Cyanide seizures

Formal oxidation of pyrrolidine to the succinimide stage affords a series of compounds used as anticonvulsant agents for treatment of seizures in petit mal epilepsy. Knoevnagel condensation of benzaldehyde with ethyl cyanoacetate affords the unsaturated ester, 9. Conjugate addition of cyanide ion leads to the di-nitrile ester (10). Hydrolysis in mineral acid affords the succinic acid (11), presumably by decarboxylation of the intermediate tricarboxyllie acid. Lactamization with methylamine gives phensuximide (12). ... 

For cyanide and cyanogen, antidote should be administered as soon as possible. The Lilly Cyanide Antidote Kit contains amyl nitrite, sodium nitrite, and sodium thiosulfate. Cobalt edentate or 4-dimethylaminophenol are alternative antidotes for cyanide poisoning. Benzodiazepines or barbiturates may be required to control severe seizures. 

The apparently quite broad structural requirements for anticonvulsant activity, noted earlier in this chapter, extend to yet another class of five-membered heterocycles that include an imide function. Imidazo-2,4-diones, better known as hydan-toins, have comprised some of the most widely used drugs for treating severe motor and psychomotor epileptic seizures. The general reaction used to prepare this heterocyclic system involves the treatment of a carbonyl compound with ammonium carbonate and potassium cyanide. The first step in the complex sequence can be visualized as the addition of the elements of ammonia and hydrogen cyanide to give an a-aminonitrile (88-2). Addition of ammonia to the cyano group would then lead to an amidine (88-3). Carbon dioxide or carbonate ion present in the reaction... 

Lactic acidosis Cyanide, carbon monoxide, ibuprofen, isoniazid, metformin, salicylates, valproic acid any drug-induced seizures, hypoxia, or hypotension... 

Cyanide Binds to cytochrome, blocks cellular oxygen use Headache, nausea, vomiting, syncope, seizures, coma... 

Yamamoto, H.-A. (1995). A hypothesis for cyanide-induced tonic seizures with supporting evidence. Toxicology 95 19-26. 

Yamamoto, H.-A., Tang, H.-W. (1996). Antagonistic effect of melatonin against cyanide-induced seizures and acute lethality in mice. Toxicol. Lett. 87 19-24. 

Cyanide exposure can cause transient CNS stimulation, followed by syncope, ataxia, dyspnea, seizures, paralysis. 

Remove animal from the affected area. Do not induce vomiting due to the rapid progression of the clinical signs and potential for seizures, coma, or apnea. One gram of activated charcoal will bind 35 mg of cyanide and activated charcoal may be beneficial if administered immediately after ingestion (Lambert et al, 1988). Irrigate eyes for at least 15 to 20 min with tepid water. Bathe animals thoroughly with soap and water. 

Blood gases and serum electrolytes should be monitored and corrected as needed (Hall and Rumack, 1986 Vogel et al, 1981). Blood cyanide levels can confirm exposure, but due to the time needed to get the results, they are not clinically useful. Provide supplemental oxygen with assisted ventilation as indicated. Animal study results for hyperbaric oxygen therapy have been questionable (Way et al, 1972). Acidosis (pH <7.1) should be corrected with intravenous sodium bicarbonate, but acidosis may not resolve until after the administration of antidotes (Hall and Rumack, 1986). Benzodiazepines or barbiturates can be used to control seizures. 

Development and validation of in vitro and/or in vivo animal models for rapid screening of molecular hbraries to identify potential medical countermeasures is another priority of the CounterACT program. These models include seizures in small mammals, models of direct lung injury from an inhaled source, animal models of cyanide intoxication, and medium throughput models of dermal or ocular injuries. It is important that models be amenable to use under GLP methodology so that the data generated are acceptable to the FDA. Since adherence to GLP standards may be expensive, earher screens to identify potential hits are usually performed under non-GLP conditions. 

Cyanide poisoning due to the accidental ingestion of these plants is rare. Acute symptoms are the same as in cyanide poisoning and include difficulty in breathing, dyspnea, muscular twitching, headache, muscle spasms, ataxia, seizures, coma, and death. The onset of symptoms may be very rapid with few premonitory signs, or may be delayed. 

Because severe exposure to both cyanide and nerve agent produces seizures in patients, a table to help clinically differentiate the two etiologies is provided (Table 24.3). Additionally, children s doses of antidotes are shown in Table 24.4. 

The seizure of cyanide ammunitions, in spite of the economical consequences for the FARCs could be seen connected with the will of cause as psychological effects on the governmental troops. 

Asphyxiant/Blood - Arsine - Cyanogen chloride - Hydrogen cyanide - Possible cherry red skin - Possible cyanosis - Possible frostbite - Confusion - Nausea - Patients may gasp for air, similar to asphyxiation but more abrupt onset - Seizures prior to death... 

Estimates of toxicity based on accidental and deliberate poisoning in humans indicates that NaCN has a lethal potential of around 2-3 mg kg 1 and KCN at 3-5 mg kg 1 (Ballantyne, 1987b). Ingestion of alkaline CN salts by humans (calcium, sodium and potassium cyanides) may cause symptomatology which is life-threatening in 30 to 60 min (Hall and Rumack, 1998). Rapid progression to coma, seizures, arrhythmias, intractable hypotension and apnoea may occur, and death is common. 

Bitner, R.S., Kanthasamy, A., Isom, G.E., and Yim, G.K.W., Seizures and selective CA-1 hippocampal lesions induced by an excitotoxic cyanide metabolite, 2-iminothia-zolidine-4-carboxylic acid, NeMrotoxico/o y, 16,115, 1995. 

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