Biotransformation cholinesterases

The answer is d. (Hardman, p T36J The addition of a vasoconstrictor, such as epinephrine or phenylephrine, to certain short-acting, local anesthetics is a common practice in order to prevent the rapid systemic absorption of the local anesthetics, to prolong the local action, and to decrease the potential systemic reactions. Some local anesthetics cause vasodilation, which allows more compound to escape the tissue and enter the blood. Procaine is an ester-type local anesthetic with a short duration of action due to rather rapid biotransformation in the plasma by cholinesterases. The duration of action of the drug during infiltration anesthesia is greatly increased by the addition of epinephrine, which reduces the vasodilation caused by procaine. 

The metabolic degradation of local anesthetics depends on whether the compound has an ester or an amide linkage. Esters are extensively and rapidly metabolized in plasma by pseudochoUnesterase, whereas the amide linkage is resistant to hydrolysis. The rate of local anesthetic hydrolysis is important, since slow biotransformation may lead to drug accumulation and toxicity. In patients with atypical plasma cholinesterase, the use of ester-linked compounds, such as chloroprocaine, procaine and tetracaine, has an increased potential for toxicity. The hydrolysis of all ester-linked local anesthetics leads to the formation of paraaminobenzoic acid (PABA), which is known to be allergenic. Therefore, some people have allergic reactions to the ester class of local anesthetics. 

The nature of the configuration is the basis upon which local anaesthetics are classified. Ester local anaesthetics are characteristically unstable compounds that are broken down in the plasma by plasma cholinesterases. In contrast, the amide agents are very stable compounds that require extensive hepatic biotransformation. The more complex the linkage, the greater the tendency for toxicity. 

Cholinesterase- Blood Level of Pesticide Inhibiting or Biotransformation... 

Donepezil, rivastigmine, and galantamine are newer cholinesterase inhibitors with adequate penetration into the CNS and a spectrum of action more limited to indirect cholinomimetic effects than tacrine s. The cholinesterase inhibitors should be used with caution in patients receiving other drugs that inhibit cytochrome P450 enzymes (eg, ketoconazole, quinidine see Chapter 4 Drug Biotransformation). 

Because of its rapid biotransformation, methomyl does not tend to cause cumulative toxicity. However, repeated, frequent exposures could lead to cumulative inhibition of cholinesterase, resulting in flu-like symptoms including weakness, loss of appetite, and myalgia. 

Besides chlorinated pesticides, some of the phosphorous pesticides are also chiral (see Table 2.1). The phosphorous pesticides also differ in their enantioselective toxicities. These pesticides were introduced in the 1950s to control insects in fruit, vegetables and other crops. Malathion is biotransformed into a racemic malaxon that has anti-acetylcholinesterate (insecticidal) activity. The /f-enantiomer has a 22 times greater inhibitory potency than the 5-enantiomer for bovine erythrocyte cholinesterase [39, 40]. The nerve agent, soman, has two chiral centres, and the two (—)-diastereoisomers are more potent inhibitors than their corresponding (-1-)-counteiparts for acetylcholinesterase and a-chymotrypsin. 

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