Plasma esterases

The answer is local anesthetic properties it can block the initiation or conduction of a nerve impulse. It is biotransformed by plasma esterases to inactive products. In addition, cocaine blocks the reuptake of norepinephrine. This action produces CNS stimulant effects including euphoria, excitement, and restlessness Peripherally, cocaine produces sympathomimetic effects including tachycardia and vasoconstriction. Death from acute overdose can be from respiratory depression or cardiac failure Cocaine is an ester of benzoic acid and is closely related to the structure of atropine. 

Esmolol hydrochloride is a competitive p-adrenergic receptor antagonist it is selective for pT adrenoceptors. In contrast to pindolol, esmolol has little intrinsic sympathomimetic activity, and it differs from propranolol in that it lacks membrane stabilizing activity Of all of the p-adrenergic blocking drugs, this compound has the shortest duration of action because it is an ester, it is hydrolyzed rapidly by plasma esterases and must be used by the intravenous route Esmolol is approved only for the treatment of supraventricular arrhythmias... 

Remifentanil This is the exceptional drug in anaesthetic practice in that it is context insensitive. Draw a straight line starting from the origin and becoming near horizontal after the CSHT reaches 5 min. This demonstrates that the half time is not dependent on the length of infusion as clearance by plasma esterases is so rapid. 

The physiological functions of carboxylesterases are still partly obscure but these enzymes are probably essential, since their genetic codes have been preserved throughout evolution [84] [96], There is some evidence that microsomal carboxylesterases play an important role in lipid metabolism in the endoplasmic reticulum. Indeed, they are able to hydrolyze acylcamitines, pal-mitoyl-CoA, and mono- and diacylglycerols [74a] [77] [97]. It has been speculated that these hydrolytic activities may facilitate the transfer of fatty acids across the endoplasmic reticulum and/or prevent the accumulation of mem-branolytic natural detergents such as carnitine esters and lysophospholipids. Plasma esterases are possibly also involved in fat absorption. In the rat, an increase in dietary fats was associated with a pronounced increase in the activity of ESI. In the mouse, the infusion of lipids into the duodenum decreased ESI levels in both lymph and serum, whereas an increase in ES2 levels was observed. In the lymph, the levels of ES2 paralleled triglyceride concentrations [92] [98],... 

Another application is the esterification of menahydroquinone-4, a water-insoluble vitamin K, with V,A-dimethylglycine [144], The 1-mono, 4-mono, and 1,4-bis esters were found to be water-soluble and rapidly hydrolyzable by liver and plasma esterases. A rapid pharmacodynamic response was seen after intravenous administration of the prodrugs. 

G. K. E. Scriba, Phenytoin-Lipid Conjugates Chemical, Plasma Esterase-Mediated, and Pancreatic Lipase-Mediated Hydrolysis in vitro, Pharm. Res. 1993, 10, 1181 — 1186. 

The interactions between transmitters and their receptors are readily reversible, and the number of transmitter-receptor complexes formed is a direct function of the amount of transmitter in the biophase. The length of time that intact molecules of acetylcholine remain in the biophase is short because acetylcholinesterase, an enzyme that rapidly hydrolyzes acetylcholine, is highly concentrated on the outer surfaces of both the prejunctional (neuronal) and postjunctional (effector cell) membranes. A rapid hydrolysis of acetylcholine by the enzyme results in a lowering of the concentration of free transmitter and a rapid dissociation of the transmitter from its receptors little or no acetylcholine escapes into the circulation. Any acetylcholine that does reach the circulation is immediately inactivated by plasma esterases. 

Esmolol is used in the treatment of supraventricular tachyarrhythmias for rapid control of ventricular rate and reduction of myocardial oxygen consumption. Discontinuation of administration is followed by a rapid reversal of its pharmacological effects because of es-molol s rapid hydrolysis by plasma esterases. 

Propacetamol, the soluble diethylglycidyl ester of paracetamol, is a prodrug which is completely and rapidly hydrolysed by non-specific plasma esterases to paracetamol, and is available for intravenous use. One gram IV propacetamol yields 0.5 g paracetamol. Propacetamol has similar analgesic efficacy to ketorolac for the treatment of postoperative pain (Varrassi and co-workers 1999). 

Metabolism of the local anesthetic procaine provides an example of esterase action, as shown in Figure 4.43. This hydrolysis may be carried out by both a plasma esterase and a microsomal enzyme. 

The hydrolysis of amides can also be catalyzed by nonspecific plasma esterases but is slower than that of esters. However, hydrolysis of amides is more likely to be catalyzed by the amidases in the liver. 

Scriba, G K. E. 1993. Phenytoin-lipid conjugates chemical, plasma esterase-mediated, and pancreatic lipase-mediated hydrolysis vitro. Pharm. Res10 1181-1186. 

Drug Discovery Today 7 25-27 Li AP (2004) In vitro approaches to evaluate ADMET drug properties. Curr Top Med Chem 4 701-706 Li W, Escarpe PA, Eisenberg EJ et al. (1998) Identification of GS 4104 as an orally bioavailable prodrug of the influenza virus neuraminidase inhibitor GS 4071. Antimicrobial Agents and Chemotherapy 42 647-653 Los LE, Welsh DA, Herold EG et al. (1996) Gender differences in toxicokinetics, liver metabolism, and plasma esterase activity observations from a chronic (27-week) toxicity study of enalapril/diltiazem combinations in rats. Drug Metab Dispos 24 28-33... 

Los LE, Welsh DA, Herold EG et al. (1996) Gender differences in toxicokinetics, liver metabolism, and plasma esterase activity observations from a chronic (27-week) toxicity study of enalapril/ditiazem combinations in rats. Drug... 

Table I shows that the cholinesterase activity in the brain 24 hours after the third Di-Syston injection was approximately one third of the control value. Erythrocyte cholinesterase activity at the same time was inhibited to about the same degree, but the activity of the plasma esterase was only 25% of the control level. During the succeeding 21 days of the injection period the brain cholinesterase activity declined further and remained at the 20% level while the activity of the plasma enzyme in-...

Procaine is hydrolysed by plasma esterases to 4-aminobenzoic acid and diethylaminoethanol. 

Augustinsson, K.B. (1958). Electrophoretic separation and classification of blood plasma esterases. Nature 131 1786-9. 

Askew, B.M. (1956). Oximes and hydroxamic acids as antidotes in anticholinesterase poisoning. Br. J. Pharmacol. 11 417-23. Augustinsson, K-B. (1948). Cholinesterases a study in comparative azymo o. Acta Physiol. Scand. 15 (Suppl. 52) 1-182. Augustinsson, K-B. (1959). Electrophoresis studies on blood plasma esterases I. Mammalian plasmata. Acta Chem. Scand. 13 571-92. 

The liver, for the amide-type anesthetics, or plasma esterases, for the ester-type, can eliminate large amoimts of local anesthetics. Within 30 to 60 minutes sufficient elimination of the overdose usually occurs to make the CNS stimulation or depression short-lived. Management objectives should therefore center on temporary respiratory and cardiovascular support. Administration of supplemental oxygen usually rapidly restores normal CNS function. In patients in whom cardiovascular collapse is evident, vasopressor therapy may take the form of metaraminol bitartrate 1% (Aramine) given intramuscularly or intravenously. The effect of this potent short-acting vasopressor lasts 20 to 60 minutes, depending on route of administration. 

Ester compounds (cocaine, procaine, tetracaine, benzocaine) are hydrolysed by liver and plasma esterases and their effects may be prolonged where there is genetic enzyme deficiency. 

Articaine is an aminoamide that also contains an ester group, which is rapidly hydrolysed by plasma esterases. It is 4-methyl-3([2-(propylamino)propion-amido)]-2-thiophenecarboxylic acid, methyl ester hydrochloride. The thiophene group increases its lipid solubility while the ester group enables it to undergo plasma esterase hydrolysis as well as hepatic enzyme metabolism. Articaine is formulated as a 4% solution with adrenaline. It is the most widely used local anesthetic agent in dentistry in some parts of Europe. 

The onset of neuromuscular blockade typically occurs in 3-5 min of i.v. administration and lasts for 20-35 min. Higher doses will result in a longer duration of blockade. Pancuronium is eliminated primarily in bile and vecuronium undergoes hepatic and renal excretion. The recovery from blockade produced by atracurium is a result of metabolism by non-specific plasma esterases (hydrolysis) and spontaneous Hoffman degradation (spontaneous at body temperature and physiological pH), which is independent of renal or hepatic function and, therefore, unaffected by renal or hepatic disease (Plumb 1995). Atracurium does not accumulate. 

Ester-containing anesthetics such as cocaine, benzocaine, and tetracaine are extensively hydrolyzed by plasma esterases in addition to a contribution from hepatic esterases. 

Pyridostigmine is absorbed poorly after oral administration thus, oral doses must be higher than by the parenteral route. The drug is hydrolyzed by plasma esterases and is metabolized in the liver. Both the... 

Fentanyl is also hepatically metabolized and renally excreted. However, the congener remifentanil is metabolically distinct when compared to other members in its chemical or pharmacological class. Remifentanil is metabolized by plasma esterases to remifentanil acid, which is approximately 3000-fold less potent than the parent opioid (67). 

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