Pilocarpine

Mechanism

Mechanism of Action

Natural tertiary alkaloid derived from leaves of shrubs of the genus *Pilocarpus*. It acts as a non-selective muscarinic agonist with rapid systemic and ophthalmic penetration. In topical ocular administration, it stimulates the M₃ receptor in the iris sphincter muscle, causing immediate pupillary contraction (miosis) and ciliary muscle (accommodation). The contraction of the ciliary muscle pulls on the scleral spur, widening the adjacent trabecular network and facilitating the drainage of aqueous humor through Schlemm's canal, drastically reducing intraocular pressure. In systemic administration, it intensely stimulates the secretion of exocrine glands (salivary, lacrimal, sweat).

Pharmacokinetics

Key Pharmacokinetics

• Routes: Topical ophthalmic (1-4% eye drops), oral (tablets).
• Oral bioavailability: Moderate, significantly reduced in the presence of previous fatty meals.
• Metabolism: Partially hepatic through enzymatic hydrolysis reactions towards pilocarpic acid and other inactive polar metabolites.
• Half-life: Approximately 0.75 to 1.35 hours for the oral formulation.
• Excretion: Renal in the form of conjugated inactive metabolites.

Indicators and dose

Approved and Off-label Indications

Approved: Ophthalmic: Emergency treatment of acute narrow-angle glaucoma; induction of miosis after diagnostic ophthalmic mydriasis. Systemic: Treatment of severe xerostomia induced by head and neck radiotherapy, or associated with autoimmune Sjögren's Syndrome.

Off-label: Diagnostic test for autonomic dysfunction (modified quantitative sweat test).

Dosage and Adjustments

Xerostomia (Oral): 5 mg orally three times a day. It can be progressively increased up to 10 mg three times a day in patients with insufficient response after one month of stable therapy.

Narrow Angle Glaucoma (Ophthalmic): Instill 1 drop of 1% or 2% solution in the affected eye every 5 to 10 minutes until completing 3-6 doses, continuing according to intraocular pressor response.

Renal adjustment: No preliminary quantitative adjustment guidelines have been described.

Hepatic adjustment: In Child-Pugh Class B/C cirrhosis, reduce the initial dose by half (2.5 mg three times daily) and increase with close clinical caution.

Security

Contraindications

Absolute: Iritis or acute uveitis (where narrow miosis is undesirable); uncontrolled bronchial asthma; Primary narrow angle glaucoma without prior iridotomy.

Relative: Advanced chronic obstructive pulmonary disease, active cholelithiasis or urolithiasis, moderate renal failure.

Adverse Effects (ADR)

Common: Profuse diaphoresis (marked sweating), hypersalivation, urgent frequency, excessive tearing, blurred vision in dim conditions (due to fixed pharmacological miosis), supraorbital ciliary pain.

Serious: Retinal detachment (secondary to intense mechanical traction of the ciliary muscle), extreme bradycardia, refractory symptomatic systemic hypotension.

Interactions Systemic β-adrenergic blockers:

Drugs with intrinsic anticholinergic effect (antidepressants, neuroleptics): Direct antagonism of the secretory effect.

Pregnancy and Breastfeeding

FDA Classification: Category C. Potential toxicity to the fetus in experimental animal models. It is unknown if it is excreted in breast milk; Its use is not recommended during this period.