Cholinesterase indirect

In AChE-based biosensors acetylthiocholine is commonly used as a substrate. The thiocholine produced during the catalytic reaction can be monitored using spectromet-ric, amperometric [44] (Fig. 2.2) or potentiometric methods. The enzyme activity is indirectly proportional to the pesticide concentration. La Rosa et al. [45] used 4-ami-nophenyl acetate as the enzyme substrate for a cholinesterase sensor for pesticide determination. This system allowed the determination of esterase activities via oxidation of the enzymatic product 4-aminophenol rather than the typical thiocholine. Sulfonylureas are reversible inhibitors of acetolactate synthase (ALS). By taking advantage of this inhibition mechanism ALS has been entrapped in photo cured polymer of polyvinyl alcohol bearing styrylpyridinium groups (PVA-SbQ) to prepare an amperometric biosensor for... 

Toxicology. Azinphos-methyl is an indirect inhibitor of cholinesterase. 

Some cholinesterase inhibitors also inhibit butyrylcholinesterase (pseudocholinesterase). Flowever, inhibition of butyrylcholinesterase plays little role in the action of indirect-acting cholinomimetic drugs because this enzyme is not important in the physiologic termination of synaptic acetylcholine action. Some quaternary cholinesterase inhibitors also have a modest direct action as well, eg, neostigmine, which activates neuromuscular nicotinic cholinoceptors directly in addition to blocking cholinesterase. 

Toxic substances can interfere with normal neurotransmission in a variety of ways, either directly or indirectly, and cause various central effects. For example, cholinesterase inhibitors such as the organo phosphate insecticides cause accumulation of excess acetylcholine. The accumulation of this neurotransmitter in the CNS in humans after exposure to toxic insecticides leads to anxiety, restlessness, insomnia, convulsions, slurred speech, and central depression of the respiratory and circulatory centers. 

FIGURE 19-1 T Mechanism of action of cholinergic stimulants. Direct-acting stimulants bind directly to the postsynaptic cholinergic receptor. Indirect-acting stimulants inhibit the cholinesterase enzyme, thus allowing acetylcholine to remain in the synaptic cleft. 

Cholinesterase inhibitors have less marked effects on vascular smooth muscle and on blood pressure than direct-acting muscarinic agonists. This is because indirect-acting drugs can modify the tone of only those vessels that are innervated by cholinergic nerves and because the net effects on vascular tone may reflect activation of both the parasympathetic and sympathetic nervous systems. The cholinomimetic effect at the smooth muscle effector tissue is minimal since few vascular beds receive cholinergic innervation. Activation of sympathetic ganglia may increase vascular resistance. 

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). 

Determination of cholinesterase activity is based on a number of principles. In general, an enzyme is added to the buffered or unbuffered mixture and the enzymatic reaction is initiated by adding the substrate. Different parts of the reaction mixture are determined (continually or noncontinuaUy), i.e. unhydrolyzed substrate or reaction products, either directly or indirectly (Augustinsson, 1971 Holmstedt, 1971 Witter, 1963). The conditions must be... 

The product was also compared to Fuller s earth in a pig model. The potency of the RSDL/sponge was statistically better than Fuller s earth against skin injury induced by sulfur mustard, observed 3 days post-exposure. RSDL was more efficient than Fuller s earth in reducing the formation of perinuclear vacuoles and inflammation processes in the epidermis and dermis. The potencies of the RSDL/sponge and Fuller s earth were similar to severe inhibition of plasma cholinesterases induced by VX poisoning. Both systems completely prevented cholinesterase inhibition, which indirectly indicates a prevention of toxic absorption through the skin (Taysse et al, 2007). 

Cholinesterase inhibitors increase parasympathetic nervous system (cholinergic) activity indirectly by inhibiting acetylcholinesterase, thereby preventing the breakdown of acetylcholine. They are only effective in the presence of acetylcholine. They are listed in Table 1. 

Trichlorfon is primarily an indirect inhibitor of AChE, that is, it is converted in the body to the active chemical inhibitor dichlorvos. In fact, trichlorfon is considered to be a slow release cholinesterase inhibitor, transformed nonenzymatically to dichlorvos. This leads to irreversible AChE inhibition by phosphorylation, primarily at the synapses of the nervous system and at the neuromuscular junctions. Dichlorvos is... 

Increase blood sugar Increase peristalsis Indirect-acting Cholinesterase Inhibitors (anticholinesterase) Increase muscle tone... 

Cholinergic medication (cholinesterase inhibitors, anticholinesterase) has either a direct- or indirect-acting effect on receptor sites. Direct and indirect effects inhibit the action of the enzyme cholinesterase (acetylcholinesterase). By inhibiting cholinesterase, more acetylcholine is available to stimulate the receptor and remains in contact with the receptor longer. 

Miotics Cholinergics and beta-adrenergic blockers Indirect-acting cholinesterase inhibitors Short acting Beta-adrenergic blockers Carbonic anhydrase Inhibitors... 

Compounds that inhibit or inactivate the body s normal hydrolysis of acetylcholine by acetylcholinesterase in nervous tissue and/or by butyrylcholinesterase (pseudocholinesterase, cholinesterase) in the plasma are called anticholinesterases. The gross observable pharmacological effects of both types of compounds are quite similar. More recently, compounds have been found that enhance the release of acetylcholine from cholinergic nerve terminals, thus (like the anticholinesterases) producing cholinergic effects by an indirect mechanism. 

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