Hydrocyanic acid; cyanogenic glycosides, Sodium thiosulfate, cytochrome oxidase

1. Cyanide Poisoning – A Review

2. CYANIDE POISONING
(HYDROCYANIC ACID POISONING; CYANOGENIC GLYCOSIDE
POISONING)
Dr. Muhammad Avais
Associate Professor
Department of Clinical Medicine and Surgery
University of Veterinary and Animal Sciences,
Lahore, Pakistan

3. Cyanide Poisoning – A Review
•notorious poison dating back to antiquity
•isolated from cherry laurel---Karl Wilheim Scheele
1782
•1786 ------first victim of this rapid poison
•1795 Fonatana-----investigated mechanism of action
•Blakes’s attempts to antogonise its toxic affects.
(Maduh, 1989; Borowitz et al.1992)
HISTORY

4. Cyanide Poisoning – A Review
Etiology
 Ingestion of plants containing cyanogenic
glycosides.
 Normally glycosides are non toxic
 HCN is liberated by the action of beta
glycosidase and lyase
 Ruminal microorganism -beta glycosidase.
 Horses are less susceptible
 acidity ----- inactivate beta glycosidase
(Radostits et al. 2000)
Sorghum-sudangrass

5. Cyanide Poisoning – A Review
Etiology
 2000 plants --- contain enough
cyanogenic glycosides.
 contents of CGs---varies
widely between seasons and
parts of the plants.
 Greatest conc.--young growing
leafs.
Poison hemlock

6. Cyanide Poisoning – A Review
Difference between plant species.
 varieties of same species often have different
toxicities.
 Sudan grass, sorghum (S. bicolor) ---- used
extensively as forage -- cause heavy mortalities
 Linseed in the form of cake may be highly toxic
if eaten in large quantities.
(Radostits et al. 2000)
Tansy ragwort
Chokecherry

7. Cyanide Poisoning – A Review
Glycosides
 By-products of plant’s metabolism
 Part of defense system against herbivorous.
 Specific glycosides:
 Linamarin----------------linseed
 Dhurrin-------------------sorghum
 Amygdalin---------------bitter almond
 Minimum lethal dose of HCN --- 2mg/Kg
 Plant materials >20mg of HCN per 100gm
(200ppm) may have toxic effects.
 Highly poisonous plants ---- 6000ppm.

8. Cyanide Poisoning – A Review
Risk factors
 Rapidly growing plants----------regrowth
 Wilted, frostbitten or just young plants.
 Plants growing on high nitrogen content
and low phosphorus contents soil.
 Hungry animals get access to dense plant
growths
 Animals unaccustomed to local plants.

9. Cyanide Poisoning – A Review
Human exposure to cyanide
 Global consumption of CN - 1.5 million tons
annually
 Used in chemical manufacture where a
carbon atom is to be added to a molecule
 Bulk consumption goes into methyl-
methcrylate (Perspex) and adiponitril
(precursor of nylon).
 Sodium and potassium salts are used in gold
extraction and electroplating industries.
 manufacture of methionine and other amino
acids in animal feed industry.
(Cummings, 2004)

10. Cyanide Poisoning – A Review
Human exposure to cyanide
 In fire, cyanide is generated through combustion of
nitrogen containing compounds (melamine, nylon etc.)
 Cassava, cherry, apple, almond seeds, apricot kernels
 Laetrile extracted from apricot kernels cause some
considerable cyanide toxicity.
(Cummings, 2004)

11. Cyanide Poisoning – A Review
Pathogenesis
 inhibition of cytochrome oxidase
(mitochondria respiratory chain enzyme) -
-- cytotoxic hypoxia.
 enzyme contains two heme A and two
copper ions.
 Cyanide has special affinity for heme ion
 Cyanide-heme-cytochrome oxidase
complex
 Render the enzyme incapable of utilizing
the oxygen.
 oxygen saturation imparts cherry red color
of blood
(Way, 1983; Ballantyne, 1987)

12. Cyanide Poisoning – A Review
Pathogenesis
 Inhibition of cytochrome
oxidase results in interruption
of electron transport chain
 Resultant anaerobic
metabolism with decreased
ATP and concomitant
increased lactic acid
production leads to tissue
anoxia and metabolic acidosis.
(Solomonson, 1981; Isom, 1975)

13. Cyanide Poisoning – A Review
Clinical Findings
 Affected animal rarely survive for more than 1-2hours.
 Most acute cases animal become affected within 10-
15minutes of eating toxic material and die within 2-3
minutes.
 Dyspnea, anxiety, restlessness, stumbling gait,
tremors, recumbancy and clonic convulsions with
opisthotonos.
 Mucosae are bright red.

14. Cyanide Poisoning – A Review
Clinical Findings
 Hyperesthesia and lacrimation.
 Muscle tremors are evident first in head and neck, then
whole body.
 Pulse is weak and rapid and irregular.
 Dilatation of pupil, nystagmous
 Congestion and cyanosis of mucosae in terminal
stages.

15. Cyanide Poisoning – A Review
Clinical Findings
Chronic poisoning
 Goiter: pregnant ewes and lambs may develop goiter.
 Myelomalacia (cystitis-ataxia syndrome): urinary
incontinence, incoordination of hind limbs
 Arthrogryposis: leads dystocia in foals, lambs and
claves born to dams grazing on sorghum

16. Cyanide Poisoning – A Review
Diagnosis
 History
 Picric acid test

17. Cyanide Poisoning – A Review
Treatment
Antidotes
 Methaemoglobin generators:
– oxidizing agents change the ferrous ion of Hb into ferric
– resultant methaemoglobin binds strongly to cyanide to from
cyanmethaemoglobin
– Sod. Nitrite, amyl nitrite, dimethyl aminophenol.
 Direct binding agents: chelate the cyanide ion
directly. i.e. cobalt edetate, hydroxycobalamin.

18. Cyanide Poisoning – A Review
Treatment
 Sulphur donors: normal rout of detoxification is conversion
of cyanide to thiocyanate with sulphur moiety. Sod.
Thiosulphate contribute sulphur and enzyme rhodanase.
 Mixture of sodium nitrite (5gms) and sodium thiosulphate
(15gms) in 200 ml water for cattle.
 1 gm sodium nitrite and 3 gms sodium thiosulphate in 50 ml
water for sheep
 Sodium thiosulphate heavy doses 660mgs/kg BW combined
with sod. Nitrite 22 mg/kg BW
 Garlic extract at 500mg/kg
 Combinamide
 3MPT

19. Cyanide Poisoning – A Review
Iceland Poppy
Acasia robinea Clover
Chenopodium Woody pear
Sacred Bamboo
Sorghum Sudan grass Sweet grass

20. Cyanide Poisoning – A Review
Apricot
Peach Johnson grass
Christmas berry Necklace fern
Common apple
Crow foot Maiz Sorghum