Acetylcholine

Acetylcholine is the endogenous neurotransmitter of all autonomic ganglia, parasympathetic postganglionic endings, the neuromuscular junction and many central synapses. As a medicine it is used almost only as an intraocular miotic during anterior segment surgery and, in specialist catheter laboratories, as an intracoronary provocation agent. Its action is brief because tissue and plasma cholinesterases hydrolyse it within seconds.

Classification. Direct acting cholinergic agonist; choline ester with both muscarinic and nicotinic activity.

Mechanism. Binds muscarinic M3 receptors on the iris sphincter, producing rapid miosis. In coronary arteries with intact endothelium it releases nitric oxide and dilates; where endothelium is damaged, direct smooth muscle M3 stimulation causes constriction, which is the basis of vasospasm testing.

Pharmacodynamics. Intracameral miosis begins within seconds and lasts about 10 to 20 minutes. Systemic effects, if any drug is absorbed, are bradycardia, hypotension, flushing, bronchoconstriction and increased secretions.

Pharmacokinetics. Hydrolysed by acetylcholinesterase and butyrylcholinesterase to choline and acetate; half life is measured in seconds. Oral and systemic routes have no therapeutic use.

Intraoperative miosis, adult. Acetylcholine chloride intraocular solution 1% (10 mg/mL after reconstitution), 0.5 to 2 mL instilled gently into the anterior chamber by the surgeon, single dose. No loading, maintenance or titration applies. Where longer miosis is needed, the surgeon adds or substitutes intracameral carbachol.

Coronary vasospasm provocation, specialist use. Incremental intracoronary boluses, usually 20, 50 and 100 micrograms into the left coronary artery and 20 to 50 micrograms into the right, each over about 20 seconds, with angiography and ECG after each dose. The test stops at a positive response, chest pain with ischaemic ECG change, or the maximum dose. This is off label and is done only by an interventional team with temporary pacing available.

Children. Intraocular use in paediatric cataract surgery follows the adult volume range at the surgeon's judgement; no weight based dose exists.

Contraindications. Hypersensitivity to the product. For intracoronary testing: unstable coronary syndrome, severe left main disease and uncontrolled asthma.

Warnings. Systemic absorption is uncommon but can cause bradycardia, hypotension and bronchospasm. Caution in asthma, heart failure, heart block, active peptic ulcer, hyperthyroidism, parkinsonism and urinary outflow obstruction.

Adverse effects. Ocular: corneal oedema, corneal clouding and decompensation with excess volume, transient raised intraocular pressure. Intracoronary: transient complete heart block, sinus bradycardia, severe spasm, atrial fibrillation.

Interactions. Topical nonsteroidal anti-inflammatory eye drops given before surgery may blunt the miotic effect. Systemic cholinesterase inhibitors prolong any absorbed drug.

Special groups.

• Pregnancy: no human data; systemic exposure after intraocular use is negligible.

• Breastfeeding: compatible after intraocular use.

• Older adults: no adjustment.

• Kidney and liver impairment: no adjustment; elimination is by esterases.

Reversal. Atropine 0.5 to 1 mg IV reverses systemic muscarinic effects in adults; in the catheter laboratory, intracoronary glyceryl trinitrate 100 to 200 micrograms relieves induced spasm.

Preparation. Reconstitute immediately before use; the solution is unstable once mixed. Use only if clear and colourless and discard any remainder. Do not use a cloudy or precipitated solution.

Administration. Instil slowly through a blunt cannula into the anterior chamber, after lens delivery. Never give intravenously.

Monitoring. Intraoperative: degree of miosis and corneal clarity. Postoperative: intraocular pressure at the first review. Intracoronary: continuous 12 lead ECG, blood pressure, symptoms and angiography after each increment.

Common prescribing errors. Using a solution that was reconstituted earlier; overfilling the anterior chamber; attempting intracoronary testing without pacing back up.