Therapeutic Problems in Cyanide Poisoning

Heijst, A. N. P. van; Douze, J. M. C.; Kesteren, R. G. Van; Bergen, Jan E. A. M. van; Dijk, Anouk van

doi:10.3109/15563658708992641

Cited by 39 publications

(13 citation statements)

References 9 publications

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“…Treatments for cyanide poisoning are many but there is no global unanimity on which is the best treatment [16]. However, combination of sodium nitrite (SN) and sodium thiosulfate (STS) continues to be the most prevalent treatment for cyanide poisoning [17].…”

Section: Introductionmentioning

confidence: 99%

Effect of Alpha-Ketoglutarate on Neurobehavioral, Neurochemical and Oxidative Changes Caused by Sub-Chronic Cyanide Poisoning in Rats

et al. 2010

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Recent studies revealed that alpha-ketoglutarate (A-KG) alone or with sodium thiosulfate (STS) provide significant protection against acute and sub-acute cyanide poisoning in rodents. This study addresses the protective effect of A-KG and/or STS in sub-chronic (90 days) cyanide poisoning. Wistar rats were divided into seven groups (n = 10): Control animals, potassium cyanide (KCN) A-KG, STS, KCN ? A-KG, KCN ? STS and KCN ? A-KG ? STS. Spontaneous motor activity and motor coordination were recorded every 15th day. Lipid peroxidation (LPO), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in blood, brain, liver and kidney, and glutamate, aspartate and dopamine in discrete regions of brain were measured following 90 days exposure. Cyanide significantly decreased motor coordination, accompanied by increase in LPO (blood, brain and liver) and dopamine (corpus striatum and cerebral cortex) levels, and depletion in GSH (blood, brain and liver), GPx (brain and liver), SOD (brain and liver), and CAT (blood and brain) levels. Although treatment of A-KG and STS alone significantly blunted the toxicity of KCN, concomitant use of both afforded the maximum protection. This study shows a promising role of A-KG and STS as treatment regime for long term cyanide exposure.

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Section: Introductionmentioning

confidence: 99%

Effect of Alpha-Ketoglutarate on Neurobehavioral, Neurochemical and Oxidative Changes Caused by Sub-Chronic Cyanide Poisoning in Rats

et al. 2010

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“…1 Although, methaemoglobin inducers are the drug of choice in cyanide poisoning, in many instances their use remains questionable. 6,7 Agents that rapidly complex cyanide without compromising the vascular system are likely to be more beneficial and may have wider applications. With this in mind, α-ketoglutarate (α-KG) was found to be a more effective and suitable alternative for the treatment of cyanide poisoning because it rapidly complexes cyanide to form cyanohydrin.…”

Section: Introductionmentioning

confidence: 99%

Acute toxicity studies of α‐Ketoglutarate: a promising antidote for cyanide poisoning

Bhattacharya

Kumar

Sugendran

et al. 2001

J of Applied Toxicology

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Recently we have shown that cyanide poisoning by the oral (p.o.) route could be antagonized significantly by pretreatment or simultaneous treatment of alpha-ketoglutarate (alpha-KG), administered p.o. in rodents. The protective effect of alpha-KG was dose dependent (0.125-2.0 g kg(-1)) and the effect was significant at a dose above 1.0 g kg(-1). In order to establish the safety of alpha-KG, various haematological, biochemical and histological parameters were studied following p.o. administration of 2.0 g kg(-1)alpha-KG in female rats, and various physiological parameters were studied following p.o. administration of 2.0 or 4.0 g kg(-1)alpha-KG in anaesthetized male rats. The p.o. LD(50) of alpha-KG in male and female rats was >5.0 g kg(-1) and no toxic signs were observed in the surviving animals. Except for an increase in plasma alkaline phosphatase and urea levels after 1 h and a decrease in inorganic phosphorus levels after 7 days of treatment, no significant change in haematology, biochemistry or histology of the vital organs were observed. Mean arterial pressure and neuromuscular transmission were decreased at 4.0 g kg(-1)alpha-KG but other physiological variables such as heart rate, respiratory rate, rectal temperature, left ventricular pressure (systolic), arterial pressure (systolic) and arterial pressure (diastolic) were not altered. The changes observed at 4.0 g kg(-1)alpha-KG are unlikely to be of toxicological concern. The results indicate that alpha-KG at 2.0 g kg(-1) (p.o.)-a dose offering maximum antidotal efficacy-is non-toxic and therefore can be considered suitable for cyanide poisoning.

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“…However, most of the treatments suffer from serious limitations (Bhattacharya, 2000;Van Heijst et al, 1987). Except amyl nitrite, all the antidotes are discouraged as self-aid or first aid during out-of-hospital mass casualty management (Lavon & Bentur, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Other popular treatments include 4-dimethylaminophenol, dicobalt edetate and hydroxocobalamin (Bhattacharya, 2000). Due to several limitations of these antidotes, there is a lack of consensus in the international medical community on the risk-benefit ratio of cyanide antidotes (Cummings, 2004;Hall et al, 2009;Van Heijst et al, 1987). Except amyl nitrite, all the antidotes have to be administered intravenously, which is discouraged during prehospital mass casualty management following cyanide exposure (Lavon & Bentur, 2010).…”

Section: Introductionmentioning

confidence: 99%

Accelerated stability and bioassay of a new oralα-ketoglutarate formulation for treating cyanide poisoning

Bhattacharya

Gopalan

Singh

et al. 2013

Pharmaceutical Biology

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Context: Due to several limitations of existing cyanide antidotes, a-ketoglutarate (a-KG) has been proposed as a promising treatment for cyanide. Objective: This study reports the accelerated stability and bioassay of a new oral a-KG formulation. Materials and methods: Amber-colored PVDF bottles containing 100 ml of 10% a-KG in 70% sorbitol, preservative (sodium methyl paraben and sodium propyl paraben), sweetener (sodium saccharine), flavor (American ice-cream soda and peppermint) and color (tartrazine), at pH 7.0-8.0 were stored in stability chamber (40 AE 2 C and 75 AE 5% humidity) for 6 months in a GMP compliant facility. Various physical (pH, color, evaporation, extractable volume and clarity), chemical (identification and quantification of active ingredient) and microbiological (total aerobic count) analyses, together with protection studies were carried periodically in mice. Acute toxicity of the formulation and bioavailability of a-KG were assessed in rats at the beginning of the experiment. Results: No physical changes and microbiological growth were observed in the formulation. After 6 months, a-KG content in the formulation diminished by $24% but its protective efficacy against cyanide remained at 5.9-fold. Protection was further characterized spectrophotometrically by disappearance of a-KG spectrum in the presence of cyanide, confirming cyanohydrin formation. Oral LD 50 of a-KG formulation in rats was 47.0 g/kg body weight, and did not produce any acute toxicity of clinical significance. Also, an appreciable amount of a-KG was measured in blood. Conclusion: As per the guidelines of International Conference on Harmonization, the new a-KG formulation exhibited satisfactory stability, bioefficacy and safety as cyanide antidote.

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Therapeutic Problems in Cyanide Poisoning

Cited by 39 publications

References 9 publications

Effect of Alpha-Ketoglutarate on Neurobehavioral, Neurochemical and Oxidative Changes Caused by Sub-Chronic Cyanide Poisoning in Rats

Effect of Alpha-Ketoglutarate on Neurobehavioral, Neurochemical and Oxidative Changes Caused by Sub-Chronic Cyanide Poisoning in Rats

Acute toxicity studies of α‐Ketoglutarate: a promising antidote for cyanide poisoning

Accelerated stability and bioassay of a new oralα-ketoglutarate formulation for treating cyanide poisoning

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