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Organophosphates: Overview |  |
| Organophosphates (OP) have replaced the banned organochlorine compounds and are a major cause of animal poisoning. They vary greatly in toxicity, residue levels, and excretion. Many OP have been developed for plant and animal protection, and in general, they offer a distinct advantage by producing little tissue and environmental residue. |
| Many of the OP now used as pesticides are not potent inhibitors of esterases until activated in the liver by microsomal oxidation enzymes; they are generally less toxic, and intoxication occurs more slowly. Certain OP preparations are microencapsulated, and the active compound is released slowly; this increases the duration of activity and reduces their toxicity, but the toxic properties are still present. (See also
Insecticide and Acaricide (organic) Toxicity: Introduction.) |
| Clinical Findings: |
| In general, OP pesticides have a narrow margin of safety, and the dose-response curve is quite steep. Signs of OP poisoning are those of cholinergic overstimulation, which can be grouped under 3 categories: muscarinic, nicotinic, and central. Muscarinic signs, which are usually first to appear, include hypersalivation, miosis, frequent urination, diarrhea, vomiting, colic, and dyspnea due to increased bronchial secretions and bronchoconstriction. Nicotinic effects include
muscle fasciculations and weakness. The central effects include nervousness, ataxia, apprehension, and seizures. Cattle and sheep commonly show severe depression. CNS stimulation in dogs and cats usually progresses to convulsions. Some OP (eg, amidothioates) do not enter the brain easily, so that CNS signs are mild. Onset of signs after exposure is usually within hours but may be delayed for >2 days. Severity and course of intoxication is influenced principally by the dosage
and route of exposure. In acute poisoning, the primary clinical signs may be respiratory distress and collapse followed by death due to respiratory muscle paralysis. |
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| Diagnosis: |
| An important diagnostic aid is the cholinesterase activity in blood and brain. Unfortunately, the depression of blood cholinesterase does not necessarily correlate with the severity of poisoning; signs are seen when nerve cholinesterase is inhibited, and the enzyme in blood reflects, only in a general way, the levels in nervous tissue. The key factor appears to be the rate at which the enzyme activity is reduced. Analyses performed after exposure may be negative because OP do
not remain long in tissues as the parent compound. Chlorinated OP compounds have greater potential for tissue residue. Frozen stomach and rumen samples should be analyzed for the pesticide because OP are generally more stable in acids. |
Lesions:
| Animals with acute OP poisoning have nonspecific or no lesions. Pulmonary edema and congestion, hemorrhages, and edema of the bowel and other organs may be found. Animals surviving >1 day may become emaciated and dehydrated. |
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| Treatment: |
| Three categories of drugs are used to treat OP poisoning: 1) muscarinic blocking agents, 2) cholinesterase reactivators, and 3) emetics, cathartics, and adsorbants to decrease further absorption. Atropine sulfate blocks the central and peripheral muscarinic effects of OP; it is administered to effect in dogs and cats, usually at a dosage of 0.2-2 mg/kg body wt (cats are dosed at the lower end of the range), every 3-6 hr or as often as clinical signs indicate. For horses and
pigs, the dosage is 0.1-0.2 mg/kg, IV, repeated every 10 min as needed; for cattle and sheep, the dosage is 0.6-1 mg/kg, one-third given IV, the remainder IM or SC, and repeated as needed. Atropinization is adequate when the pupils are dilated, salivation ceases, and the animal appears more alert. Animals initially respond well to atropine sulfate; however, the response diminishes after repeated treatments. Overtreatment with atropine should be avoided. Atropine does not
alleviate the nicotinic cholinergic effects, such as muscle fasciculations and muscle paralysis, so that death from massive overdoses of OP can still occur. Including diazepam in the treatment reduced the incidence of seizures and increased survival of nonhuman primates experimentally. Using barbiturates to treat the convulsions must be done very carefully, as they seem to be potentiated by anticholinesterases. |
| An improved treatment combines atropine with the cholinesterase-reactivating oxime, 2-pyridine aldoxime methchloride (2-PAM, pralidoxime chloride). The dosage of 2-PAM is 20-50 mg/kg body wt, given as a 5% solution IM or by slow IV (over 5-10 min), repeated as needed. IV 2-PAM must be given very slowly to avoid musculoskeletal paralysis and respiratory arrest. Response to cholinesterase reactivators decreases with time after exposure; therefore, treatment with oximes must be
instituted as soon as possible (within 24-48 hr). The rate at which the enzyme/organophosphate complex becomes unresponsive to activators varies with the particular pesticide. |
| Removal of the poison from the animal also should be attempted. If exposure was dermal, the animal should be washed with detergent and water (about room temperature) but without scrubbing and irritating the skin. Emesis should be induced if oral exposure occurred <2 hr previously; emesis is contraindicated if the animal is depressed. Oral administration of mineral oil decreases absorption of pesticide from the GI tract. Activated charcoal (3-6 g/kg as a water slurry) adsorbs
OP and helps elimination in the feces. This is particularly recommended in cattle. Continued absorption of OP from the large amount of ingesta in the rumen has caused prolonged toxicosis in cattle. Artificial respiration or administration of oxygen may be required. Phenothiazine tranquilizers should be avoided, as well as the xanthine stimulants theophylline and aminophylline. Succinylcholine should not be used for at least 10 days after OP exposure. |
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