Carbamates poisoning

Antidotes are administrated to patients after there has been exposure to OPs. They are also sometimes given as a protective measure when there is a risk of exposure, for example, to troops fighting in the Gulf War. Of the two types of antidote mentioned earlier, only atropine is effective against carbamate poisoning. 

It tends to limit the duration of N-methyl carbamate poisoning. 

Pralidoxime (2-PAM) Organophosphate cholinesterase inhibitors Adult dose is 1 g IV, which should be repeated every 3-4 hours as needed or preferably as a constant infusion of 250-400 mg/h. Pediatric dose is approximately 250 mg. No proved benefit in carbamate poisoning. 

Organophosphate and carbamate cholinesterase inhibitors (see Chapter 7) are widely used to kill insects and other pests. Most cases of serious organophosphate or carbamate poisoning result from intentional ingestion by a suicidal person, but poisoning has also occurred at work (pesticide application or packaging) or, rarely, as a result of food contamination or terrorist attack (eg, release of the chemical warfare nerve agent sarin in the Tokyo subway system in 1995). 

Adlakha A, Philip PJ, Dhar KL. 1988. Organophosphorus and carbamate poisoning in Punjab. J Assoc Physicians India 36(3) 210-212. 

The antidote for carbamate poisoning is atropine only. 2-PAM will stabilize the enzyme-carbamate complex and so exacerbate the poisoning. 

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,... 

Saadeh, A.M. (2001). Metabolic complications of organophosphate and carbamate poisoning. Trap. Doct. 31 149-52. 

Paul, N., Mannathukkaran, T.J. (2005). Intermediate syndrome following carbamate poisoning. Clin. Toxicol. 43 867-8. 

These compounds inhibit the hydrolysis of the neurotransmitter acetylcholine by the enzyme acetylcholinesterase within the mammalian nervous system (Zwiener and Ginsburg, 1988). This inhibition causes acetylcholine levels to rise, thus causing cholinergic hyperstimulation at muscarinic and nicotinic receptors. There are important differences in the way carbamates and OPs bind to acetylcholinesterase as well as their abililty to affect the CNS. Carbamates are reversible inhibitors of cholinesterase enzymes. Carbamates create a reversible bond to the cholinesterase enzyme through carbamylation which can spontaneously hydrolyze, reversing toxicity. Carbamate poisoning produces toxicity similar to that of OPs however, the toxicity is usually of a shorter duration and less severe in nature (Lifshitz et al, 1994). In contrast, OPs inhibit cholinesterase via an irreversible bond of phosphate radicals... 

OPs and carbamates have different receptor activities in the mammalian nervous system. OPs have effects on muscarinic and nicotinic receptors and can cause neurological effects in the CNS (Levy-Khademi et al., 2007). Carbamates are thought to cause only parasympathetic muscarinic effects with limited nicotinic and CNS effects (Sofer et al, 1989). However, there are case reports in children that have revealed the presence of CNS effects with carbamate exposures (de Tollenaer et al, 2006). One pediatric case series stated that the signs and symptoms from carbamate poisoning were indistinguishable from OP exposures, with severe CNS depression with stupor and coma occurring in eight cases (Sofer et al, 1989). 

Key findings that have been reported inclnde significant hypoxia, acidosis, and carbon dioxide retention (Sofer et al, 1989). Also hyperglycemia, hypokalemia, and lenkocytosis were observed in a case series of organophosphate exposures (Levy-Khademi et al, 2007). A prospective study done on 17 children with typical organophosphate or carbamate poisoning looked at laboratory abnormalities that are associated with acute pancreatitis. Five of the patients (30%) had laboratory values consistent with pancreatitis with elevated immunoreactive trypsin, amylase, and serum... 

Lifshitz, M., Rotenberg, M., Sofer, S., Tamiri, T., Almog, S. (1994). Carbamate poisoning and oxime treatment in children a clinical and laboratory study. Pediatrics 93 652-5. 

Zwiener, R.J., Ginsburg, C.M. (1988). Organophosphate and carbamate poisoning in infants and children. Pediatrics 81 121-6. 

Atropine is used in the management of sinus bradycardia with hemodynamic instability and in the treatment of peptic ulcer disease, irritable bowel syndrome, urinary incontinence, and organophos-phate and carbamate poisoning. It is also present in ophthalmic preparations to induce mydriasis and cyclopegia. Atropine is often administered preope-ratively to decrease secretions. 

Administration of 2-PAM chloride (protopam and pralidoxime) is generally not recommended in carbamate poisoning since it has been shown to interfere with the efficacy of atropine. It was reported that the condition of patients suffering carbaryl-related poisoning deteriorated rapidly following the administration of 2-PAM. Seizure control with diazepam, phenobarbital, or phenytoin may be required. Cardiovascular support and intensive supportive care may be required in serious cases. 

It has been almost 40 years since B. Wilson et al. observed that nucleophiles, oximes like hydroxamic acid, reactivated OP-inhibited AChE above and beyond that occurring from spontaneous reactivation, opening the way to a treatment for OP poisoning. The oxime registered for use in the United States is 2-PAM Cl (Protopam) its methanesulfonate salt (P2S) is used in Europe. Oxime therapy should be recommended with caution for carbamate poisonings. Although beneficial in the case of aldicarb, there is evidence that 2-PAM treatment increases the toxicity of carbaryl. 

Bardin PG, van Eeden SF, Moolman JA, Foden AP, Joubert JR. Organophosphate and carbamate poisoning. Arch Int Med 1994 154 1433-41. 

ACh receptor Atropine Antagonistic block, inhibiting transmission Paralysis, and reduces the effects of nicotinoids and ACh useful as an antidote against organophosphorus and carbamate poisoning... 

Willems JL, Nicaise M, DeBisschop HC Delayed neuropathy by the organophosphorus nerve agents soman and tabun. Arch Toxicol 55 76-77, 1984 Xintaras C, Burg JR, Tanaka S, et al NIOSH Health Survey of Velsicol Pesticide Workers Occupational Exposure to Leptophos and Other Chemicals. Cincinnati, OH, U.S. Department of Health, Education, and Welfare, 1978 Zwiener RJ, Ginsburg CM Organophosphate and carbamate poisoning in infants and children. Pediatrics 81 121-126, 1988... 

Goswamy, R., Chaudhuri. A., and Maha.shur, A. A. (1994), Study of respiratory failure in organophosphate and carbamate poisoning. Heart Lmg 23,466-472. 

Lifshit/, M., Shahak, E., Bolotin, A., and Snfer, S. (1997) Carbamate poisoning in early childhood and in adults. J. Toxicol. Clin. Toxicol. 35, 2,5-27,... 

Persistent acquired inhibition of red blood cell AChE through OP or possibly carbamate poisoning. 

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