Carbamate intoxication

Symptoms of carbamate intoxication develop earlier than those of OPP poisoning. Hence the exposed worker is more likely to associate his or her symptoms with the pesticide and take earlier evasive action. The antidote of choice for carbamate poisoning is atropine, as with the OPPs. However, the use of PAM is not recommended here, as it may actually prove to be deleterious in some instances (ref. 164,... 

Carbamate intoxication is treated with atropine (or scopolamine). Despite the fact that oximes, such as pralidoxime or toxogonin, given after intoxication by most carbamates, quicken the decarbamylation step and reactivation of the enzyme, the medical practice is to avoid the use of oximes. Two reasons are commonly given for this ... 

Umehara, F, l/timo, S, Arimura, K, and Osame, M. (1991). Polyneuropathy induced by m-tolyl methyl carbamate intoxication./ Neurol. 238, 47-48,... 

The Centers for Disease Control and Prevention (CDC) has not published a specific case definition for intoxication by carbamates. However, the case definition for nerve agents and organophosphates states... 

In contrast to the beneficial effects of treatment with oximes in cases of OP intoxication, reports in the literatnre suggest that treatment of poisoning with certain anticholinesterase carbamates with some oximes should be avoided because they may actually potentiate carbamate action. Other oximes decrease carbamate toxicity. The effects observed are, in general, correlated with changes in the rates of carbamylation and decarbamylation in the presence of the various oximes . ... 

The acute toxic effects of the cholinesterase inhibitors, like those of the direct-acting agents, are direct extensions of their pharmacologic actions. The major source of such intoxications is pesticide use in agriculture and in the home. Approximately 100 organophosphate and 20 carbamate cholinesterase inhibitors are available in pesticides and veterinary vermifuges used in the USA. 

The organophosphorus (OP) and carbamate insecticides are used to control a wide variety of insect pests. The acute toxicity of the OPs and carbamates varies, and many of them have high mammalian toxicity. These compounds react chemically with the active site of acetylcholinesterase, producing a blocked enzyme that cannot degrade acetylcholine. The concentration of acetylcholine then builds up and hyperexcitation occurs. The signs of intoxication include resdessness, tremors, convulsions, and paralysis. Blockage of acetylcholinesterase by OPs is persistent, and recovery of the enzyme takes many hours or even days. The mode of action of the carba-... 

For example, no difference in the toxicity of organophosphorus compounds to larvae of the midge Chrironomus riparius was observed between pulsed and continuous exposures (Kallander et al. 1997). In the same study, however, two 1-hour pulses caused significantly fewer symptoms of intoxication than 2 hours of continuous exposure to carbamate compounds, when animals were placed in clean water for at least 2 to 6 hours between treatments (Kallander et al. 1997), suggesting that detoxification or elimination of the toxicant during the toxicant-free period can reduce the toxic effects of the earlier exposures. 

Carbamates as Pre-Exposure Treatment against Organophosphate Intoxication... 

Since it is impossible to measure the inhibition inside the synapses, it is customary in cases of carbamate and organophosphate intoxication to measure the residual enzymatic activity in the blood of the victim and to calculate the percentage of inhibition. Normally, light symptoms appear not before 30% of inhibition, becoming an imminent life-threatening condition when this figure is above the 90-95% level. 

It can be seen that one of the quaternary carbamates has been chosen for this use, mainly because they are safer and also have fewer untoward effects, and since in the early years organophosphate intoxication was considered to be mainly a peripheral breathing problem (paralysis of the diaphragm muscles and edema of the lungs). The realization during the 1980s and 1990s that inhibition of the brain... 

The mode of action of the carbamate insecticides is similar to that of the organophosphates. As shown in Figure 7.15, the reaction yields a carbamylated AChE, followed by decarbamylation via hydrolysis. Carbamates also attack the CNS system, and the symptoms of intoxication are similar to those with the organophosphates. However, unlike the organophosphates, decarbamylation of acetylcholinesterase is rapid, typically in minutes, and therefore carbamate insecticides are regarded as reversible acetylcholinesterase inhibitors. 

In clinical biochemistry, BuChE determination in the plasma or serum is more frequently used than that of AChE in the red blood cells. Except for intoxication with OP or carbamates (CMs), a BuChE decrease indicates either a reduced enzyme synthesis or a decrease in the number of production of cells in the hver (Masopust, 1983). A special case of diminished BuChE activity is the hereditary affected by the presence of atypical variants of BuChE (Brown et al., 1981 Whittaker, 1980). 

Methomyl exerts toxicity by inhibiting acetylcholinesterase. As with other carbamate insecticides, acetylcholinesterase inhibition is much less persistent than with organophosphate intoxication. 

---