Cholinesterases recommendations

Organophosphates, such as methyl parathion, are known to inhibit cholinesterase activity. A method has been developed to measure the extent of this inhibition and relate it to organophosphate exposure (EPA 1980d Nabb and Whitfield 1967). In this EPA-recommended method, blood is separated into plasma and red blood cell fractions. The fractions are treated with saline solution, brought to pH 8 with sodium hydroxide, and dosed with acetylcholine perchlorate. The ensuing acetic acid releasing enzyme reaction... 

Cummings JL. Use of cholinesterase inhibitors in clinical practice evidence-based recommendations. Am J Geriatr Psych 2003 11 131-145. 

Because of the physiological variations of RBC-ACHE and PCHE levels, the sensitivity of these tests to detect low-level inhibitions can be increased by comparison with individual pre-exposure values, adopted as a reference. The World Health Organization (WHO, 1982) recommends calculating individual pre-exposure values as the average of three samples cholinesterase activities after exposure should be expressed as percentage change with... 

Occupational exposure to carbamate insecticides may be monitored by measuring RBC-ACHE and/or PCHE. However, given the low cholinesterase inhibition levels and the short time duration of this effect, ACHE inhibition can generally be used as a biomarker of exposure only when exposure levels are high. Three sequential samples are recommended to establish an individual baseline before exposure. In exposed workers, blood sampling and analysis should be carried out soon after the end of exposure (WHO, 1986). 

Procedure Cholinesterase activity in analyzed tissue or the matrix (biotest with immobilized AChE) is determined in the incubation media [consisting of substrate ATCh - 34 mmol maleate buffer 0.1 M, pH = 6.0- 6.5 ml sodium citrate 0.1 M - 0.5 ml CuS045H20 0.03M -1.0 ml distilled H20 (or inhibitor in variant with toxin analyzed) -1.0 ml potassium ferricyanide 0.005 M -1 ml.] Volume of incubation media in one test - 400 mcl. As a blank (control sample), a treatment of the exposure without the substrate is used. If inhibitory effects of allelochemical (or any toxin) are analyzed, before the substrate addition the sample was preliminary exposed to allelochemical inhibitor. Two methods for the AChE-biotests may be recommended (i) in microcells ( stationary conditions ) and (ii) in flowing columns-reactors ( dynamic conditions ). 

The WHO/FAO Joint Meeting of Experts on Pesticide Residues (JMPR) has given recommendations on interpretation of cholinesterase inhibition (FAO 1998, 1999), see Section 4.7.7.3.1. 

The therapeutic action of oximes resides largely In their capacity to reactivate cholinesterases without contributing markedly toxic actions of their own at recommended or usual doses. Other actions may contribute to their effectiveness they may react directly with the anticholinesterase agent,4 4 block its reaction with cholinesterase, 0 modulate the release of acetylcholine, 30,74 block acetylcholine s agonistic activity... 

In general, patients who miss several consecutive doses of cholinesterase inhibitors should resume treatment at the recommended... 

Cholinesterase inhibitors are the only class of drugs currently approved by most Health Authorities and recommended by professional associations (e.g. Doody et al.. 2001) for the symptomatic treatment of AD. However, ChE-Is intervene at a late stage of the pathophysiological cascade leading to AD (Fig. 7.2) furthermore, their efficacy is limited and they may cause a number of side effects, most frequently nausea, vomiting, diarrhea, anorexia and dizziness. For these reasons, major efforts are being made to alter the biological processes... 

If the products are cholinesterase inhibitors, a dermal dose-response rate protocol ( 2) is recommended. 

Studies on the scaleless chicken are underway examining its suitability as a model for assessing toxicity of organophosphates. The first compound selected for field trials was the defoliant DEF (S,S,S-tributylphosphorotrithioate) used during the harvesting of cotton in California and Arizona in the fall (October-November) when air movements are frequently restricted by inversions. DEF has been the subject of sufficient complaints to place it on the pre-RPAR list, although there are no reports of acute or delayed neurotoxicity in humans when it and related chemicals are used according to recommendations. It both inhibits cholinesterases and causes delayed neurotoxicity in hens (3,6). 

Recommendation 5c. The Army and its operating contractors should automate as much as feasible important medical information related to worker exposure to facilitate epidemiological studies. Automated information, available at the programmatic level, should include, but should not be limited to, results of medical examinations, evaluations of exposure to agents, measurements of cholinesterase levels, heat-stress data, and accident/injury information. 

The causes of syncope in patients with Alzheimer s disease treated with donepezil have been reported in 16 consecutive patients (12 women, 4 men) with Alzheimer s disease, mean age 80 years, who underwent staged evaluation, ranging from physical examination to electrophy-siological testing (54). The mean dose of donepezil was 7.8 mg/day and the mean duration of donepezil treatment at the time of syncope was 12 months. Among the causes of syncope, carotid sinus syndrome (n = 3), complete atrioventricular block (n = 2), sinus node dysfunction (n = 2), and paroxysmal atrial fibrillation (n = 1) were diagnosed. No cause of syncope was found in six patients. Non-invasive evaluation is recommended before withdrawing cholinesterase inhibitors in patients with Alzheimer s disease and unexplained syncope. 

Procedure. Initially, two families volunteered to have the Vaporizers installed in their homes in the recommended number of one per 1000 cubic feet of air. The members of the two families were observed regularly and tested for changes in the cholinesterase activity of their blood. They kept daily accounts of the amount of time spent in the house and maintained a continuous record of temperature and humidity. All were encouraged to report any hint of an adverse effect. These observations were made over the 6 months the Vaporizers were used in the homes. During the first 4 months of observation, new Vaporizers were installed monthly. Those installed at the beginning of the fourth month of observation remained, without change, during the fifth and sixth months of observation. 

Inhibition of the cholinesterase activity of the blood is the most sensitive means now available, with the possible exception of the inhibition of the esterase activity of the liver, for detecting the absorption of an organic phosphorus compound that is known to be capable of inducing this effect. The values indicative of cholinesterase activity are shown in Tables III and V. All subjects were exposed to the recommended dosage (one Vaporizer per 1000 cubic feet) except subjects 15 and 16, who were exposed to resin strips that contained no dichlorvos. 

For practical purposes (individual and interindividual variation), determination of individual norm activity is recommended (this approach is better than that of calculating the decrease from an average value) as well as separate determination of cholinesterases, the red blood cell AChE and plasma BuChE. The activity determined in the whole human blood corresponds to about 10% of BuChE and 90% of AChE. This is different to rats where this ratio is 29% of BuChE and 71% of AChE (Bajgar, 1972). Erythrocyte AChE activity seems to be more useful for these purposes than BuChE activity in plasma. 

Another laboratory value that is often obtained in these exposures is serum pseudoeholinesterase. Serum pseudocholinesterase activities are often assessed as normal in children because the reference standards may not be reliable when assessing children. To add to the complexity, the normal range of serum cholinesterase activity is wide (Sofer et al, 1989). Authors have described the limitations of this measurement in determining therapy for children. In fact, it is recommended that a therapeutic and diagnostic trial of atropine should be given whenever there is any possibility of intoxication with these chemicals (Sofer et al, 1989). 

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