Pilocarpine

Pilocarpine is a naturally occurring tertiary amine alkaloid that acts as a direct muscarinic agonist. Topically it constricts the pupil and opens the trabecular outflow; orally it stimulates residual salivary and lacrimal gland function. Its main uses are acute angle closure as a temporising miotic, presbyopia, and dry mouth after head and neck radiotherapy or in Sjögren syndrome.

Classification. Direct acting cholinergic agonist; muscarinic, with prominent M3 activity.

Mechanism. In the eye, contracts the iris sphincter, pulling the peripheral iris away from the angle, and contracts the ciliary muscle, increasing trabecular outflow. In exocrine glands, stimulates M3 receptors to increase saliva, tears and sweat.

Pharmacodynamics. Topical miosis starts in 10 to 30 minutes and lasts 4 to 8 hours; pressure falls within about 1 hour. Oral doses raise salivary flow within 20 minutes for 3 to 5 hours.

Pharmacokinetics. Oral peak about 1 hour; elimination half life about 1 hour, longer in liver impairment. Inactivated in plasma and liver and excreted in urine. Crosses the blood brain barrier.

Acute primary angle closure, adult. Start only after pressure has been lowered with acetazolamide, a topical beta blocker and alpha agonist, or a hyperosmotic agent, because an ischaemic iris sphincter does not respond.

• Pilocarpine 1% or 2% eye drops, one drop to the affected eye, repeated once after 15 to 30 minutes.

• Then one drop four times daily until laser peripheral iridotomy.

• Prophylaxis of the fellow eye: 1% one drop four times daily until iridotomy.

• Avoid 4% in the acute attack; it can worsen pupil block by forward lens movement.

Presbyopia, adult. Pilocarpine 1.25% one drop in each eye once daily; a second dose may be given 3 to 6 hours later. Newly licensed indication; availability varies.

Dry mouth after head and neck radiotherapy, adult.

• Start 5 mg orally three times daily.

• Titrate after 4 weeks to 10 mg three times daily if response is inadequate and the drug is tolerated.

• Maximum 30 mg daily.

• Assess benefit at 12 weeks; stop if no benefit.

Dry mouth in Sjögren syndrome, adult. 5 mg orally four times daily; maximum 30 mg daily. Benefit usually appears within 6 weeks.

Sweat test. Pilocarpine iontophoresis stimulates localised sweating for chloride measurement in suspected cystic fibrosis; dosing is fixed by the device.

Children. Oral use not established. Topical use in paediatric glaucoma is specialist only.

Contraindications. Uncontrolled asthma; acute iritis or uveitis; conditions where miosis is harmful, including neovascular and lens induced glaucoma; hypersensitivity.

Warnings. Caution in controlled asthma, chronic obstructive pulmonary disease, significant cardiovascular disease, cholelithiasis and nephrolithiasis (smooth muscle contraction can precipitate colic), and cognitive or psychiatric disorders. Miotics increase risk of retinal detachment in myopic eyes and those with peripheral retinal disease; examine the retina before long term use.

Adverse effects.

• Ocular: brow ache, accommodative spasm, induced myopia, dim vision in poor light, conjunctival hyperaemia.

• Systemic: sweating (most common, dose related), nausea, rhinitis, urinary frequency, flushing, diarrhoea, dizziness, bradycardia.

Interactions. Beta blockers increase the risk of conduction disturbance. Anticholinergic drugs oppose its effect. Additive effect with other cholinergic agents.

Driving. Miosis impairs vision at night and in dim light; advise against night driving.

Special groups.

• Pregnancy: limited data; topical use acceptable with punctal occlusion; oral use only where benefit is clear.

• Breastfeeding: oral use not advised because of limited data; topical use acceptable.

• Older adults: greater visual disturbance from miosis with cataract; falls risk.

• Liver impairment: Child-Pugh B, start oral at 5 mg twice daily and titrate; avoid oral use in Child-Pugh C.

• Kidney impairment: no adjustment established; titrate with care.

Formulations. Eye drops 1%, 2%, 4%; 1.25% presbyopia drops; tablets 5 mg and 7.5 mg in some markets.

Eye drop technique. Apply finger pressure over the lacrimal sac for 1 minute after instillation to cut systemic absorption. Separate from other drops by at least 5 minutes.

Oral. Take with food or a glass of water to reduce nausea; fluid intake should cover sweating.

Monitoring. Acute angle closure: intraocular pressure every 30 to 60 minutes until controlled, pupil size and gonioscopy. Long term topical use: visual acuity and peripheral retinal examination. Oral: symptom response, sweating, heart rate, and dehydration in hot climates.

Stopping. Stop oral treatment if no benefit at 12 weeks or with intolerable sweating. Stop drops after successful iridotomy unless needed for plateau iris.