Pharmacology
Sympathetic Neurotransmission
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Get access- 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
Hot Topic
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
Hot Topic
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