Ester Local Anaesthetics

Ester local anaesthetics have an ester link between the aromatic and amine groups and are hydrolysed by plasma cholinesterase. They act quickly, have short half-lives, and carry higher allergy risk because para-aminobenzoic acid is released. Their use has fallen with the growth of amides, but they remain important for topical, ophthalmic, short spinal and ear, nose and throat use.

Mechanism. Same sodium channel blockade as amides. Duration is limited by rapid hydrolysis, so systemic toxicity is less likely with usual doses.

Pharmacokinetics. Plasma half-life of procaine and chloroprocaine is under 1 minute; tetracaine is longer because it binds proteins and hydrolyses more slowly. Reduced or atypical plasma cholinesterase (pregnancy, liver disease, genetic variants, organophosphate exposure) prolongs action and raises toxicity risk.

Chloroprocaine. Preservative-free 1% (spinal) 40 to 50 mg for short procedures, onset 5 to 10 minutes, duration about 60 to 90 minutes; epidural 2 to 3%, onset 5 to 10 minutes; maximum 11 mg/kg plain (800 mg) and 14 mg/kg with adrenaline (1 g). Low risk of transient neurological symptoms.

Procaine. 1 to 2% infiltration; short, weak, low potency. Procaine benzylpenicillin contains procaine; reactions to the procaine component (anxiety, hallucination, tachycardia after inadvertent intravascular injection) are distinct from penicillin allergy.

Tetracaine (amethocaine). Topical 4% gel for venepuncture and minor skin procedures in children (30 to 45 minutes before the procedure); ophthalmic drops 0.5%; high potency and toxicity; spinal use limited.

Benzocaine. Topical lozenges, sprays and gels for mucosal pain; large doses cause methaemoglobinaemia.

Cocaine. Topical 4% in ENT surgery as local anaesthetic and vasoconstrictor; maximum 1.5 mg/kg. Contraindicated in hypertension and with monoamine oxidase inhibitors.

Proparacaine (proxymetacaine). Ophthalmic drops 0.5% for tonometry and corneal procedures; not for repeated use.

• First-line. Topical tetracaine or proparacaine in eye procedures; tetracaine gel for needle procedures in children.
• Alternative. Chloroprocaine for short spinal and epidural anaesthesia in day surgery, when rapid recovery is wanted.
• Specialist. Topical cocaine in ENT surgery; benzocaine in endoscopic mucosal anaesthesia.
• Emergency. None; amides are preferred for emergency regional anaesthesia.

Selection. Use an ester when rapid offset matters or when the surface is mucosal. Choose an amide if the patient has had a reaction to an ester; if a reaction to an amide is documented, seek allergy testing.

Contraindications. Hypersensitivity to esters or para-aminobenzoic acid; known plasma cholinesterase deficiency; sulphonamide therapy (competitive antagonism); cocaine with hypertension, tachyarrhythmia, ischaemic heart disease and monoamine oxidase inhibitor treatment.

Serious adverse effects. Allergic contact dermatitis and anaphylaxis (para-aminobenzoic acid); methaemoglobinaemia with benzocaine; seizures and cardiovascular collapse with cocaine or tetracaine overdose; corneal toxicity with repeated ophthalmic doses; prolonged block in cholinesterase deficiency.

Major interactions.

• Sulphonamides: antagonism.
• Suxamethonium and other cholinesterase substrates: competition for hydrolysis and prolonged effect.
• Organophosphate exposure: reduced hydrolysis.
• Cocaine with adrenaline or monoamine oxidase inhibitors: hypertensive crisis.

Common prescribing errors.

• Applying tetracaine gel for longer than the labelled interval.
• Repeated topical benzocaine on mucosae.
• Using ophthalmic anaesthetic drops for ongoing pain relief.
• Unrecognised cross-use with a documented ester allergy.
• Cocaine maximum dose exceeded.

Special groups.

• Pregnancy: plasma cholinesterase falls; effect may be prolonged.
• Breastfeeding: compatible at usual doses.
• Children: avoid benzocaine in infants because of methaemoglobinaemia; weight-based limits for cocaine and tetracaine.
• Older adults: lower doses for neuraxial chloroprocaine.
• Kidney: little effect.
• Liver: reduced cholinesterase prolongs effect.
• East Africa: organophosphate pesticide exposure lowers plasma cholinesterase and prolongs ester and suxamethonium effects; ask about exposure before use.

Monitoring. Continuous ECG, pulse oximetry and blood pressure for any block; skin and mucosal review after topical use; methaemoglobin level when saturation does not respond to oxygen.

Referral and escalation. Anaphylaxis, methaemoglobinaemia with symptoms or level over 20%, suspected cholinesterase deficiency, corneal injury.

Comparison with alternative classes. Esters have faster offset and little accumulation but more allergy, shorter duration and sulphonamide antagonism; amides offer longer blocks and a better allergy profile.