Pyrethrins and Pyrethroids - Insecticide

Pyrethrins and Pyrethroids

Pyrethrins are active extracts of the chrysanthemum plant (Chrysanthemum cinerariaefolium), and include pyrethrum and piperonyl butoxide. They are esters of pyrethric and chry-santhemic acids formed by the keto alcohols pyrethrolone, cinerolone, and jasmololone. Pyrethrin I and pyrethrin II are two of the most insecticidally potent pyrethric and chrysan-themic esters. Pyrethroids are synthetic analogues and number over 1000 varieties which are used as insecticides to incapaci-tate or “knock out” insects. Most mammals are resistant since they can rapidly metabolise and detoxify these agents. Common pyrethrins and pyrethroids available commercially in India are mentioned in Table 28.5.

Uses

■■   These compounds are used as household insect repellants and insecticides. They are sold as liquids, sprays, dusts, powders, mats, and coils.

■■   They are also used to prevent pest infestation in granaries, and in agriculture as pesticides.

■■   Pyrethrum extract is effective for treating pediculosis of the head, body and pubic area.

Usual Fatal Dose

·              Pyrethrum has an LD50 of over 1 gm/kg. However, the minimal lethal dose of pyrethrum is not clearly established, though it is probably in the range of 10 to 100 grams. Most cases of toxicity are actually the result of allergic reactions.

Mode of Action

Structurally, pyrethroids are of 2 types—

Type I pyrethroids do not contain a cyano group, e.g. permethrin.

Type II pyrethroids contain a cyano group, e.g. deltame-thrin, cypermethrin, fenpropathrin, fenvalerate, etc.

Like DDT, pyrethroids prolong the inactivation of the sodium channel by binding to it in the open state. Type II agents are more potent in this regard, and also act by inhibiting GABA-mediated inhibitory chloride channels. Low toxicity in mammals is probably due to rapid metabolic breakdown in the liver: pyrethrum is broken down mainly by oxidation of the isobutenyl side chain of the acid moiety and of the unsaturated side chain of the alcohol moiety with ester hydrolysis playing a role. Some organophosphates may enhance pyrethrin toxicity due to competition for carboxyesterases responsible for rapid detoxification of pyrethrins via ester hydrolysis. Very young children are perhaps more susceptible to poisoning by pyre-throids because they may not hydrolyse the pyrethrum esters efficiently.

Two types of allergens present in crude pyrethrum oleoresin have been identified: glycoproteins or glycopeptides ranging in molecular weight from 60,000 to 200,000 (most important) and the sesquiterpene lactones, principally pyrethrosin (minor importance). Refined pyrethrins and synthetic pyrethroids are said to have little or no allergenic effect.

Clinical Features

·      Skin contact: dermatitis, blistering. The usual lesion is amild erythematous dermatitis with vesicles, papules in moist areas, and intense pruritus; a bulbous dermatitis may also occur. Skin contamination with pyrethrins can cause localised paraesthesia.

·      Eye contact: Eye exposures may result in mild to severecorneal damage that generally resolves with conservative care. Corneal denudation and decreased visual acuity have been reported following ocular contact exposure during normal use of pediculicide shampoos containing pyrethrin. Chemical conjunctivitis was diagnosed in a patient after a pyrethrin-containing mist was inadvertently sprayed into the eyes.

·      Inhalation: rhinorrhoea, sore throat, wheezing, dyspnoea.Asthma or reactive airways disease syndrome can occur following inhalation exposures, as also hypersensitivity pneumonitis with chest pain, cough, dyspnoea and bron-chospasm. Eosinophilia may accompany an acute allergic reaction. Dizziness and headache have been reported following exposure to pesticide mists.

·              Ingestion (large doses): paraesthesias, nausea, vomiting,vertigo, fasciculations, hyperthermia, altered mental status, seizures, pulmonary oedema, coma. Nausea,vomiting and abdominal pain commonly occur and develop within 10 to 60 minutes following ingestion. Hypotension and tachycardia, associated with anaphy-laxis, may occur. Severe poisoning may result in marked adrenal activation, with increases in adrenaline and noradrenaline accompanying motor signs.

Diagnosis

·      Serum cholinesterase levels are normal.

·      ECG may demonstrate ST-T changes, sinus tachycardia, and ventricular premature beats.

·      A colour test with 2-2 (2-aminoethylamine) ethanol produces red to violet colour in the presence of pyre-throidal substances. It is however not suitable for analysis of pyrethrins in body fluids, except, possibly at very high concentrations.

Treatment

Skin contact—decontaminate with soap and water.

Eye contact—irrigate with normal saline or water for 10 to15 minutes.

Systemic poisoning—

·              Mild to moderate allergic reactions may be treated with antihistamines (e.g. diphenhydramine 50 mg orally, intravenously, or intramuscularly initially, then 25 to 50 mg orally every 4 to 6 hours for 24 to 72 hours) with or without inhaled beta agonists, corticosteroids (e.g methyl prednisolone 1 to 2 mg/kg intravenously every 6 to 8 hours) or adrenaline (1:10,000 solution, 3 to 5 ml diluted in 10 ml 0.9% saline slow intravenous push over 5 to 10 minutes). Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, adrenaline, ECG monitoring and IV fluids.

·              In massive ingestions, stomach wash can be done after making sure that there are no petroleum distillate addi-tives.

·              Activated charcoal is beneficial. However, if the pyre-thrin is formulated in an organic solvent, activated charcoal is unlikely to be of benefit. If the pyrethrin is formulated in a petroleum base, the risk of hydrocarbon pneumonitis may exceed the toxic hazard of the insec-ticide. Gastric decontamination is therefore, generally not recommended.

·              Oils and fats (including milk) promote the intestinal absorption of pyrethroids and should be avoided.

·              Oxygen and ventilatory asistance must be administered as indicated.

·              Bronchospasm is treated with standard bronchodilators. Administer beta₂ adrenergic agonists. Consider use of inhaled ipratropium and systemic corticosteroids.

·              Monitor peak expiratory flow rate, monitor for hypoxia and respiratory failure, and administer oxygen as neces-sary. Consider systemic corticosteroids in patients with significant bronchospasm, e.g. prednisone 60 mg/day (adult), or 1 to 2 mg/kg/day (child).

·              Seizures can be controlled with diazepam. Consider phenobarbitone if seizures recur after diazepam 30 mg (adults) or 10 mg (children > 5 years).

·              If hypotensive give 500 to 2000 ml crystalloid initially (20 ml/kg in children) and titrate to desired effect (stabilisation of vital signs, mentation, urine output); adults may require up to 6 to 10 litres/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypoten-sion. Vasopressors such as dopamine should be used in refractory cases unresponsive to repeated doses of adrenaline, and after vigorous intravenous crystalloid rehydration Atropine and oximes are contraindicated, but some investigators recommend the former for drying up secretions.

·              Cutaneous paraesthesias are said to respond to topical applications of vitamin E.