1. Hypoxia Producing Poisons 2) Cyanide Poisoning
Cyanide is 1st isolated in pure form in 1786 by Scheele from the dye Prussian blue
Its sever toxicity was also discovered by Scheele (was killed when inhaling the vapor)
One of the most rapidly acting lethal poisons known to the public
i.e., homicidal disasters as the Jonestown massacre 33 years ago
Cyanide-laced Tylenol in Chicago in 1982

2. Cyanide Poisoning Cyanide (CN- ) negatively charged ion
It present either in the gas form as Hydrogen Cyanide (HCN), as a liquid or solid forms as Cyanide salts
At physiological pH 7.4 (unbound), in present in the form of HCN
HCN Can be formed when acid added to a Cyanide salt
It is concentrated in the RBC than in plasma (100:1)
In RBC, 92-95% CN- is bound to Hb

3. Cyanide Poisoning Sources of exposure
1) Industry:
electroplating (HCN gas or particulates in the air)
Extraction of Ores (gold and silver)
Metal processing
Manufacturing of plastics, pesticide, rodentcidies
Hair removal from hides (in tanning industry)
In pressure-treated wood (lumber)
Acetonitrile: a chemical widely used in laboratories & some cosmetic removal is metabolized to CN when ingested

4. Cyanide Poisoning Sources of exposure
2) Plants: (food/dietary supplements)
Many plants (fruit pits of Apricot, Bitter Almond, Peach, Plum) containing Amygdalin a cyanogenic glycoside, a cyanide producing substance (glucose, benzaldehyde + CN)
The enzyme -glucosidase (found in these plants and in human GI tract) will hydrolyze the glycosides  HCN
Amygdalin (active ingredient in Laetrile) is hydrolyzed by the enzyme emulsin (in GI)  HCN
CN poisoning will develop if the kemels (i.e. Almond) is eaten raw
Once the kemels are processed, destroying the emulsin and CN poisoning will not occur

5. Cyanide Poisoning Sources of exposure
3: Combustion:
- Small amount is endogenously produced in human body (Vit B12 metabolism)
- Polyurethane, a commonly used in modern plastic furniture, release CN on combustion
Silk and wool will release CN during fires
Smoke inhalation, death will be due to both CO & CN
Cigarette smoking (each release g of HCN)
Burning pressure treated wood in close place will release HCN gas

6. Cyanide Poisoning Mechanism of Action
Toxicity occurs by either respiratory, PO and dermal routes.
Produces cytotoxic hypoxia (interferes with cell metabolism in the presence of normal blood and O2 supply) = metabolic inhibitor.
HCN binds to heme iron in the cytochrome oxidase (a-a3) (has high affinity for Fe+++) forming a complex
This complex inhibits the final step of oxidative phosphorylation where O2 is used for the production of ATP
Aerobic metabolism stops (cells will not be able to use Q2), Patient essentially suffocates

7. Cyanide Poisoning Mechanism of Action
Cyanide inhibits mitochondrial cytochrome oxidase , thus blocks electron transport, resulting in decreased oxidative metabolism and oxygen utilization
Lactic acidosis occurs as a consequence of anaerobic metabolism (accumulation of Lactic acid).
Most affected cells are at the heart & CNS

8. Cyanide Poisoning Symptoms
Acute:
Depends on the dose, route of exposure & duration
CNS (most sensitive), headache, nausea, vomiting, confusion, restlessness & anxiety, tachypnea with convulsion (are immediate, within few min)
Severe poisonings progress to tachycardia and tachypnea, comma, fixed dilated pupils and death (occur within minutes)

9. Cyanide Poisoning Symptoms
Acute
Skin/Ocular:
In sever poisoning, skin is cold
Cyanosis may be develop late
Retinal veins and arteries may appears similar in color
CVS: (required higher dose than that of CNS dose)
Tachycardia followed by bradycardia
Hypotension followed by peripheral vascular collapse
Abnormal ECG & pulmonary edema

10. Cyanide Poisoning Symptoms
Chronic:
Long-term CN exposure  Occupational –related, heavy smoker will cause headache, dizziness, nausea, or vomiting, psychosis
Tobacco Amblyopia: visual impairment not due to lesion & abnormalities in the optic disk, but due to direct effect of CN on the eye
(Vit B12a) improve visual acuity in some patients)

11. Cyanide Poisoning Management
  For prevention: small doses of Na+ Nitrite: (Sequesters CN before it gets into the cells)
* Give a mild nitrite by inhalation (2 pearls of Amyl Nitrite (crushed and rubbed on the face)
* Several drugs are used:
1) Amyl nitrite (by inhalation), followed by
2) Na nitrite (by IV), initial dose 300 mg/adult
* these combination will convert Hb to methemoglobin and the formation of Fe+++ heme
* The Fe+++ will bind to CN forming a stable complex Cyanmethemoglobin
* As a result the free CN in circulation will ↓
Be careful with the Nitrites, massive vasodilation and server hypotension are possible

12. Cyanide Poisoning Management
* Permanent & irreversible intoxication of CN is by IV injection of Na thiosulfate
-25% Na + Thiosulfate 50ml, IV (Provides Sulfur for the
enzymes Rhodanase)
    - The enzyme Rhodanase converts CN to Thiocyanate (inactive) which is excreted in the urine

13. Cyanide Poisoning Laetrile
* Used to be found in health food stores as a nutritional supplement for malignancy
*Obtained from the kemels of peaches, apricots, and almonds
* Contain amygdalin (a cyanogenetic glycoside), CN is liberated by the enzyme, emulsin (which works better in alkaline pH)
- Used in more than 22 countries for cancer treatment (falsely)
- It kills cancerous and normal cells
- Children have a higher incidence of toxicity because they have a more alkaline environment in their GI
- 2-3 tablets are lethal

14. Toxicity induced by household chemicals 1. Corrosive Alkalis

15. Toxicity induced by household chemicals 1. Corrosive Alkalis
*Occurs most often in Toddler’s and children
*Alkalis are present in many household products:
Liquid plumber, Drano, Oven cleaners, Glass cleaners (ammonia), Dishwasher detergents, Lye, Drain openers, Alkaline batteries
* Alkaline batteries are dangerous to children because they are small and easily swallowed.
* Alkaline dissolve tissues
Liquefy membrane by interacting with proteins to form water soluble salts & lipids through saponification
* Solubilized cellular membranes
- Protein, Na, K, Salt
-Very penetrative & cause perforation
    

16. Toxicity induced by household chemicals 1. Corrosive Alkalis
* Penetrating effect:
-Least: sticking together of esophagus walls –stricture
- Worst: perforation of membranes if swallowed
·At high dose Alkalis, can produce either an immediate death to a delayed death
************************
Acute effects:
- Severe irritation of the eye, skin and other dermatoses
Eye: disintegration and sloughing of the conjunctival and corneal epithelium, corneal opacification, edema, ulceration)
Skin: severe burn, deep skin ulceration, loss of hair
mucous membrane: corrosion of the lips, mouth, tongue and pharynx,

17. Toxicity induced by household chemicals 1. Corrosive Alkalis
Chronic effects:
§  Esophageal strictures may occur in small doses, which can lead to respiratory distress.
§  Burns (can be 1st to 3rd degree burns) causing skin scaring
§  Permanent corneal opacification
§  Dehydration which can lead to immediate death (From traumatic shock and severe pain that leads to cardiovascular and CNS collapse)
§  Delayed death (24-48 hours later), (Due to internal injury caused by perforation)
§  If the alkalis ingested is a small amount and make it into the stomach, usually the acid will neutralize the toxin.
§ If ingestion occurred, usually bloody emesis will be seen and the patient will be unable to swallow so drooling may result.

18. Toxicity induced by household chemicals 1. Corrosive Alkalis
 Management
*Removal from exposure ASAP
*Flushing the eyes and skin with lots of water
*Use of an antibiotics ointment to prevent ocular adhesions
*Nothing should be given by mouth to dilute the poison (unless the patient is in the act of swallowing)
* If is already swallowed, give diluted vinegar or fruit juice to balance GI pH, followed by administering eggs or gelatin, followed by stomach emptying where possible
*Stomach intubation’s is not recommended because the possibility of penetrating of the abdomen
* If the alkalis were spilled onto the body, use Morphine to reduce the pain and IV fluids should be given to reduce shock

19. Toxicity induced by household chemicals 1. Corrosive Alkalis
* Treatments of esophageal stricture,
§  Antibiotics (Penicillin or Ampicllin)
§  Prednisolone to decrease inflammation of the esophagus
§  Feed with a gastric tube 2-3 days after the ingestion
§ Use special catheters (which have Mercury on the end which slide down the esophagus by gravity and do not have to be pushed forcefully).
      * Esophageal replacement:
Previously, a portion of the colon was used
Recently, a Reserve (inverted) gastric tube replacement is performed
A portion of the stomach is formed into a tube to act like the esophagus (Continuity is not broken and the blood supply is not interrupted)

20. Toxicity induced by household chemicals 1. Corrosive Alkalis
Batteries
·Alkaline
· Toddler’s favorite are attracted to their size
· If swallowed and there is no obstruction, the batteries will not burst and leak their contents
· If the battery is excreted into the feces, no action should be taken
· Observe the child for hours, if the battery is not passed, then an x-ray should be performed
· If the battery is obstructed, the alkaline content may leak and perforation may occur.
· At this point, the battery should be removed by surgery