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Direct-Acting Cholinergic Agonists: Therapeutic Uses01:11

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Direct-acting cholinergic agonists have many therapeutic uses in various medical fields. Choline esters, including acetylcholine, have limited clinical utility due to their non-selectivity and short duration of action. Still, acetylcholine and carbachol are applied topically during ophthalmologic surgery to induce miosis. Pilocarpine, a muscarinic and ganglionic stimulator, effectively treats open-angle glaucoma and alleviates xerostomia and dry mouth caused by radiotherapy or Sjögren...
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Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...
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Direct-Acting Cholinergic Agonists: Pharmacological Actions00:59

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Direct-acting cholinergic agonists exert their pharmacological actions by mimicking the effects of acetylcholine on postsynaptic muscarinic receptors to generate parasympathetic responses. These agents elicit a range of physiological responses, including cardiovascular effects. For example, activation of muscarinic receptors induces bradycardia, decreased cardiac output, reduced peripheral resistance, and consequent hypotension. In the eye, stimulation of M3 receptors leads to smooth muscle...
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In open-angle glaucoma, the iridocorneal angle remains open, but the trabecular meshwork becomes stiff, slowing down the outflow of aqueous humor. This causes a buildup of aqueous humor in the anterior chamber, leading to a sudden increase in intraocular pressure. The treatment for open-angle glaucoma focuses on reducing the elevated intraocular pressure by either decreasing the secretion of aqueous humor or increasing its outflow.
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Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
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Area of Science:

  • Ophthalmology
  • Pharmacology

Background:

  • Pharmacological mydriasis during dilated eye exams can cause prolonged light sensitivity and blurred vision.
  • Delayed visual recovery after mydriasis presents a barrier to routine eye examinations.

Purpose of the Study:

  • To evaluate the efficacy of phentolamine mesylate ophthalmic solution (PMOS) in rapidly reversing pharmacologically induced mydriasis.
  • To assess the impact of PMOS on pupil diameter and accommodative function.

Main Methods:

  • A double-masked, placebo-controlled, randomized, two-arm crossover phase 2b trial was conducted.
  • 1% PMOS was administered bilaterally to subjects whose pupils were dilated with phenylephrine or tropicamide.
  • Key endpoints included changes in pupil diameter, return to baseline pupil diameter, and accommodative function.

Main Results:

  • PMOS significantly reduced pupil diameter compared to placebo from 30 minutes onwards.
  • A higher percentage of subjects treated with PMOS returned to baseline pupil diameter at 2 and 4 hours post-administration.
  • PMOS improved accommodative amplitude recovery in the tropicamide subgroup, with no severe adverse events reported.

Conclusions:

  • 1% phentolamine mesylate ophthalmic solution effectively and rapidly reverses medically induced pupil dilation.
  • PMOS demonstrates a tolerable safety profile, regardless of the mydriatic agent used.
  • This solution may reduce barriers to dilated eye examinations by expediting visual recovery.