Indirect-Acting Cholinergic Agonists: Pharmacokinetics

Indirect-acting cholinergic agonists act by inhibiting acetylcholinesterases, to prevent ACh hydrolysis and enhance cholinergic activity in the body.

The pharmacokinetic properties of these agents are influenced by their structural characteristics.

For instance, agents bearing a quaternary nitrogen are relatively polar, resulting in poor oral absorption. So, the effective oral doses required are higher than the equivalent parenteral dose. Additionally, their low-lipid solubility restricts CNS distribution.

In contrast, agents with tertiary substitution being less polar are well absorbed by different routes, including the ocular route. So, they are commonly used as topical eye drops.

Organophosphates, on the other hand, are highly lipid-soluble and are rapidly absorbed by all routes. They are readily distributed throughout the body, including the CNS.

Following the distribution, these agents are metabolized by esterases in the liver, plasma and skeletal muscles.

The resulting metabolites formed are primarily excreted unchanged through the renal route.