Pseudocholinesterase plasma

Acetylcholinesterase (EC 3.1.1.7) (AChE) Acetylcholine acetylhydrolase True ChE ChE I ChE Acet-ylthiocholinesterase Acetylcholine hydrolase Acetyl (3-methylcholinesterase Erythrocyte ChE Butyrylcholinesterase (EC 3.1.1.8) (BChE or BuChE) ChE Pseudocholinesterase Plasma ChE Acylcholine acylhydrolase Non-specific ChE ChEII Benzoylcholinesterase Propionylcholinesterase... 

Ester linkages are metabolized primarily by pseudocholinesterase, plasma cholinesterase and red... 

There is a second type of cholinesterase called butyrylcholinesterase, pseudocholinesterase, or cholinesterase. This enzyme is present in some nonneural cells in the central and peripheral nervous systems as well as in plasma and serum, the liver, and other organs. Its physiologic function is not known, but is hypothesized to be the hydrolysis of esters ingested from plants (Lefkowitz et al. 1996). Plasma cholinesterases are also inhibited by organophosphate compounds through irreversible binding this binding can act as a detoxification mechanism as it affords some protection to acetylcholinesterase in the nervous system (Parkinson 1996 Taylor 1996). 

Sanz P, Rodriguez-Vicente MC, Diaz D, et al. 1991. Red blood cell and total blood acetylcholinesterase and plasma pseudocholinesterase in humans Observed variances. Clin Toxicol 29 81-90. 

Certain enzymes, proenzymes, and their substrates are present at all times in the circulation of normal individuals and perform a physiologic function in the blood. Examples of these functional plasma enzymes include lipoprotein Upase, pseudocholinesterase, and the proenzymes of blood coagulation and blood clot dissolution (Chapters 9 and 51). The majority of these enzymes are synthesized in and secreted by the liver. 

Succinylcholine 1-1.5 mg/kg IV up to 150 mg total dose ° Contraindications may include use in patients with a personal or family history of malignant hyperthermia, extensive/severe burns, myopathies with elevated creatine phosphokinase, penetrating eye injuries, pre-existing hyperkalemia, narrow-angle glaucoma, and disorders of plasma pseudocholinesterase... 

Consistent decreases in plasma cholinesterase may not have been observed in rats and dogs because they were treated with lower doses of diisopropyl methylphosphonate. In general, depression of plasma cholinesterase, also known as pseudocholinesterase or butyrylcholinesterase, is considered a marker of exposure rather than an adverse effect. Depression of cholinesterase activity in red blood cells (acetylcholinesterase) is a neurological effect thought to parallel the inhibition of brain acetylcholinesterase activity. It is considered an adverse effect. Acetylcholinesterase is found mainly in nervous tissue and erythrocytes. Diisopropyl methylphosphonate was not found to inhibit RBC... 

The inhibition of two cholinesterase activities in blood can also be used to confirm exposure to certain organophosphate ester compounds. Red blood cell acetylcholinesterase is the same cholinesterase found in the gray matter of the central nervous system and motor endplates of sympathetic ganglia. Synonyms for this enzyme include specific cholinesterase, true cholinesterase, and E-type cholinesterase. Plasma cholinesterase is a distinct enzyme found in intestinal mucosa, liver, plasma, and white matter of the central nervous system. Synonyms for this enzyme include nonspecific cholinesterase, pseudocholinesterase, butyrylcholinesterase, and S-type cholinesterase (Evans 1986). Nonspecific cholinesterase is thought to be a very poor indicator of neurotoxic effects. 

The classical role of AChEs is to terminate transmission of neuronal impulses by rapid hydrolysis of ACh. The closely related butyrylcholin-esterases (BuChEs) or pseudocholinesterases have a less stringent substrate specificity but their function remains ill-defined. In mammals, BuChE is found at high concentration in the plasma and the gut, where it has been... 

Inhibition of the two principal human cholinesterases, acetylcholinesterase and pseudocholinesterase, may not always result in visible neurological effects (Sundlof et al. 1984). Acetylcholinesterase, also referred to as true cholinesterase, red blood cell cholinesterase, or erythrocyte cholinesterase is found in erythrocytes, lymphocytes, and at nerve synapses (Goldfrank et al. 1990). Inhibition of erythrocyte or lymphocyte acetylcholinesterase is theoretically a reflection of the degree of synaptic cholinesterase inhibition in nervous tissue, and therefore a more accurate indicator than pseudocholinesterase activity of inhibited nervous tissue acetylcholinesterase (Fitzgerald and Costa 1993 Sundlof et al. 1984). Pseudocholinesterase (also referred to as cholinesterase, butyrylcholinesterase, serum cholinesterase, or plasma cholinesterase) is found in the plasma, serum, pancreas, brain, and liver and is an indicator of exposure to a cholinesterase inhibitor. 

Remifentanil, recently approved for use in the United States and Europe, is the first truly ultra-shortacting opioid. Remifentanil s uifique ester linkage allows it to be rapidly degraded to an inactive carboxylic acid metabolite by nonspecific esterases found in tissue and red blood cells. Since it is not a good substrate for plasma pseudocholinesterase, deficiency of the enzyme does not influence its duration of action. Also, hepatic and renal insufficiencies do not influence remifentanil s pharmacokinetics, so it is useful when liver or kidney failure is a factor. Because of its rapid clearance following infusion, remifentanil has gained popularity as an agent for maintenance of anesthesia when an IV technique is practical. 

Pharmacokinetics Systemic absorption of tetracaine is variable. Metabolized by plasma pseudocholinesterase. Excreted in the urine. 

The body contains two main classes of cholinesterase acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8).27 The former, sometimes referred to as true cholinesterase, Is mainly a tissue enzyme and Is found mainly In such tissues as the synapses of the cholinergic system It Is also found In other tissues, such as erythrocytes, where Its function Is uncertain. The latter, referred to as pseudocholinesterase, Is a soluble enzyme that is synthesized In the liver and circulates in the plasma-... 

Ester-type local anesthetics are hydrolyzed very rapidly in the blood by circulating butyrylcholinesterase (pseudocholinesterase) to inactive metabolites. Therefore, procaine and chloroprocaine have very short plasma half-lives (< 1 minute). 

The extremely short duration of action of succinylcholine (5-10 minutes) is due to its rapid hydrolysis by butyrylcholinesterase and pseudocholinesterase in the liver and plasma, respectively. Plasma cholinesterase metabolism is the predominant pathway for succinylcholine elimination. Since succinylcholine is more rapidly metabolized than mivacurium, its duration of action is shorter than that of mivacurium (Table 27-1). The primary metabolite of succinylcholine, succinylmonocholine, is rapidly broken down to succinic acid and choline. Because plasma cholinesterase has an enormous capacity to hydrolyze succinylcholine, only a small percentage of the original intravenous dose ever reaches the neuromuscular junction. In addition, as there is little if any plasma cholinesterase at the motor end plate, a succinylcholine-induced blockade is terminated by its diffusion away from the end plate into extracellular fluid. Therefore, the circulating levels of plasma cholinesterase influence the duration of action of succinylcholine by determining the amount of the drug that reaches the motor end plate. 

The major action resulting from human exposure to diazinon is the inhibition of cholinesterase activity (refer to Section 2.4 for discussion). Two pools of cholinesterases are present in human blood acetylcholinesterase in erythrocytes and serum cholinesterase (sometimes referred to as pseudocholinesterase or butyrlcholinesterase) in plasma. Acetylcholinesterase, present in human erythrocytes, is identical to the enzyme present in neural tissue (the target of diazinon action) while serum cholinesterase has no known physiological function. Inhibition of both forms of cholinesterase have been associated with exposure to diazinon in humans and animals (Coye et al. 1987 Edson and Noakes 1960 Soliman et al. 1982). Inhibition of erythrocyte, serum, or whole blood cholinesterase may be used as a marker of exposure to diazinon. However, cholinesterase inhibition is a common action of anticholinesterase compounds such as organophosphates (which include diazinon) and carbamates. In addition, a wide variation in normal cholinesterase values exists in the general population, and there are no studies which report a quantitative... 

Succinylcholine is a neuromuscular blocking agent, which is used clinically to cause muscle relaxation. Its duration of action is short due to rapid metabolism—hydrolysis by cholinesterases (pseudocholinesterase or acylcholine acyl hydrolase)—in the plasma and liver to yield inactive products (Fig. 7.55). Thus, the pharmacological action is terminated by the metabolism. However, in some patients, the effect is excessive, with prolonged muscle relaxation and apnea lasting as long as two hours compared with the normal duration of a few minutes. 

One of the drugs that is metabolized in the blood is succinylcholine, a muscle relaxant that is hydrolyzed by the pseudocholinesterase of liver and plasma to succinylmonocholine. The short duration of action of succinylmonocholine (5 min) is due to its rapid hydrolysis in plasma. Patients... 

After release from the presynaptic terminal, acetylcholine molecules may bind to and activate an acetylcholine receptor (cholinoceptor). Eventually (and usually very rapidly), all of the acetylcholine released will diffuse within range of an acetylcholinesterase (AChE) molecule. AChE very efficiently splits acetylcholine into choline and acetate, neither of which has significant transmitter effect, and thereby terminates the action of the transmitter (Figure 6-3). Most cholinergic synapses are richly supplied with acetylcholinesterase the half-life of acetylcholine in the synapse is therefore very short. Acetylcholinesterase is also found in other tissues, eg, red blood cells. (Another cholinesterase with a lower specificity for acetylcholine, butyrylcholinesterase [pseudocholinesterase], is found in blood plasma, liver, glia, and many other tissues.)... 

Flydrolysis is an important metabolic reaction for drugs whose structures contain ester and amide groups. All types of ester and amide can be metabolized by this route. Ester hydrolysis is often catalysed by specific esterases in the liver, kidney and other tissues as well as non-specific esterases such as acetylcholinesterases and pseudocholinesterases in the plasma. Amide hydrolysis is also catalysed by non-specific esterases in the plasma as well as amidases in the liver. More specific enzyme systems are able to hydrolyse sulphate and glucur-onate conjugates as well as hydrate epoxides, glycosides and other moieties. 

Quon et al. (1985) investigated the stability of esmolol in blood, plasma, red blood cells, and purified enzymes (human serum pseudocholinesterase, human and dog serum albumin, acetyl choline esterase, carbonic anhydrases A and B and human haemoglobin). Udata et al. (1999) studied the hydrolysis of propranolol ester prodrugs in purified acetylcholine esterase. 

PROCAINE ECOTHIOPATE t plasma concentrations and risk of unconsciousness, and cardiovascular collapse with injections of prilocaine Ecothiopate inhibits pseudocholinesterase, which metabolizes prilocaine Do not co-administer. Use an alternative local anaesthetic not subject to metabolism by pseudocholinesterases... 

PROCAINE DEPOLARIZING Possibly t plasma concentrations of both drugs, with risk of toxic effects Due to competition for metabolism by pseudocholinesterase Avoid co-administration... 

Plasma or serum cholinesterase (pseudocholinesterase) is inhibited by a munber of compounds and can also be decreased in ftie presence of liver impairment. Erythrocyte cholinesterase (true cholinesterase) reflects more accurately the cholinesterase status of the central nervous system. However, pseudocholinesterase activity responds more quickly to an inhibitor and returns to normal more rapidly than eiythrocyte-cholinesterase activity. Thus, measurement of pseudocholinesterase activity is quite adequate as a means of diagnosing acute exposure to organophosphorus compounds, but cases of illness which may be due to chronic exposure to these compounds should also be investigated by determining the erydirocyte-cholinesterase activity. A colorimetric method for this purpose has been reported (K.-B. Augustinsson et ah, Clinica chim. Acta, 1978, 89, 239-252). 

Pseudocholinesterase deficiency. The neuromuscular blocking action of suxamethonium is terminated by plasma pseudocholinesterase. True cholinesterase (acetylcholinesterase) hydrolyses acetylcholine released by nerve endings, whereas various tissues and plasma contain other nonspecific, hence pseudo, esterases. Affected individuals form so little plasma pseudocholinesterase that metabolism of suxamethonium is seriously reduced. The deficiency characteristically comes to light when a patient fails to breathe spontaneously after a surgical operation, and assisted ventilation may have to be undertaken for hours. Relatives of an affected individual—for this as for other inherited abnormalities carrying avoidable risk—should be sought out, checked to assess their own risk, and told of the result. The prevalence of pseudocholinesterase deficiency in the UK population is about 1 in 2500. 

Suxamethonium is destroyed by plasma pseudocholinesterase and so its persistence in the body is increased by neostigmine, which inactivates that enzyme, and in patients with hepatic disease or severe malnutrition whose plasma enzyme concentrations are lower than normal. Approximately 1 in 3000 of the European population have hereditary defects in amount or kind of enzyme, and cannot destroy the drug as rapidly as normal individuals. Paralysis can then last for hours and the individual requires ventilatory support and sedation until recovery occurs spontaneously. 

Low plasma pseudocholinesterase Succinylcholine Prolonged neuromuscular blockade leading to apnea... 

Plasma pseudocholinesterase Slow hydrolysis Succinylcholine Prolonged apnea... 

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