Pilocarpine

Mechanism

💊 Commercial Names

Isopto Carpine, Pilocar, Pilogel (ophthalmic gel).

🔬 Pharmacological Group

Direct muscarinic cholinergic agonist (parasympathomimetic). Natural alkaloid.

Mechanism of Action

Pilocarpine directly stimulates the receptors of the parasympathetic autonomic system in the anterior pole of the eye:

• Activation of Muscarinic M₃ Receptors: It selectively couples to the M₃ receptors located in the iris sphincter muscle and the ciliary muscle, coupled to G proteins of the cell stimulant type (G_q).
• Active Pupillary Miosis: Contraction of the iris sphincter muscle causes intense symmetrical bilateral miosis. By pulling the iris toward the center of the pupil, it is physically removed from the iridocorneal angle, mechanically opening the occluded trabecular meshwork in narrow-angle glaucoma.
• Contraction of the Ciliary Muscle and Traction of the Scleral Spur: The stimulation of the M₃ receptors of the ciliary body causes the contraction of its longitudinal fibers. This contraction pulls the scleral spur and mechanically expands the cribriform trabecular meshwork, reducing conventional hydraulic resistance and maximizing the outflow of aqueous humor through Schlemm's canal.

Pharmacokinetics

Quantitative Ocular and Systemic Pharmacokinetics

Security

Risk of Retinal Detachment in Predisposed Eyes

The massive pilocarpine-induced contraction of the ciliary muscle physically pulls the choroid and peripheral retina forward, inducing shear forces at the base of the vitreous. In patients with high axial myopia, peripheral palisade reticular degeneration or a history of retinal tears, this sudden mechanical traction can trigger the formation of a de novo hole or an acute rhegmatogenous retinal detachment of severe progression. The use of pilocarpine requires indirect ophthalmoscopy with indentation of the retinal periphery prior to its initiation.

Contraindications

• Absolute: Neovascular or glaucoma secondary to active inflammation (miosis increases the probability of subsequent synechiae formation); acute anterior uveitis; high myopia (> -6.00 diopters) or history of active peripheral retinal pathology; pre-existing retinal detachment or family history.
• Relative: Young patients under 40 years of age (accommodation spasm induces induced myopization that is difficult to tolerate refractively).

Adverse Effects (ADR)

• Local Ocular: Accommodation spasm (induced myopization) with blurred vision for distant objects; Dull ciliary pain or supraorbital headache (due to continuous contraction of the ciliary body, it subsides after a few weeks); reduced visual field in low lighting conditions (due to persistent extreme miosis); conjunctival congestion and injection of ciliary vessels.
• Systemic: Profuse sweating (diaphoresis), intense sialorrhea, bronchial spasm with wheezing, cardiac bradycardia, gastrointestinal cramps and increased bladder motility of cholinergic origin.

Drug Interactions

• Topical Anticholinergics (Atropine, Tropicamide): Reciprocal competitive pharmacodynamic antagonism that completely cancels the miotic effect and the ocular hypotensive effect of pilocarpine.