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SUMMARY
KEY WORDS
Cyanide poisoning
cyanide antagonism
INTRODUCTION
Cyanide is regarded as a notorious poison dating
back to antiquity. Hydrogen cyanide (HCN) was first
isolated from cherry laurel by Swedish chemist, Karl
Wilheim Scheele in 1782 and in 1786 he was feared
to be the first victim of this rapid poison1,2. Later in
1795 Fontana investigated its mechanism of action,
followed by Blakess attempts to antagonise its toxic
effects. However, molecular basis for the biochemical mechanism of cyanide antagonism was first demonstrated in 1933 only3. The ubiquitous existence of
cyanide in the environment is associated with the
toxic gases produced by pyrolysis of plastic or nitrile-based polymer fibres, ingestion of extracts of
plants containing cyanogenic glycosides (e.g., cassava) or inhalation from industrial or occupational
causes (e.g., electroplating). Administration of certain drugs (e.g., sodium nitroprusside and laetrile)
also release cyanide when metabolised in the body.
Cyanide poisoning also results from exposure to
aliphatic nitrile compounds ( e.g. acetonitrile) or by
dermal absorption /ingestion of cyanide salts and
aliphatic nitriles. Its notoriety as a suicidal, homicidal
and genocidal agent is well known2,4-7. Use of HCN
as a potent chemical warfare agent is also well
documented 8. Cyanide is a very rapid poison which
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R. BHATTACHARYA
CLINICAL MANIFESTATIONS
The clinical picture of acute cyanide poisoning varies in both time and intensity depending upon the
magnitude of exposure. Various non-specific signs
and symptoms like headache, dizziness, nausea,
vomiting, confusion, coma and incontinence of faeces and urine occur10. Physiologically a series of
events like dyspnoea, incoordination of movement,
cardiac irregularities, convulsive seizures, coma and
respiratory failure may occur leading to death 4,5,7,10.
Pathologically no particular lesions can delineate
cyanide toxicity, albeit animal experiments indicate
that the lesions are principally in the central nervous
system, predominantly necrosis in the white matter5,6,10. Probably the most wide-spread pathologic
condition attributed to chronic cyanide poisoning is
tropic ataxic neuropathy following cassava consumption11.
MECHANISM OF TOXICITY
ANTIDOTES
to form cyanmethemoglobin3-5,20. Thereby, the activity of inhibited cytochrome oxidase is restored. The
various methemoglobin formers employed as cyanide antidotes are discussed below.
Amyl nitrite: Inhalation of amyl nitrite as a first aid
measure to cyanide poisoning is known for many
years3-5,9,19. However, the efficacy of amyl nitrite as
methemoglobin inducer remained disputed on account of its inability to generate methemoglobin
greater than 6% 20,21, while about 15% is required to
challenge one LD50 dose of cyanide9. Now the protective effect of amyl nitrite is attributed to its
vasodilatory effect that can reverse the early cyanide induced vasoconstriction 9,19. Artificial ventilation
with amyl nitrite broken into ambu bags has been
reported as a life saving therapy in cyanide poisoned dogs, prior to induction of significant level
of methemoglobinemia22.
Sodium nitrite: Sodium nitrite (SN) is the most prevalent drug of choice for cyanide poisoning 3-5,23. When
given intravenously (i.v.) it takes about 12 min to generate approximately 40% of methemoglobin 9. Inspite
of this delay in inducing a significant level of methemoglobinemia, a reasonable protection offered by SN
can be ascribed to its vasodilatory property19. A serious drawback with SN is that i.v. administration may
be accompanied by serious cardiovascular embarrassment, particularly in children, for whom an adjusted dose is recommended24. Since SN induced
methemoglobinemia impairs oxygen transport, it cannot be recommended for fire victims where in most
instances HCN exposure is accompanied by carbon
monoxide poisoning. Since carbon monoxide also
impairs oxygen carrying capacity of blood, administration of SN would further aggravate the hypoxic condition. SN is also not advised for individuals with glucose-6-phosphate dehydrogenase (G6PD) deficient
red cells because of possibility of serious hemolytic
reactions19.
4 - Dimethylaminophenol: The relatively slow rate
of methemoglobin formation by SN prompted the development of rapid methemoglobin formers like
aminophenols. 4-dimethylaminophenol (DMAP) is the
treatment of choice for cyanide poisoning in Germany.
A dose of 3.25 mg/kg., i.v. of DMAP was reported to
produce methemoglobin level of 30% within 10 min
and 15% methemoglobinemia was attained within
one minute without any immediate effect on cardio-
96
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98
99
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14.
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Knowles, J. Westley & F. Wissing, San Diego, Academic
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ACKNOWLEDGEMENT
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Leung P, Sylvester DM, Chiou F, Way LL, Way EL, Way JL.
A Professor Remembers
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dwells on his impressions on the
freedom movement, the Second
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He traces the introduction of new
drugs from 1943 and writes about
his experience with LSD, the drug
which was largely misused in the
Sixties and Seventies.
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