Strychnine exposure

There is no specific antidote for strychnine but recovery from strychnine exposure is possible with early hospital treatment. Treatment consists of removing the drug from the body (decontamination) and getting supportive medical care in a hospital setting. Supportive care includes intravenous fluids, medications for convulsions and spasms, and cooling measures for high temperature. 

The extent of poisoning caused by strychnine depends on the amount and route of strychnine exposure and the person s condition of health at the time of the exposure. 

Recovery from strychnine exposure is possible with early hospital treatment. Therefore, the best thing to do is get medical care as quickly as possible. 

Shown in Fig. 6 is the correlation of real concentrations of strychnine and those concentrations that are predicted by the ANN analysis of experimental data of strychnine exposure [25, 26]. In the left part of the figure, the good correlation within the same experiment is shown. This means that a part of the data of one experiment was chosen to train the ANN, whereas the other data of the same experiment was used as the independent test data. 

Struxine, C2iH3(,04N2, obtained by Schaefer from deteriorated nux-vomica seeds in about 0-1 per cent, yield, is regarded as a decomposition product of strychnine or brucine. It forms rhombic crystals from alcohol, is colourless, but becomes yellow on exposure to light and chars at 250°. It yields normal and acid salts, the latter only from excess of acid. With sulphuric acid it gives no coloration, but addition of potassium dichromate produces a yellow colour changing to green. 

Woodward s strychnine synthesis commences with a Fischer indole synthesis using phenylhydrazine (24) and acetoveratrone (25) as starting materials (see Scheme 2). In the presence of polyphosphor-ic acid, intermediates 24 and 25 combine to afford 2-veratrylindole (23) through the reaction processes illustrated in Scheme 2. With its a position suitably masked, 2-veratrylindole (23) reacts smoothly at the ft position with the Schiff base derived from the action of dimethylamine on formaldehyde to give intermediate 22 in 92% yield. TV-Methylation of the dimethylamino substituent in 22 with methyl iodide, followed by exposure of the resultant quaternary ammonium iodide to sodium cyanide in DMF, provides nitrile 26 in an overall yield of 97%. Condensation of 2-veratryl-tryptamine (20), the product of a lithium aluminum hydride reduction of nitrile 26, with ethyl glyoxylate (21) furnishes Schiff base 19 in a yield of 92%. 

The following factors have been suggested as alternatives to consider when presented with a potential case of exposure to bicyclophosphates history of epilepsy exposure to alcohol, cocaine, lead, camphor, strychnine, and/or carbon monoxide medicinals such as phenothiazines head trauma, heatstroke encephalitis, meningitis, and tetanus. 

Strychnine poisoning may also occur from dermal exposure. In one recent case report a women experienced marked pain in the lower limbs, dermal sensitivity, and stif iess in her jaw 24 hours after cleaning up a strychnine spill. Strychnine was confirmed in the plasma and urine by gas chromatography-mass spectrometry. ... 

The permeability of the skin to a toxic substance is a function of both the substance and the skin. The permeability of the skin varies with both the location and the species that penetrates it. In order to penetrate the skin significantly, a substance must be a liquid or gas or significantly soluble in water or organic solvents. In general, nonpolar, lipid-soluble substances traverse skin more readily than do ionic species. Substances that penetrate skin easily include lipid-soluble endogenous substances (hormones, vitamins D and K) and a number of xenobiotic compounds. Common examples of these are phenol, nicotine, and strychnine. Some military poisons, such as the nerve gas sarin (see Section 18.8), permeate the skin very readily, which greatly adds to then-hazards. In addition to the rate of transport through the skin, an additional factor that influences toxicity via the percutaneous route is the blood flow at the site of exposure. 

Strychnine is rapidly absorbed from the gastrointestinal tract, mucous membranes, and parenteral sites of injection (Thienes and Haley, 1972) and also from the oral cavity (LaDu et al, 1971). A nonfatal case of strychnine poisoning through dermal exposure is also described (Greene and Meatherall, 2001). Strychnine is transported by plasma and... 

The hiunan health assessment for strychnine is based on the acute toxicity. Strychnine has been placed in Toxicity Category I, indicating the greatest degree of acute toxicity, for oral and ocular effects. It has been reported that the probable lethal oral dose is 1.5 to 2mg/kg (Gosselin et al, 1984). Inhalation toxicity is also presumed to be high. An oral dose of 1.5 to 2 mg/kg is equivalent to 70 to 93 mg/m exposure for 30 min for a 70 kg human being. 

The strychnine oral reference dose (RfD) of 0.0003 mg/kg/ day or 0.02 mg/day for a 70 kg person is derived from the Seidl and Zbinden (1982) short-term to subchronic study by applying an uncertainty factor of 10,000. This factor accounts for extrapolation from a less than chronic to a chronic exposure study, extrapolation from animals to humans, and differences in sensitivity among the human population. An additional factor of 10 is used because an LOAEL/FEL (2.5 mg/kg/day) was utilized in the estimation of the RfD instead of an NOAEL. The immediately dangerous to life and health (IDLH) dose for strychnine by NIOSH REE is 0.15 mg/m and the current OSHA PEL is 0.15mg/m. ... 

Greene, R., Meatherall, R. (2001). Dermal exposure to strychnine. J. Anal. Toxicol. 25 344-7. 

The primary pathways for unintentional or intentional exposure to strychnine are inhalation and ingestion. Ocular and dermal exposures can also occur. 

Strychnine is a compound of high acute toxicity. The oral LD value in rats is 15mgkg. Parenteral routes of exposure are more toxic LD50 values in laboratory rodents range from 1 to 4 mg kg... 

Prevention of further absorption. Although free strychnine is absorbed rapidly from the gut, it is often taken in a form (e.g. rodenticide pellets) which retards absorption. By the time that the symptoms have started to appear, often only a relatively small portion of the total dose has been absorbed. The destruction or removal of the strychnine in the gut prevents further absorption and shortens the period of exposure for the patient. 

The question whether cyanobacterial hepatotoxins constitute a human health risk is still debated and is not easy to answer since in comparison to other waterborne diseases, e.g., cholera epidemics, the number and severity of cyanotoxin related illnesses appears less dramatic. On the other hand, microcystins and cylindrospermopsins are potent toxins with LD50S similar to or even lower than that of some of the most notorious natural toxins, like a-amanitin (Amanita phalloides), strychnine (Strychnos nux-vomica), or aconitine (Aconitum sp.). Compared to these natural toxins, exposure to cyanobacterial toxins is much harder to avoid and the cyanotoxin-related epidemics indicate that potentially a large number of people can be affected when, for example, drinking water is contaminated. Among chemicals to which humans are exposed through water, cyanobacterial toxins probably occur most frequently in a global perspective. 

As outlined in Scheme 6, isovanillin (35) was converted to aryl iodide 36 via MOM-protection, protection of the aldehyde, and subsequent iodination. Hydrolysis of the acetal and Wittig olefination delivered phenol 37 after exposure of the intermediate aldehyde to methanolic hydrochloric acid. Epoxide 41, the coupling partner of phenol 37 in the key Tsuji-Trost-reaction, was synthesized from benzoic acid following a procedure developed by Fukuyama for the synthesis of strychnine [62]. Birch reduction of benzoic acid with subsequent isomerization of one double bond into conjugation was followed by esterification and bromohydrin formation (40). The ester was reduced and the bromohydrin was treated with base to provide the epoxide. Silylation concluded the preparation of epoxide 41, the coupling partner for iodide 37, and both fragments were reacted in the presence of palladium to attain iodide 38. 

People exposed to high doses of strychnine may have the following signs and symptoms within the first 15 to 30 minutes of exposure ... 

The answer b 4 /ff O T b Tabh 4-2]. Vomi-tus from a live animal or the stomach contents of a dead animal is Invaluable evidence of recent oral exposure to a toxicant The clinician must remember that this sample reflects only what has been ingested in the previous 1-6 hours. In some rare cases irwolving basic drugs (eg., strychnine alkaloid) a small portion of the toxicant in blood may partition b k into the stomach. However, for the many toxicants that have a delayed onset or whose effects occur only after many days exposure, the most recent ingestion may not represent a known toxic dose or may not contain any of the significant toxicant Rn- fiib reason, storr>-... 

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