Reverse the metals toxic effects
Enhance the excretion of the metal
The chelate formed is a stable compound
Chelates are water soluble
Chelates are excreted by the kidneys

57. Chelating Agents, cont.
How effective these chelating agents are depends upon:
1) the affinity of the chelator for the metal
2) distribution of the chelator to the parts of the body where the metal is
3) ability of the chelator to mobilize the metal from the body once the chelate is formed

58. Chelating Agents, cont. Properties of the ideal chelating agent:
1) greater affinity for the metal than for ligands of tissues
2) high water solubility
3) can penetrate into tissues
4) resistant to metabolic degradation by the body
5) forms a tight stable bond with the metal which is non toxic to the body

59. Chelating Agents, cont. Properties of the ideal chelating agent, cont.
6) be readily excreted unchanged
7) low affinity for calcium
8) minimal inherent toxicity
9) be absorbed readily when given orally

60. No drug has a single effect, drugs are two edged swords.
Chelating Agents, cont.
No drug has a single effect, drugs are two edged swords.
Examples of a chelating agent:
calcium disodium EDTA - can cause renal problems, fever, dermatitis, used to treat lead toxicity

61. Heavy Metals

62. Lead toxicity
Sources - used in the past in medicines (sugar of lead), insecticides, pesticides, gasoline (tetraethyl lead), batteries, paints, manufacturing, automobile exhaust.
The fall of the Roman empire was due to the fact they used lead for pipes to carry water and for drinking goblets and utensils.

63. Lead Toxicity, cont. Clinical features, plumbism:
Acute intoxication: not common
colic
metallic taste to mouth
vomiting, diarrhea or constipation
increased thirst
hemolysis, hemoglobinuria
oliguria
paresis and paresthesias

64. Lead Toxicity, cont. Chronic lead intoxication - much more common
Burtonian line - dark gray bluish black line on the gingival margin (H2S + Pb = PbS)
Basophilic stippling (clumping of RNA)
Anemia
Colic, diarrhea, vomiting
Skeletal muscle weakness
Increase uric acid in blood
Headache, confusion, insomnia
Lead palsy (wrist drop and foot drop)

65. Lead Toxicity, cont. Patient management:
Acute intoxication - induce vomiting, give cathartics, give proteins to delay absorption (milk, egg whites), chelating agents
Chronic toxicity - give chelating agents

66. Iron Toxicity Seen mostly in children, 40, 000 exposures/yr.
Toxic doses:
20-60 mg/kg of elemental iron is potentially toxic
mg/kg is toxic but not usually fatal
> 120 mg/kg is potentially fatal
Only 10% of ingested iron is absorbed
Most iron tablets contain 10-30% elemental iron by weight

67. Iron Toxicity, cont. Sources - dietary supplements Clinical features:
toxicity develops when serum iron levels exceed the iron binding capacity of transferrin in the blood
body is poorly equipped to handle excessive amounts of iron - can eliminate only very small amounts/day
free iron damages tissues by direct corrosive effects, free iron is a potent vasodilators, directly injures blood vessels, causes hepatocellualr death, coagulation disturbances, and metabolic acidosis

68. Iron Toxicity, cont. Acute GI corrosive effects of iron, nausea,
Clinical presentation of acute toxicity- 4 Stages
Stage I - 30 min. to 6 hrs. post ingestion
Acute GI corrosive effects of iron, nausea,
abdominal pain, vomiting, and diarrhea,
hematemesis, hematochezia and melena.
Most patients with mild to moderate toxicity do not progress beyond this phase.
Stage II hours post ingestion
sometimes called the latent or quiescent period
transient resolution of patient’s GI signs

69. Iron Toxicity, cont. Stage III - 12-48 hours post ingestion
recurrence of GI hemorrhage, hematemesis, melena and bowel perforation may be seen
acute circulatory shock, metabolic acidosis, respiratory distress syndrome
death is common is this stage
Stage IV weeks post ingestion
gastric outlet obstruction or pyloric stenosis as a result of gastric scarring, vomiting

70. Iron Toxicity, cont. Chronic toxicity: Treatment:
pigmented hepatic cirrhosis, diabetes mellitus, hyperpigmentation of the skin, hemosiderosis
hemochromatosis
Treatment:
induce vomiting
activated charcoal is of no value
transport
chelators

71. Mercury Toxicity Sources: Hg (Gr. - hydrargyros - water silver)
drugs (antisyphilitic agents, diuretics, cathartics, topical salves), batteries, paint, shell fish, neon lamps, thermometers, industry (“mad as a hatter”), BP cuffs, wood preservatives, vaccines
dental amalgam fillings (50% mercury, 35% silver, 13% tin, 2% copper with a trace of zinc)

72. Mercury Toxicity, cont. Exists in nature in 3 major forms:
organic (methyl mercury)
inorganic
elemental
Mechanism of Action:
Forms covalent bonds with sulfide groups disrupting many important cellular functions

73. Mercury Toxicity, cont. Elemental mercury - quicksilver
liquid at room temperature
vaporizes easily at room temperature
lung is major target organ due to inhalation of volatilized fumes
lipid soluble and passes rapidly into blood stream
see acute pulmonary symptoms, fever, chills, dyspnea, lethargy, confusion, vomiting

74. Mercury Toxicity, cont. Elemental mercury - quicksilver, cont.
Chronic exposure - tremors, gingivitis, insomnia, shyness, memory loss, anorexia, depression
ingestion is usually no problem - poor absorption from GIT

75. Mercury Toxicity, cont. Inorganic mercury - mercurial salts
route of exposure - oral
source - disc batteries, mercurous chloride, vaccines (0.01% thimerosal)
clinical signs associated with the caustic effects
signs and symptoms - pain, vomiting, hematemesis, renal failure

76. Mercury Toxicity, cont. Organic mercury:
source - contaminated food products, methyl mercury contaminated seafood in the 1950’s in Japan killed over 1000 people (Minamata Bay)
elevated levels found in blood stream of mothers and infants - source? (tuna)
major signs and symptoms are neurological, visual field constriction, ataxia, paresthesia, hearing loss, muscle tremors, and even death

77. Mercury Toxicity, cont. Diagnosis is based on: Treatment:
patient history and clinical signs
urinary levels of mercury (values greater than ug/L is abnormal)
Treatment:
acute therapy - same as any poison
chronic - chelation therapy (BAL)

78. Arsenic Toxicity
Commonly found throughout the earth’s crust, contaminates well water
used in manufacture of herbicides and pesticides and computer chips
tasteless and resembles sugar
has been used as a therapeutic agent and as a poison for more than 2000 years
most exposures are accidental and deaths are very rare

79. Arsenic Toxicity, cont. Mechanism of action:
Inhibition of sulfhydryl group-containing cellular enzymes and the replacement of phosphate molecules in “high energy” compounds
Trivalent arsenic is a carcinogen (lung and skin cancer) and is the most toxic form
Toxic dose ranges from 1 mg to 10 grams
Can be recovered from the hair, nails and skin

80. Arsenic Toxicity, cont. Clinical presentation: Acute exposure
burning of the mouth and throat, nausea, vomiting, profuse diarrhea (rice water stool), garlic like odor to breath, increased capillary permeability, shock, renal damage

81. Arsenic Toxicity, cont. Chronic toxicity:
skin pigmentation changes, palmar and plantar hyperkeratosis
anorexia, GI symptoms
anemia (see pale patient with areas of increased pigmentation and hyperemia - “Milk and Roses” complexion)
Mee’s lines (white transverse bands in the nails)
metallic taste to the mouth
gangrene of the feet (“blackfoot disease”)
encephalopathy

82. Arsenic Toxicity, cont. Diagnosis:
Urine sample provide the most reliable diagnostic testing, >200ug/L are abnormal
use of hair or nails is generally not useful in evaluating individual patients
Treatment:
supportive care and chelation therapy

83. Natural Chelators
Chlorella (from algae) is a natural immune stimulant and has a high affinity for heavy metals (it contains sulfur bound amino acids and acts as a natural chelator)
Garlic and cilantro (Chinese parsley) aid in the removal of heavy metals