Insecticide poisoning anticholinesterase insecticides

Atropine is often used for colds for temporarily draining the nasopharynx. Atropine is also used in combination with other drugs as an antidote for poisonous anticholinesterase agents such as organophosphorous insecticides and neuroparalytic gases, hi such situations, atropine removes or balances toxicities that are a result of a high concentration of acetylcholine. 

Action on receptors provides numerous examples. Beneficial interactions are sought in overdose, as with the use of naloxone for morphine overdose (opioid receptor), of atropine for anticholinesterase, i.e. insecticide poisoning (acetylcholine receptor), of isoproterelol (isoprenaline) for overdose with a P-adrenoceptor blocker (p-adrenoceptor), of phentolamine for the monoamine oxidase inhibitor-sympathomimetic interaction (a-adrenoceptor). 

Poisoning and drug overdose with acetaminophen, anticholinesterase insecticides, calcium channel blockers, iron, and tricyclic antidepressants are the focus of the remainder of this chapter because they represent commonly encountered poisonings for which pharmacotherapy is indicated. These agents also were chosen because they represent common examples with different mechanisms of toxicity, and they illustrate the application of general treatment approaches as well as ... 

The clinical manifestations of anticholinesterase insecticide poisoning include any or all of the following pinpoint pupils, excessive lacrimation, excessive salivation, bronchorrhea, bron-chospasm and expiratory wheezes, hyperperistalsis producing abdominal cramps and diarrhea, bradycardia, excessive sweating, fas-ciculations and weakness of skeletal muscles, paralysis of skeletal muscles (particularly those involved with respiration), convulsions, and coma. Symptoms of anticholinesterase poisoning and their response to antidotal therapy depend on the action of excessive acetylcholinesterase at different receptor types (Table 10-11). 

The time of onset and severity of symptoms depend on the route of exposure, potency of the agent, and total dose received (see below). Toxic signs and symptoms develop most rapidly after inhalation or intravenous injection and slowest after skin contact. Anticholinesterase insecticides are absorbed through the skin, lungs, conjunctivae, and gastrointestinal tract. Severe symptoms can occur from absorption by any route. Within 6 hours, most patients are symptomatic, and without treatment, death may occur within 24 hours. Death typically is caused by respiratory failure owing to the combination of pulmonary and cardiovascular effects (Fig. 10-4). Poisoning may be complicated by aspiration pneumonia, urinary tract infections, and sepsis. ... 

Anticholinesterase insecticides are among the most poisonous substances commonly used for pest control and are a frequent source of serious poisoning in children and adults in rural and urban settings. The 2003 AAPCC-TESS report documented 11,332 nonfatal exposures and 19 deaths from anticholinesterase insecticides alone or in combination with other pesticides, with 31% of the exposures in children younger than 6 years of age. ... 

Some references indicate that prahdoxime should be avoided in the treatment of carbamate (another type of anticholinesterase insecticide) poisoning because of reports of worsened toxicity in animals. Prahdoxime may be considered when exposure to carbamates is not known but an anticholinesterase is suspected based on symptoms or when respiratory paralysis due to nicotinic effects is not managed sufficiently by mechanical ventilation. 

Organophosphorus and carbamate insecticides are the two classes of anticholinesterase insecticides. All anticholinesterases inhibit nervous tissue acetylcholinesterase, the enzyme that deactivates the neurotransmitter acetylcholine (Ecobichon 1996). Poisoning causes accumulation of acetylcholine in the synaptic cleft, resulting in continuous electrical stimulation (Chambers 1992 Costa 1988). Described best by Chambers (1992), the mechanism of acute symptoms of poisoning occurs through three pathways ... 

Toxification rates may vary. For example, when humans are acutely poisoned by the systemic insecticide menazon, there is an incubation period (of up to one day) and a slow growth in the anticholinesterase activity when the PS-form with low toxicity becomes the active PO-form [A17]. 

Irreversible anticholinesterases include the organophosphorus inhibitors and ambenonium, which irreversibly phosphorylate the esteratic site. Such drugs have few clinical uses but have been developed as insecticides and nerve gases. Besides blocking the muscarinic receptors with atropine sulphate in an attempt to reduce the toxic effects that result from an accumulation of acetylcholine, the only specific treatment for organopho-sphate poisoning would appear to be the administration of 2-pyridine aldoxime methiodide, which increases the rate of dissociation of the organophosphate from the esteratic site on the enzyme surface. 

Poisoning - In anticholinesterase poisoning from exposure to insecticides, give large doses of at least 2 to 3 mg parenterally repeat until signs of atropine intoxication appear. 

There is a vast chemistry of organophosphorus compounds, and even for arsenic, antimony, and bismuth, the literature is voluminous. Consequently only a few topics can be discussed here. It must also be noted that we discuss only the compounds that have P—C bonds. Many compounds sometimes referred to as organophosphorus compounds that are widely used as insecticides, nerve poisons, and so on, as a result of their anticholinesterase activity, do not, in general, contain P—C bonds. They are usually organic esters of phosphates or thiophosphates examples are the well-known malathion and parathion, (EtO)2Pv(S)(0C6H4NO2). Compounds with P—C bonds are almost entirely synthetic, though a few rare examples occur in Nature. 

Organophosphates. The acute toxicity of organophosphate pesticides is basically derived from the anticholinesterase property of these chemicals. This property, which results in accumulation of acetylcholine at synapses and myoneural junctions, is responsible for both the insecticidal activity and mammalian toxicity. Early symptoms of organophosphate poisoning in humans include, among others, miosis (pinpoint pupils) and blurred vision, and a response known as the SLUD (salivation, lacrimation, urination, and diarrhea) syndrome all of these are the result of muscarinic effects (12-15). Clinical manifestations of more severe poisoning involve predominantly nicotinic and central effects which include convulsions, paralysis, depressed respiration and cardiovascular functions, and coma (12-15). Death is usually due to respiratory failure, accompanied by cardio-vascular failure (13). 

Reversible anticholinesterases widely used as insecticides. Absorbed all routes. Usual signs of anti-AChE poisoning salivation, sweating, bradycardia, gut spasm, involuntary micturition, convulsions, coma. 

Poisoning Atropine in the treatment of poisoning by anticholinesterase organophosphorus insecticides... 

Atropine is also useful in cases of poisoning. In particular, it may be employed in the treatment of anticholinesterase poisoning by organophosphorus insecticides, and of the muscarinic effects due to Amanita muscaria ingestion. 

The use of atropine in large doses for the treatment of poisoning by anticholinesterase organophos-phorus insecticides is discussed in Chapter 8. Atropine also may be used to antagonize the parasympathomimetic effects pyridostigmine or other anticholinesterase agents administered in the treatment of myasthenia gravis. 

Two well-known alkaloids, cocaine (3.11) and atropine (3.12), are ester derivatives of the 8-azabicyclo[3.2.1]octane ring system. Cocaine, isolated from a variety of the poppy plant, has been used as a topical anesthetic, but it is highly addictive if it enters the bloodstream and is now a controlled substance. Atropine, however, is highly useful in medicine with anticholinergic properties. It is isolated from the Belladonna plant and has been used for many years to dilate the pupil of the eye. It is also an effective antidote to poisoning by anticholinesterase chemicals, when these are used as insecticides or in extremely toxic form as chemical warfare agents. 

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