Indirect-acting cholinomimetics

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. 

The actions of acetylcholine released from autonomic and somatic motor nerves are terminated by enzymatic hydrolysis of the molecule. Hydrolysis is accomplished by the action of acetylcholinesterase, which is present in high concentrations in cholinergic synapses. The indirect-acting cholinomimetics have their primary effect at the active site of this enzyme, although some also have direct actions at nicotinic receptors. The chief differences between members of the group are chemical and pharmacokinetic—their pharmacodynamic properties are almost identical. 

AChE is a target for inhibitory drugs (indirect-acting cholinomimetics). Note that such drugs can influence cholinergic function only at innervated sites where ACh is released. 

Describe the pharmacodynamic differences between direct-acting and indirect-acting cholinomimetic agents. 

Indirect-acting cholinomimetic drug One that amplifies the effects of endogenous acetylcholine by inhibiting acetylcholinesterase... 

A. Classification and Prototypes The indirect-acting cholinomimetic drugs fall into two major chemical classes carbamic acid esters (carbamates neostigmine is a prototype) and phosphoric acid esters (phosphates, organophosphates echothiophate is a prototype). A third class has only one member edrophonium is an alcohol (not an ester) with a very short duration of action. 

Neostigmine is the prototypical indirect-acting cholinomimetic it is a quaternary (charged) substance with poor lipid solubility its duration of action is about 2-4 hours. The answer is (E). 

Following are a few examples of indirectly acting cholinomimetics (anticholinesterase drugs) demecarium bromide edrophonium chloride physostigmine salicylate and pyridostigmine bromide. 

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