Neurotransmitters

Acetylcholine: acts at autonomic ganglia
Adrenaline (epinephrine)
Noradrenaline (norepinephrine)

The hydroxylation of tyrosine synthesises DOPA which is then converted to dopamine and finally to adrenaline and noradrenaline

Dopamine beta-hydroxylase converts dopamine to noradrenaline
Adrenaline is formed by methylation of noradrenaline

The action of adrenaline and noradrenaline is terminated by presynaptic reuptake and enzyme degradation by monoamine oxidases and catechol-0-methyltransferase (COMT)

## Adrenergic agonists

Phenylephrine: synthetic sympathimometric

Acts directly on alpha-receptors

Phenylephrine cannot produce mydriasis in bright light and produces a rebound miosis. Hence it is often combined with cyclopentolate

Cocaine: works by preventing noradrenaline reuptake into nerve endings

Can be used to diagnosis pre- or post-ganglionic Horner syndrome (fails to dilate)

Apraclonidine: alpha2-agonist (with weak alpha1 agonist activity, hence use in Horner’s)

Lowers IOP be decreasing aqueous humour formation (as above, alpha2-receptors stimulate aqueous production via adenylate cyclase)
Does not penetrate the blood aqueous barrier

Brimonidine: selective alpha2-agonist

Used to reduce IOP by reducing aqueous production (by interfering with adenyl cyclase) and increasing outflow (by stimulating TM adrenergic receptors, increasing cAMP)
Less effective than latanoprost
Causes miosis (can sometimes be utilised intentionally)
Ocular side effects: allergic blepharoconjunctivits, CMO in aphakia
Contraindicated in heart block/bradycardia

Hydroxyamphetamine: releases noradrenaline from nerve terminals

Adrenergic agonists are mydriatic but anticholinergics are both mydriatic and cycloplegic (since the ciliary body is primarily under parasympathetic control)

## Adrenergic antagonists

Timolol: beta-antagonist (non-selective)

Beta-adrenergic blockade in the non-pigmented ciliary epithelium{' '} reduces aqueous production (by disrupting adenyl cyclase action)
Side effects: bronchospasm, bradycardia, syncope, CNS depression, may mask hypoglycaemia
10% of patients do not show therapeutic response to beta-blockers

And the response is reduced in those on systemic beta-blockers

The additive effect of beta-blockers is greatest with topical carbonic anhydrase inhibitors
Betaxolol is a selective blocker but is less effective than timolol
Carteolol produces less bradycardia than timolol

Guanethidine: inhibits release of noradrenaline from nerve terminals (chemical sympathectomy)

Inhibits Mullers muscle: narrows palpebral fissure