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The work was commissioned and funded by the UK Departments of Health, and was designed as a source of detailed information for use by poisons information centres. Following substantial ingestion, patients may develop coma, convulsions and severe muscle fasciculations and may take several days, occasionally weeks, to recover. Recovery was uneventful O'Malley, Fatalities have occurred rarely after pyrethroid exposure, usually following ingestion He et al, Three fatalities have been reported after deltamethrin exposure He et al, ; Peter et al, Features Dermal exposure - Tingling and pruritus with blotchy erythema on the face or other exposed areas, exacerbated by sweating or touching.

Systemic toxicity may ensue following substantial exposure see below. Ocular exposure - Lacrimation and transient conjunctivitis may occur. Inhalation Brief exposure: - Respiratory tract irritation with cough, mild dyspnoea, sneezing and rhinorrhea.

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Substantial and prolonged exposure: - Systemic toxicity may ensue - see below. Ingestion - May cause nausea, vomiting and abdominal pain. Systemic toxicity may ensue following substantial ingestion see below. Systemic toxicity - Systemic symptoms may develop after widespread dermal exposure, prolonged inhalation or ingestion. Features include headache, dizziness, anorexia and hypersalivation. It usually follows substantial ingestion and causes impaired consciousness, muscle fasciculations, convulsions and, rarely, non-cardiogenic pulmonary oedema.

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Chronic exposure - Long-term exposure is no more hazardous than short-term exposure. Management Dermal 1. Remove soiled clothing and wash high blood pressure treatment nhs skin with soap and water. Institute symptomatic and supportive measures as required. Topical vitamin E tocopherol acetate has been shown to reduce skin irritation if applied soon after exposure Flannigan et al,but it is not available as a pharmaceutical product in the UK.

Symptoms usually resolve within 24 hours without specific treatment. Ocular 1.

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Irrigate with lukewarm water or 0. A topical anaesthetic may be required for pain relief or to overcome blepharospasm. Ensure no particles remain in the conjunctival recesses. Use fluorescein stain if corneal damage is suspected. If symptoms do not resolve following decontamination or if a significant abnormality is detected during examination, seek an ophthalmological opinion.

Inhalation 1.

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Remove to fresh air. Ingestion 1. Do not undertake gastric lavage because solvents are present in some formulations and lavage may increase risk of aspiration pneumonia. Atropine may be of value if hypersalivation is troublesome, 0. Mechanical ventilation should be instituted if non-cardiogenic pulmonary oedema develops.

Isolated brief convulsions do not require treatment but intravenous diazepam should be given if seizures are prolonged or recur frequently. Rarely, it may be necessary to give intravenous phenytoin or to paralyze and ventilate the patient. A systemic reaction following exposure to a pyrethroid insecticide.

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Hum Exp Toxicol ; Synthetic pyrethroid insecticides: a dermatological patero clinic moscow. Br J Ind Med ; Clinical manifestations and diagnosis of acute pyrethroid poisoning. Arch Toxicol ; Lessenger JE. Five office workers inadvertently exposed to cypermethrin.

J Toxicol Environ Health ; O'Malley M. Clinical evaluation of pesticide exposure and poisonings. Lancet ; Pyrethroid poisoning. J Assoc Physicians India ; Substance name Deltamethrin Origin of substance Deltamethrin was high blood pressure treatment nhs synthesized in and is marketed as a single isomer [1R, cis; alpha S]. It is used against high blood pressure treatment nhs crawling and flying insects and pests in stored grain and timber.

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Deltamethrin is also used as an animal ectoparasiticide Pesticide Manual, The active principles of these see Fig. These natural pyrethrins have the disadvantage that they are rapidly decomposed by light. Once the basic structure of the pyrethrins had been discovered, synthetic analogues, pyrethroids, were developed and tested.

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Initially esters were produced using the same cyclopropane carboxylic acids, with high blood pressure treatment nhs in the alcohol portion of the compounds. The first commercial synthetic pyrethroid, allethrin, was produced infollowed in the s by others including dimethrin, tetramethrin and resmethrin. Synthetic pyrethroids with the basic cyclopropane carboxylic ester structure and no cyano group substitution are known as type I pyrethroids. In animal studies type I pyrethroids have been shown generally to produce a typical toxic syndrome see below.

The insecticidal activity of synthetic pyrethroids was enhanced further by the addition of a cyano group at the benzylic carbon atom to give alpha-cyano type II pyrethroids such as deltamethrin. In animal studies type II pyrethroids have been shown generally to produce a typical toxic syndrome see below. Despite the lack of the cyclopropane ring, similar insecticidal activity was found in a high blood pressure treatment nhs of phenylacetic 3-phenoxybenzyl esters.

This led to the development of fenvalerate, high blood pressure treatment nhs alpha-cyanophenoxy-benzyl ester, and other related compounds such as fluvalinate. These all contain the alpha-cyano group and hence are type II pyrethroids. Animal studies suggest that the two structural types of pyrethroids give rise generally to distinct patterns of systemic toxic effects. Type I pyrethroids produce in animals the so-called "T tremor syndrome", characterized by tremors, prostration and altered "startle" reflexes.

These observations are consistent with some differences in the mechanisms of toxicity between type I and type II pyrethroids see below but the division of reactions by chemical structure is not exclusive.

Some compounds produce a combination of the two syndromes, and different stereoisomeric forms can produce different syndromes Dorman and Beasley, The classification into "T" and "CS" syndromes is not used clinically.

All pyrethroids have at least four stereoisomers, with different orientation of the substituents on the cyclopropane ring or the equivalent part of the phenylacetate though deltamethrin is marketed as a single isomer.

The isomers have different biological activities, as discussed below see Mechanisms of toxicity. Different isomers may have separate common names, reflecting their commercial importance Aldridge et al, Further details are given in the pyrethroid generic monograph. The closure of sodium channels begins high blood pressure treatment nhs process of action potential inactivation.

Delayed sodium channel closure thus increases cell membrane excitability. Pyrethroids modify the gating characteristics of voltage-sensitive sodium channels in mammalian and invertebrate neuronal membranes Eells et al, ; Narahashi, to delay their closure. They are dissolved in the lipid phase of the membrane Narahashi, and bind to a receptor site on the alpha sub-unit of the sodium channel Trainer et al, This binding is to a different high blood pressure treatment nhs from local anaesthetics, batrachotoxin, grayanotoxin, and tetrodotoxin Narahashi, The interaction of pyrethroids with sodium channels is highly stereospecific Soderlund and Bloomquist,with the 1R and 1S cis isomers binding competitively to one site and the 1R and 1S trans isomers binding non-competitively to another.

The 1S forms do not modify channel function but do block the effect of the 1R isomers Ray, The prolonged opening of sodium channels by the neurotoxic isomers of pyrethroids produces a protracted sodium influx which is referred to as a sodium "tail current" Miyamoto et al, ; Soderlund high blood pressure treatment nhs Bloomquist, ; Vijverberg and van den Bercken, This lowers the threshold of sensory nerve fibres for the activation of further action potentials, leading to repetitive firing of sensory nerve endings Vijverberg and van den Bercken, which may progress to hyperexcitation of the entire nervous system Narahashi et al, At high pyrethroid concentrations, the sodium "tail current" may be sufficiently great high blood pressure treatment nhs depolarize the nerve membrane completely, generating more open sodium channels Eells et al, and eventually causing conduction block.

Only low pyrethroid concentrations are necessary to modify sensory neurone function. For example, when tetramethrin was added to a preparation of rat cerebellar Purkinje neurons, only about 0. These effects on sodium channels are common to all pyrethroids although specific effects of type II pyrethroids such as deltamethrin have been clarified in experimental studies.

These show that type II compounds: i Cause depolarization of myelinated nerve membranes without repetitive discharges Dorman and Beasley, ; Vijverberg and van den Bercken, ; ii Are associated with a decrease in action potential amplitude Dorman high blood pressure treatment nhs Beasley, ; iii Stabilize a variety of sodium channel states by reducing transition rates between them Dorman and Beasley, ; Eells et al, ; Narahashi,causing a greatly prolonged open time Vijverberg and van den Bercken,and producing stimulus-dependent nerve depolarization and block Soderlund and Bloomquist, ; iv May act post-synaptically by interacting with nicotinic acetylcholine and GABA receptors Dorman and Beasley, ; Eells et al, ; v Produce effects on cultured neurons that are largely irreversible after washing cells with a pyrethroid-free solution Song et al, In addition, type II pyrethroids, such as deltamethrin, enhance noradrenaline norepinephrine release High blood pressure treatment nhs and Brooks, Oral deltamethrin increases monoamine oxidase activity selectively in different parts guarana és magas vérnyomás rat magas vérnyomás egy régi vagy már nem csak betegség, and produces morphological changes in Purkinje neurons in the cerebellum Husain et al, In human investigations, maximal conduction velocity in sensory nerve fibres of the sural nerve showed some increase in subjects exposed to pyrethroids, but there were no abnormal neurological signs, and other electrophysiological studies were normal in the arms and legs Le Quesne et al, He et al assessed nerve excitability using an electromyograph high blood pressure treatment nhs pairs of stimuli at variable intervals.

They showed a prolongation of the "supernormal period" in the median nerve in individuals who had been exposed to pyrethroids occupationally for three days.

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The "supernormal period" was even more prolonged two days after cessation of exposure. Note: the "supernormal period" is the period for which the action potential induced by a second stimulus is greater than the action potential produced by an initial stimulus.

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Pyrethroids are some times more toxic to insects than mammals. This can be explained in terms of differences in their potency as neuronal toxins and differences in rates of detoxification between invertebrates and vertebrates Narahashi, ; Narahashi et al, ; Song and Narahashi, The sensitivity of invertebrate neuronal sodium channels to pyrethroids is ten times greater than in mammals Song and Narahashi, Furthermore, invertebrates typically have body temperatures some 10°C lower than mammals and in vitro studies show tetramethrin to be more potent at evoking repetitive neuronal discharges at lower temperatures Song and Narahashi, In these experiments it was noted that the recovery of sodium channels from tetramethrin intoxication after washing was some five times faster in mammals than invertebrates.

High blood pressure treatment nhs addition pyrethroid hepatic metabolism detoxification is faster in mammals.

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Finally small insect size increases the likelihood of end-organ neuronal toxicity prior to detoxification Song and Narahashi, Absorption Dermal Based on excretion studies involving other pyrethroids Nassif, et al, ; Chester et al, ; Eadsforth et al, ; IPCS, c; Woollen et al, ; Chester, ; Woollen et al, ; dermal absorption of deltamethrin is likely to be low less than 1.

When protective clothing was used the concentrations of deltamethrin and metabolites in urine at the end of a working day were at the limit of detection IPCS, d. Oral Between 19 and 57 per cent of orally administered cypermethrin another type II pyrethroid was absorbed in human studies Woollen et al, ; Woollen et al, though there are no human data specific to deltamethrin.

Metabolism Pyrethroids are hydrolyzed rapidly in the liver to their inactive acid and high blood pressure treatment nhs components Hutson, ; Ray,probably by microsomal carboxylesterase Hutson, Further degradation and hydroxylation of the alcohol at the 4' position then occurs, and oxidation produces a wide range of metabolites Hutson, ; Leahey, There is some stereospecificity in metabolism, with trans-isomers being hydrolyzed more rapidly than the cis-isomers, for which oxidation is the more important metabolic pathway Soderlund and Casida, Although the alpha-cyano group reduces the susceptibility of the molecule to hydrolytic and oxidative metabolism Hutson, ; Soderlund Chaga a magas vérnyomást kezeli Casida,the cyano group is converted to the corresponding aldehyde with release of the cyanide ionfollowed by oxidation to the carboxylic acid, sufficiently rapidly for efficient excretion by mammals Leahey, Other differences in the chemical structure of pyrethroids have less effect on rates of metabolism Soderlund and Casida, The pattern of metabolites varies between oral and dermal dosing in humans Wilkes et al, Such measurements might be useful in high blood pressure treatment nhs the route of exposure Woollen, ; Woollen et al, ; Woollen et al, Experiments with chickens Abou-Donia et al, showed that pyrethroid permethrin toxicity was also enhanced by pyridostigmine bromide and by the insect repellent N,N-diethyl-m-toluamide DEET.

The authors hypothesized that competition for hepatic and plasma esterases by these compounds led high blood pressure treatment nhs decreased pyrethroid breakdown and increased transport of the pyrethroid to neural tissues. Elimination Deltamethrin is excreted mainly as metabolites in urine but a proportion is excreted unchanged in faeces.

An overview of human pyrethroid elimination data is included in the generic pyrethroid monograph. After occupational exposure, deltamethrin and metabolites were detectable in urine for up to 12 hours Zhang et al, Deltamethrin and metabolites were detectable in the urine of workers spraying the pyrethroid early on high blood pressure treatment nhs first day of spraying, and persisted for up to two days after spraying had ceased He et al, Inhalation is more likely when pyrethroids are used in confined spaces Llewellyn et al, The use of protective clothing can reduce dermal exposure Chester et al, The physical formulation also affects exposure, with inhalation being more important for dust and powder formulations, and dermal exposure more important for liquids Llewellyn et al, Dermal exposure This is the most common route of pyrethroid exposure.

Adverse effects manifest primarily as peripheral neurotoxicity with reversible hyperactivity of sensory nerve fibres paraesthesiaethough erythema and pruritus are also described see below.

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Peripheral neurotoxicity Paraesthesiae have been reported frequently after deltamethrin exposure Chen et al, ; He et al, ; He et al, ; IPCS, d; Le Quesne et al, ; Wang et al, ; Zhang et al,particularly after inappropriate handling. Paraesthesiae occur most commonly on the face He et al, It seems probable that paraesthesiae are related to the repetitive firing of sensory nerve endings in contaminated skin Aldridge, and not to inflammation as there is little effect on neurogenic vasodilatation Flannigan and Tucker, b.

The symptoms are exacerbated by sensory stimulation heat, sun, scratching Aldridge,sweating or application of water and high blood pressure treatment nhs prevent sleep Tucker and Flannigan, In two studies, paraesthesiae were reportedly more severe after deltamethrin than after other pyrethroid exposure Aldridge, ; Flannigan and Tucker, a.

Twenty-two of 44 farmers exposed to airborne deltamethrin 2. Contamination of face, hands and feet with large quantities of 2. One drop of 2.