Usage
Pilocarpine is prescribed for the treatment of dry mouth (xerostomia) caused by radiation therapy for head and neck cancer or Sjögren’s syndrome. It is also used in ophthalmology to treat glaucoma and ocular hypertension. Other ophthalmic uses include inducing miosis (pupil constriction) to reverse mydriasis (pupil dilation), treating presbyopia, and prior to or during some laser eye surgeries. Pilocarpine can also be used to induce status epilepticus in animal models of epilepsy.
Its pharmacological classification is a cholinergic agonist or parasympathomimetic agent, specifically a muscarinic agonist.
Pilocarpine’s mechanism of action involves stimulating muscarinic receptors, mimicking the effects of acetylcholine. This leads to increased secretions from exocrine glands, such as salivary, lacrimal, and sweat glands, resulting in increased salivation, tear production, and sweating, respectively. In the eye, it causes miosis, ciliary muscle contraction, and increased aqueous humor outflow, which helps lower intraocular pressure.
Alternate Names
Pilocarpine hydrochloride, pilocarpine nitrate.
Brand names include Salagen, Isopto Carpine, Pilocar, and Qlosi.
How It Works
Pharmacodynamics: Pilocarpine acts as a non-selective muscarinic receptor agonist, binding to and activating M1, M2, and M3 receptors. Stimulation of M3 receptors on salivary gland cells leads to increased saliva production. Similarly, stimulation of M3 receptors in the eye causes miosis, ciliary muscle contraction, and increased aqueous humor outflow.
Pharmacokinetics:
- Absorption: Pilocarpine is well-absorbed orally. Food can increase the absorption rate. Following ophthalmic administration, systemic absorption can occur, especially with higher concentrations.
- Metabolism: Pilocarpine is metabolized by pilocarpine esterase in the plasma and liver. The metabolites have negligible pharmacological activity.
- Elimination: Primarily renal excretion, with a half-life of approximately 0.76-1.35 hours after oral administration and about 4 hours after ophthalmic administration.
Mode of Action: Pilocarpine binds directly to muscarinic receptors, triggering a cascade of intracellular events, including increased phosphoinositide turnover and calcium mobilization, leading to the physiological effects described above.
Receptor Binding: Pilocarpine is a non-selective muscarinic agonist, meaning it can bind to all subtypes of muscarinic receptors (M1-M5), but its clinical effects primarily result from M3 receptor activation.
Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Xerostomia: 5 mg orally three or four times a day. The dose can be titrated up to 10 mg per dose, not exceeding 30 mg/day. For Sjögren’s syndrome: 5 mg orally four times a day.
- Glaucoma/Ocular Hypertension: 1-2 drops of 1%, 2%, or 4% pilocarpine ophthalmic solution instilled in the affected eye(s) up to four times daily.
- Presbyopia: One drop of pilocarpine 1.25% ophthalmic solution daily in each eye.
Children:
- Use and dose must be determined by a doctor. Ophthalmic use of up to 2% pilocarpine appears to be safe in children.
Special Cases:
- Elderly Patients: Increased risk of mental status changes (psychosis, dementia). Start with lower doses and titrate cautiously.
- Patients with Renal Impairment: Caution advised. No specific dosage adjustments are available, but close monitoring is necessary.
- Patients with Hepatic Dysfunction: Mild impairment: No dosage adjustment necessary. Moderate impairment: 5 mg twice daily, then adjust based on response and tolerability. Severe impairment: Not recommended.
- Patients with Comorbid Conditions: Caution advised in patients with asthma, cardiovascular disease, peptic ulcer disease, urinary tract obstruction, and Parkinson’s disease.
Clinical Use Cases
- Intubation: Not typically used for intubation in clinical practice. Other neuromuscular blocking agents are preferred.
- Surgical Procedures: Used in ophthalmic surgery to induce miosis prior to procedures or during surgery for acute angle-closure glaucoma.
- Mechanical Ventilation: Not typically used. Other agents are preferred for muscle relaxation during mechanical ventilation.
- Intensive Care Unit (ICU) Use: Limited role in the ICU setting. May be used occasionally for the treatment of glaucoma.
- Emergency Situations: Used in the emergency treatment of acute angle-closure glaucoma.
Dosage Adjustments:
Dosage adjustments may be needed based on patient-specific factors like renal/hepatic dysfunction and individual response to therapy.
Side Effects
Common Side Effects
Sweating, nausea, rhinitis, chills, flushing, urinary frequency, asthenia, headache, vision changes (blurred vision, myopia), eye irritation or pain (with ophthalmic use).
Rare but Serious Side Effects
Bradycardia, hypotension, bronchospasm, pulmonary edema, acute angle closure glaucoma (especially in predisposed individuals), retinal detachment.
Long-Term Effects
Potential for chronic complications like cataracts and visual field defects with long-term ophthalmic use.
Adverse Drug Reactions (ADR)
Severe bradycardia, hypotension, bronchospasm, and anaphylaxis require immediate intervention.
Contraindications
- Hypersensitivity to pilocarpine.
- Conditions where miosis is undesirable (e.g., acute iritis, anterior uveitis, some forms of secondary glaucoma).
- Uncontrolled asthma.
- Peptic ulcer disease.
Drug Interactions
- Beta-blockers: May potentiate bradycardia.
- Cholinesterase inhibitors: May enhance cholinergic effects.
- Anticholinergic drugs: May antagonize the effects of pilocarpine.
Pregnancy and Breastfeeding
Pilocarpine is Pregnancy Category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is unknown if pilocarpine is excreted in human milk. Caution should be exercised when administering to nursing mothers.
Drug Profile Summary
- Mechanism of Action: Muscarinic receptor agonist, stimulating exocrine gland secretions and causing miosis.
- Side Effects: Sweating, nausea, urinary frequency, blurred vision, eye irritation.
- Contraindications: Hypersensitivity, acute iritis, asthma, peptic ulcer.
- Drug Interactions: Beta-blockers, cholinesterase inhibitors.
- Pregnancy & Breastfeeding: Category C; use with caution.
- Dosage: Varies depending on indication and formulation; see detailed dosage section.
- Monitoring Parameters: Heart rate, blood pressure, respiratory function, intraocular pressure, visual acuity.
Popular Combinations
- Pilocarpine is sometimes combined with other glaucoma medications like beta-blockers or carbonic anhydrase inhibitors to achieve better control of intraocular pressure.
Precautions
- General Precautions: Assess for allergies, cardiac and respiratory disease, and other relevant medical conditions before starting treatment.
- Specific Populations: See detailed information above.
- Lifestyle Considerations: Advise patients to avoid driving or operating machinery if blurred vision or dizziness occurs.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Pilocarpine?
A: The dosage varies depending on indication and formulation. For dry mouth, it’s usually 5 mg three or four times daily, up to 30 mg/day. For glaucoma, 1-2 drops of 1%, 2%, or 4% ophthalmic solution up to four times daily. For presbyopia, one drop of pilocarpine 1.25% ophthalmic solution daily in each eye.
Q2: What are the common side effects of Pilocarpine?
A: Sweating, nausea, rhinitis, chills, flushing, urinary frequency, headache, blurred vision, eye irritation.
Q3: How does Pilocarpine work in treating glaucoma?
A: Pilocarpine activates muscarinic receptors in the eye, causing miosis, ciliary muscle contraction, and increased aqueous humor outflow, thus lowering intraocular pressure.
Q4: Can Pilocarpine be used during pregnancy?
A: Pilocarpine is Pregnancy Category C. Use only if the benefit outweighs the risk. Consult with an obstetrician.
Q5: Are there any drug interactions I should be aware of?
A: Yes, pilocarpine can interact with beta-blockers and cholinesterase inhibitors. Inform patients to report all medications they are taking, including OTC drugs and supplements.
Q6: What should I do if a patient experiences severe side effects?
A: Discontinue pilocarpine immediately and provide supportive care as needed. Severe bradycardia or bronchospasm may require treatment with atropine or epinephrine, respectively.
A: No, pilocarpine is not considered habit-forming.
Q8: Can Pilocarpine be used for other conditions besides dry mouth and glaucoma?
A: Yes, ophthalmic pilocarpine is used for inducing miosis, prior to some laser eye surgeries, and treating presbyopia.
Q9: What is the difference between pilocarpine hydrochloride and pilocarpine nitrate?
A: These are different salt forms of pilocarpine. They are essentially equivalent in terms of their clinical effects. The choice between them may depend on the specific formulation and manufacturer.
Q10: How long does it take for pilocarpine to start working for dry mouth?
A: Patients may experience some improvement within the first few doses, but it may take up to 12 weeks of therapy to fully assess the benefit.
