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J Allister Vale

Publications and source records attributed to J Allister Vale.

12 recordsLinked to original sources
PubMed2005

Poisoning due to pyrethroids.

The first pyrethroid pesticide, allethrin, was identified in 1949. Allethrin and other pyrethroids with a basic cyclopropane carboxylic ester structure are type I pyrethroids. The insecticidal activity of these synthetic pyrethroids was enhanced further by the addition of a cyano group to give alpha-cyano (type II) pyrethroids, such as cypermethrin. The finding of insecticidal activity in a group of phenylacetic 3-phenoxybenzyl esters, which lacked the cyclopropane ring but contained the alpha-cyano group (and hence were type II pyrethroids) led to the development of fenvalerate and related compounds. All pyrethroids can exist as at least four stereoisomers, each with different biological activities. They are marketed as racemic mixtures or as single isomers. In commercial formulations, the activity of pyrethroids is usually enhanced by the addition of a synergist such as piperonyl butoxide, which inhibits metabolic degradation of the active ingredient. Pyrethroids are used widely as insecticides both in the home and commercially, and in medicine for the topical treatment of scabies and headlice. In tropical countries mosquito nets are commonly soaked in solutions of deltamethrin as part of antimalarial strategies. Pyrethroids are some 2250 times more toxic to insects than mammals because insects have increased sodium channel sensitivity, smaller body size and lower body temperature. In addition, mammals are protected by poor dermal absorption and rapid metabolism to non-toxic metabolites. The mechanisms by which pyrethroids alone are toxic are complex and become more complicated when they are co-formulated with either piperonyl butoxide or an organophosphorus insecticide, or both, as these compounds inhibit pyrethroid metabolism. The main effects of pyrethroids are on sodium and chloride channels. Pyrethroids modify the gating characteristics of voltage-sensitive sodium channels to delay their closure. A protracted sodium influx (referred to as a sodium 'tail current') ensues which, if it is sufficiently large and/or long, lowers the action potential threshold and causes repetitive firing; this may be the mechanism causing paraesthesiae. At high pyrethroid concentrations, the sodium tail current may be sufficiently great to prevent further action potential generation and 'conduction block' ensues. Only low pyrethroid concentrations are necessary to modify sensory neurone function. Type II pyrethroids also decrease chloride currents through voltage-dependent chloride channels and this action probably contributes the most to the features of poisoning with type II pyrethroids. At relatively high concentrations, pyrethroids can also act on GABA-gated chloride channels, which may be responsible for the seizures seen with severe type II poisoning. Despite their extensive world-wide use, there are relatively few reports of human pyrethroid poisoning. Less than ten deaths have been reported from ingestion or following occupational exposure. Occupationally, the main route of pyrethroid absorption is through the skin. Inhalation is much less important but increases when pyrethroids are used in confined spaces. The main adverse effect of dermal exposure is paraesthesiae, presumably due to hyperactivity of cutaneous sensory nerve fibres. The face is affected most commonly and the paraesthesiae are exacerbated by sensory stimulation such as heat, sunlight, scratching, sweating or the application of water. Pyrethroid ingestion gives rise within minutes to a sore throat, nausea, vomiting and abdominal pain. There may be mouth ulceration, increased secretions and/or dysphagia. Systemic effects occur 4-48 hours after exposure. Dizziness, headache and fatigue are common, and palpitations, chest tightness and blurred vision less frequent. Coma and convulsions are the principal life-threatening features. Most patients recover within 6 days, although there were seven fatalities among 573 cases in one series and one among 48 cases in another. Management is supportive. As paraesthesiae usually resolve in 12-24 hours, specific treatment is not generally required, although topical application of dl-alpha tocopherol acetate (vitamin E) may reduce their severity.

Adult↗
PubMed2005

Poisoning due to urea herbicides.

Urea herbicides, which act by inhibiting photosynthesis, were introduced in 1952 and are now used as pre- and post-emergence herbicides for general weed control in agricultural and non-agricultural practices. Urea herbicides are generally of low acute toxicity and severe poisoning is only likely following ingestion when nausea, vomiting, diarrhoea and abdominal pain may occur. As urea herbicides are metabolised to aniline derivatives, which are potent oxidants of haemoglobin, methaemoglobinaemia (18-80%) has been documented, as well as haemolysis. Treatment is supportive and symptomatic. Methylthioninium chloride (methylene blue) 1-2mg (the dose depending on the severity of features) should be administered intravenously over 5-10 minutes if there are symptoms consistent with methaemoglobinaemia and/or a methaemoglobin concentration >30%.

Herbicides↗
PubMed2005

Management of the cardiovascular complications of tricyclic antidepressant poisoning : role of sodium bicarbonate.

Experimental studies suggest that both alkalinisation and sodium loading are effective in reducing cardiotoxicity independently. Species and experimental differences may explain why sodium bicarbonate appears to work by sodium loading in some studies and by a pH change in others. In the only case series, the administration of intravenous sodium bicarbonate to achieve a systemic pH of 7.5-7.55 reduced QRS prolongation, reversed hypotension (although colloid was also given) and improved mental status in patients with moderate to severe tricyclic antidepressant poisoning. This clinical study supports the use of sodium bicarbonate in the management of the cardiovascular complications of tricyclic antidepressant poisoning. However, the clinical indications and dosing recommendations remain to be clarified. Hypotension should be managed initially by administration of colloid or crystalloid solutions, guided by central venous pressure monitoring. Based on experimental and clinical studies, sodium bicarbonate should then be administered. If hypotension persists despite adequate filling pressure and sodium bicarbonate administration, inotropic support should be initiated. In a non-randomised controlled trial in rats, epinephrine resulted in a higher survival rate and was superior to norepinephrine both when the drugs were used alone or when epinephrine was used in combination with sodium bicarbonate. Sodium bicarbonate alone resulted in a modest increase in survival rate but this increased markedly when sodium bicarbonate was used with epinephrine or norepinephrine. Clinical studies suggest benefit from norepinephrine and dopamine; in an uncontrolled study the former appeared more effective. Glucagon has also been of benefit. Experimental studies suggest extracorporeal circulation membrane oxygenation is also of potential value. The immediate treatment of arrhythmias involves correcting hypoxia, electrolyte abnormalities, hypotension and acidosis. Administration of sodium bicarbonate may resolve arrhythmias even in the absence of acidosis and, only if this therapy fails, should conventional antiarrhythmic drugs be used. The class 1b agent phenytoin may reverse conduction defects and may be used for resistant ventricular tachycardia. There is also limited evidence for benefit from magnesium infusion. However, class 1a and 1c antiarrhythmic drugs should be avoided since they worsen sodium channel blockade, further slow conduction velocity and depress contractility. Class II agents (beta-blockers) may also precipitate hypotension and cardiac arrest.

Alkalosis, Respiratory↗
PubMed2005

Anticoagulant rodenticides.

Anticoagulant pesticides are used widely in agricultural and urban rodent control. The emergence of warfarin-resistant strains of rats led to the introduction of a new group of anticoagulant rodenticides variously referred to as 'superwarfarins', 'single dose' or 'long-acting'. This group includes the second generation 4-hydroxycoumarins brodifacoum, bromadiolone, difenacoum, flocoumafen and the indanedione derivatives chlorophacinone and diphacinone. Most cases of anticoagulant rodenticide exposure involve young children and, as a consequence, the amounts ingested are almost invariably small. In contrast, intentional ingestion of large quantities of long-acting anticoagulant rodenticides may cause anticoagulation for several weeks or months. Occupational exposure has also been reported. Anticoagulant rodenticides inhibit vitamin K(1)-2,3 epoxide reductase and thus the synthesis of vitamin K and subsequently clotting factors II, VII, IX and X. The greater potency and duration of action of long-acting anticoagulant rodenticides is attributed to their: (i) greater affinity for vitamin K(1)-2,3-epoxide reductase; (ii) ability to disrupt the vitamin K(1)-epoxide cycle at more than one point; (iii) hepatic accumulation; and (iv) unusually long biological half-lives due to high lipid solubility and enterohepatic circulation. Substantial ingestion produces epistaxis, gingival bleeding, widespread bruising, haematomas, haematuria with flank pain, menorrhagia, gastrointestinal bleeding, rectal bleeding and haemorrhage into any internal organ; anaemia may result. Spontaneous haemoperitoneum has been described. Severe blood loss may result in hypovolaemic shock, coma and death. The first clinical signs of bleeding may be delayed and patients may remain anticoagulated for several days (warfarin) or days, weeks or months (long-acting anticoagulants) after ingestion of large amounts. There are now sufficient data in young children exposed to anticoagulant rodenticides to conclude that routine measurement of the international normalised ratio (INR) is unnecessary. In all other cases, the INR should be measured 36-48 hours post exposure. If the INR is normal at this time, even in the case of long-acting formulations, no further action is required. If active bleeding occurs, prothrombin complex concentrate (which contains factors II, VII, IX and X) 50 units/kg, or recombinant activated factor VII 1.2-4.8 mg or fresh frozen plasma 15 mL/kg (if no concentrate is available) and phytomenadione 10mg intravenously (100 microg/kg bodyweight for a child) should be given. If there is no active bleeding and the INR is < or =4.0, no treatment is required; if the INR is > or =4.0 phytomenadione 10mg should be administered intravenously.

Animals↗
PubMed2004

Hydrogen peroxide poisoning.

Hydrogen peroxide is an oxidising agent that is used in a number of household products, including general-purpose disinfectants, chlorine-free bleaches, fabric stain removers, contact lens disinfectants and hair dyes, and it is a component of some tooth whitening products. In industry, the principal use of hydrogen peroxide is as a bleaching agent in the manufacture of paper and pulp. Hydrogen peroxide has been employed medicinally for wound irrigation and for the sterilisation of ophthalmic and endoscopic instruments. Hydrogen peroxide causes toxicity via three main mechanisms: corrosive damage, oxygen gas formation and lipid peroxidation. Concentrated hydrogen peroxide is caustic and exposure may result in local tissue damage. Ingestion of concentrated (>35%) hydrogen peroxide can also result in the generation of substantial volumes of oxygen. Where the amount of oxygen evolved exceeds its maximum solubility in blood, venous or arterial gas embolism may occur. The mechanism of CNS damage is thought to be arterial gas embolisation with subsequent brain infarction. Rapid generation of oxygen in closed body cavities can also cause mechanical distension and there is potential for the rupture of the hollow viscus secondary to oxygen liberation. In addition, intravascular foaming following absorption can seriously impede right ventricular output and produce complete loss of cardiac output. Hydrogen peroxide can also exert a direct cytotoxic effect via lipid peroxidation. Ingestion of hydrogen peroxide may cause irritation of the gastrointestinal tract with nausea, vomiting, haematemesis and foaming at the mouth; the foam may obstruct the respiratory tract or result in pulmonary aspiration. Painful gastric distension and belching may be caused by the liberation of large volumes of oxygen in the stomach. Blistering of the mucosae and oropharyngeal burns are common following ingestion of concentrated solutions, and laryngospasm and haemorrhagic gastritis have been reported. Sinus tachycardia, lethargy, confusion, coma, convulsions, stridor, sub-epiglottic narrowing, apnoea, cyanosis and cardiorespiratory arrest may ensue within minutes of ingestion. Oxygen gas embolism may produce multiple cerebral infarctions. Although most inhalational exposures cause little more than coughing and transient dyspnoea, inhalation of highly concentrated solutions of hydrogen peroxide can cause severe irritation and inflammation of mucous membranes, with coughing and dyspnoea. Shock, coma and convulsions may ensue and pulmonary oedema may occur up to 24-72 hours post exposure. Severe toxicity has resulted from the use of hydrogen peroxide solutions to irrigate wounds within closed body cavities or under pressure as oxygen gas embolism has resulted. Inflammation, blistering and severe skin damage may follow dermal contact. Ocular exposure to 3% solutions may cause immediate stinging, irritation, lacrimation and blurred vision, but severe injury is unlikely. Exposure to more concentrated hydrogen peroxide solutions (>10%) may result in ulceration or perforation of the cornea. Gut decontamination is not indicated following ingestion, due to the rapid decomposition of hydrogen peroxide by catalase to oxygen and water. If gastric distension is painful, a gastric tube should be passed to release gas. Early aggressive airway management is critical in patients who have ingested concentrated hydrogen peroxide, as respiratory failure and arrest appear to be the proximate cause of death. Endoscopy should be considered if there is persistent vomiting, haematemesis, significant oral burns, severe abdominal pain, dysphagia or stridor. Corticosteroids in high dosage have been recommended if laryngeal and pulmonary oedema supervene, but their value is unproven. Endotracheal intubation, or rarely, tracheostomy may be required for life-threatening laryngeal oedema. Contaminated skin should be washed with copious amounts of water. Skin lesions should be treated as thermal burns; surgery may be required for deep burns. In the case of eye exposure, the affected eye(s) shod eye(s) should be irrigated immediately and thoroughly with water or 0.9% saline for at least 10-15 minutes. Instillation of a local anaesthetic may reduce discomfort and assist more thorough decontamination.

Administration, Inhalation↗
PubMed2004

Poisoning due to chlorophenoxy herbicides.

Chlorophenoxy herbicides are used widely for the control of broad-leaved weeds. They exhibit a variety of mechanisms of toxicity including dose-dependent cell membrane damage, uncoupling of oxidative phosphorylation and disruption of acetylcoenzyme A metabolism. Following ingestion, vomiting, abdominal pain, diarrhoea and, occasionally, gastrointestinal haemorrhage are early effects. Hypotension, which is common, is due predominantly to intravascular volume loss, although vasodilation and direct myocardial toxicity may also contribute. Coma, hypertonia, hyperreflexia, ataxia, nystagmus, miosis, hallucinations, convulsions, fasciculation and paralysis may then ensue. Hypoventilation is commonly secondary to CNS depression, but respiratory muscle weakness is a factor in the development of respiratory failure in some patients. Myopathic symptoms including limb muscle weakness, loss of tendon reflexes, myotonia and increased creatine kinase activity have been observed. Metabolic acidosis, rhabdomyolysis, renal failure, increased aminotransferase activities, pyrexia and hyperventilation have been reported. Substantial dermal exposure to 2,4-dichlorophenoxy acetic acid (2,4-D) has led occasionally to systemic features including mild gastrointestinal irritation and progressive mixed sensorimotor peripheral neuropathy. Mild, transient gastrointestinal and peripheral neuromuscular symptoms have occurred after occupational inhalation exposure. In addition to supportive care, urine alkalinization with high-flow urine output will enhance herbicide elimination and should be considered in all seriously poisoned patients. Haemodialysis produces similar herbicide clearances to urine alkalinization without the need for urine pH manipulation and the administration of substantial amounts of intravenous fluid in an already compromised patient.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed2004

Glyphosate poisoning.

Glyphosate is used extensively as a non-selective herbicide by both professional applicators and consumers and its use is likely to increase further as it is one of the first herbicides against which crops have been genetically modified to increase their tolerance. Commercial glyphosate-based formulations most commonly range from concentrates containing 41% or more glyphosate to 1% glyphosate formulations marketed for domestic use. They generally consist of an aqueous mixture of the isopropylamine (IPA) salt of glyphosate, a surfactant, and various minor components including anti-foaming and colour agents, biocides and inorganic ions to produce pH adjustment. The mechanisms of toxicity of glyphosate formulations are complicated. Not only is glyphosate used as five different salts but commercial formulations of it contain surfactants, which vary in nature and concentration. As a result, human poisoning with this herbicide is not with the active ingredient alone but with complex and variable mixtures. Therefore, It is difficult to separate the toxicity of glyphosate from that of the formulation as a whole or to determine the contribution of surfactants to overall toxicity. Experimental studies suggest that the toxicity of the surfactant, polyoxyethyleneamine (POEA), is greater than the toxicity of glyphosate alone and commercial formulations alone. There is insufficient evidence to conclude that glyphosate preparations containing POEA are more toxic than those containing alternative surfactants. Although surfactants probably contribute to the acute toxicity of glyphosate formulations, the weight of evidence is against surfactants potentiating the toxicity of glyphosate. Accidental ingestion of glyphosate formulations is generally associated with only mild, transient, gastrointestinal features. Most reported cases have followed the deliberate ingestion of the concentrated formulation of Roundup (The use of trade names is for product identification purposes only and does not imply endorsement.) (41% glyphosate as the IPA salt and 15% POEA). There is a reasonable correlation between the amount ingested and the likelihood of serious systemic sequelae or death. Advancing age is also associated with a less favourable prognosis. Ingestion of >85 mL of the concentrated formulation is likely to cause significant toxicity in adults. Gastrointestinal corrosive effects, with mouth, throat and epigastric pain and dysphagia are common. Renal and hepatic impairment are also frequent and usually reflect reduced organ perfusion. Respiratory distress, impaired consciousness, pulmonary oedema, infiltration on chest x-ray, shock, arrythmias, renal failure requiring haemodialysis, metabolic acidosis and hyperkalaemia may supervene in severe cases. Bradycardia and ventricular arrhythmias are often present pre-terminally. Dermal exposure to ready-to-use glyphosate formulations can cause irritation and photo-contact dermatitis has been reported occasionally; these effects are probably due to the preservative Proxel (benzisothiazolin-3-one). Severe skin burns are very rare. Inhalation is a minor route of exposure but spray mist may cause oral or nasal discomfort, an unpleasant taste in the mouth, tingling and throat irritation. Eye exposure may lead to mild conjunctivitis, and superficial corneal injury is possible if irrigation is delayed or inadequate. Management is symptomatic and supportive, and skin decontamination with soap and water after removal of contaminated clothing should be undertaken in cases of dermal exposure.

Animals↗
PubMed2003

Ricin poisoning.

Ricin is a naturally occurring toxin derived from the beans of the castor oil plant Ricinus communis. It is considered a potential chemical weapon. Ricin binds to cell surface carbohydrates, is internalised then causes cell death by inhibiting protein synthesis. Oral absorption is poor and absorption through intact skin most unlikely; the most hazardous routes of exposure being inhalation and injection. Features of toxicity mainly reflect damage to cells of the reticuloendothelial system, with fluid and protein loss, bleeding, oedema and impaired cellular defence against endogenous toxins. It has been estimated that in man, the lethal dose by inhalation (breathing in solid or liquid particles) and injection (into muscle or vein) is approximately 5-10 micrograms/kg, that is 350-700 micrograms for a 70 kg adult. Death has ensued within hours of deliberate subcutaneous injection. Management is supportive. Prophylactic immunisation against ricin toxicity is a developing research initiative, although presently not a realistic option in a civilian context.

Animals↗
PubMed2003

Does urine alkalinization increase salicylate elimination? If so, why?

Urine alkalinization is a treatment regimen that increases poison elimination by the administration of intravenous sodium bicarbonate to produce urine with a pH > or = 7.5. Experimental and clinical studies confirm that urinary alkalinization increases salicylate elimination, although the mechanisms by which this occurs have not been elucidated. The conventional view is that ionisation of a weak acid, such as salicylic acid, is increased in an alkaline environment. Since the ionisation constant (pKa) is a logarithmic function then, theoretically, a small change in urine pH will have a disproportionately larger effect on salicylate clearance. Hence, elimination of salicylic acid by the kidneys is increased substantially in alkaline urine. However, as salicylic acid is almost completely ionised within physiological pH limits, alkalinization of the urine could not, therefore, significantly increase the extent of ionisation further and the conventional view of the mechanism by which alkalinization is effective is patently impossible. Further experimental studies are required to clarify the mechanisms by which urine alkalinization enhances salicylate elimination.

Adolescent↗
PubMed2003

Abrin poisoning.

Abrin is a toxic protein obtained from the seeds of Abrus precatorius (jequirity bean), which is similar in structure and properties to ricin. Abrin is highly toxic, with an estimated human fatal dose of 0.1-1 microgram/kg, and has caused death after accidental and intentional poisoning. Abrin can be extracted from jequirity beans using a relatively simple and cheap procedure. This satisfies one criterion of a potential chemical warfare agent, although the lack of large scale production of jequirity seeds means that quantity is unavailable for ready mass production of abrin for weapons. This contrasts with the huge cultivation of Ricinus seeds for castor oil production. At the cellular level, abrin inhibits protein synthesis, thereby causing cell death. Many of the features observed in abrin poisoning can be explained by abrin-induced endothelial cell damage, which causes an increase in capillary permeability with consequent fluid and protein leakage and tissue oedema (the so-called vascular leak syndrome). Most reported cases of human poisoning involve the ingestion of jequirity beans, which predominantly cause gastrointestinal toxicity. Management is symptomatic and supportive. Experimental studies have shown that vaccination with abrin toxoid may offer some protection against a subsequent abrin challenge, although such an approach is unlikely to be of benefit in a civilian population that in all probability would be unprotected.

Abrin↗
PubMed2002

American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning.

EPIDEMIOLOGY: Almost all cases of acute methanol toxicity result from ingestion, though rarely cases of poisoning have followed inhalation or dermal absorption. The absorption of methanol following oral administration is rapid and peak methanol concentrations occur within 30-60minutes. MECHANISMS OF TOXICITY: Methanol has a relatively low toxicity and metabolism is responsible for the transformation of methanol to its toxic metabolites. Methanol is oxidized by alcohol dehydrogenase to formaldehyde. The oxidation of formaldehyde to formic acid is facilitated by formaldehyde dehydrogenase. Formic acid is converted by 10-formyl tetrahydrofolate synthetase to carbon dioxide and water. In cases of methanol poisoning, formic acid accumulates and there is a direct correlation between the formic acid concentration and increased morbidity and mortality. The acidosis observed in methanol poisoning appears to be caused directly or indirectly by formic acid production. Formic acid has also been shown to inhibit cytochrome oxidase and is the prime cause of ocular toxicity, though acidosis can increase toxicity further by enabling greater diffusion of formic acid into cells. FEATURES: Methanol poisoning typically induces nausea, vomiting, abdominal pain, and mild central nervous system depression. There is then a latent period lasting approximately 12-24 hours, depending, in part, on the methanol dose ingested, following which an uncompensated metabolic acidosis develops and visualfunction becomes impaired, ranging from blurred vision and altered visual fields to complete blindness. MANAGEMENT: For the patient presenting with ophthalmologic abnormalities or significant acidosis, the acidosis should be corrected with intravenous sodium bicarbonate, the further generation of toxic metabolite should be blocked by the administration of fomepizole or ethanol and formic acid metabolism should be enhanced by the administration of intravenous folinic acid. Hemodialysis may also be required to correct severe metabolic abnormalities and to enhance methanol and formate elimination. For the methanol poisoned patient without evidence of clinical toxicity, the first priority is to inhibit methanol metabolism with intravenous ethanol orfomepizole. Although there are no clinical outcome data confirming the superiority of either of these antidotes over the other, there are significant disadvantages associated with ethanol. These include complex dosing, difficulties with maintaining therapeutic concentrations, the need for more comprehensive clinical and laboratory monitoring, and more adverse effects. Thus fomepizole is very attractive, however, it has a relatively high acquisition cost. CONCLUSION: The management of methanol poisoning includes standard supportive care, the correction of metabolic acidosis, the administration of folinic acid, the provision of an antidote to inhibit the metabolism of methanol to formate, and selective hemodialysis to correct severe metabolic abnormalities and to enhance methanol and formate elimination. Although both ethanol and fomepizole are effective, fomepizole is the preferred antidote for methanol poisoning.

Ethanol↗